Name	Title	Description	Data type
biogrid	biogrid	BioGRID	Interaction
gsea_cgp	gsea_cgp	GSEA CGP	GSEA perturbations
gsea_mir	gsea_mir	GSEA MIR	GSEA microRNA targets
intact	intact	IntAct	Interaction
jaspar_human	jaspar_human	Jasper	TF binding
microcosm	microcosm	microRNA targets	microRNA targets
mint	mint	MINT	Interaction
mips	mips	MIPS	Interaction
DRP000425	Homo sapiens T24 human bladder cancer cell line Transcriptome	No description.	Co-expression
DRP000464	pre-miRNA profiles obtained through application of locked nucleic acids reveals complex 5'/3' arm variation including concomitant cleavage and polyuridylation patterns	Recent research hints at an underappreciated complexity in pre-miRNA processing and regulation. Global profiling of pre-miRNA and its potential to increase understanding of the pre-miRNA landscape is impeded by overlap with highly-expressed classes of other non-coding RNA. Here we present a dataset excluding these RNA before sequencing through locked nucleic acids (LNA), greatly increasing pre-miRNA sequence counts with no discernable effects on pre-miRNA or mature miRNA sequencing. Analysis of profiles generated in total, nuclear, and cytoplasmic cell fractions reveals pre-miRNAs are subject to a wide range of regulatory processes involving loci-specific 3'- and 5'-end variation entailing complex cleavage patterns with co-occurring polyuridylation. Additionally, examination of nuclear-enriched flanking sequences of pre-miRNA, particularly those derived from polycistronic miRNA transcripts, provides insight into miRNA and miRNA-offset (moRNA) production. Our findings point to particularly intricate regulation of the let-7 family, introduce novel and unify known forms of pre-miRNA regulation and processing, and shed new light on the byproducts of miRNA processing pathways. none provided	Co-expression
DRP000499	Homo sapiens strain:Human ICESeq Genome sequencing	No description.	Co-expression
DRP000527	RNA sequencing of wild-type or mutant U2AF35 transduced HeLa Cells	To appreciate the biological/biochemical impact of these splicing mutations, we expressed the wild-type and the mutant (S34F) U2AF35 in HeLa cells and performed RNA sequencing.	Co-expression
DRP000665	Global transcriptional response against glucose deprivation	Using next generation sequencer, we investigated the global transcriptional time course-change against glucose deprivation in T24 bladder carcinoma cell line cells, which produced N-GlcNAc2-modified protein under glucose deprivation.	Co-expression
DRP000929	Human inactive X chromosome is compacted through a polycomb-independent SMCHD1-HBiX1 pathway [RNA-seq]	Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). These two histone marks are distributed in distinct domains, and XIST (X inactive specific transcript) preferentially colocalizes with H3K27me3 domains. Here, we show that Xi compaction requires HBiX1, a heterochromatin protein 1 (HP1)–binding protein, and SMCHD1 (structural maintenance of chromosomes hinge domain containing 1), both of which are enriched throughout the Xi chromosome. HBiX1 localization to H3K9me3 and XIST-associated H3K27me3 (XIST-H3K27me3) domains was mediated through interactions with HP1 and SMCHD1, respectively. Furthermore, HBiX1 was required for SMCHD1 localization to H3K9me3 domains. Depletion of HBiX1 or SMCHD1, but not Polycomb repressive complex 2 (PRC2), resulted in Xi decompaction, similarly to XIST depletion. Thus, the molecular network involving HBiX1 and SMCHD1 links the H3K9me3 and XIST-H3K27me3 domains to organize the compact Xi structure.	Co-expression
DRP000987	Interactive Transcriptome Analysis of Malaria Patients and Infecting Plasmodium falciparum in Indonesia	To understand the mutual association of the transcriptomes between host humans and infecting malaria parasites, Plasmodium falciparum (Pf), in vivo, we conducted the RNA-Seq analysis of 116 Indonesian malaria patients. Using RNAs extracted from peripheral blood of the patients as the mixture of the human and Pf transcripts, we generated a total of 3 billion RNA-Seq tags. Analysis of these tags allowed us to identify genes and pathways which were associated with clinical symptoms both on human and parasite sides. Particularly, we observed characteristic expression changes in the human innate immune response pathway genes depending on severity of malaria. We also identified a group of transcription regulatory factors and signaling molecule genes which have positive or negative correlations between humans and Pfs. These genes may change their expression patterns to accommodate the respective organisms to mutually conflicting environments. Furthermore, it was possible to utilize the RNA-Seq data for genotyping of the parasites to identify possible drug resistant genetic variations. By bypassing technical difficulty in preparing samples in field, this approach should provide a practically useful mean to describe mutually interacting transcritpomes of humans and parasites, which should eventually explain diverse malaria symptoms.	Co-expression
DRP001048	Transcriptome analysis of MCF-7 cells under hormonal deprivation and resveratrol treatment	MCF-7 human breast cancer cells acquire estrogen independent cell proliferation ability, when they are grown in the medium deprived of estrogen for an extended period (long term estrogen deprivation; LTED). This represents a cellular model for hormonal therapy resistance. On the other hand, phytoestrogen resveratrol (RES) inhibits the growth of breast cancer cells. In this study, we analyzed transcriptome of MCF-7 cells under LTED and RES treatment.	Co-expression
DRP001055	RNA sequence of mock/wild-type/mutant transduced Kasumi-1 cells	A cohesin component RAD21 is recurrently mutated in myeloid neoplasms. To investigate the role of RAD21 mutation in leukemogenesis, we performed RNA sequencing of mock, wild-type or mutant RAD21 transduced Kasumi-1 cells and compared their effect on global gene expression.	Co-expression
DRP001150	A promoter level mammalian expression atlas (human, RNA-Seq)	The FANTOM5 promoter expression atlas provides a rich source of expression and functional annotation of human and mouse cell-type specific transcriptomes with wide applications in biomedical research.	Co-expression
DRP001358	Single cell analysis of lung adenocarcinoma cell lines and the response to an anti-cancer drug stimulation	To understand heterogeneous behaviors of individual cancer cells, it should be important to investigate gene expression levels as well as their divergences between individual cells. Here we conducted a single cell RNA Seq analysis of a series of lung adenocarcinoma cell lines. We analyzed a total of 337 RNA Seq libraries of single cells and found gene expression diversities between individual cells are characteristic depending on genes. The genes showing highly variable expressions were enriched in particular pathways. Particularly, the EGFR pathway genes originally showed wider variations and further diversity was induced in response to an anticancer-drug stimulation. We also observed that cancer-related genes, which were identified from recent clinical cancer sequencing projects, showed potential expression variations, which firstly became apparent on the anti-cancer drug stimulation.	Co-expression
DRP001919	Omics catalogue of lung adenocarcinoma cell lines	Cancer cells carry various types of aberrations at the levels of genome, epigenome and transcriptome. For future studies on the biological relevance of the aberrations and their mutual relations, we generated a multi-omics catalogue of 26 lung adenocarcinoma cell lines. By whole-genome sequencing, we detected SNVs and indels, copy number aberrations and chromosome rearrangements. We used RNA-Seq to examine whether those mutation-harboring genes are expressed in the corresponding cell lines or whether their expression levels are deviated between the cell lines. Also, we could detect known and novel abnormal transcripts, such as RET- and ALK-fusion transcripts and transcripts caused by splice site mutations. Similarly, target-captured bisulfite sequencing and ChIP-Seq analyses revealed epigenomic status in each cell line and their deviations. We integrated these multi-omics data to explain possible causes of the observed aberrant gene expressions, particular for the representative cancer-related genes. We unexpectedly found that the patterns of aberrations were highly diverse between genes; namely irregular chromatin status revealed by ChIP-Seq was the characteristic to the EGFR, while a large genomic deletion and hyper-DNA methylation in the promoter region were the most frequent for the CDKN2A gene. Our datasets, by complementing current whole-exome or whole-genome sequencing of clinical cancers, should lay valuable base for interpreting how various types of genomic and epigenomic aberration lead to aberrant transcriptomic appearances in cancers.	Co-expression
DRP001953	Interactive Transcriptome Analysis of Malaria Patients and Infecting Plasmodium falciparum in Indonesia	To understand the mutual association of the transcriptomes between host humans and infecting malaria parasites, Plasmodium falciparum (Pf), in vivo, we conducted the RNA-Seq analysis of 116 Indonesian malaria patients. Using RNAs extracted from peripheral blood of the patients as the mixture of the human and Pf transcripts, we generated a total of 3 billion RNA-Seq tags. Analysis of these tags allowed us to identify genes and pathways which were associated with clinical symptoms both on human and parasite sides. Particularly, we observed characteristic expression changes in the human innate immune response pathway genes depending on severity of malaria. We also identified a group of transcription regulatory factors and signaling molecule genes which have positive or negative correlations between humans and Pfs. These genes may change their expression patterns to accommodate the respective organisms to mutually conflicting environments. Furthermore, it was possible to utilize the RNA-Seq data for genotyping of the parasites to identify possible drug resistant genetic variations. By bypassing technical difficulty in preparing samples in field, this approach should provide a practically useful mean to describe mutually interacting transcritpomes of humans and parasites, which should eventually explain diverse malaria symptoms.	Co-expression
DRP002315	Long Noncoding RNA NEAT1-Dependent SFPQRelocation from Promoter Region to ParaspeckleMediates IL8 Expression upon Immune Stimuli	Although thousands of long noncoding RNAs(lncRNAs) are localized in the nucleus, only a fewdozen have been functionally characterized. Herewe show that nuclear enriched abundant transcript1 (NEAT1), an essential lncRNA for the formation ofnuclear body paraspeckles, is induced by influenzavirus and herpes simplex virus infection as well asby Toll-like receptor3-p38 pathway-triggered polyI:C stimulation, resulting in excess formation ofparaspeckles. We found that NEAT1 facilitates theexpression of antiviral genes including cytokinessuch as interleukin-8 (IL8). We found that splicingfactor proline/glutamine-rich (SFPQ), a NEAT1-bindingparaspeckle protein, is a repressor of IL8 transcription,and that NEAT1 induction relocates SFPQfrom the IL8 promoter to the paraspeckles, leadingto transcriptional activation of IL8. Together, ourdata show that NEAT1 plays an important role inthe innate immune response through the transcriptionalregulation of antiviral genes by the stimulusresponsivecooperative action of NEAT1 and SFPQ.	Co-expression
DRP002435	Single-cell RNA-seq analysis of the cell cycle	The goal of these libraries is to find transcriptome signatures of the different phases of the cell cycle.  Single HeLa cells expressing fluorescent reporters that peak in G1 and G2/M phases were captured in C1 Single-Cell Auto Prep systems (Fluidigm  recording red and green fluorescence for each cell individually, each cell was lysed and their RNAs converted to cDNAs in the C1 systems using SMARTer kits (Clontech).  The cDNAs were then collected and converted to RNA-seq libraries by tagmentation using Illumina/Nextera kits.  The cells used in this experiment are unpublished as of today, and precise details will be given later, together with the fluorescence values.  In the meantime, this dataset can be used to assess reproducibility of single-cell RNA-seq over 5 runs in the Fluidigm system.	Co-expression
DRP002586	Single cell analysis of lung adenocarcinoma cell lines and the response to an anti-cancer drug stimulation	To understand heterogeneous behaviors of individual cancer cells, it should be important to investigate gene expression levels as well as their divergences between individual cells. Here we conducted a single cell RNA Seq analysis of a series of lung adenocarcinoma cell lines. We analyzed a total of 337 RNA Seq libraries of single cells and found gene expression diversities between individual cells are characteristic depending on genes. The genes showing highly variable expressions were enriched in particular pathways. Particularly, the EGFR pathway genes originally showed wider variations and further diversity was induced in response to an anticancer-drug stimulation. We also observed that cancer-related genes, which were identified from recent clinical cancer sequencing projects, showed potential expression variations, which firstly became apparent on the anti-cancer drug stimulation.	Co-expression
DRP002625	Transcriptome Sequencing and Comparative Analysis of Two Types of Exosomes in Human Whole Saliva by Next Generation Sequencing	Exosomes are small membrane vesicles (30-100 nm in diameter) secrted by numerous cells. Exosome have been shown to contain mRNA and DNA. We found at least two types of salivary exosomes (exosome I and exosome II) that are different in size and have different proteome. In previous study, we performed small RNA transcriptome analysis by next generation sequencing technology and reported that many types of small RNA, such as miRNA, piwi-interacting RNA (piRNA), small nucleolar RNA (snoRNA), other small RNAs and genomic repeats were contained in exosome I, II and whole saliva. In this study, we performed whole-transcriptome analysis using cDNA libraries constructed from total RNA except small RNAs. We found that 11-32% of reads from salivary exosomes and whole saliva were mapped to pseudogene.  The Data Access Committee of the National Bioscience Database Center (NBDC) approved that this personal genetic data were made published according to NBDC data sharing guidelines (http://humandbs.biosciencedbc.jp/).	Co-expression
DRP002835	RNA-Seq of MDA-MB231 cells harboring ANGPTL2 knockdown (MB231/miANGPTL2)	To determine the factors which might promote metastasis at downstream of ANGPTL2 in breast cancer cell, mRNA sequencing analyses of MDA-MB231 cells harboring ANGPTL2 knockdown (MB231/miANGPTL2) and relative to control (MB231/miLacZ) cells were carried out by using illumina GAIIx sequencer.	Co-expression
DRP002851	Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1	1. To identify lncRNA regulating colorectal tumorigenesis, we performed RNA-seq analysis of cells with high and low tumorigenicity 2. To study the role of UPAT in colorectal cancer cells, we investigated the gene expression profiles of HCT116 cells in which UPAT expression had been suppressed by siRNA.	Co-expression
DRP002860	PAX6 Isoforms, with OCT4 and KLF4, Differentially Regulate the Induction of Cornea-Specific Genes	The cell sheet engineering improved the function of the ocular surface, but the impairment of full recovery of visual acuity still remains. To address this problem, we transduced PAX6 isoforms, OCT4 and KLF4 into oral mucosal epithelial cells and investigated the molecular mechanism for induced corneal epithelium specific genes. This study will improve the clinical outcome of epithelial sheet transplantation.	Co-expression
DRP002866	The role of BCL6 induced in multiple myeloma cells	BCL6 is a transcriptional repressor, and plays important biological roles in various types of cells of the immune system, and also plays a fundamental role in lymphomagenesis. Recent study showed that BCL6 is expressed in multiple myeloma (MM) cells in the bone marrow. However the role of BCL6 in MM has not yet been elucidated. This project is aiming to investigate the role of BCL6 induced in MM. We retrovirally induced BCL6 to a MM cell line, KMS12PE, and performed RNA sequencing analysis. Differentially expressed genes were determined by comparing with mock infected cells.	Co-expression
DRP003120	Comprehensive analysis of cancer-stromal interactome	Cancer-microenvironment interaction is an important target for cancer therapy. However, finding new druggable interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome.  We propose CASTIN (CAncer-STromal INteractome analysis), a novel system for the evaluation of cancer-stromal interactome from RNA-seq data using cancer xenograft models. Three interactome evaluation indices coupled with curated ligand-receptor interaction database in our system provide quantitative and comprehensive view of interactome and enable the identification of critical cancer-microenvironment interactions. We applied the system to pancreas cancer dataset and successfully characterized the individual tumor in terms of cancer-stromal relationships, and identified well-known druggable interactions.	Co-expression
DRP003223	transcriptome analysis of Y14-kockdown HeLa cells	To investigate whether the EJC regulates pre-mRNA splicing, we performed a transcriptome analysis of Y14-kockdown HeLa cells using next generation RNA-sequencing.	Co-expression
DRP003241	Full-parasites: database of full-length cDNAs of apicomplexa parasites, 2014 update	Full-Parasites (http://fullmal.hgc.jp/) is a transcriptome database of apicomplexa parasites, which include Plasmodium and Toxoplasma species	Co-expression
DRP003316	Genome-wide identification of IGF2BP3-targeted mRNA degradation reveals the functional linkage of two proto-oncogenes IGF2BP3 and EIF4E	RNA-binding proteins (RBPs) play important roles in tumorigenesis. IGF2BP3, an evolutionally conserved RBP, has been reported as a useful diagnostic marker for various cancers. Although IGF2BP3 has been considered a regulator of tumorigenesis, little is known of the function of IGF2BP3 because of lack of information regarding IGF2BP3 target mRNAs. Here we report the identification of IGF2BP3 target mRNAs and IGF2BP3 function in cancer proliferation. We identified mRNAs with altered expression in IGF2BP3-depleted cells by massive sequencing analysis and IGF2BP3 binding RNAs by immunoprecipitation of IGF2BP3 followed by massive sequencing analysis, resulting in the identification of 110 candidates that are negatively regulated by IGF2BP3. We found that IGF2BP3 destabilized EIF4EBP2 and MEIS3 mRNAs. Co-immunoprecipitation analysis revealed the interaction between IGF2BP3 and ribonucleases such as XRN2 and exosome component. The retarded proliferation of IGF2BP3-depleted cells was partially rescued by the depletion of EIF4EBP2 which negatively regulates EIF4E, an activator of translation and a well-known proto-oncogene. Consistent with this observation, IGF2BP2 depletion reduced phosphorylated EIF4E, the active form, and translational efficiency of EIF4E target transcripts. Finally, we found an inverse correlation between the expression level of IGF2BP3 and EIF4EBP2 in human lung adenocarcinoma tissues. Together these results suggest that IGF2BP3 promotes EIF4E-mediated translational activation through the reduction of EIF4EBP2 via mRNA degradation, leading to enhanced cell proliferation. Namely, we found the first evidence of functional linkage between previously well-known cancer biomarker, IGF2BP3 and EIF4E. This is also the first report demonstrating that IGF2BP3 is an RNA destabilizing factor.	Co-expression
DRP003353	Transcriptome analysis of oncogene induced transformation in human diploid fibroblasts (TIG-3)	To estimate the impact of oncogenesis on transcriptome, we established cell lines as cellular oncogenic models induced by combinations of oncogenes using human lung diploid fibroblasts (HDFs: TIG-3). We performed transcriptome analysis of TIG-3 (parental), TIG-3 TS (hTert/SV40, immortalized), TIG-TSM (hTert/SV40/c-Myc transformed) and TIG-TSM (hTert/SV40/c-Myc transformed).	Co-expression
DRP003718	Identification of RNA target of Matrin3 and PTBP1 in neuroblastoma cell line SH-SY5Y by PAR-CLIP	RNA-binding proteins (RBPs)  act on each target separately or the same target cooperatively or competitively.  The aberrance in RBPs leads to neurological disorders such as amyotrophic lateral sclerosis (ALS). Matrin3 is highly conserved DNA/RNA binding protein whose point mutations are found in familial ALS patients. However, the function and target of Matrin3 in neuronal cells remain unclear. Here, we report the transcriptome-wide binding sites of Matrin3 in neuroblastoma SH-SY5Y cell lines using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). These data will provide us first step to understand pathological mechanism of ALS.	Co-expression
DRP003745	Examination of gene expression in sunitinib resistant cells and its HIF2a knock out cells	Next Generation Sequencing Facilitates Quantitative Analysis of sunitinib resistant cells and its HIF2a knock out cells.	Co-expression
DRP003825	A distinct subset of CD25 negative T-follicular regulatory cells localizes in the germinal centers	T-follicular helper cells (Tfh) differentiate through a multistep process culminating in germinal center (GC) resident GC-Tfh that provide support to GC B-cells. T-follicular regulatory cells (Tfr) have been shown to have critical roles in the control of Tfh and germinal center formation. While Tfh cells are inhibited by IL-2, Treg cells depend on it. Here we describe a novel CD25 negative subset within both murine and human PD1+CXCR5+Foxp3+ Tfr that is preferentially located in the GC and can be clearly differentiated from non-GC Tfr, Tfh and effector Tregs by expression of a wide range of molecules. In comparison to Tfr and effector Tregs, GC-Tfr cells partially downregulate IL-2 dependent canonical Treg features, but retain suppressive function, while simultaneously upregulating genes associated with Tfh and GC-Tfh. We suggest that, similar to Tfh, Tfr follow a differentiation pathway culminating in a distinct GC resident subset, GC-Tfr.	Co-expression
DRP003828	Analysis of gene expression profiles of 48 ABC transporters in normal colon and colon cancer tissues	Description  We aim to identify the expression levels of 48 ABC transporters comprehensively in normal colon and colon cancer tissues and compared expression profiles between those for elucidating mechanisms which regulate the expression of ABC transporters related anticancer drugs resistance. We sampled tumor tissues and corresponding normal tissues from 3 colon cancer patients who were underwent surgical resection of primary tumor without neoadjuvant chemotherapy in Tohoku University Hospital. Patient 1 is a 69 years old male had UICC stage IIIB ascending colon cancer. Patient 2 is a 61 year old male had UICC stage IIA ascending colon cancer. Patient 3 is a 56 year old female had UICC stage I sigmoid colon cancer. The expression levels of five colon cancer cell lines (COLO205, HCT116, HCT15, HT29, and SW620) registered in NCI60 were also analyzed.	Co-expression
DRP003868	Global transcriptional response to acidosis	Using a next generation sequencer, the global transcriptional responses to acidosis were investigated in variable human cells	Co-expression
DRP003950	Time-course mRNA expression analysis of human breast cancer MCF-7 cells treated with tamoxifen up to 12 weeks	In current study, we performed 12-weeks time-course mRNA expression analysis on the biological sextuplicate samples of estrogen receptor (ER)-positive MCF-7 breast cancer cells in presence or absence of tamoxifen to capture cellular state changes associated with acquisition of tamoxifen resistance. mRNA (1 mg) obtained from the MCF-7 cells was used for Poly A+ mRNA-sequence using the Illumina TruSeq RNA Library Prep Kit v2 according to the manufacturer protocol. 100 base pair-end reads or 36 base single-end-reads were obtained using Hiseq2500 (Illumina) and analyzed by analysis software provided by Illumina. To ensure the validity of the experiment, expression of representative genes (such as EGFR, ErbB2 (HER2), IGF-IR, NCOA3 (AIB1), MYC, CCND1 (cyclin D1) and CCNE1) known for tamoxifen resistance in vitro and clinical setting  (Musgrove 2009) were confirmed.	Co-expression
DRP003981	Combinatory use of the distinct single cell RNA-seq analytical platforms reveals heterogeneous transcriptome response to an anti-cancer drug in lung adenocarcinoma cell lines	Single cell RNA-seq (scRNA-seq) is a powerful tool to reveal the heterogeneity in cancer cells. Cancer heterogeneity would provide crucial information to understand eventual development of drug resistant cells or metastatic disseminations in cancers. In our study, we particularly focused on transcriptomic heterogeneity in response to an anti-cancer drug in five lung adenocarcinoma-derived cell lines. We generated single-cell RNA-seq by the two different platforms, the micro-droplet based platform and the micro-chamber platform, then we attempted to combine those datasets to complete information of datasets.	Co-expression
DRP004207	ShRNA-mediated SALL4 knockdown stud	ShRNA-mediated SALL4 knockdown study in basal-like breast cancer cell line, SUM159. The control is shGFP.	Co-expression
DRP004271	Expression profiles of HB1119 and 293T cell lines	HB1119 cells and 293T cells were  analysed by mRNA-seq. HB1119 cells are human leukemia cells that endogenously express the MLL-ENL fusion protein. 293T cells express wildtype MLL and ENL.aaaa	Co-expression
DRP004279	RNA sequencing of VHL reintroduction in RCC4 cells	Renal cell-derived RCC4 cells are lacking functional VHL. We investigated VHL reintroduction in RCC4 cells by RNA sequencing.	Co-expression
DRP004290	Control vs ferrichrome	The colon cancer cells, SW620, were treated ferrichrome. The change of mRNA in ferrichrome treated cells was analyzed by transcriptome analysis.	Co-expression
DRP004370	UHRF1-KAT7 complex regulates H3K14 modification	UHRF1 (ubiquitin-like PHD and RING finger domain-containing protein 1) is an epigenetic factor consists of multiple domain implicated in the maintenance of DNA methylation patterns during replication. Moreover, knockout of UHRF1 in mice is embryonic lethal. UHRF1 also possesses E3 ubiquitin ligase activity and ubiquitinates histones and DNA methyltransferase 1 (DNMT1), thereby regulating the chromatin structure and stability of DNMT1. UHRF1 regulates transcription by regulating DNA methylation and histone modification. UHRF1 is upregulated in various cancer cells, including colon, breast, bladder, prostate, lung cancers and plays a critical role in the proliferation and survival of tumor cells. To study the role of UHRF1 in colorectal cancer cells, we investigated the gene expression profiles of HCT116 cells in which UHRF1 expression had been suppressed by siRNA.	Co-expression
DRP004385	Gene expression profiles in human breast tumor cell line MCF7	TGF-beta is known to promote apoptosis in normal epithelial cells, whereas breast tumor cells have resistance to TGF-beta-induced apoptosis, and this resistance is associated with tumor progression. Because we found that the forkhead box protein A1 (FOXA1) has a suppressive role in TGF-beta-induced apoptosis in human breast tumor cell line MCF7, we analyzed gene expression profiles in TGF-beta1-stimulated or unstimulated MCF7 cells after transfection with siRNA for luciferase or FOXA1 or siRNAs for FOXA1 and Smad3.	Co-expression
DRP004433	Global transcriptional differences between a deprivation- resistant RCC and a deprivation-sensitive RCC	We analyzed the global transcriptional differences between a deprivation- resistant RCC and a deprivation-sensitive RCC using a next generation sequencer to search new biomarkers and therapeutic targets for RCCs. Then, the analysis demonstrated that hydroxyl-HIF2-alpha could become an advisable therapeutic target for RCCs.	Co-expression
DRP004445	RNA-seq analysis of HK2 under hypoxic condition with Dznep.	Hypoxia plays important roles in progression of chronic kidney diseases. HIF1 (hypoxia inducible factor 1) is a master transcriptional factor under hypoxic condition. To clarify the molecular mechanisms of HIF1 and identify novel lincRNAs under hypoxia, we performed RNA-seq using human renal proximal tubular cells (HK2: human kidney-2). In addition, we use Dznep which is an inhibitor of H3K27me3 to examine the relationship between HIF1 and epigenetic modifiers under hypoxia.	Co-expression
DRP004576	Primary B cells infected with Epstein-Barr virus	To examine the effect of Epstein-Barr virus (EBV) infection in primary B cells, we infected B cells from a healthy volunteer with EBV in vitro and harvested them after 48 hours.	Co-expression
DRP004645	RNA-seq of left ventricular tissue	Examination of myocardium tissue samples of patients with advanced non-ischemic heart failure by RNA-seq to identify factors that can be used to predict the occurrence of LVRR.	Co-expression
DRP004695	Induced pluripotent stem cell (201B7) classified by morphological difference	We performed mRNA-seq. Our samples are induced pluripotent stem cell (iPSC:201B7), which proportion of total colonies were controlled by morphological analysis and colony pickup/elimination. To mimic the slightly different culture conditions resulting from differences in human skills even when using the same protocol, we set the proportion of colonies with irregular morphologies to either increase or decrease using a combination of morphology analysis and colony pickup. First, when a certain number of colonies were obtained in 6-well plates during the preparation culture of iPSCs, phase contrast images were acquired. Acquired images were processed using image analysis software with colony recognition recipes. Two conditions showing altered morphological variation were set; Bad morphology area minimized condition (BM_min), and Bad morphology area enhanced condition (BM_enhance). To prepare either condition in a well, cellular objects outside the field of view (1.6 cm2 in the center position of a well) were scraped off using a scraper. Next, the entire cellular area recognized by colony recognition recipe was scraped off with a pipette and scraper. The remaining cells were then picked up for seeding into new 6-well plate using scraper. This condition was designated as BM_min. In contrast, the cellular area recognized by GM_recipe was removed in the same manner and the remaining cells were picked up for seeding into new 6-well plate in the same manner, designated as BM_enhance. This manipulation day was counted as day 0. At day 4, when cell growth was in the logarithmic growth stage, the cellular objects outside the field of view were again scraped off to eliminate the cellular existence outside the analyzed images. Next, poly-dimethylpolysiloxane (PDMS) was inserted to fill the space except for the field of view. In the well containing the PDMS insert, the recognition and quantification of cellular area was analyzed. As a result  the coverage ratio of bad morphology recognized by image analysis software were 0.2% (BM_min-1), 0.3% (BM_min-2), 20.8% for (BM_enhance-1), and 22.8% (BM_enhance-2). By measuring the lactate production rate per cell (LacR) and the glucose consumption rate per cell (GLuR), the contrast value of LacR/GluR was calculated to select 2 wells in each BM_min or BM_enhance. From the selected 2-wells from BM_min or BM_enhance, total mRNAs were extracted using TRIzol reagent (Thermo Fisher Scientific, Inc.) and RNeasy Mini Kit (Qiagen, Hilden, Germany) following the manufacturers instructions. The integrity of rRNA in each sample was checked using an Agilent TapeStation 2200 (Agilent Technologies, Santa Clara, CA, USA). The library was prepared for conventional RNA-seq using a commercial kit (TruSeq RNA Sample Kit; Illumina, San Diego, CA, USA) in accordance with the manufacturers protocol. Sequencing of the libraries using conventional RNA-seq was carried out using NextSeq 500 (Illumina) according to the manufacturers protocol.	Co-expression
DRP004718	human induced pluripotent stem cell containing a human artificial chromosome vector	human induced pluripotent stem cell containing a human artificial chromosome vector for high-efficiency recombination cloning of heterologous genes	Co-expression
DRP004910	RNA-seq of the lung adenocarcinoma cell line H1299 transfected with negative control or PLK1 siRNA.	PLK1 is an essential mitotic kinase in the mitotic progression and spindle bipolarity. It is known that PLK1 inhibition induces cell-cycle arrest and apoptosis in tumor cells. However, small things are known about apoptosis induced by PLK1 depletion. To know the gene that contributes to apoptosis induced by PLK1 inhibition, we comprehensively analyzed RNA expressions of the lung adenocarcinoma cell line H1299. We prepared two types of H1299 cells; PLK1 -depleted and -normal types.	Co-expression
DRP005114	Akt Inhibition Synergizes with PRC2 inhibition in the Treatment of Multiple Myeloma	Polycomb repressive complex 2 (PRC2) components, EZH2 and its homolog EZH1, and PI3K/Akt signaling pathway are focal points as therapeutic targets for multiple myeloma (MM). However, the exact crosstalk between their downstream targets remains unclear. We herein elucidated epigenetic interactions following Akt inhibition and demonstrated the efficacy of the combined inhibition of Akt and PRC2. We found that TAS-117, a potent and selective Akt inhibitor, down-regulated EZH2 expression at the mRNA and protein levels via an interference with the Rb-E2F pathway, while EZH1 was compensatively up-regulated to maintain H3K27me3 modifications. Consistent with these results, the dual EZH2/EZH1 inhibitor, UNC1999, but not the selective EZH2 inhibitor, GSK126, synergistically enhanced TAS-117-induced cytotoxicity and provoked the apoptosis of myeloma cells. RNA-seq analysis revealed the activation of FOXO signaling pathway after TAS-117 treatment. Ezh1 is one of the direct targets of Foxo transcription factors. FOXO3/4 mRNA and their downstream targets were up-regulated with the enhanced nuclear localization of the FOXO3 protein after TAS-117 treatment. ChIP assays confirmed the direct binding of FOXO3 to the EZH1 promoter, which was enhanced by TAS-117 treatment. Moreover, FOXO3 knockdown down-regulated EZH1 expression. Collectively, the present results unravel (or investigate) some molecular interactions between Akt signaling and epigenetic modulators, which emphasize the benefits of targeting PRC2 full activity and the Akt pathway as a therapeutic option for MM.	Co-expression
DRP005256	Post-transcriptional regulation of immune system by RNase Regnase-1	The aim of this research is to uncover the molecular mechanisms of how Regnase-1 degrades cytokine mRNAs. Inflammation is mediated by proinflammatory cytokines and cytokine expression is tightly regulated in innate immune cells such as macrophages and dendritic cells controlling their activation and maturation. Cytokine mRNA expression is controlled at both transcriptional and post-transcriptional levels, and post-transcriptional damping of cytokine expression is a critical step for resolution of inflammation and prevention of unintended tissue damage. However, the mechanisms of RNA metabolism in immune system is not clear. Thus, the aim of this research project is to investigate the molecular mechanisms of RNA metabolism by Regnase-1 in immune system.	Co-expression
ERP000546	Illumina bodyMap2 transcriptome	No description.	Co-expression
ERP000573	RNA and chromatin structure	No description.	Co-expression
ERP000619	ExpressionPlot: A web-based framework for analysis of RNA-Seq and microarray gene expression data	RNA-Seq and microarray platforms have emerged as important tools for detecting changes in gene expression and RNA processing in biological samples. We present ExpressionPlot, a software package consisting of a default back end, which prepares raw sequencing or Affymetrix microarray data, and a web-based front end, which offers a biologically centered interface to browse, visualize, and compare different data sets. Download and Installation instructions, user’s manual, discussion group, and a prototype are available at http://expressionplot.com/.	Co-expression
ERP000992	The effect of estrogen and progesterone and their antagonists in Ishikawa cell line compared to MCF7 and T47D cells	No description.	Co-expression
ERP001304	mRNA Sequencing of STG in schizophrenia	No description.	Co-expression
ERP001317	Sequencing_of_small_transcript_processed_RNAs_from_T_cells_that_are_involved_in_gene_expression_regulation_and_control_of_the_immune_response_	Sequencing of small transcript processed RNAs from T-cells that are involved in gene expression regulation and control of the immune response.	Co-expression
ERP001458	Transcription profiling by high throughput sequencing of HNRNPC knockdown and control HeLa cells	No description.	Co-expression
ERP001782	HeLa Adenovirus timecourse	A timecourse of adenovirus infection of human HeLa cells, using RNA-seq	Co-expression
ERP001895	lncRNAs at 13q14.3	Investigation of the upregulation of lncRNA genes in 13q14.3 and ist correlation with downregulation in cis of a gene cluster regulating NF-kB	Co-expression
ERP001908	CIT_VADS_BW_OMICS	A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net); Integrative study based on 89 patients with Head and Neck Squamous Cell Carcinoma (HNSCC); 89 Affymetrix HG-U133 Plus 2.0 GeneChips arrays;  88 samples on HumanCNV370-Quad GeneChips arrays; 84 samples on Illumina Human Methylation 27K arrays;Micro-RNA sequencing of  64 tumors. Please note: Characteristics[MetastasisFreeSurvivalEvent] indicates if there is a metastasis-free survival for a particular sample / patient (it is like an event-free survival variable where the event considered is a metastasis).  Characteristics[MetastasisFreeSurvivalDelay] - whenever the MetastasisFreeSurvivalEvent is 1, gives the duration of the metastasis-free survival period in months.	Co-expression
ERP001942	RNA-sequencing of 465 lymphoblastoid cell lines from the 1000 Genomes	This RNA sequencing data set of 465 human lymphoblastoid cell line samples from the CEU, FIN, GBR, TSI and YRI populations from the 1000 Genomes sample collection was created by the Geuvadis consortium (www.geuvadis.org, http://www.geuvadis.org/web/geuvadis/our-rnaseq-project). The data is under embargo until the first publication by the investigators in early 2013. This accession contains mRNA sequencing data, and small RNA data from the same samples are available under accession E-GEUV-2.	Co-expression
ERP001948	Total RNA from three cell lines (A431, U2OS, U251MG) were sequenced.	We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.	Co-expression
ERP001971	IGR_MERCHER_LAM7	Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups and several genetic alterations have been characterized in the past years, including the t(1;22)(p13;q13) and the trisomy 21 associated with GATA1 mutations. However, the majority of patients do not present with known mutations and the limited access to primary patient leukemic cells also prevents efficient development of novel therapeutic strategies. Using a xenotransplantation approach, we have modeled human pediatric AMKL in immunodeficient mice. High-throughput sequencing of engrafted cases identified recurrent fusions genes that define new molecular subgroups. A group of patients present with MLL or NUP98 fusion genes leading to upregulation of the HOX A cluster genes as described in other subtypes of AML. Also, a novel CBFA2T3-GLIS2 fusion gene resulting from a cytogenetically invisible inversion of chromosome 16 was identified and observed in 31% of non Down syndrome AMKL. These data provide new markers that will be useful for the diagnosis and follow-up of patients. Finally, we show that AMKL xenograft models constitute a relevant preclinical screening platform to validate the efficacy of novel therapies such as dimethylfasudil, a novel small molecule ploidy inducer.	Co-expression
ERP002021	CA9 Transcriptional Profiling Experiment	MCF7 cells exposed in 0.1% hypoxia for 72h and then stained and sorted into CA9+ve and CA9-ve populations and a differential gene expression analysis was performed between the 2 cell populations.	Co-expression
ERP002049	Common fusion transcripts identified in colorectal cancer cell lines by high throughput RNA sequencing	From altogether 220 million paired-end sequence reads from seven CRC cell lines we identified 3391 candidate fused transcripts, each with at least five-fold coverage across the fusion partners and at least three sequence-reads spanning the actual chimeric breakpoint. Stringent requirements left a set of eleven candidate fusion transcripts nominated for further experimental validation, of which ten were positive by RT-PCR and Sanger sequencing. Six of the fusions were intra-chromosomal transcripts and, interestingly, three of these, AKAP13-PDE8A, COMMD10-AP3S1, and CTB-35F21.1-PSD2, were present in respectively 18, 18 and 20 of 21 analyzed cell lines, and in respectively 18, 61 and 48 (17 to 58 percent) of 106 primary cancer tissues. These three fusion transcripts were also detected in two to four of 14 normal colonic mucosa samples (14 to 28 percent).	Co-expression
ERP002063	A significant number of human malignancies -- for instance, most cancers of the cervix and the liver -- are caused by infections with tumor viruses. Identification of these pathogens is now considered a critical contribution to cancer prevention. Deep sequencing enables us to systematically investigate transcription of both known and novel viruses in order to either verify or exclude the existence of viruses in idiopathic human cancers. We have developed a novel computational approach for identifying tumor viruses that addresses several important biological factors that may confound detection. We applied our method in the first systematic search, to our knowledge, for cancer-causing viruses in metastatic neuroblastoma, the most common form of cancer in infancy.	In excess of 12% of human cancer incidents have a causal viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses.  We have developed a novel computational approach for detecting viral transcripts in human tumors and conducted the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The striking diversity in clinical progression of this malignancy as well as previous epidemiological and virological findings are highly suggestive of a viral cofactor. We computationally mapped deeply sequenced transcriptomes of neuroblastoma and several cancers with known viral cofactors to the human and all known viral genomes. We analyzed the homologous context of putative viral transcripts in a new and sensitive manner in order to detect both known and unknown viruses under consideration of the aforementioned confounds.	Co-expression
ERP002075	RNAseq sequencing of 5 unrelated individuals to study RNA-DNA Differences in Human Mitochondria Restore Ancestral Form of 16S Ribosomal RNA	RNA sequences are generally identical to the underlying DNA sequences but there are known exceptions.  These RNA-DNA differences (RDDs) have been found in the nuclear genomes of human cells and in the mitochondria of plants and animals but not in human mitochondria.  Here by deep sequencing of DNA and RNA of human mitochondria, we identified 3 RDD sites including an A-to-U and an A-to-G RDD at position 2617.  Examination of the precursor polycistronic mitochondrial transcripts shows that the RDD formation occurs post-transcriptionally.  Phylogenetic analysis shows that the ancestral allele at position 2617 was a thymine or a guanine.  Thus the RDD formation recapitulates the ancestral form of 16S rRNA. Our findings show that RDD formation like other RNA processing steps is conserved across species and likely has functional significance.	Co-expression
ERP002232	Limbal Niche	Comprehensive transcriptome analysis of four distinct human limbal compartments, including basal limbal crypts (BLCs), superficial limbal crypts (SLCs), cornea, and the supporting stroma, with the aid of laser capture microdissection and deep RNA sequencing.	Co-expression
ERP002319	RNA-Seq of healthy human dendritic cells after challenge with four different fungal pathogens, and of four fungal pathogens after challenge with healthy human dendritic cells, SYBARIS project.	Dendritic cells from three healthy human donors were cultured in the presence or absence of either Aspergillus fumigatus, Saccharomyces cerevisiae, Candida albicans or Candida parapsilosis. Each of the four fungi were also cultured in the absence of human cells. RNA-sequencing was used to evaluate differences in the transcriptomes of human cells challenged and unchallenged with each fungal pathogen, as well as in those of each fungus challenged and unchallenged by cells from the human immune system.	Co-expression
ERP002323	RNA-Seq of human dendritic cells from aspergillosis and asthma patients after challenge with Aspergillus fumigatus, SYBARIS project.	Aspergillosis covers a range of infections cause by Aspergillus species, and in many cases can be life threatening. Individuals with weakened immune systems are particularly at risk. Dendritic cells were derived from patients with allergic brochopulmonary aspergillosis (ABPA), chronic cavitary pulmonary aspergillosis (CCPA), and asthma, as well as from healthy donors. Each sample was split in two, and one sample from each pair was cultured with Aspergillus fumigatus. RNA-sequencing was used to assess transcriptional changes in the human cells in response to pathogen challenge. Many genes known to be important in immunity were found to exhibit differential expression after fungal challenge between healthy and diseased individuals, including chemokines and C-type lectins.	Co-expression
ERP002414	human_plasma	We adapted the NextGen sequencing technology to obtain more accurate spectra of mRNA and miRNA in circulation, specifically to explore the plasma-miRNA association with colorectal cancer and ulcerative colitis.	Co-expression
ERP002588	RNA-seq data for cell lines in the haematopoietic lineages, hematological malignancy	RNA-seq data for cell lines in the haematopoietic lineages, hematological malignancy	Co-expression
ERP003259	RNA-Seq after knockdown of SON in human embryonic stem cells	Human embryonic stem cells (hESCs) harbor the ability to undergo lineage-specific differentiation into clinically relevant cell types. Transcription factors and epigenetic modifiers are known to play important roles in the maintenance of pluripotency of hESCs. However, little is known about regulation of pluripotency through splicing. In this study, we identify the spliceosome-associated factor SON as a novel factor essential for the maintenance of hESCs. Depletion of SON in hESCs results in the loss of pluripotency and cell death. Using genome-wide RNA profiling, we identified transcripts that are regulated by SON. Importantly, we confirmed that SON regulates the proper splicing of transcripts encoding for pluripotency regulators such as PRDM14, OCT4, E4F1 and MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In summary, we connect a splicing-regulatory network for accurate transcription production to the maintenance of pluripotency and self-renewal of hESCs.	Co-expression
ERP003460	Influence of RNA extraction methods and library selection schemes on RNA-seq data	Background: Gene expression analysis by RNA sequencing is now widely used in a number of applications surveying the whole transcriptomes of cells and tissues. The recent introduction of ribosomal RNA depletion protocols, such as RiboZero, has extended the view of the polyadenylated transcriptome to the poly(A)- fraction of the RNA. However, substantial amounts of intronic transcriptional activity has been reported in RiboZero protocols, raising issues regarding their potential nuclear origin and the impact on the actual sequence depth in exonic regions.   Method: Using HEK293 human cells as source material, we assessed here the impact of the two commonly used RNA extraction methods and of the library construction protocols (rRNA depletion versus mRNA) on 1) the relative abundance of intronic reads and 2) on the estimation of gene expression values.   Results: We benchmarked the rRNA depletion-based sequencing with a specific analysis of the cytoplasmic and nuclear transcriptome fractions, suggesting that the large majority of the intronic reads correspond to unprocessed nuclear transcripts rather than to independent transcriptional units.  We show that Qiagen or TRIzol extraction methods retain differentially nuclear RNA species, and that consequently, rRNA depletion-based RNA sequencing protocols are particularly sensitive to the extraction methods.  Conclusions: We could show that the combination of Trizol-based RNA extraction with rRNA depletion sequencing protocols led to the largest fraction of intronic reads, after the sequencing of the nuclear transcriptome. We discuss here the impact of the various strategies on gene expression and alternative splicing estimation measures.  Further, we propose guidelines and a double selection strategy for minimizing the expression biases, without loss of information.	Co-expression
ERP003467	VZV infection of primary keratinocytes	Our aim was to investigate the interaction between epidermal differentiation and VZV infection.  By means of a calcium-induced keratinocyte differentiation model and RNA-seq we show VZV infection has a profound effect on differentiating keratinocytes and hijacks the normal process of epidermal gene expression to generate a signature resembling patterns of gene expression seen in both heritable and acquired skin-blistering disorders.  Analysis of the viral transcriptome provides evidence that VZV replication in skin is tightly linked to differentiation and critically, that late viral gene expression is associated with cellular differentiation.  The experiment was performed on human primary keratinocytes under four conditions: undifferentiated/uninfected,  uninfected/differentiated, VZV-infected/undifferentiated and VZV-infected/differentiated.	Co-expression
ERP003471	RNA-seq transcript assembly evaluation	To assess the performance of computational methods for exon identification, transcript reconstruction and expression level quantification from RNA-seq data, 24 protocol variants of 14 independent software programs (AUGUSTUS, Cufflinks, Exonerate, GSTRUCT, iReckon, mGene, mTim, NextGeneid, Oases, SLIDE, Transomics, Trembly, Tromer and Velvet) were evaluated against transcriptome data from human cells and two model organisms.	Co-expression
ERP003495	GSK-inhibitor treatment in IMR32 neuroblastoma cell line	Cells were cultured in RPMI 1640 (Gibco), supplemented with 10% fetal bovine serum (FBS) (Gibco), 2mM L-glutamine (Gibco) and 1% Penicillin-Streptomycin solution (Gibco). IMR32 cells were treated as follows; untreated control, 24h 1uM azakenpaullone, 24h 1uM BIO or 24h 28mM LiCl with biological duplicates.	Co-expression
ERP003536	RNA-seq read alignment evaluation	To assess the performance of read mapping software for RNA-seq, 26 spliced alignment protocols based on 11 programs and pipelines (BAGET, GEM, GSNAP, GSTRUCT, MapSplice, PALMapper, PASS, ReadsMap, SMALT, STAR and TopHat) were applied to four human and mouse transcriptome data sets.	Co-expression
ERP003613	HPA RNA-seq normal tissues	RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes.	Co-expression
ERP003789	Osteogenesis RNA-Seq	Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular  differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation.  Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).	Co-expression
ERP003791	IGR_U985_RNASeq	Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in western countries, is a clonal accumulation of mature B-lymphocytes and its natural history is yet unclear. By using sequencing and cellular biology approaches on a cohort of CLL patient samples, we show here that acquired CLL mutations are observed in hematopoietic multipotent progenitor fractions in the majority of patients. These early CLL mutations include recurrent inactivating mutations in NFKBIE (10.7%) and missense mutations in BRAF (3.6%) and EGR2 (8.3%). Functional analyses demonstrated that BRAF-G469R affects lymphoid differentiation and transforms the T-cell lineage in vivo. In addition, the EGR2 recurrent mutations were associated with transcriptional activation of EGR2 target genes in patients and cell cycle abnormality in cellular model. Our findings indicate that CLL may develop from an initial infra-clinic, pre-leukemic phase affecting immature hematopoietic cells. We perform RNA-seq experiments on three EGR2-E356K samples, one EGR2-H384N sample and seven EGR2 wildtype patients. The RNA was extracted from B cells. The cDNA libraries were prepared using the ScriptSeq Complete Kit (Epicentre) and we performed paired-end sequencing (100 bp) using HiSeq2000 sequencing instruments.	Co-expression
ERP003815	AKS1-S3	RNA-sequencing analysis of human platelet rRNA-depleted total RNA from two normal males and one female. The goal of this experiment was to identify genes expressed in unstimulated circulating platelets. Data from platelet polyA-mRNA has also been deposited at ArrayExpress, under accession number E-MTAB-715, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-715/ .	Co-expression
ERP003917	Identification of putative target genes of the transcription factor RUNX2	We overexpress RUNX2 in ten human cell lines and identify genes that are affected by RUNX2 expression. These target genes provide a valuable resource into pathways regulated by RUNX2	Co-expression
ERP003933	Epigenetic_regulatory_pathways_in_human_leukaemia	Analysis of the role of KAT2A in  maintenance vs. differentiation of human leukaemia.	Co-expression
ERP004062	BPA impacts on HEK 293 cells	Bisphenol A (BPA) is an environmental endocrine disruptor which has been detected in almost all human bodies. Many studies have implied that BPA exposure is harmful to human health. Previous studies mainly focused on BPA effects on ER-positive cells. Genome-wide impact of BPA on gene regulation in ER-negative cells is unclear. In the present study, we performed RNA-seq to characterize BPA-induced gene regulation on ER-negative HEK 293 cells.	Co-expression
ERP004078	Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.	Transcriptome sequencing (RNA-seq) experiment of 14 human lymphoblastoid cell line samples from the 1000 Genomes sample set (http://www.1000genomes.org/). Dataset includes two parent-daughter trios (CEU and YRI populations) and additional eight unrelated individuals (CEU population). This accession contains raw and mapped RNA-seq read data, other assays in this study are available under accession XX (ChIP-seq) and YY (GRO-seq).	Co-expression
ERP004151	RNA-seq of mRNA from MCF7 breast cancer cells and samples derived from normal breast tissues	To improve our understanding of the effect of differential methylation on gene expression between normal and tumor breast cells, we carried out RNA sequencing evaluate mRNA expression changes in normal breast tissue and MCF7 breast cancer cell line. We identified 6632 protein-coding genes to be significantly differentially expressed (FDR threshold of 0.05) in the MCF7 cells. IPA Bio-Function enrichment analysis showed the 'cell death and survival' and 'cellular growth and proliferation' are the top 2 terms associated with differentially expressed genes. Cancer versus normal analysis of The Cancer Genome Atlas (TCGA) Breast data revealed genes that were differentially up and down-regulated in MCF7 are mostly respectively over- and under-expressed in clinical specimens.	Co-expression
ERP004211	RNA-Seq of 3iL human embryonic stem cells	Human embryonic stem cells (hESCs) are isolated from the inner cell mass of the blastocysts.  The pluripotent properties of hESCs enable the derivation of cell-types or tissues of different lineages for potential applications such as therapeutics discovery and regenerative medicine.  Even though hESCs are pluripotent, differences have been observed when compared to the native pluripotent epiblast cells of the blastocyst. We use a chemical approach (3iL: 3 small molecule inhibitor and cytokine) to induce an expression signature that more closely resembles native pluripotent cells. To better understand the difference between this hESC state and the conventional hESC state, we generated the global expression profiles using RNA-seq.	Co-expression
ERP004269	RNA-seq	Comprehensive analysis of coding and non -coding transcriptome using ribo-depleted total RNA-seq and poly A selected RNA-seq of MCF-7 cells grown in hypoxia and normoxia. Breast cancer cell line (MCF-7) is cultured in normoxic condition (21% O2) and hypoxic condition (1%O2) for 24 hours.  Expression of HIF-1alpha and/or HIF-2alpha subunits was suppressed using siRNAs in hypoxic MCF-7 cells. Total RNA was isolated from both hypoxia and normoxia conditions were subjected for ribosomal depleted stand specific RNA-seq and poly A selected RNA-seq	Co-expression
ERP004270	Ago2-bound ShortRnas in HCT116 cell line and Dicer_hypomorphic(DICER_Ex5 cells) HCT116 cell line	DICER_Ex5 cells were created by disrupting exon 5 of the human Dicer gene using an AAV targeting construct, thereby interrupting a well conserved segment of the N-terminal helicase domain while sparing the RNase III domains. In DICER_Ex5 cells, Dicer is expressed at a level lower than the wild type. This experiment started with RIP-anti-Ago2 pull-down, followed by high throughput sequencing analysis in wild type and Dicer-hypomorphic HCT116 cell lines.	Co-expression
ERP004298	RNA-Seq after knockdown of the endogeneous retrovirus HERVH in human embryonic stem cells	Human endogenous retrovirus subfamily H (HERVH) is a class of transposable elements whose members are expressed preferentially in human pluripotent stem cells. Here, we report that the long-terminal repeat regions of HERVH function as enhancers which are regulated by OCT4. Strikingly, we found that HERVH is a nuclear-localized long non-coding RNA that is required to maintain the undifferentiated state of human embryonic stem cells. Furthermore, we showed that HERVH is associated with OCT4 and co-activators such as P300, CBP and mediator subunits. Together, these results uncover a new and unexpected role of species-specific transposable elements in specifying the pluripotency of human cells.	Co-expression
ERP004352	AGO2 bound short RNAs in Jurkat cell line	Characterization of AGO2 bound short RNAs from nuclear extracts of Jurkat cell line. Nuclei were isolated from cells; a fraction of Nuclear lysates was harvested and sequenced as the "input" samples. The rest of nuclear lysates were Immunoprecipitated using AGO2 monoclonal antibodies or Isotype matched IgG. Following immunoprecipitation, RNA was extracted from AGO2 or control IgG IP for short RNA sequencing. Two independent biological replicates were carried out.	Co-expression
ERP004375	Cellular_phenotyping_of_host_pathogen_interactions	High-throughput cellular phenotyping to understand the etiology and pathology of host-pathogen interaction.	Co-expression
ERP004402	RNA-seq of AGO2 knock-down HeLaS3 cell line	In order to assess the effect of AGO2 on the transcriptional and post-transcriptional regulation of gene expression, RNA expression was profiled in untreated, CTRL siRNA transfected and AGO2 siRNA transfected HeLaS3 cells	Co-expression
ERP004573	Human_transcriptome_comparison_in_response_to_Staphylococcus_aureus_exposure	S. aureus infection stimulates de novo synthesis and secretion of Nerve Growth Factor beta (NGF beta). The release of NGF beta does not depend on phagocytosis and can be stimulated by exo-products from S. aureus growth conditioned media. Mutants of the SaeR/SaeS two-component regulatory system that modulate exoprotein release in S. aureus do not elicit the same response, suggesting that specific S. aureus proteins are involved in the induction of NGF beta. In this study, we aim to perform gene expression profiling of human monocytic cell line THP1 cells that have been incubated with live wild type S. aureus, a saeS- mutant, and dead wild type S. aureus.  The aims of the experiment is to identify a set of genes expressed in the wild type S. aureus but not in cells lacking either the response regulator or sensor kinase components of the sae global regulator.	Co-expression
ERP004592	RNA-seq of micro RNAs (miRNAs) in Human prefrontal cortex to identify differentially expressed miRNAs between Huntington's Disease and control brain samples	To identify genome-wide differentially expressed microRNAs (miRNAs) between Huntington's disease (HD) and control Human pre-frontal cortex samples	Co-expression
ERP004617	RNA-Seq of Acute Myeloid Leukemia Cell lines with a 3q-aberration and Acute Myeloid Leukemia cell line controls	Using RNA deep sequencing we determined gene expression patterns and expression genotypes in Acute Myeloid Leukemia (AML) cell lines harboring a 3q-aberration. These cell lines specifically overexpress the gene EVI1 which plays a significant part in leukomogenesis. Additionally we RNA sequenced AML cell lines that overexpress EVI1 resulting from different genetic causes or do not express EVI1 at all.	Co-expression
ERP004682	Transcriptional profiling upon knockdown of the RNA-binding protein Unkempt	RNAseq to assess changes in transcript abundance upon knockdown of the RNA-binding protein Unkempt in human SH-SY5Y cell lines.	Co-expression
ERP004683	Ribosome profiling upon overexpression of the RNA-binding protein Unkempt	Ribosome profiling to assess changes in ribosome occpancy upon overexpression of the RNA-binding protein Unkempt (most likely acts as a translational regulator) in human HeLa cell lines.	Co-expression
ERP004684	Transcriptome-wide mapping of RNA binding sites of the RNA-binding protein Unkempt using iCLIP-seq	iCLIP experiments tomap the RNA binding sites of the RNA-binding protein Unkempt across the transcriptome in SH-SY5Y cells, HeLa cells with ectopic Unk expression and mouse E15 embryonic brain samples. Expression of Unk is normally largely restricted to the nervous system. We therefore mapped the binding sites in human SH-SY5Y and mouse E15 brain to detect its physiological binding sites (in SH-SY5Y, we also performed the RNAseq experiment upon Unk knockdown). HeLa cells on the other hand normally don't express Unk, but convert to neuron-like shape when the protein is ectopically expressed. So, here we hoped to identify those binding events (and hence target transcripts) that are critical for this morphological transformation.	Co-expression
ERP004697	Allele-Specific Expression in Human Brain and Liver	Systematic survey of gene and isoform allele-specific expression in human brain and liver tissues, and description of optimised bioinformatic and statistical methods to accurately measure allele-specific expression. DNA-seq data for the same set of samples have been deposited at the European Nucleotide Archive under project accessino PRJEB5279 ( http://www.ebi.ac.uk/ena/data/view/PRJEB5279 ).	Co-expression
ERP005189	Human corneas treated with 'cold plasma' (APCP) in presence or absence of NAC	Atmospheric pressure cold plasma (APCP) is a novel tool in medicine for tissue disinfection. It is  produced by a device that ionizes a flow of helium gas partially mixed with air. We recently reported that 2-minute of APCP application significantly reduce the microbial viability without evident damage on the ocular cells and tissues. To validate its use as antimicrobial for biomedical purposes such as ophthalmic applications, with this study we verified the functional changes in human corneas exposed to APCP by means of global gene expression analysis. To our knowledge, this is the first analysis of the effects of cold plasma on gene expression.	Co-expression
ERP005274	Human granulosa	We are human embryologists from center for reproductive medicinel of Anhui Provincial Hospital Affiliated to Anhui Medical University, and we have the expertise to do all that properly in humans. By deep sequencing, the current experiment determined the miRNA profile of two intrafollicular somatic cell types: CRCs and COCs, isolated from women undergoing controlled ovarian stimulation and in vitro fertilization treatment. Ovarian follicles, which are a densely-packed shell of granulosa cells that contains an immature or mature oocyte, are above all responsible for the development, maturation, and release of mature egg for fertilization. They are also responsible for synthesizing and secreting hormones that are essential for follicular development, menstrual and estrous cycle, maintenance of the reproductive tracts and their functions, development of female secondary sex characteristics, and metabolism. During folliculogenesis, ovarian granulosa cells surrounding the oocyte differentiate into mural granulosa cells, involved in gonadal steroidogenesis, and into cumulus cells, which are ovulated with the oocyte at ovulation. These cumulus cells derive from the same population of early follicles, but differentiate into two distinct groups of cells: 1) Those directly lie on the zona pellucida are composed of the so called "corona radiata cells".(CRCs)  2) The other group surrounds the CRCs and consists of more numerous cells, forming the so called "cumulus oophorus cells (COCs)". In the present study, we described the miRNA expression profile to characterize the ensemble of both known and novel miRNAs expressed in CRCs, as well as in COCs, by using high-throughput Solexa technology.	Co-expression
ERP005301	Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes	Investigating the response of long non-coding RNA expression to LPS stimulation in human monocytes.  This experiment is related to the microarray study E-MTAB-2408.	Co-expression
ERP005426	heat shock SUMO-2 RNA-seq	RNA-seq analysis of poly-A RNA from untreated U2OS cells, and from U2OS cells exposed to heat stress (43 C) for 4 hours	Co-expression
ERP005583	293_hORF3.1_drug_treatments_partII	Overexpression of the transcription factor RHOXF2 in the HEK293_M2 cells confers resistance to several DNA damaging agents. To understand that resistance mechanism, we cultured HEK293_M2 with or without overexpression of RHOXF2 in the presence of 40nM of mitomycin C or DMSO (control) and profiled their transcriptional response by RNA-seq.	Co-expression
ERP005598	RNA-seq of achilles tendon from young and old donors to study age-related changes in tendon	Tendon from young and old donors was used for RNA-Seq analysis. The aim of the study was to identify differentially expressed tendon transcripts in ageing in order to to characterize molecular mechanisms associated with age-related changes in tendon.	Co-expression
ERP005876	Effect of hypoxia on the Represser Element-1 Silencing Transcription factor (REST) in Human	The Represser Element-1 Silencing Transcription factor (REST) was knocked-down in HEK293 cells using RNA intereference in cells exposed to 21% or 1% oxygen for 24 hours, the effects on transcript expression (poly(A)+ RNA)) were analyzed using genome wide sequencing (RNAseq).	Co-expression
ERP005938	RNAseq of matched normal epithelium, oral dysplasia and oral squamous cell carcinoma using strand-specific methods that capture both coding and non-coding genes	Whole transcriptome sequencing of 19 matched patient sample trios: normal oral epithelium, oral dysplasia and oral squamous cell carcinoma from the same patent. All material is from FFPE blocks that have been stained and sections and had sample histology confirmed by 2 independent pathologists. A ScriptSeq library kit was used to create strand specific 100bp paired-end sequencing libraries following RiboZero treatment to deplete rRNA. Both coding and non-coding RNA <200bp is sequenced on an Illumina HiSeq2500 with an average of 4 samples per lane.	Co-expression
ERP005953	Isolation and Characterization of Clonal Adult Human Brown Adipocytes	Brown adipose tissue (BAT) evolved in mammals as a natural defence system against hypothermia and obesity. While existence of BAT in adult humans has been recently appreciated, its cellular origin and molecular identity remain elusive due in large to high cellular heterogeneity within adipose tissues.  Here we isolated clonal adipocytes from adult human BAT as well as WAT (control) and critically analyzed their transcriptome to identify bona fide BAT markers and its new functions.	Co-expression
ERP006028	RNA-Seq of YM155 treated KMB7 wild-type and SLC35F2 knock-out cells	SLC35F2 was identified as a transporter of DNA damage inducing agent YM155. We then did a comparative transcriptomics experiment comparing wild-type and SLC35F2 knock-out KBM7 cells.	Co-expression
ERP006097	Microbe enriched dual RNA sequencing of Mycobacterium bovis BCG infecting macrophage-like THP-1 cells	We infected the human macrophage-like cell line THP-1 with the attenuated M. tuberculosis surrogate M. bovis Bacillus Calmette–Guérin (M. bovis BCG). We employed microbial enrichment combined with specific ribosomal RNA depletion to simultaneously analyze the transcriptional responses of host and pathogen during infection by dual RNA sequencing.	Co-expression
ERP006121	Functional and genetic heterogeneity of distinctive leukaemic stem cell populations in CD34- human Acute Myeloid Leukaemia	We performed RNA-sequencing of normal haematopoietic stem cells and progenitor populations and of Leukemic Stem Cells in CD34- Acute Myeloid Leukaemia.	Co-expression
ERP006200	Isoform-specific depletion of U2AF1	RNA-Seq data of U2AF1 isoform depletion experiments.	Co-expression
ERP006216	Global_gene_expression_profiles_during_differentiation_of_human_induced_pluripotent_stem_cells_to_macrophages	In this study, we aim to perform gene expression profiling of undifferentiated human pluripotent stem cells (hIPSC)  and macrophages and their progenitors derived from hIPSC.  The aims of the experiment is to identify a set of genes uniquely expressed in hIPSC but not in hIPSC derived monocytes/macrophages (hIPSdM) and define them as "stemness" genes. We will also identify genes upregulated in hIPSC-derived monocytes/macrophages but not hIPSC to provide insights into the regulatory switches of hIPSC differentiation.  We established protocols to generate monocytes and macrophages from hIPSC CRL1 line in vitro. Briefly,  hIPSC were grown in bacteriological dishes in the presence of hIPSC base medium to generate embryoid bodies (EBs). Subsequently, EBs were transferred to gelatinized tissue culture dish in medium supplemented with M-CSF and IL-3. Supernatants containing macrophage progenitors were collected, spun down and plated onto bacteriological dishes  to differentiate into macrophages. Two or three biological replicates of undifferentiated hIPSCs, macrophage progenitors and macrophages were collected and their RNA were isolated via the Qiagen RNA Isolation Kit. The RNA were treated with RNAse free DNase and eluted in RNase-free water. THe RNA integrity (RIN >8) were obtained for all samples by Agilent 2100 Bioanalyzer. We aim to sequence 5GBp per replicate per lane on an Illumina platform.	Co-expression
ERP006368	A3G and A3F CLIP	APOBEC3G and APOBEC3F are cell-encoded restriction factors that have evolved to counteract virus infections. When packaged into HIV-1 particles, A3G and A3F impair reverse transcription and induce the hypermutation of viral DNA. We employed a next generation sequencing approach to identify the RNAs that these proteins bind in HIV-1 infected cells and HIV-1 virions. We then analysed the mechanism of packaging of APOBEC3 in detail.	Co-expression
ERP006533	Neuroblastoma cell lines	Untreated neuroblastoma cell lines SMS-KCN, SMS-KCNR, Kelly, and SH-SY5Y were sequenced on an Illumina GA IIx sequencer.	Co-expression
ERP006538	MYCN overexpression in SH-SY5Y/6TR(EU)/pTrex-Dest-30/MYCN cell line	MYCN overexpression in the doxycline MYCN inducible cell line SH-SY5Y/6TR(EU)/pTrex-Dest-30/MYCN (SY5Y-MYCN) using the dynamic transcriptome analysis (DTA) protocol. Samples at different time-points after MYCN over-expression and uninduced controls (0h) were sequenced in duplicates. The experimental setup consists of [A] total mRNA at 0h, 1h, 4h, 24h, which corresponds to the standard mRNA-seq protocol, [B] 4-thioUridine (4sU) labelled mRNA 30 min before extraction at time-points 0h, 1h, 4h, which is the freshly transcribed mRNA within the last 30 min before the time-point and [C] the counter-part, 4sU unlabelled mRNA 30 min before extraction which corresponds to the mRNA from before 30 min of extraction. The samples were sequenced on an Illumina GA IIx using the Illumina protocols.	Co-expression
ERP006577	The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation.	Neuroblastoma is one of the most common extracranial solid tumors in children. By sequencing transcriptomes of low- and high-risk neuroblastomas, we have identified differentially expressed annotated and novel long noncoding RNAs (lncRNAs). Our analysis identifies a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker for predicting the clinical outcome of the neuroblastoma patients. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to differential expression of NBAT-1. Loss of NBAT-1 results in increased proliferation and invasion of cells. It controls these processes via epigenetic silencing of target genes. Its loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.	Co-expression
ERP006662	Single_cell_transcriptomics_of_haemopoetic_stem_and_progenitor_cells_	The aim of the study is to analise the transcriptional profile of single leukemic cells in order to understand the early stage of leukaemogenesis. Oligoclonal haemopoetic and progenitor cell populations from several leukemic mutants were flow sorted into single cells and processed for RNAseq.	Co-expression
ERP006696	Olfactory_transcriptomics_in_mammals	In this study RNA was extracted from the olfactory mucosa of three individuals of four mammalian species: cow, macaque, marmoset and humans. The RNA was sequenced using the Illumina Hiseq2500 platform.	Co-expression
ERP006823	RNA sequencing of conventional and reset human pluripotent stem cells	Human pluripotent cells were reset to ground state pluripotency by transient overexpression of NANOG and KLF2 and subsequent inhibition of ERK and protein kinase C. Transcriptional profiling of reset cells and conventional pluripotent stem cell cultures was carried out by RNA-seq, in tandem with mouse embryonic stem cells propagated under similar conditions to assess the combinatorial effects of MEK inhibitor PD0325901, GSK3 inhibitor CHIR99021 and PKC inhibitor Go6983.	Co-expression
ERP006834	Single_cell_sequencing_of_early_mouse_embryos	Single cell RNA-seq libraries from early mouse embryos  are to be sequenced to understand the regulatory network of genes in these stages. Several embryo stages have been collected for this purpose and the aim  is to compare across the different stages	Co-expression
ERP006964	DUSP4 deficiency due to promoter hypermethylation drives oncogenic JNK signaling and tumor cell survival in diffuse large B-cell lymphoma	The epigenetic dysregulation of tumor suppressor genes is a major driver of human carcinogenesis. We have combined genome-wide methylation analyses with functional screening to identify novel candidate tumor suppressor genes in diffuse large B-cell lymphoma (DLBCL). We find that the dual-specificity phosphatase DUSP4 is aberrantly silenced in nodal and extranodal DLBCL due to promoter hypermethylation; ectopic expression of wild type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. JNK inhibition prevents DLBCL survival in vitro and in vivo, and synergizes strongly with inhibitors of chronic active B-cell receptor signaling. Our results provide a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, alone or in synthetic lethal combinations. A methylation profiling data set related to this experiment was also deposited at ArrayExpress under accession number E-MTAB-2926: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2926/	Co-expression
ERP007008	Expression profiling by high throughput sequencing	RNAseq was prepared in parallel with ribosome profiling, using the same protocol for cDNA library preparation.	Co-expression
ERP007109	Timecourse total transcriptome sequencing of MCF10A cells undergoing acinus formation.	RNA-seq was performed for transcriptional analysis of MCF10A cells, an epithelial mammary cell line. MCF10A cells were cultured in 3D acinus forming conditions (in Matrigel). Timepoints analysed were 24h, 34h, 36h, 38h and 48h into acinus formation. Control cells were monoloayer.	Co-expression
ERP007111	HipSci___RNAseq___healthy_volunteers	The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS cells generated from skin biopsies from healthy volunteers.	Co-expression
ERP007180	Dynamic_Equilibrium_of_human_ESC_populations	ES cells grown in culture are heterogeneous with respect to their transcriptional profiles, their methylation landscape and, functionally, their potency. This study is investigating overall changes in transcriptional landscape of ES cells upon overexpression of epigenetic regulators which can indicate a shift in the distribution of subpopulations.	Co-expression
ERP007185	RNAseq of matched normal epithelium, oral dysplasia and oral squamous cell carcinoma using strand-specific methods that capture both coding and non-coding genes	Whole transcriptome sequencing of 19 matched patient sample trios: normal oral epithelium, oral dysplasia and oral squamous cell carcinoma from the same patent. All material is from FFPE blocks that have been stained and sections and had sample histology confirmed by 2 independent pathologists. A ScriptSeq library kit was used to create strand specific 100bp paired-end sequencing libraries following RiboZero treatment to deplete rRNA. Both coding and non-coding RNA <200bp is sequenced on an Illumina HiSeq2500 with an average of 4 samples per lane.	Co-expression
ERP008445	RNA content of transcription factories	We have develop a simple fact method to isolate transcription factories and analyzed their RNA content as compared to total poly(A)+ and chromatin associated RNA fractions in presence or absence of pro-inflammatory cytokine.	Co-expression
ERP008458	Regulation of constitutive and alternative messenger RNA splicing across the human transcriptome by PRPF8 is determined by 5' splice site strength	RNA-sequencing experiments performed on control siRNA treated and PRPF8 depleted cells	Co-expression
ERP008492	RNA-seq of osteosarcoma cell lines	RNA-seq of 11 osteosarcoma cell lines	Co-expression
ERP008608	RNA-Seq analysis of human fibroblasts, induced neurons and cortex from donors of several ages	RNA-Seq analysis of human fibroblasts, induced neurons and cortex from donors of several ages	Co-expression
ERP008803	A genomewide map of PPARb/d target genes in human macrophages identifies a unique agonist-induced activation state - RNAseq	PPARb/d agonist and antagonist response was characterized in (human) monocyte derived macrophages.	Co-expression
ERP008834	RNA-Seq of wild-type HEK293 and K562 celllines	RNA-Seq was carried out in order to obtain the expression profile of Solute Carrier Family (SLC) of proteins in two commonly used celllines. We were specifically interested in the subset of SLCs that are capable of transporting amino acids.	Co-expression
ERP008967	Mapping_embryonic_stem_cell_surface_interactions_to_transcriptional_phenotypes	The activation of receptors displayed on the surface of cells typically initiates cytoplasmic signalling cascades that lead to changes in cellular transcriptional responses so that a cell expresses proteins that enable it to behave appropriately as a function of their position within an organism. Understanding these signals and learning how to either prevent or ectopically activate them could have many therapeutic benefits and applications. In some cases these signals are highly localised, being delivered by directly neighbouring cells that express ligands which specifically bind to and activate receptors; for example, stem cells display receptors for ligands provided by cells within their niche to both ensure continual production of cells, and that their cellular progeny are directed towards appropriate fates. While for some cell types we know something of these signals enabling the in vitro differentiation of stem cells towards certain cellular fates, the differentiation processes is often not complete and so “immature” cell types which are not fully functional are produced, implying that some important signals are missing. Here, we propose to systematically identify receptor-triggered signalling pathways by stimulating receptors on the surface of human stem cells by using a library of soluble recombinant oligomerised protein ligands and measuring the consequent transcriptional perturbations using RNA-seq. We propose to screen an existing library of ~50 oligomerised human ligands previously used in receptor protein interaction screens and first test them for their ability to bind to human stem cells to identify those ligands for which the stem cells express a cell surface receptor. For those ligands which interact with the stem cells (we estimate between 2 and 5), they will be added to stem cell cultures and their effects on transcription quantified. The budget requested is sufficient for us to include controls and test important parameters such different time points after addition of the proteins.	Co-expression
ERP008992	Transcriptional Profiling of human pluripotent stem cells and and derived tissues	RNAseq was carried out to compare global transcriptional profiles of human pluripotent H9 stem cells with tissues derived from these cells through directed differentiation, including endoderm and human intestinal organoids.	Co-expression
ERP009022	Deregulation of PPAR-beta/delta target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment - RNAseq	The transcriptome of serous ovarian cancer tumor associated macrophages was characterized. Additionally, their transcription response to PPARD agonists and inverse agonists in cell culture was analyzed.	Co-expression
ERP009050	Detection of posttranscriptional inosine modification at the precursor tRNA level	Transfer RNAs (tRNAs) are key adaptor molecules in the protein translation machinery. In order to become fully active, they are heavily modified posttranscriptionally. Inosine at the first residue of the anticodon (position 34; I34) is an essential tRNA modification that has been poorly studied thus far. The modification in eukaryotes results from a deamination reaction of adenine that is catalysed by the heterodimeric Adenosine Deaminase Acting on tRNA (hetADAT), composed of two subunits: ADAT2 and ADAT3. Using high-throughput small RNA sequencing, we show that this modification takes place in human tRNAs at the precursor tRNA level and as this precursor maturates. We also functionally validated the human genes encoding for hetADAT and show that in cells, HsADAT2 and HsADAT3 co-localize in nucleus. Lastly, we knocked down HsADAT2 and show for the first time that it is possible to modulate the levels of I34 modification on all human hetADAT tRNA substrates. These findings give mechanistic insights on the biology of tRNA modifications and the tools reported in this study will prove useful in the future to address the exact molecular role of I34 modification on protein translation.	Co-expression
ERP009114	Metagenomics of sputum from patients with respiratory infection	Sputum samples were collected from patients with respiratory infection and RNA were extracted for RNA-Seq to explore the metgenomic environment of sputum.	Co-expression
ERP009260	Differential expression analysis by RNA-Seq reveals perturbations in the platelet mRNA transcriptome triggered by pathogen reduction systems	Pathogen reduction (PR) systems are used for prevention of infectious agents in blood components such as platelets, but have also shown to increase bleeding in some clinical studies. PR cross-link and damage nucleic acids of pathogens. Here, we show that Intercept (amotosalen + ultraviolet-A [UVA] light) significantly alter the platelet transcriptome. We used the RNA-Seq approach and analyzed transcriptomes of five platelet groups. We found that platelets treated with Intercept significantly changed the expression of more than 1000 genes (p<0.05) relative to the untreated, control platelets. In contrast, platelets treated with the Mirasol PR system (riboflavin + UVB light), or subjected to gamma-irradiation did not show these effects. A cluster of more than 170 mRNAs were identified that were differentially expressed at P<0.001. A vast majority of these transcripts were down-regulated at >2 folds. We also found the SSP+ additive solution present in Intercept constitutes a partial, though small, effect on the platelet transcriptome.  We conclude that Intercept significantly affects and interferes the platelet transcriptome, a finding that coincides with previously reported studies showing that Intercept induces platelet activation, impaired platelet aggregation, reduced platelet mean volume, increased release of platelet microparticles and down-regulation of microRNAs in platelets.	Co-expression
ERP009263	Genome-wide profiling analysis reveals annexin A6 is a novel EZH2 target gene involving gastric cellular proliferation	Polycomb repressive complexes (PRC) play a critical role during tumorigenesis and development. The histone methyltransferase Enhancer of Zeste homologue 2 (EZH2), as a core component of PRC2, is frequently overexpressed in a wide variety of cancers. EZH2-mediated gene silencing contributes to carcinogenesis. To further the understanding of the EZH2 biology in gastric cancer, here we performed transcriptome analyses and identified EZH2-responsive genes upon EZH2 knockdown by RNA-seq.	Co-expression
ERP009282	Systems biology approaches reveal low-dose effects of nanoparticles	Here, we show that systems biology approaches can uncover mechanisms underlying cellular responses to nanomaterials. Using RNA Seq, we found that cationic nanoparticles are capable of triggering down-regulation of cell cycle-related genes in primary human bronchial epithelial cells at doses that do not elicit acute cytotoxicity. Bioinformatics analyses implicated NF-kappaB as a putative transcriptional regulator and functional assays confirmed that cationic nanoparticles caused NF-kappaB-dependent cell cycle arrest. Our study demonstrates the feasibility of applying systems biology tools to assess cellular responses to nanomaterials, not least at low doses.	Co-expression
ERP009283	The RNA binding protein Quaking regulates formation of circRNAs	Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function, or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesised and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT.	Co-expression
ERP009309	Senescent and myofibroblastic cancer-associated fibroblasts share a contractile phenotype regulated by NOX4 generation of reactive oxygen species in the tumour microenvironment	Cancer associated fibroblasts characterized by an myofibroblastic phenotype play a major role in the tumour microenvironment, being associated with poor prognosis. We found that this cell population is made in part by senescent fibroblasts in vivo. As senescent fibroblasts and myofibroblasts have been shown to share similar tumour promoting functions in vitro we compared the transcriptosomes of these two fibroblast types and performed RNA-seq of human foetal foreskin fibroblasts 2 (HFFF2) treated with 2ng/ml TGF-beta-1 to induce myofibroblast differentiation or 10Gy gamma irradiation to induce senescence. We isolated RNA 7 days upon this treatments changing the medium 3 days before the RNA extraction.	Co-expression
ERP009437	RNAseq of left ventricle heart tissue of 128 dilated cardiomyopathy (DCM) cases	DCM,dilated cardiomyopathy, is a major cause of chronic heartfailure.  In this study,128 samples from DCM patients (left ventricle) have been sequenced by RNAseq. We obtained cardiac tissue from 128 subjects with end-stage heart failure.  All subjects were transplanted at the Royal Brompton and Harefield NHS Foundation Trust (London, United Kingdom).  On this occasion, cardiac samples were obtained and immediately frozen in liquid nitrogen.	Co-expression
ERP009514	ribo-depleted RNA-Seq of HepG2 cells exposed to Benzo[a]pyrene for 6,12,18,24,36 and 48h.	HepG2 cells (human liver hepatocarcinoma) were exposed for 6 different time points (6,12,18,24,36 and 48h) to Benzo[a]pyrene (BaP) in duplicate. Total RNAs were ribo-depleted and sequenced on an Illumina Hiseq2000 in pair-end 100 bp reads. One of the duplicates for BaP-treated sample at the 24 hour time point was found to have a minor fastq file integrity issue and was removed from this data set as a precaution.	Co-expression
ERP009612	Transcriptional characterization of Human Lung Organoids (HLOs) using RNAseq	Human lung organoids (HLOs) were derived from human embryonic stem cell line H9 NIH registry #0062. Sequencing of HLOs was performed by the UM DNA Sequencing Core, using Illumina Hi-Seq platform and single-end 50 bp reads. The UM Bioinformatics Core downloaded the reads files from the Sequencing Core storage, and concatenated those into a single .fastq file for each sample. 3 HLOs were cultured for 65 days and 3 HLOs were cultured in vitro for 110 days.  HLO Culture Protocol 4-day Activin A (R&D systems) differentiation protocol was used to derive definitive endoderm from human pluripotent stem cells (hPSCs). Cells were treated with Activin A (100 ng ml−1) for three consecutive days in RPMI 1640 media (Life Technologies) with increasing concentrations of 0%, 0.2% and 2% HyClone defined fetal bovine serum (dFBS, Thermo Scientific). The fourth day was a repeat of day 3 media (2% HyClone FBS).   After differentiation into definitive endoderm, cells were incubated in foregut media (advanced DMEM/F12 plus N-2 and B27 supplement, 10mM Hepes, 1x L-Glutamine (200mM), 1x Penicillin-streptomycin (5,000 U/mL, all from Life Technologies)) with 200ng/mL Noggin (NOG, R&D Systems) and 10µM SB431542 (SB, Stemgent) for 4 days, SB, 500ng/mL FGF4 (R&D Systems), and 2 µM CHIR99021 (Chiron, Stemgent), and 1µM SAG (Enzo Life Sciences) for 4-6 days. After 4 days with treatment of growth factors, three-dimensional floating spheroids were present in the culture. Three-dimensional spheroids were transferred into Matrigel to support 3D growth. Spheroids were embedded in a droplet of Matrigel (BD Bioscience  #356237) in one well of a 24 well plate, and incubated at room temperature for 10 minutes. After the Matrigel solidified, foregut media with 1% Fetal bovine serum (FBS, CAT#: 16000-044, Life Technologies) and 500ng/mL FGF10 (R&D Systems) were overlaid and replaced every 4 days. Organoids were transferred into new Matrigel droplets every 10 to 15 days.	Co-expression
ERP009695	Epigenetic_regulation_of_pre_implantation_development	Pre-implantation development is exemplified by extensive transcriptional and epigenetic changes, including zygotic genome activation, chromatin remodelling and global DNA demethylation. Excitingly, the advent of single-cell technologies will enable unprecedented high-resolution transcriptional and epigenetic profiling of this critical developmental stage. Furthermore, through the development of an in vitro model system I will identify key totipotency regulators, develop mechanistic insight into their mode of action and link these findings to somatic reprogramming. This study involves the use of RNA-sequencing (polyA+, ribominus and single-cell), ChIP-Sequencing and bisulfite sequencing.	Co-expression
ERP009756	Transcriptome profiling of human pancreatic cell lineage specification reveals functional signaling pathways and lncRNAs for cell fate determination	To guide the beta cell differentiation process in vitro, a complete understanding of the transcriptome and their regulatory network during the differentiation process is essential. Using RNA-seq, we have performed the transcriptome profiling of human embryonic stem cells (ESCs), purified ESC-derivate definitive endoderm (DE), pancreatic progenitors (PP), as well as sorted human primary pancreatic alpha cells, beta cells and exocrine cells.	Co-expression
ERP009768	Human granulocyte transcriptome annotation and analysis reveals increased expression variability for lncRNAs compared to mRNAs in healthy individuals	In this study we used human primary granulocytes to assess natural variability of lncRNA expression. We used polyA+ granulocyte RNA-seq from 10 healthy individuals to define granulocyte lncRNA transcriptome, which was not available before. We annotated 6,249 lncRNA transcripts forming 1,591 lncRNA loci, contributing 268 novel loci to the human genome annotation. We show that focusing on granulocytes allows identification of less well expressed, less efficiently spliced and more granulocyte specific lncRNAs. We used Ribosomal depleted granulocyte RNA-seq from 7 healthy individuals sampled in 3 replicates to estimate reproducibility and variability of lncRNA expression and found that though being as well reproducible between replicates, lncRNAs are significantly more variable in their expression than mRNAs. We confirmed this finding in publicly available Geuvadis lymphoblastoid cell line (LCL) RNA-seq dataset from 462 individuals and also used this dataset to show that the number of identified lncRNA increases with the number of donors analyzed. Overall, we showed that high variability of lncRNAs is an important feature that distinguishes them from mRNAs and influences their identification strategy, making it necessary to include as many individuals as possible into the identification effort for every given cell type in order to comprehensively annotate all the lncRNAs in the human genome.	Co-expression
ERP009793	PPARβ/δ ligand response in monocyte derived macrophages	The PPARD ligand response (agonist and inverse agonist) in monocyte derived macrophages from 3 healthy donors was assesed via RNAseq.	Co-expression
ERP009841	Olfactory_transcriptomics_in_humans	In this study RNA was extracted from the olfactory mucosa of three human individuals. The RNA was sequenced using the Illumina Hiseq2500 platform.	Co-expression
ERP009913	RNA-seq comparison: before/after MARIS protocol and library construction technique test	The aim of this experiment was to determine the amount of RNA-seq signal degradation that results from MARIS and to test how well 4 different RNA-seq library construction techniques perform on partially degraded RNA.	Co-expression
ERP009935	RNA-seq of Ins+ cells in human differentiation protocol across lines and isolated from human islets	The aim of this experiment was to observe the transcriptional profile of Ins+ cells in human cadaveric islets and at the terminal stage of our in vitro beta-cell differentiation protocol across both the Hues8 and H1 cell lines. One polyhormonal sample (Ins+/Gcg+) was also sorted  for additional comparison.	Co-expression
ERP009992	The definition of SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of mitochondrial factors like PINK1	Ataxin-2 (ATXN2) polyglutamine domain expansions of large size result in an autosomal dominantly inherited multi-system-atrophy of the nervous system named Spinocerebellar ataxia type 2 (SCA2), while expansions of intermediate size act as polygenic risk factors for levodopa-responsive Parkinson’s disease (PD) and for motor neuron disease (ALS and FTLD). In view of the established role of ATXN2 for RNA processing and the expression of ATXN2 in blood cells such as platelets, we investigated whether global deep RNA sequencing of whole blood from SCA2 patients identifies a molecular profile which might serve as diagnostic biomarker. The bioinformatic analysis of the SCA2 blood transcriptome revealed various significant effects, prominently on the pathways of Huntington’s disease and PD where mitochondrial dysfunction is crucial. Notably, an induction of PINK1 and PARK7 expression was observed.  Conversely, PINK1 expression was severely decreased upon global transcriptome profiling of Atxn2-knockout mouse cerebellum and liver, in parallel to strong effects on OPA1 and GHITM, which encode known mitochondrial dynamics regulators.  These results were validated by quantitative PCR and immunoblots. ATXN2 expression was induced by nutrient deprivation of human SH-SY5Y neuroblastoma cells, with a time course in parallel to PINK1 expression, and PINK1 levels appeared to depend on ATXN2 knockdown. Thus, ATXN2 may be upstream of or parallel to PINK1 in mitochondrial quality control and autophagy. Given that PINK1 is responsible for autosomal recessive juvenile Parkinson’s disease (PD), this genetic interaction offers an explanation how the degeneration of nigrostriatal dopaminergic neurons and the Parkinson phenotype are triggered by ATXN2 mutations.	Co-expression
ERP010003	BLOOD BIOMARKERS OF RISK FOR SYNUCLEINOPATHY,  A VARIANT OF PARKINSON’S DISEASE	Parkinson’s disease (PD) is a frequent neurodegenerative process at old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity are intensely investigated. In view of physiological SNCA roles in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation), to identify effects of SNCA gain-of-function as potential disease biomarkers. The expression of other Parkinson’s disease gene was not, but CPLX1 mRNA downregulation was correlated with genotype. In global RNAseq profiling of blood from presymptomatic PARK4, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, toll like receptor signalling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH, and PLTP mRNA upregulations were validated in PARK4. Analysing prodromal stages of general PD, only blood CPLX1 levels were altered in cases with REM sleep behaviour disorder (RBD). Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3’-UTR of the CPLX1 gene we identified a SNP that is significantly associated with PD risk. In summary, our data provide functional insights into the role and regulation of blood alpha-synuclein levels. The novel blood biomarkers of synucleinopathy may become useful for PD prediction.	Co-expression
ERP010060	RNA-seq of NEAT1 knockdown in neuronal excitability	We investigated the role of NEAT1 knockdown on neuronal excitability in iPSC-derived neurons.	Co-expression
ERP010065	Baseline gene expression profile of human extrahepatic biliary cells/biliospheres in vitro	Aim: To determine the baseline gene expression profile of human gallbladder and cystic duct cells at various stages from isolation in fresh biopsy samples to early and later passages in culture.	Co-expression
ERP010082	Baseline miRNA expression profile of human extrahepatic biliary cells/biliospheres in vitro	Aim: To determine the baseline miRNA expression profile of human gall bladder and cystic duct cells at various stages from isolation in fresh biopsy samples to early and later passages in culture.	Co-expression
ERP010177	Alu element-containing RNAs maintain nucleolar structure and function	We have isolated, analyzed and compared the RNA content of various cell compartments including total RNA, nucleolplasmic RNA and nucleolar RNA.  In addition, cells have been subjected to various treatment to specifically inhibit each of the RNA polymerases I, II and III, as well as protein synthesis. Cells were also treated with antisense oligos to induce the degradation of specific RNA transcripts. The whole RNA content of the cells after these specific treatments was isolated and sequenced.	Co-expression
ERP010227	Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells.	The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 plays an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue specific regulation of an unknown subset of genes. To address both tissue- and subtype subtype-specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue tissue-specificity of the response, and identified a subset of tissue tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelia.	Co-expression
ERP010353	CTTV020_epigenomes_of_cell_lines_PILOT___RNA	There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. Within GSK there have been a small number of focussed studies to understand the relationship between transformed cell lines used in cellular assays and primary cell types using transcriptomic data. However, there is an opportunity to establish a systematic approach for performing this type of analysis on a broader scale across a large number of cell types with multiple genomic data sets. A collated list of cellular assays has been pulled together within GSK across DPUs and Molecular Discovery Research from which the cellular reagents used in these assays can be categorised as follows: (1) Transformed cell lines used across multiple programs (2) Primary human cells (3) Co-culture & complex cellular reagents (e.g. PBMC) We will perform a systematic analysis of transcriptomic & epigenomic profiles in cell types of interest.	Co-expression
ERP010372	Transcriptome of Normal and Cystic Fibrosis Human Bronchial Epithelial Cells Infected with Pseudomonas Aeruginosa	In cystic fibrosis (CF), chronic Pseudomonas aeruginosa infection of the lower respiratory tract is associated with epithelial inflammation that eventually causes tissue damage. To identify the molecular determinants of an effective response to P. aeruginosa infection, we performed a transcriptomic analysis of primary human bronchial epithelial cells from healthy donors (CTRL) 2, 4, and 6 h after induced P. aeruginosa infection.	Co-expression
ERP010553	Posttranscriptional mRNA expression changes in stress	HEK T293 cells were treated with Anisomycin or the solvent control DMSO. Cells were fractionated and cytoplasmic and nuclear RNA were isolated. pre-mRNA-Seq was performed on stressed and unstressed nuclear RNA samples. mRNA-Seq was performed on stressed and unstressed cytoplasmic RNA samples. In addition, polyadenylation sites were globally mapped by applying the 3'T-fill method on the same stressed and unstressed cytoplasmic RNA samples.	Co-expression
ERP010561	Gene expression profiles of H16N2 cells expressing EZH2 variants	A cytosolic role for EZH2 in regulating cell signaling via interaction with the VAV family of proteins has been reported by us previously. However, it is unclear whether EZH2 interactions with VAV are critical for tumorigenesis. Here, we show that cytosolic EZH2 exhibits greater transforming/metastatic capacity than wild-type EZH2 and that targeted disruption of the EZH2-VAV interaction abolishes EZH2-promoted tumorigenesis. We also found that interaction of cytosolic EZH2 with VAV is critical for EZH2-mediated talin methylation and subsequent STAT3 activation. Both cytosolic EZH2 and a methyl-mimicking talin mutant substantially promoted STAT3 activation and tumor growth. We therefore propose that the VAV-dependent cytosolic function of EZH2 may be a critical step in the initiation of cellular transformation, preceding the well-established function of EZH2 in epigenetic silencing of tumor suppressors. Thus, disrupting EZH2-VAV interaction could be an alternative intervention strategy for treatment of cancers associated with EZH2 overexpression.	Co-expression
ERP010784	RNA-seq of spinal cord, brain, liver, and muscle from an SMA mouse model	This study describes RNA-seq results from total spinal cord, brain, liver and muscle samples taken at PND1 and PND5 from an SMA mouse model paired with samples taken from heterozygous litter-mates. There are four mouse in each group.	Co-expression
ERP010795	Transcriptome sequencing identifies dysregulated WNT signaling in precursor lesion and recurrent mutations of tumor suppressor RNF43 during malignant transformation in multistep gastric carcinogenesis	A subset of gastric cancers develops gradually through multistep carcinogenesis, but genomic landscape of early stage of gastric carcinogenesis through adenoma-carcinoma sequence remains unclear. We performed RNA sequencing on 12 low grade dysplasia (LGDs), 10 high grade dysplasia (HGDs), and 17 intestinal-type early gastric cancers (EGCs).	Co-expression
ERP010889	RNA-seq of gastric biopsies from subjects at different stages of gastric inflammation and histological changes.	In this study we performed RNA-seq analysis of gastric corpus biopsies to study transcriptional changes during early gastric carcinogenesis. We included patients with non-atrophic gastritis, with intermediate and extensive corpus atrophy, and patients with intestinal metaplasia. We also included a control group of H. pylori-negative subjects. All subjects were from Nicaragua, which has a population of high gastric cancer risk.  Total RNA samples were treated with RiboZero Magnetic (Human/Mouse/Rat) Kit (Epicentre Biotechnologies) to deplete rRNA and the cDNA libraries were prepared using ScriptSeqTM v2 RNA-Seq Library Preparation Kit (Epicentre). Sequencing was performed on the Illumina HiScan2500 platform, 2*100bp reads.	Co-expression
ERP010930	Low grade gliomas subtype analysis	Low grade gliomas (LGG; WHO grade 2 astrocytomas, oligodendrogliomas and oligoastrocytomas) account for about 25% of diffuse gliomas. Most occur in young adults between the ages of 30 and 45 years, and are usually only diagnosed after a seizure. In general, they can be characterised by a long period of continuous slow growth, followed by malignant transformation that will be the cause of death up to 25 years after onset. However, there is a significant number of patients for whom malignant progression is more rapid, with mortality observed within 5 years. This suggests that, as with other tumour types, there may be different subtypes of LGG with specific prognosis. It follows that being able to identify these subtypes may permit better patient stratification and aid targeted treatments. Until recently, our understanding of the variables involved in patient prognosis included the type of tumour – oligodendroglial tumours indicate better prognosis than oligoastrocytic or astrocytic – and presence of the 1p-19q co-deletion. In addition, the recent discovery of mutations in IDH1&2 in the majority of LGGs provided another means of stratifying patients, while offering an important insight into their biology. However, we still understand very little of the biology behind the genesis and progression of the 70-80% of LGG that bear IDH1&2 mutations, let alone the remaining IDH wild-type tumours.	Co-expression
ERP011000	Elucidation of FOXP1 target genes in DLBCL by RNA-Seq	Elucidation of FOXP1 target genes by RNA-Seq of DLBCL cell lines transfected with siRNAs targeting FOXP1 expression	Co-expression
ERP011057	RNASeq_stable_cell_lines	RNA-seq study on stably transfected cell lines	Co-expression
ERP011097	CML CD34+ cells were treated with RITA, CPI-203, the combination thereof and nilotinib.	To identify the molecular effects of combining the p53 activator RITA and MYC inhibitor CPI-203, we treated CML CD34+ cells with RITA, CPI-203, the combination thereof and nilotinib.	Co-expression
ERP011202	SK-OV-3 cells under Carboplatin	SK-OV-3 cells under prolonged carboplatin exposition turn into giant cells. This dataset contains the transcriptome of cultured SK-OV-3 cells with and without carboplatin.	Co-expression
ERP011233	RNA-seq of MCF-7 (breast adenocarcinoma) and 2102Ep (embryonic carcinoma) cells upon LINE-1 knockdown.	To measure the levels of expression of retrotransposon individual copies, and particularly of LINE-1 (L1) elements of the L1HS-Ta subfamily, we performed 2x150 bp paired-end and strand-specific RNA-seq on polyA+ RNA of MCF-7 and 2102Ep cells, which express high levels of L1. To confirm the origin of the L1-specific signal, we also performed RNA-seq upon shRNA-mediated L1 knockdown. sh960 relates to a scramble shRNA control. sh1083 and sh1085 relate to two distinct shRNAs directed against the ORF1 region of L1.3 (GenBank L19088) as a prototype L1HS-Ta.	Co-expression
ERP011243	5Aza and TSA treatment of MCF7 cells (RNA-seq)	The goal of this study is to identify the gene expression changes caused by exposure of to the DNMT inhibitor 5-aza-2'-deoxycytidine (5Aza) and HDAC inhibitor Trichostatin A (TSA). We performed rRNA-depleted RNA sequencing of the untreated and drug-treated MCF7 breast cancer cell lines and carried out differential gene expression analysis. Although 5Aza caused a stranger demethylation effect than TSA, there were fewer differentially expressed gene in the 5Aza-treated MCF7 than the TSA-treated cells.	Co-expression
ERP011264	Interleukin-7 abrogates the immunosuppressive function of human double-negative T cells by activating Akt/mTOR signaling	Recently, a novel subset of TCRαβ+ CD4- CD8- double-negative (DN) T cells has been described to suppress immune responses in both mice and humans. Moreover, in murine models infusion and/or activation of DN T cells specifically suppressed alloreactive T cells and prevented development of Graft-versus-Host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We have demonstrated that human DN T cells like their murine counterparts are highly potent suppressor cells of both, CD4+ and CD8+ T-cell responses. After HSCT and other lymphopenic conditions, Interleukin (IL)-7 plays an important role in the reconstitution, survival, and homeostasis of the T-cell compartment. Since IL-7 was shown to interfere with T-cell functionality, we asked whether IL-7 affects the functionality of human DN T cells. Intriguingly, IL-7 diminished the suppressive activity of DN T cells towards allogeneic CD4+ effector T cells.  Of interest our studies revealed that IL-7 activates the Akt/mTOR pathway in human DN T cells. Importantly, selective inhibition of the protein kinases Akt or mTOR was able to reverse the IL-7 effect thereby restoring the functionality of DN T cells, whereas inhibition of other central T-cell signaling pathways did not. Further analyses suggest that the IL-7/Akt/mTOR signaling cascade downregulates anergy-associated genes and upregulates activation- and proliferation-associated factors which may be crucial for DN T cell functionality. These findings indicate that IL-7 and Akt/mTOR signaling are critical factors for the suppressive capacity of DN T cells. Targeting of these pathways by pharmacological agents may restore and/or enhance DN T-cell functionality in GvHD.	Co-expression
ERP011275	Nucleocytoplasmic shuttling of immunosuppressive Yersinia effector YopM is mediated by DEAD box helicase DDX3 and controls nuclear Ribosomal S6 Kinase 1	YopM is an immunosuppressive virulence protein of pathogenic Yersinia species. After translocation into host cells it enters the nucleus but neither a nuclear activity nor the mechanisms underlying nucleocytoplasmic shuttling of YopM have been reported. Here we identify the DEAD-box helicase DDX3 as a novel interaction partner of YopM and describe a 2:1 YopM:DDX3 molecular complex in solution. Knockdown of DDX3 or inhibition of the exportin CRM1 increased the nuclear level of YopM and enhanced phosphorylation of nuclear Ribosomal S6 Kinase 1 (RSK1). Transcriptome analysis of Y. enterocolitica infected human macrophages revealed extensive suppression of immune/inflammatory pathways by YopM. Thus, YopM binds DDX3 to exit the nucleus via the CRM1 export pathway and the enabled nucleocytoplasmic shuttling of YopM adjusts phosphorylation of nuclear RSK1. These YopM activities result in a coordinated subversion of immune response pathways.	Co-expression
ERP011282	RNA-sequencing analysis of quiescent and activated human skeletal muscle stem cells	Quiescent and activated human skeletal muscle stem cells are analyzed by whole-transcriptome RNA-sequencing. These cells are prospectively isolated from latissimus dorsi muscle. Quiescent cells are analyzed immediately following prospective isolation. Activated cells are analyzed after 1 week in culture. Additionally, activated cells (again cultured for one week) and treated with a p38 MAPK inhibitor are analyzed.	Co-expression
ERP011301	Increased Expression of Phosphodiesterase Type 5 Promotes the Invasive Potential of Breast Cancer Cells: Implications for Targeted Therapy.	Purpose: By catalyzing hydrolysis of cyclic guanosine monophosphate, phosphodiesterase (PDE) 5 is a critical regulator of its concentration and biological effects in different (patho)physiological processes, including cancers. Being PDE5 a known druggable target, we investigated the clinical significance of its expression in breast cancers and the underlying molecular mechanisms by which it may contribute to breast cancer progression. Experimental Design: RT-PCR and immunoblotting analyses were used for PDE5 expression in eight breast cancer cell lines. To examine PDE5’s impact on cancer phenotype, MCF-7 cells, expressing the lowest levels of PDE5, were engineered to stably overexpress PDE5. Cell proliferation was assessed by MTT assays, motility and invasion by wound-healing, transmigration, matrigel-based invasion assays. RNA sequencing identified differentially-expressed genes. Clinical relevance of PDE5 was investigated by immunohistochemistry on tissues and retrospective studies from the Metabric cohort. Results: PDE5 was expressed at lower levels in luminal A-type breast cancer cells (MCF-7) compared to luminal B-like, HER2-overexpressing and basal-like cells. MCF-7 cells stably overexpressing PDE5 exhibited an increased cell motility and invasion through activation of Rho family of GTPases. Treatment of PDE5 clones with selective ROCK or PDE5 inhibitors completely restored the less motile and weak invasive behavior of control cells. In patients, PDE5 expression was found in ~85% of tumor entities analyzed, with the highest intensity staining in high-grade tumors. Retrospective analyses showed that higher PDE5 levels correlated with poorer survival.   Conclusion:  PDE5 expression enhances breast cancer cell invasive potential, highlighting its role as a novel molecular candidate with prognostic significance and a potential target in the treatment of breast cancers.	Co-expression
ERP011411	Pancreatic ductal adenocarcinoma primary cultures enriched or not in cancer stem cells	RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) primary cultures from five different patient-derived xenograft models grown either in adherent conditions selecting for non-CSCs or in CSC-enriching anchorage-independent sphere conditions. A and B are two biological duplicates, from the same patient-derived xenograft model of PDAC.	Co-expression
ERP011528	SNRPB knockdown in U251 cells	SNRPB was knocked down in U251 GBM cell lines to identify its impact on splicing regulation	Co-expression
ERP011837	RNA-Seq of human embryonic stem cells over expressing NANOS3 and DAZL	Human embryonic stem cells (cell line HS401) were transfected with piggyBac over expression constructs for germ cell specific RNA binding proteins, Nanos homolog 3 (NANOS3) or Deleted in azoospermia-like (DAZL). Cells transfected with a construct without open reading frame (MOCK), were used as control. Biological triplicates from separate transfections were used for analysis. Total RNAs were ribodepleted and sequenced on one lane on an Illumina HiSeq2500 with a 2x101 setup in HighOutput mode.	Co-expression
ERP012180	Integrated Genomic Analysis of Survival Outliers in Glioblastoma	We identified cohort of 18 glioma patients and performed Next Generation Sequencing (Exome, RNA, and Whole Genome Sequencing) and methylation profiling to identify genetic, epigenetic, and transcriptomic differences between long-term survivors (LTS, OS > 33 months) and short-term survivors (STS, OS < 7 months).	Co-expression
ERP012188	Functional Heterogeneity of Cancer-Associated Stromal Fibroblasts Show Differential Gene Expression Profile in Chondrosarcoma	The project aims to identify functional heterogeneity of cancer-associated stromal fibroblasts (CAF) which show specific gene expression profile in Chondrosarcoma (CS). The current knowledge of the role of CAF in the tumour microenvironment in CS regulating the expression of tumour cells is limited. In this study, we have determined the capability of primary CAFs to promote tumorigenesis of CS cancer cells. In order to confirm whether the primary fibroblast have activated features, we performed indirect co- culture (Trans- well migration assay) with CS tumour cell lines. On the basis of this migration assay we have identified that each primary fibroblast exhibited different induction of migration of CS tumour cells.   This differential pro- migratory capacity of CAFs will help identifying a gene expression signature that allows classification of patients with CS into high and low risk groups by RNA- sequencing	Co-expression
ERP012527	Identification_and_molecular_charaterization_of_new_tumor_suppressor_genes_on_prostate_cancer	As mentioned before, the goal of this study consists of depicting the molecular mechanisms by which recently discovered tumor suppressor are able to constraint tumor development.	Co-expression
ERP012552	Single-cell RNA-seq reveal lineage formation and X-chromosome dosage compensation in human preimplantation embryos	Single-cell RNA-seq of 1,469 cells obtained from 79 human preimplantation embryos ranging from embryonic day 3 to 7.	Co-expression
ERP012646	FLT3_Insertional_Mutagenesis_Mapping_in_AML	RNA sequencing of mouse AML samples has reveled different spectra of genetic interactions between mice sensitised to developing AML (by gene targeting approaches), specific to the sensitising mutation. These large data sets have identified mutually exclusive and shared spontaneously arriving interactions that closely mimick those seen in the human condition. On a gene by gene basis these are to be verified using RNASeq.	Co-expression
ERP012748	Transcriptome analysis of bladder wall from patients with bladder outlet obstruction induced lower urinary tract dysfunction	Introduction and Objectives: Bladder outlet obstruction (BOO) results in profound structural and functional changes in the detrusor, including hypertrophy and bladder decompensation (fibrosis). Previously we determined miRNA profiles characteristic of defined states of BOO in human patients and used bioinformatic prediction of their target genes to identify the regulated signalling pathways. Here we aim to do the mRNA transcriptome analysis of the same samples and correlate microRNA and mRNA regulation patterns in order to validate functional ontology.  Materials and Methods: Controls, BOO with and without detrusor overactivity (DO and BO groups, respectively) and underactive bladders (UA group) were defined by urodynamics in human subjects. Bladder dome biopsies were collected and RNA isolated using mirVANA kit for miRNA. mRNA sequencing (mRNA-seq) method was used for gene expression profiling of BOO stages (4 groups, n = 6 per group). The Enrichment analysis using GeneGo MetaCore software was applied to the significantly altered mRNAs. Functional analysis of a network identified the most significant biological functions of the genes in the network.	Co-expression
ERP012838	Epigenetic evolution of endocrine therapy resistant cells	Endocrine therapies target the activation of the estrogen receptor alpha (ERα) via distinct mechanisms but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specific epigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes with invasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonal genomics analysis of reprogrammed regulatory regions identifies individual drug-induced epigenetic states involving large topological domains (TAD) and the activation of super-enhancers. AI resistant cells activate endogenous cholesterol biosynthesis (CB) through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks the constitutive activation of estrogen receptors alpha (ERα) in AI resistant cells, partly via the biosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERα binding is reduced and cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in a subset of ERα positive patients.	Co-expression
ERP012914	Transcriptional profiling of HAP1 kinase-knockout cells upon stimulation with polypeptides and small molecules	This dataset is a systematic study of transcriptional profiles of HAP1 cells under environmental and genetic perturbations. Samples were prepared using wildtype HAP1 cells and HAP-derived cell lines that included CRISPR/Cas9-induced gene knockout in tyrosine kinases. Cells were cultured in reduced serum conditions for 16h, then stimulated with a polypeptide or small molecule for 6 hours. Cells were harvested and extracted RNA was subjected to RNA-seq library preparation in 96-well plates using the QuantSeq protocol. Sequencing was performed on an Illumina HiSeq 2000 system following a T-fill reaction, with 48 samples multiplexed on each lane.	Co-expression
ERP012939	Transcriptome profiling of cells depleted of hnRNPC, Upf1, or co-depleted of hnRNPC and Upf1.	The purpose of this experiment was to compare differences in Alu-exon inclusion in cells depleted of hnRNPC, Upf1, or both.	Co-expression
ERP012951	Knuuttila et al.   Castration induces up-regulation of intratumoral androgen biosynthesis and androgen receptor expression in an orthotopic VCaP human prostate cancer xenograft model.  Am J Pathol. 2014 Aug;184(8):2163-73. doi: 10.1016/j.ajpath.2014.04.010. Epub 2014 Jun 17.	Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration). Tumor growth was monitored through weekly serum prostate-specific antigen measurements, and mice with recurrent tumors after castration were randomized to treatment groups. Serum prostate-specific antigen concentrations showed significant correlation with tumor volume. Castration-resistant tumors retained concentrations of intratumoral androgen (androstenedione, testosterone, and 5α-dihydrotestosterone) at levels similar to tumors growing in intact hosts. Accordingly, castration induced up-regulation of enzymes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. The AR antagonists enzalutamide (MDV3100) and ARN-509 suppressed PSA production of castration-resistant tumors, confirming the androgen dependency of these tumors. Taken together, the findings demonstrate that our VCaP xenograft model exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC.	Co-expression
ERP012958	Transcription profiling of cytoplasmic and nuclear RNA of hnRNPC depleted cells and ER-Raf1 activated HR1 cells	The purpose of this experiment was to compare differences in gene expression in cytoplasmic and nuclear RNA of cells depleted of hnRNPC.	Co-expression
ERP012979	Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers	Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8–PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non–BRAF–Non–RAS (NBNR), as well as BRAF–like and RAS–like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8–PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.	Co-expression
ERP013068	Human BAT/WAT under Cold Exposure/Thermoneutrality	RNA-seq data of two human subjects (1 and 2) of BAT and WAT under cold or thermoneutral.	Co-expression
ERP013191	RNA-seq of liver tissue and liver cancer cell lines	This dataset has been designed to test whether codons in mRNAs and anticodons in tRNAs vary in order to maximize translation in specific cellular conditions in mammals. Prokaryotes and simple unicellular eukaryotes optimize their translational rates by adjusting the codons in the protein-coding transcriptome to the available pool of anticodons in the tRNA transcriptome. We found no evidence supporting this mechanism in mammals, even when subsets of genes were considered, such as those found in Gene Ontology functional categories or in tissue-specific transcriptional signatures. The simplest explanation accounting for the observed codon distributions in mammals is the variation in GC content of gene categories. GC variation across the mammalian genome is most likely to result from the interplay of genome repair and gene duplication mechanisms, rather than selective pressures caused by codon-driven translational rates. This work is part of experiment series: ChIP-Seq E-MTAB-23282326.	Co-expression
ERP013206	Whole transcriptome profiling of Esophageal adenocarcinoma and Barrett's	RNA-seq was performed on Esophageal adenocarcinoma (EAC), Barrett's without dysplasia, Barrett's with low-grade dysplasia (LGD) and normal squamous esophagus tissue to find early alterations in the transcriptome level turning Barrett's dysplastic.	Co-expression
ERP013215	Expression profiling of budding cells in colorectal cancer suggests an EMT-like phenotype and molecular subtype switching	Tumour buds undergo phenotype switching while detaching from the main tumour, as they acquire more migratory characteristics and tend to stop proliferating. Simultaneously, an EMT-like signature is observed in the tumour buds under the form of active WNT, TGF and receptor tyrosine kinase signalling. In addition, FOXA2 and RUNX2  well known transcription factors in other cancer types  were also differentially expressed in the buds compared to the main tumour mass, hinting at the potential role in tumour budding and initiation of metastasis in colorectal cancer.	Co-expression
ERP013260	Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating T regulatory cells	To assess the gene expression landscape of tumor infiltrating CD4+ T cells, we isolated different CD4+ lymphocytes subsets from two different tumors, NSCLC and CRC, from the adjacent normal tissues, and from peripheral blood samples. From all these tissues, we purified by flow cytometry CD4+ Treg (36 samples from 18 individuals), Th1 (30 samples from 21 individuals) and Th17 (22 samples from 14 individuals) cells. The polyadenylated RNA fraction extracted from the sorted CD4+ Treg, Th1 and Th17 cells was then analyzed by paired-end RNA sequencing.	Co-expression
ERP013303	miR-515 and migration in cancer	We performed RNA-seq analyses of both estrogen receptor-positive and negative breast cancer cells over-expressing miR-515-5p which revealed down-regulation of several transcripts coding for migration promoting proteins. Modulating the expression of such proteins and miR-515 we found that miR-515 reduced migration and metastatic behaviour through direct inhibition of such pro-metastatic genes.	Co-expression
ERP013387	Large-scale study of total and polysomial mRNA after DDX6 depletion in HEK293 cells	DDX6 is an abundant cytoplasmic DEAD-box RNA helicase which is involved in disparate aspects of mRNA stability and translation, leading to a confused understanding of its global function. We carried out a large-scale study of total and polysomial mRNA after DDX6 depletion to get an accurate picture of its roles in human cells.	Co-expression
ERP013422	Dfifferential gene expression in human KBM-7  clone  B  and  KBM-7-NuKO (NUDT2 KO) cells	The  KBM-7  reference  clone  B  (product  no.  P00174E07)  and  the  KBM-7-NuKO  derivative (P01289H04) in which the NUDT2 gene has been inactivated by retroviral gene-trap insertion were  obtained  from  Haplogen and  maintained. Three independent samples of total RNA were prepared from both KBM-7 and NuKO cells and sequenced using Illumina HiSeq2000.	Co-expression
ERP013498	CRISPR_Screening_in_Glioblastoma	Human glioblastoma stem cells are thought to be extremely important in causing recurrence of this aggressive brain tumour and resistance to therapy. However, little is known of the genes needed for these cells to survive. We are performing a genome-wide CRISPR/cas9 screen for the genes essential for proliferation of these cells in vitro. Such genes will have depletion of their guide RNAs, and these candidates will be validated in downstream in vitro and in vivo experimental work, representing potential novel therapeutic targets.	Co-expression
ERP013561	Effect of hypoxia and atpenin A5 on the human monocyte transcriptome	Monocyte-enriched peripheral blood mononuclear cells of apparently healthy human blood donors were cultured under normoxia or hypoxia (1% O2) for 24 hours at a high density (>20 million/ml). Normoxic cultures were also treated with 1 uM atpenin A5 for 48 hours. Afterwards, CD14+ monocytes were isolated using magnetic beads and their transcriptomes examined by sequencing rRNA-depleted total RNA (Illumina TruSeq Stranded Total RNA library preparation kit; HiSeq 2000 sequencer; paired 101 b reads; 6 libraries per flow lane).	Co-expression
ERP013700	A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome	Transcriptome of high grade serous ovarian carcinoma isolated from patient acites and associated macrophages was analyzed using RNASeq.	Co-expression
ERP013713	Gene expression patterns in developing intestinal organoids exposed to prolonged FGF4- and Wnt-signaling	Based on the ability of FGF and/or WNT signaling to control posterior fate and intestinal lineage commitment, several groups have reported that treating mouse or human Pluripotent Stem Cell (PSC) derived definitive endoderm (DE) with small molecules or ligands that activate WNT signaling, or a combination of WNT and FGF signaling can induce an intestinal fate in human DE.  In this current study, we leverage hESC derived human intestinal organoids (HIOs) to test the hypothesis that the duration of exposure to high levels of FGF and WNT signaling controls regional intestinal identity, with shorter durations generating intestine similar to the proximal duodenum, and longer durations distalizing HIOs to become similar to jejunum/ileum. Our results demonstrate that exposing human definitive endoderm (DE) cultures to short or long incubations of media that activate WNT and FGF siganling results in gene and protein expression profiles that are consistent with tissue that has been patterned into proximal (duodenum) or distal (ileum) small intestine, respectively.	Co-expression
ERP013849	RNA-Seq (HEK93_Homo Sapiens)	The regulation of the heterogeneity of the transcriptome and proteome represents a key step in understanding the differences in diversity between organisms of similar genetic complexities. TIA1 and TIAR intracellular antigens have been involved in the regulation and / or modulation of gene expression in different aspects of RNA metabolism, including: 1) transcription, through its interaction with DNA and RNA polymerase II; 2) pre-mRNA alternative splicing, through the selection of atypical 5' splice sites; 3) the location, stability and / or translation of eukaryotic mRNA through interaction with the 5 'and 3' UTRs and 4) control of biological programs that are for cellular survival (inflammation, proliferation, apoptosis, stress or virus infections). Accordingly, our research hypothesis is that these proteins play an important role in controlling gene expression by adapting the human proteome and transcriptome expression and function in order to survive over aberrant situations compromising cellular homeostasis in pathophysiological conditions such as cellular stress, tumorigenesis or aging and age-related diseases. This project aims to define changes in the transcriptome and proteome associated with the gain of function of these proteins, as phenomenon that contrasts and prevents the development of proliferative aberrant cell phenotype associated with reduced expression of TIA1 and / or TIAR.	Co-expression
ERP013870	BMI1 regulates myogenic differentiation, Hippo signaling, and oncogene expression in embryonal rhabdomyosarcoma.	The purpose of our study was to examine the function of BMI1 in fusion positive and fusion negative rhabdomyosarcoma cell lines and validate these findings in patient tissue.  RD and RH30 cell lines were treated with control-siRNA or BMI1-siRNA and the RNA was subsequently sequenced on a HiSeq2500.  The resultant sequencing data was used for Gene Set Enrichment Analysis and pathway analysis.	Co-expression
ERP013914	RNA-Seq analysis of human intact and damaged osteoarthrtitic cartilage following total knee replacement.	This experiment captures the expression of genes between two sites of human cartilage within the same patients to allow investigation of genomic responses to damage during osteoarthritis. Eight patients with symptomatic OA undergoing total knee replacement (n=8, age range 65-79 years, mean age 70.3) were used in this study. Cartilage from paired osteochondral samples were isolated from the intact PLC (posterior lateral condyle) and the damaged DMC (distal medial condyle) for RNA-seq analysis.	Co-expression
ERP014004	Next generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia	Little is known about the impact of DNA methylation on the evolution/progression of chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. While only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared to controls, ~6,500 differentially methylated CpG sites were found in cells from BC-CML patients. In the majority of affected CpG sites methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes which were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared to CP-CML-derived cells. Several of them are well-known tumor suppressor genes or regulators of cell proliferation. 5-aza-2 -deoxycytidine treatment of CML cells resulted in gene re-expression and in a dose-dependent cell growth reduction. Single nucleotide variants of certain epigenetic modifiers during CML progression were not found. Together, our results demonstrate that methylation changes occur frequently during CML progression and may provide a useful basis for revealing new targets of therapy in advanced CML.	Co-expression
ERP014062	Unliganded Estrogen Receptor Beta cooperates with Argonaute 2 in the modulation of transcription rate and splicing of target genes in breast cancer cells.	Estrogen receptors (ERs) are primary targets for chemoprevention and endocrine therapy of breast cancer (BC) and provide prognostic and predictive information concerning tumor response to endocrine therapies. Expression of ER reduces cancer cell proliferation and tumor growth, pointing to an anti-proliferative action of this transcription factor and its positive prognostic value. Moreover, it has emerged that unliganded ER exhibits an active role in constitutive regulation of target genes transcription.  Indeed, gene expression profiling of hormone-deprived human BC cells expressing ER revealed a great impact of this ER subtype in the modulation of gene expression in absence of hormonal ligands. Starting from this observation, and to identify key nuclear factors acting in concert with ligand-free ER, Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) was applied to isolate nuclear protein complexes associated to unliganded ER in BC cells. Among the >300 proteins identified, we focused our attention on the functional significance of a complex comprising ER and AGO2, since this argonaute protein has been implicated in key biological processes in the cell nucleus. ER association with AGO2 and other known AGO2 interacting proteins was confirmed by co-immunoprecipitation in MCF-7 cells expressing tagged ER. ChIP-Seq allowed the identification of a number of ER- and AGO-binding sites to breast cancer cells genome, while AGO2 knock down resulted in significant changes in transcription rate and co-transcriptional mRNA splicing of a group of genes, comprising in particular a significant number of those modulated by unliganded ER. In conclusion, these experimental evidences suggest that AGO2 is a functional partner of ER involved in hormone-independent gene regulation in BC cells	Co-expression
ERP014117	Transcriptional profiling of human serotonergic neurons in vitro	"Human serotonergic neurons are derived using published transdifferentiation protocols. ""Human Fibroblasts"" correspond to human fibroblasts (from Line#1, Coriell bought (AG08498)). Samples labeled ""human neurons or induced neurons (iN)"" correspond to neurons transdifferentiated from fibroblasts using two transcription factors, as previously described (#1-AG08498 or #2:ERF-1, Erlangen Germany, a line given to us by collaborators) into primarily glutamatergic neruons. Samples labled ""5-HT neurons or serotonergic neurons or iSN"" correspond to serotonergic neurons derived from the stated fibroblast lines, using an additional four transcription factors. For transdifferentiation of iN and iSN, fibroblasts were made to overexpress the stated transcription factors in a doxycycline inducible manner for up to 3 weeks, and then neurons are sorted out and collected directly into Trizol for RNA preparation and sequencing. The non-transdifferentiated fibroblast lines were collected in bulk withtout differentiation into neurons. The line number corresponds to the same fibroblast line either being transdifferentiated into iN or iSN, as labeled - for direct and groupwise comparison."	Co-expression
ERP014247	Transcriptional profiling of human naive embryonic stem cells	Human pluripotent cell lines were derived from blastocyst-stage embryos and propagated in self-renewal conditions that maintain features of naive pluripotency characteristic of mouse embryonic stem cells. Transcriptional activity of HNES1, HNES2 and HNES3 cell lines was assessed with RNA-seq.	Co-expression
ERP014344	The Functional Analysis of Granulins and Progranulin	Recombinant PGRN and GRN peptides were used to treat fully differentiated SH-SY5Y cells. Post-treatment cells were lysed and used for RNA Seq using the ion-Torrent proton platform. Results were validated using real time PCR.	Co-expression
ERP014449	RNA-seq in HUVECs overexpressing Sox18 and treated with Sm4	We investigated the transcriptome of HUVECs under basal conditions and overexpression of Sox18 in presence or absence of small molecule protein-protein disruptor Sm4. Various RNA fractions were prepared and sequenced in order to characterise Sox18 and Sm4 responsive genes in HUVECs	Co-expression
ERP014531	RNA-Seq analysis of unstimulated and LPS-stimulated monocytes from manifest HD and control subjects.	Previous work has shown that HD myeloid cells are functionally abnormal, producing significantly more proinflammatory cytokines following LPS stimulation compared to control cells. While their phenotypic abnormalities are relatively well characterised, considerably less is known about the transcriptional profile underpinning these changes. Monocytes were isolated from the peripheral blood of 30 manifest HD patients and 33 controls, before culturing with and without 4 h LPS stimulation. RNA-Seq was then carried out to characterise gene expression changes across the entire HD monocyte transcriptome.	Co-expression
ERP014707	RNA-Seq profiling of dopaminergic neurons from iPSCs of Parkinson's disease patients	The fact that Parkinson’s disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. In order to address this hypothesis, an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling was taken to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, neurons harboring disease-causing mutations were generated from patient-specific, induced pluripotent stem cells (iPSCs) and found to recapitulate several disease-related phenotypes. Signs of degeneration in PD midbrain dopaminergic (mDA) neurons were observed, reflecting the cardinal feature of PD. In addition, novel gene expression signatures were revealed for PD mDA neurons, providing molecular insights to disease phenotype observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, detailed transcriptome profiling of PD neurons showed that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, is responsible for a pattern of alternative RNA processing associated with PD-specific phenotypes in vitro.	Co-expression
ERP015139	Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy	Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive head injury (RHI) with distinctive neuropathological features that differentiate it from other neurodegenerative diseases. Intraneuronal tau aggregates, albeit in different patterns, are diagnostic neuropathological features of CTE but the exact mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of postmortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. We found that genes related to MAP Kinase and calcium signaling pathways were significantly down regulated in CTE. Altered expression of protein phosphatases (PP) in these networks further suggest that the tauopathy found in CTE shares common pathological mechanisms as similar to Alzheimer’s disease (AD). Using cell lines and animal models we also showed that reduced PPP3CA/PP2B phosphatase activity is directly linked to increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration that may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.	Co-expression
ERP015145	Expression RNA-Seq data of matched cases of pre-treatment Fine-needle aspiration (FNA) and the respective post neo-adjuvant treatment operative sample of breast cancer patients.	"Neoadjuvant treated patients were selected from the \""Genomstudy\"" of the University Women`s Clinic Heidelberg (2009-2016). This study includes primary breast cancer cases that were newly diagnosed at the University women's clinic of Heidelberg and had given their informed consent for participating in this study. This study was approved by the Ethical Committee of the Medical Faculty in Heidelberg.  All cases were female and Caucasian.  Fresh core needle biopsies and fresh tumor tissue were examined by a pathologist, snap-frozen in liquid nitrogen and stored at -80째C within 15 min after sampling.   Total RNA as well as DNA and protein were extracted by applying the QIAGEN All Prep Kit. All eluates were stored at -80째C until usage.  A sample swap most probably occurred for patient 207, so 207-S is actually in the T condition and 207-T in the S condition."	Co-expression
ERP015178	Unliganded Estrogen Receptor Beta cooperates with Argonaute 2 in the modulation of transcription rate and splicing of target genes in breast cancer cells. Part 1	Estrogen receptors (ERs) are primary targets for chemoprevention and endocrine therapy of breast cancer (BC) and provide prognostic and predictive information concerning tumor response to endocrine therapies. Expression of ERβ reduces cancer cell proliferation and tumor growth, pointing to an anti-proliferative action of this transcription factor and its positive prognostic value. Moreover, it has emerged that unliganded ERβ exhibits an active role in constitutive regulation of target genes transcription.  Indeed, gene expression profiling of hormone-deprived human BC cells expressing ERβ revealed a great impact of this ER subtype in the modulation of gene expression in absence of hormonal ligands. Starting from this observation, and to identify key nuclear factors acting in concert with ligand-free ERβ, Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) was applied to isolate nuclear protein complexes associated to unliganded ERβ in BC cells. Among the >300 proteins identified, we focused our attention on the functional significance of a complex comprising ERβ and AGO2, since this argonaute protein has been implicated in key biological processes in the cell nucleus. ERβ association with AGO2 and other known AGO2 interacting proteins was confirmed by co-immunoprecipitation in MCF-7 cells expressing tagged ERβ. ChIP-Seq allowed the identification of a number of ERβ- and AGO-binding sites to breast cancer cells genome, while AGO2 knock down resulted in significant changes in transcription rate and co-transcriptional mRNA splicing of a group of genes, comprising in particular a significant number of those modulated by unliganded ERβ. In conclusion, these experimental evidences suggest that AGO2 is a functional partner of ERβ involved in hormone-independent gene regulation in BC cells. Additional data related to this study has also been deposited in ArrayExpress under accession number E-MTAB-4639 (http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-4639)	Co-expression
ERP015292	_SMA_transcriptomics_and_non_canonical_translation	Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutation of SMN, which encodes a protein critical for snRNP assembly and splicing. SMN loss-of-function induces motor neuron death and disrupts neuromuscular communication. Approved treatments for SMA are lacking, and will benefit from increased knowledge of additional functional pathways disrupted in SMA. We are undertaking simultaneous global proteomic and transcriptomic profiling of spinal cord tissue from SMA mice and control mice across a developmental timecourse (P2, P6, and P10). We will cross-reference these data to examine changes in translational regulation, examine differential splicing of individual mRNAs, and examine non-canonical translation products in SMA disease. Together these results give insight into molecular mechanisms underlying SMA and neurodegenerative disease.	Co-expression
ERP015294	Transcriptome of dermal fibroblasts from healthy human donors differing by donor age, donor gender and UV exposition (Gerontosys).	RNA-seq data from short term cultivated fibroblasts were sequenced on an Illumina HiSeq 2000 sequencer. Donors were differentiated by age (Years) and gender (F=female; M=male). Two samples were obtained from each individual from different locations (B=buttock, not UV exposed; S=shoulder, UV exposed).	Co-expression
ERP015444	Jinfukang enhances the pro-apoptotic activity of cisplatin via activation of AIFM2 in human lung cancer cells	Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and drug resistance. In this study, we aimed to examine whether Jinfukang (JFK), an effective herbal medicine against lung cancer, enhances DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines NCI-H1975, NCI-H1650 and NCI-H2228. Particularly, we demonstrated AIFM2 is activated by the combined treatment of JFK and DDP, and partially mediate the synergistic pro-apoptosis effect. Collectively, this study gives the first evidence that activation of AIFM2 contributes to induction of pro-apoptosis by combined treatment with JFK and DDP in human lung cancer cells and provides an insight for its potential clinical application in lung cancer treatment.	Co-expression
ERP015474	In Vivo Functional Platform Targeting Patient- Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer	Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify new druggable targets essential for PDAC maintenance. We developed an unbiased, in vivo target discovery approach to interrogate tumor-initiating cell (TIC) vulnerabilities in low- passage, patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1- 4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, a critical ATR substrate, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR inhibitors currently in development for activity in this disease as well as prospecting the opportunity to discover novel WDR5 inhibitors.	Co-expression
ERP015518	RNA-seq analysis of two cell line models of lung diseases in Project 3 of Open Targets - Epigenomes of Cell Lines	This experiment captures the baseline expression of two cell lines (A549, BEAS-2B) selected for Project 3, Open Targets (http://opentargets.org/, formerly CTTV). These cell lines are both possible models for lung disease.  This RNA-seq experiment is being carried out as part of the Open Targets project to identify a gene expression signature of common immortalised cell lines/models. This signature will be used in combination with data from ChIP-seq experiments from the same cell lines against primary cells and tissues. The overall aim of the Open Targets Cell Line Epigenome project is to establish a systematic approach for the determination of human biological and disease relevance through the generation of transcriptomic and epigenomic data in cell lines of interest. Comparison of cell line mRNA expression and epigenome data with existing and newly generated reference data from human tissue and cell types will identify assay systems that will provide greater confidence in translating target biology and compound pharmacology to patients.	Co-expression
ERP015593	RNA_expression_profile_of_Cas9_cancer_cells	The aim of this study is to investigate the gene expression profiles of Cas9 expressing cancer cell lines.	Co-expression
ERP015595	Identification of AMKL deregulated genes by RNAseq	Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups, and several genetic alterations have been characterized in the past years, including the t(1;22)(p13;q13) and the trisomy 21 associated with GATA1 mutations. However, the majority of patients do not present known mutations, and the limited access to primary patient leukemic cells impedes the efficient development of novel therapeutic strategies. In this study, using a xenotransplantation approach, we have modeled human pediatric AMKL in immunodeficient mice. Analysis of high-throughput RNA sequencing identified recurrent fusion genes defining new molecular subgroups.	Co-expression
ERP015612	Differential gene expression for A2780 human ovarian cancer cells when exposed to a new osmium-based anticancer agent	Platinum-based metallodrugs are the most widely used anticancer agents. Their reduced effectiveness after repeat dosing (resistance) constitutes a major clinical problem. In this experiment we study a potent organo-osmium compound with improved activity over cisplatin and no cross-resistance in platinum-resistant cancers. A2780 cells were exposed to an osmium anticancer compound and to a negative control solution, in triplicate. At 0, 4, 12, 24 and 48 h, cells were collected for each condition, and whole cell RNA was extracted. Samples were purified and QC checked before Truseq library preparation and Illumina sequencing. Each sample had approximately 30 million paired-end reads. Samples were mapped to the human genome using Tophat2 and differential expression analysed using edgeR.	Co-expression
ERP015684	RNA-seq of LGR5(+) and LGR5(-) cells isolated from human colon adenoma organoids	Human colon adenoma organoids (n=3 patients) were dissociated into single cells. Cells were incubated with a magnetic bead bound to an LGR5 antibody and run through a magnetic column. Magnet bound cells and flow through negative (FTN) cells were obtained. Magnet bound and FTN cells were incubated with an APC-check reagent (which binds to the magnetic bead on the LGR5 antibody) and DAPI, before being sorted by flow cytometry. 3 populations of live (DAPI-) cells were collected: FTN: Flow through negative. LGR5 negative by magnet and by flow cytometry SortedNeg: Magnet bound cells that were negative for LGR5 by flow cytometry SortedPos: Magnet bound cells that were positive for LGR5 by flow cytometry	Co-expression
ERP015750	BASIC: B-cell receptor (BCR) assembly from single cell RNA-seq	The B-cell receptor (BCR) enables individual B cells to identify diverse antigens, including bacterial and viral proteins. While advances in RNA-seq have enabled high throughput profiling of transcript expression in single cells, the unique task of assembling the full-length heavy and light chain sequences from single cell RNA-sequencing (scRNA-seq) in B cells has been largely unstudied.  We developed a new software tool, BASIC, which allows investigators to use scRNA-seq for assembling BCR sequences at single cell level. To demonstrate the utility of our software, we subjected single B cells from a human donor to scRNA-seq, assembled the full-length heavy and the light chains, and experimentally confirmed these results by using single cell primer based nested PCRs and Sanger sequencing.	Co-expression
ERP015769	DNA methylation variations are required for reversible EMT induced by cancer-associated fibroblasts in PCa cells	Epithelial-to-mesenchymal transition (EMT) and cancer stem cells play relevant roles in metastasis and drug resistance in castration-resistant PCa. Conditioned-media from Cancer-Associated Fibroblasts from two patients with aggressive PCa induce EMT, reversible DNA methylation and transcriptional variations in androgen independent PC3, but not in androgen dependent LN-CaP cells. Focal CpG islands hyper-methylation associated to transcriptional repression of epithelial markers occurs together with widespread hypo-methylation, including promoters of EMT and stemness regulating genes resulting in their transcriptional activation. Remarkably, DNA methylation and transcription patterns are entirely reverted upon exposure to serum-free medium (mesenchymal-to-epithelial transition). DNMT3A is required for de novo methylation and silencing of CDH1 and GRHL2, the ZEB1 direct repressor, while its knock-down prevents EMT entry. These unprecedented results highlight that CAF-released factors induce reversible DNA methylation patterns required for transcriptional variations essential for EMT and stemness in androgen independent PCa cells, suggesting that similar plasticity might occur in tumour microenvironment.	Co-expression
ERP015831	Whole Transcriptome sequencing TSCC (tongue squamous cell carcinoma)	Of the multiple anatomical sites represented in oral cancer, squamous cell carcinoma of the tongue (TSCC) shows the highest incidence among younger age group. Chewing betel leaf, areca nut & slaked lime and smoking tobacco are common practises in India which have direct clinical implication in TSCC carcinogenesis. Here, for the first time we define the landscape of genomic alterations in TSCC from the Indian diaspora which would help to identify novel therapeutic targets for clinical intervention and define the genetic basis for TSCC. We performed high throughput sequencing of fifty four tongue samples using whole exome sequencing (n=47, 23 paired normal tumor and 1 unpaired) and transcriptome sequencing (n=17, 10 tumor and 5 normal). Mutation, copy number analysis were carried out using exome sequencing data and transcriptome analysis provided expressed genes and transcript fusions in tongue cancer patients. Further, integrated analysis were performed to identify biologically relevant alterations.  Our preliminary analysis revealed presence of most frequently altered mutations in TSCC which includes mutations in TP53, NOTCH1, CDKN2A, USP6, KMT2D etc, consistent with literature. We observed high frequency of C→G/T(G→C/A) transversions in non-CpG islands, a signature associated with tobacco exposure. Somatic copy number analysis revealed copy number gain in known hallmarks such as CCND1, MYC, ORAOV1 genes along with copy number alteration in novel genes. Significant positive correlation was observed in the genes harbouring copy number gains and showing increased expression.	Co-expression
ERP015848	The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization and disease progression	RNAseq of peritoneal macrophages from patients with non-malignent peritoneal afflictions.	Co-expression
ERP015852	RNASeq profiling of AZD8186-treated HCC70 xenografts	HCC70 xenografts treated with 11 doses of AZD8186 (100mg/kg BID) were compared to DMSO-treated control xenografts	Co-expression
ERP015932	Galectin-3 interacts with components of the nuclear ribonucleoprotein complex	The multifunctional β-galactoside-binding protein galectin-3 is found in many distinct subcellular compartments including the cell nucleus. Expression and distribution of galectin-3 between the cell nucleus and the cytosol changes during cell differentiation and cancer development. Nuclear functions of galectin-3 and how they contribute to tumorigenesis are not understood. In order to identify nuclear galectin-3 interaction partners, we used affinity chromatography and co-immunoprecipitation. Spatial proximity in the nucleus was assessed by immunofluorescence and proximity ligation assay. We also investigated the function of galectin-3 on mRNA-export by fluorescence in situ hybridization and on mRNA-processing by RNA-sequencing.	Co-expression
ERP016036	Two classes of L1-associated somatic variants in human brain - RNA-Seq	RNA-Seq of NPCs with knowckdowns for PWRN2 and controls	Co-expression
ERP016064	Anatomic specialization of synovial fibroblasts – integrating positional stromal signatures with joint specific pathways in arthritis.	A number of human diseases, including arthritis and atherosclerosis, shows characteristic predilection for specific anatomic locations. We studied the role of site-specific stromal cell biology in defining location-specific pathology in arthritis as a model disease. We demonstrate that synovial fibroblasts (SF), the main resident cells of the synovium, exhibit large anatomic differences in their transcriptomes. Site-specific HOX gene signatures determined joint-specific origins of murine and human SF and synovial tissues. We show that alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Transcriptional diversity translated into joint-specific phenotypes of SF with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNFα, creating a unique microenvironment in each joint. These findings deeply alter the current understanding of synovial biology and offer a concept that local stroma governs positional disease patterns not only in arthritis but any disease with a prominent stromal component.	Co-expression
ERP016099	MCF7_Mimic	MCF7 mimic, RNA-seq	Co-expression
ERP016243	Human Developmental Biology Resource (HDBR) expression resource-RNAseq	"The Human Developmental Biology Resource (HDBR) expression resource is a new resource for studying prenatal human brain development. It consists of two parts which have been uploaded as two submissions: HDBR expression resource- RNAseq (E-MTAB-4840, this submission) and HDBR expression resource- SNP data (E-MTAB-4843). It is unique in the age range (4 post conception weeks [PCW] to 17PCW) and number of brains studied, particularly those under 8PCW. It is also unique in that both the large-scale data sets and the corresponding RNA and DNA samples are available, the latter via the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR; http://www.hdbr.org). There are 628 RNA-seq datasets from different regions of the brains studied. The number of regions depends on the stage and size of the sample and/or the tissue available. Embryos (4-8PCW) have been staged using a modified Carnegie staging system, details can be found at http://database.hudsen.eu/. All the RNAseq datasets from the same brain have the same embryo/fetus number (e.g. RNAseq datasets HDBR251-HDBR254 are from different tissues from embryo number 1406). The embryo/fetus ID number is recorded in the “individual” column. The majority of the brains studied are between 4 and 12PCW.  During this time the major brain regions are established and there are the early stages of cortex development.  DNA was prepared from all the tissues used for RNA-seq analysis and SNP genotype data generated from one tissue from each brain.  RNA-seq data and SNP-data from the same tissue and brain have the same name (e.g. HDBR469). There are also SNP genotype data from 229 additional specimens in paraffin wax blocks available for individual gene expression studies. These data are in the accompanying ""HDBR expression resource- SNP data"" (E-MTAB-4843). "	Co-expression
ERP016265	Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans	RNA-seq of C.elegans strain N2 (wt) with and without sfa-1 RNAi at adult day 3 and day 15, C. elegans strain DA1116 (eat-2(ad1116)) with and without sfa-1 RNAi at adult day 3, day 15, and day 27, C. elegans strain SS104 (glp-4(bn2)) with and without hrp-2 RNAi at adult day 1, and HeLa cells with and without SF1 siRNA.	Co-expression
ERP016268	Transcriptome profiling of DA neurons, human midbrain-like organoids and prenatal midbrain	Recent advances in three dimensional (3D) culture systems have led to the generation of brain organoids that share resemblance to different parts of the human brains; however, a 3D organoid model of the midbrain that contains functional midbrain dopaminergic (mDA) neurons has not been reported. In this study, we develop a method to differentiate human PSCs into a large multicellular organoid-like structure that contains distinct layers of neuronal cells with a transcriptomic profile that resembles human prenatal midbrain. Importantly, we detected electrically active and functionally mature mDA neurons, and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using non-3D methods or in the MLOs generated from mouse embryonic stem cells, our human MLOs uniquely produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a novel tractable in vitro system to study the human midbrain and its related diseases.	Co-expression
ERP016347	RNASeq of musculoskeletal ageing using human mesenchymal stem cells and their tissue constructs	Human bone-marrow-derived mesenchymal stem cells from young and old donors  and tenogenic, chondrogenic and osteogenic constructs derived from these were subject to RNASeq and miRNASeq. We wished to identify common pathways of musculoskeletal ageing.	Co-expression
ERP016378	A mouse model for a liver disorder	A mouse model for a liver disorder	Co-expression
ERP016409	RNA-seq of whole blood samples from human visceral leishmaniasis compared to samples from healthy uninfected controls	To ascertain which genes are involved in pathogenesis of human visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, we investigated the transcriptional profile of whole blood samples from patients diagnosed with active VL compared to healthy control samples.	Co-expression
ERP016418	Transcriptome analysis of HUVEC	Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical cords from four different donors, as previously described (Cooke et al., 1993). Cells were maintained in Medium 199 (M199, Invitrogen) containing 20% fetal calf serum, 28μg/ml gentamycin, 2.5μg/ml amphotericin B, 1ng/ml epidermal growth factor and 1μg/ml hydrocortisone (all from Sigma) for 48 hours prior to processing. HUVEC cultures isolated using this method were 96-98% pure, determined by positive staining by flow cytometry of CD105, CD31 and vWF and the expression of elevated levels of intracellular adhesion molecule (ICAM-1) and E-selectin following stimulation with the inflammatory cytokine interleukin-1β. Total HUVEC RNA was isolated using the RNeasy mini kit with QIAshredder (Qiagen) according to the manufacturer’s instructions. RNA integrity number was >8.0 for all samples.	Co-expression
ERP016433	RNA-seq of sh2-H2AFJ and sh-NoTarget in WI-38hTERT cells induced into senescence by etoposide	Study the role of H2A.J in gene expression in senescent human fibroblasts by comparing RNA-seq of WI-38hTERT fibroblasts expressing either an sh2-H2AFJ or sh-NoTarget RNAs. Senescence was induced by treating cells with 20 µM etoposide for 2 weeks followed by one further week of incubation without etoposide. 3 biological replicates of sh2-H2AFJ and sh-NoTarget were sequenced.	Co-expression
ERP016435	Transcriptome analysis of neuronal cells infected with tick-borne encephalitis virus reveals strong induction of host response-associated genes that exclude type I and II IFNs	Here we describe the host response to TBEV infection as well as IFN-β treatment in human DAOY medulloblastoma cells. Thus, these data can serve as a base for further studies of host-TBEV interactions and identification of ISGs and/or lncRNAs with potent antiviral effect in case of TBEV infection in human neuronal cells.	Co-expression
ERP016484	MCF10A cells expressing GATA3 mutants	Patterns of somatic mutations in cancer genes provide information about their functional role in tumourigenesis and thus indicate their potential for therapeutic exploitation. Yet, the classical distinction between oncogene and tumour suppressor may not always apply. For instance, TP53 has been simultaneously associated with tumour suppressing and promoting activities. Here, we uncover a similar phenomenon for GATA3, a frequently mutated, yet poorly understood breast cancer gene. Surprisingly, we identify two functional classes of frameshift mutations that are associated with distinct expression profiles in tumours, differential disease-free patient survival and gain- and loss-of-function activities in a cell line model. We performed RNA sequencing on MCF10A cells expressing wild-type and two different GATA3 mutants (GATA3-wt, GATA3-ext, GATA3-trunc) or control vector expressing cells to characterise the effects of GATA3 mutations at the cellular level. These data indicated that expression of GATA3-ext and GATA3-trunc invoke starkly distinct changes in gene expression and the large number of uniquely regulated genes in GATA3-ext expressing cells supports a gain-of-function of this mutant.	Co-expression
ERP016616	Transcriptomics in Zika virus-infected human brain organoids	PolyA+ RNA sequencing of Zika virus-infected human brain organoids at 5 days post-infection.	Co-expression
ERP016636	Tuning the transcriptional response to hypoxia through HIF prolyl- and asparaginyl-hydroxylase inhibition:Sequencing Data	The hypoxia inducible factor (HIF) system orchestrates cellular responses to hypoxia in animals. HIF is an α/β-heterodimeric transcription factor that regulates the expression of hundreds of genes in a context dependent manner. A hypoxia-sensing component of the HIF system involves oxygen-dependent catalysis by the HIF hydroxylases; in humans there are three HIF prolyl hydroxylases (PHD1-3) and an asparaginyl hydroxylase (FIH). PHD catalysis regulates HIFα levels and FIH catalysis regulates HIF activity. How differences in HIFα hydroxylation status relate to variations in the induction of HIF target gene transcription is unknown. We report studies using small molecule inhibitors of the HIF hydroxylases to investigate the extent to which HIF target gene upregulation is induced by reduced PHD catalysis. The results reveal substantial differences in the role of prolyl- and asparaginyl-hydroxylation in regulating hypoxia responsive genes in cells. Selective PHD inhibitors with different structural scaffolds behave similarly. However, under the tested conditions, a broad-spectrum 2OG dioxygenase inhibitor is a better mimic of the transcriptional response to hypoxia than the selective PHD inhibitors, consistent with an important role for FIH in the hypoxic transcriptional response. Indeed, combined application of selective PHD and FIH inhibitors resulted in transcriptional induction of a subset of genes that were not fully responsive to PHD inhibition alone. Thus, for the therapeutic regulation of HIF target genes, it is important to consider both PHD and FIH activity, and in the case of some sets of target genes, simultaneous inhibition of the PHDs and FIH catalysis may be preferable.	Co-expression
ERP016691	Repression of miR-31 expression by BCL6 specifies helper function of human follicular helper T cells	Repression of miR-31 expression by BCL6 specifies helper function of human follicular helper T cells	Co-expression
ERP016798	Whole transcriptome profiling of 63 breast cancer tumours	RNA-Seq was used to profile the transcriptomes of 63 breast cancer patient tumour samples (51 x ER+, 12 x triple negative) collected from the Utah Breast Cancer Study (UBCS).	Co-expression
ERP016801	TSLPR expression marks a functionally discrete subset of human monocytes elicited by TLR4 activation.	TSLPR+ and TSLPR- monocytes were isolated form 3 adult healthy donors and stimulated with LPS. RNA-sequencing has been performed using Illumina technology.	Co-expression
ERP016816	Transcriptomic profiling of human purified intestinal epithelial samples and organoids from paediatric and foetal small and large intestine	Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. Here, we provide the following reference datasets of transcriptomic profiling by RNA-sequencing:    Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Intestinal organoid cultures from paediatric ileum and colon,  Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells.	Co-expression
ERP017123	Whole-islet RNA-sequencing analysis of human pancreas and type 2 diabetes.	We performed whole-islet RNA-sequencing of human pancreatic islets from healthy and T2D individuals in order to compare the expression data to the corresponding single-cell RNA-sequencing data from the same donors (related single-cell study: Single-cell analysis of human pancreas and T2D).	Co-expression
ERP017126	Single-cell RNA-seq analysis of human pancreas from healthy individuals and type 2 diabetes patients	We used single-cell RNA-sequencing to generate transcriptional profiles of endocrine and exocrine cell types of the human pancreas. Pancreatic tissue and islets were obtained from six healthy and four T2D cadaveric donors. Islets were cultured and dissociated into single-cell suspension. Viable individual cells were distributed via fluorescence-activated cell sorted (FACS) into 384-well plates containing lysis buffer. Single-cell cDNA libraries were generated using the Smart-seq2 protocol. Gene expression was quantified as reads per kilobase transcript and per million mapped reads (RPKM) using rpkmforgenes. Bioinformatics analysis was used to classify cells into cell types without knowledge of cell types or prior purification of cell populations. We revealed subpopulations in endocrine and exocrine cell types, identified genes with interesting correlations to body mass index (BMI) in specific cell types and found transcriptional alterations in T2D.	Co-expression
ERP017153	IL-12 protects from psoriasiform skin inflammation	Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17 committed γδT (γδT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional program that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis.	Co-expression
ERP017213	RNAseq libraries to study developmental alternative polyadenylation in human primitive streak progenitors derived from hESCs.	Illumina TRUseq method to generate highly strand-specific next-generation sequencing (NGS) libraries	Co-expression
ERP017433	Transcriptional differences between the peripheral and the transcription zone of the prostate	The occurrence of cancer is not equally distributed across the three zones of the  prostate gland; the peripheral (PZ), central and transition zones (TZ). The majority (~70%) of diagnosed prostate cancer (PCa) is found in the PZ compared to the TZ. In this study we comprehensively measure whole genome expression by next-generation sequencing of the PZ and TZ from prostate tissue. Our aim was to identify the molecular and metabolic differences between the two zones that could underlie the differential susceptibility to PCa incidence. Following histological assessment of tissue adjacent to the biopsies used for RNAsequencing we identified 4 out of the 18 samples to be cancerous. Although these are included in the ArrayExpress submission, they were not included in the final analysis of data that reported the molecular differences between morphologically normal peripheral and transition zones.	Co-expression
ERP017435	nascent RNAseq  of hESC.	Nascent RNAseq in conjunction with Illumina TRUseq method to sequence total RNAs including short lived RNAs using highly strand-specific next-generation sequencing (NGS) libraries	Co-expression
ERP017549	RNA-seq of fetal urinary bladder and lung tissue	The gene activity during human urinary bladder development is largely unknown. Our aim is to provide gene expression data to identify active genes during development and to facilitate future candidate gene identification for bladder malformations. Here, we make the first step to provide RNA-Seq of time-series bladder tissues between week 5 to 10. Fetal lung is used as reference sample.	Co-expression
ERP017706	Transcription profiling of oesophageal adenocarcinoma by RNA-seq	Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer which is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood although genomic sequencing studies have identified several genes encoding chromatin remodeling enzymes that are frequently mutated in OAC. This finding is consistent with the knowledge that one important change that occurs in cancer cells is a reprogramming of the chromatin environment which leads to subsequent changes in their transcriptional profile.	Co-expression
ERP017989	Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles	Time course transcriptomic profiling of human bronchial epithelial cell BEAS-2B exposed to a single dose of diesel and biomass ultrafine particles	Co-expression
ERP018533	RNA-seq analysis of cell-line models for monocyte to macrophage transformation: Project 3 of Open Targets - Epigenomes of Cell Lines	The goal of this experiment is to characterize the expression of two cell-line models of monocyte to macrophage transformation. Either PMA (phorbol myristate acetate) and LPS (lipopolysaccharide) or VD3 (vitamin D3) and LPS were used as stimuli to induce differentiation.  Cells from single replicates were cultured in parallel. At 0 hrs, cells were split into 6 aliquots with two aliquots in each of three treatment conditions; no treatment,  2 nM PMA or 66 nM Vitamin D3. At 24 hrs, one aliquot of cells from each treatment condition was stimulated with a spike-in of LPS to a final concentration of 100 ng/mL or given an equal amount of medium as a control. 18 hrs after LPS stimulation cells were harvested.  This RNA-seq experiment is being carried out as part of the Open Targets project to identify a gene expression signature of common immortalised cell lines/models. This signature will be used in combination with data from ChIP-seq experiments from the same cell lines against primary cells and tissues. The overall aim of the Open Targets Cell Line Epigenome project is to establish a systematic approach for the determination of human biological and disease relevance through the generation of transcriptomic and epigenomic data in cell lines of interest. Comparison of cell line mRNA expression and epigenome data with existing and newly generated reference data from human tissue and cell types will identify assay systems that will provide greater confidence in translating target biology and compound pharmacology to patients.	Co-expression
ERP019583	The transcriptional signature of ascites-associated macrophages is linked to interferon signaling and a favorable clinical outcome in a subgroup of ovarian carcinoma patients	mRNA from tumor associated macrophages from high grade serous ovarian carcinoma patients was sequenced.	Co-expression
ERP019983	Comparative transcriptome analysis between immortalized ovarian surface epithelial (iOSE) and immortalized fallopian tube secretory epithelial (iFTE) cells	The transcriptomes of three immortalized ovarian surface epithelial cell lines (iOSE, PMID: 17266044) and primary OSE cells (Innoprot, Derio, Spain) and four immortalized fallopian tube secretory epithelial (iFTE) cell lines (PMID: 21502498, 22936217) were compared. RNA-sequencing was done from rRNA depleted total RNA (Ribo-Zero rRNA Removal Kit) to approx. 20 million 50 bp paired end reads per sample. A discriminative gene expression signature comprised of 211 genes was developed and used to classify isolated and EpCAM enriched primary ovarian cancer cells (PMID: 25991672). Impact of this signature on overall survival was assessed from several publicly available ovarian cancer gene expression data sets. Background: High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries.	Co-expression
ERP019993	Effect on gene expression after 4 days of a single, 15 Gy dose of ionizing X ray radiation on A549, H460 and H1299 human lung cancer cell-lines	A549, H460 and H1299 human lung cancer cells were grown adherent to 60%-80% confluence on 10-cm dishes in 8 ml RPMI-1640/+DMEM medium with 10% fetal bovine serum. Cells were irradiated with one dose of 15 Gy ionizing X rays in a Faxitron FX-650 machine; control cell culture dishes were not irradiated. After a day of radiation, adherent cells were detached by trypsinization and replated on 10-cm dishes in 8 ml RPMI-1640/+DMEM medium with 10% fetal bovine serum to reach 70%-90% confluence after three days, when adherent cells were harvested by scraping. Harvested cells were pelleted and kept frozen at -80 ºC. For each cell-line, three experiments were performed to obtain three pairs of control and irradiated cell pellets. One µg of total RNA isolated from each of the cell pellets using Norgen-Biotek Total RNA Isolation kit with an on-column DNAse I treatment step was used to prepare sequencing library for directional RNA sequencing to obtain paired 101 b reads on an Illumina HiSeq 2500 instrument. Twelve libraries were sequenced in each flow lane, and each library was sequenced in two lanes. On-system CASAVA 1.8.2 was used to demultiplex sequencing data.	Co-expression
ERP020187	RNA-seq of A431 cell line after gefitinib treatment	RNA sequencing of A431 cell line samples before and after gefitinib treatment, at 0, 2, 6 and 24 hours, was performed in order to characterize the cell line's early and late response to this drug, and to compare against proteomics (mass spectrometry) characterization of the cell line using the same setup. These data were used in Branca et al., HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics., Nat Methods. 2014 Jan;11(1):59-62 (doi: 10.1038/nmeth.2732).	Co-expression
ERP020415	Dual RNA-seq of M. tuberculosis H37Rv infecting macrophage-like THP-1 cells during 48h	Transcriptional changes during early infection of macrophage-like THP-1 cell line with pathogenic bacterium Mycobacterium tuberculosis. RNAseq samples were taken at 0h (THP-1 cells growing in the RPMI medium), and after 4h, 24h and 48h post infection. Bacterial enrichment was performed to increase the amount of bacterial mRNA in the samples. Non-enriched samples were used to map THP-1 cells transcripts; enriched samples were used to map M. tuberculosis transcripts the corresponding genomes.	Co-expression
ERP020461	CSF of Trypanosoma infected human RNAseq	Transcriptomes of Trypanosoma rhodesiense from human cerebrospinal fluid	Co-expression
ERP020462	RNAseq of blood samples of Trypanosoma infected human patients	Poly(A)+, globin-depleted mRNA from sleeping sickness patients.	Co-expression
ERP020468	RNA-Seq of human regulatory T cells and effector T cells cultured at standard 37°C temperature and in mild hypothermia (33°C).	Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Numerous clinical trials confirmed safety and efficacy of Treg treatment of for deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. In our experiment we demonstrate that mild hypothermia of 33ºC induces robust proliferation of human Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33°C showed stronger immunosuppressive potential and anti-inflammatory phenotype. We show that a simple change in temperature can preserve Treg stability, function and accelerate their proliferation in vitro.	Co-expression
ERP020471	RNAseq of the membrane-bound complement regulator genes (CR1, CR1L, CR2, CD55, CD46, CD34) in eight normal human eyes, comparing peripheral retina and macular retina, pigmented epithelium and choroid/sclera.	RNAseq expression of the membrane-bound complement regulator genes (CR1, CR1L, CR2, CD55, CD46, CD34) in eight normal human postmortem eyes, comparing peripheral retina and macular retina, pigmented epithelium and choroid/sclera. This contains a small subset (chromosome 1: 207,494,717 to 208,084,842 on hg19) of the data generated for another study by Li et al, 2014: https://www.ncbi.nlm.nih.gov/pubmed/24634144	Co-expression
ERP020523	AGR_Project___African_Genome_Resource__total_RNA_sequencing_for_1000_Genomes_African_populations	As part of the African Genome Resource (AGR) project we aim to create an African transcriptome panel. Using 1000 genomes cell lines, we generated high coverage RNAseq data (Illumina HiSeq) from 6 different populations across Africa; the first large-scale resource to examine eQTLs within Africa. Specifically we sequenced transcriptomes from 600 unrelated individuals from six populations from West (Gambian, The Gambia; Mende, Sierra Leone; Esan and Yoruba, Nigeria) and East Africa (Luhya and Masai, Kenya). Such a resource will help understand the transcriptional landscape in African populations, population differences in the diversity of splicing isoforms, as well as identify novel transcripts and exons across the genome.	Co-expression
ERP020535	this work combines newly developed methods of host gene expression analysis in duodenal tissues with unique approaches to the identification of specific pathobiont bacteria in the duodenal microbiome to elucidate mechanisms of GI dysfunction in Common Variable Immunodeficiency (CVID).  As such it provides new insights into how the mucosal immune response controls gut function in general.	Common variable immunodeficiency (CVID), the most frequently occurring form ofsymptomatic immunodeficiency, is a heterogeneous disease that is most likely due to manydifferent genetic defects. In recent years, some of these have been described, but the vastmajority of patients with CVID are still without a defined genetic abnormality (ref).With the advent of early gamma globulin replacement therapy, CVID patients are relativelyfree from life-threatening infections and have a more prolonged survival (REF). The latter,however, has revealed that CVID can be associated with other problems not due tocommon infectious agents. One of these, CVID enteropathy is characterized by villousatrophy, malabsorption and diarrhea and occurs in up to 25% of CVID patients insymptomatic form and perhaps in a larger percentage in asymptomatic form (PMID:20551941; other ref). It is not clear why only a subset of patients with CVID developenteropathy since this manifestation of the disease has not been coupled to a particulargenetic defect or environmental exposure.The villous atrophy accompanying CVID enteropathy is histologically similar to that in celiacdisease and, as such, is characterized by lamina propria inflammation accompanied bypolymorphonuclear cell infiltration and increased numbers of intra-epithelial lymphocytes;however, the prominent plasma cell infiltration seen in celiac disease is not present (PMID:20551941). These studies also showed that intraepithelial lymphocytes (IELs) in CVIDenteropathy differed from those in celiac disease in regarding some natural killer cellmarkers and TCR/ characteristic of those in celiac disease were generally not present inCVID. Further, studies of the immunologic features of this gastrointestinal syndromeconducted by Mannon et al. (PMID: 16952544) revealed that lamina propria cells wereproducing increased amounts of IL-12 and IFN- but little if any IL-17.In previous studies we have shown using systems biology methodology that totalimmunoglobulin and IgA deficiency in mice or indeed CVID in humans is associated with aremarkable up-regulation of interferon-inducible genes accompanied by a down-regulationof GATA4-related metabolic genes in the gut epithelium (PMID: 22101768). Since thesechanges were not seen in germ-free mice it clearly implied that they were dependent onone or more organisms in the gut microbiota. These studies therefore suggested that thepathogenesis of CVID enteropathy may be related to the presence of an immune defect thatleads to the colonization with an organism that drives these multiple gene expressionchanges. In the present study, we have again applied a systems biology approach to addressthis possibility, in this case including human transcriptome and microbiome analyses ofduodenal tissues of patients and healthy controls. To our surprise, we found that CVIDenteropathy was strictly limited to those CVID patients with vanishing low gut tissue IgAlevels irrespective of accompanying gut IgG levels and serum IgA levels. We used this globalomics data for transkingdom network analysis (PMID: 25614621;) to identify candidatebacteria capable of inducing the interferons response causing the villous atrophy andmalabsorption. Lastly, also using gene expression network of CVID enteropathy we pinpointand later validated in vitro two immune genes that mediate inhibitory effect of interferonson lipid metabolism in epithelium.	Co-expression
ERP020551	IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP	Innate immune activation by macrophages is an essential part of the host defence against pathogen infections. Cytosolic recognition of microbial DNA in macrophages leads to induction of type I interferons (IFNs) and numerous cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have also been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway has not been elucidated. Here, we report that IFI16 acts in the cGAS-STING pathway at two distinct levels. Depletion of IFI16 in human macrophages impairs cGAMP production upon DNA stimulation, whereas overexpression of IFI16 amplifies the function of cGAS. Furthermore, IFI16 is found to be vital for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-binding kinase 1 (TBK1) in the STING complex. Collectively, our results suggest that IFI16 is essential for efficient sensing and signalling upon DNA challenge to drive expression of IFNs and establish an antiviral state.	Co-expression
ERP020581	hDBR1 OVEREXPRESSED CALU6 AND 293T CELLS VS. CONTROL CELLS	RNA debranching enzyme (hDBR1) is the only known enzyme to turn over lariat intron RNA during splicing. We compared the transcriptome differences  between hDBR1 overexpressed and control Calu6 and 293T cells, to see its general effect on RNA splicing.	Co-expression
ERP020609	Persistent KSHV infection increases EBV-associated tumor formation in vivo via enhanced EBV lytic gene expression	The human tumor viruses Epstein Barr virus (EBV) and Kaposi Sarcoma associated herpesvirus (KSHV) establish persistent infections in B cells and can cause primary effusion lymphoma (PEL) upon dual infection. So far, no in vivo model exists to study KSHV persistence and associated lymphomagenesis. Here, we report that EBV/KSHV dual infection of mice with reconstituted human immune system components enhanced KSHV persistence and tumorigenesis with plasma cell-like gene expression similar to PELs. KSHV persisted in EBV transformed B cells and was associated with early lytic EBV gene expression, resulting in increased tumor formation. Evidence of lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders of patients. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication.	Co-expression
ERP020724	RNASeq reveals conservation of function among the yolk sacs of human, mouse and chicken	The human yolk sac is often considered vestigial. Here, we report RNA-sequencing analysis of the human and murine yolk sacs and compare with that of the chicken. We relate the hu- man RNA-sequencing data to coelomic fluid proteomic data. Conservation of transcripts across the species indicates the human secondary yolk sac likely performs key functions early in development, particularly uptake and processing of macro- and micronutrients, many of which are found in coelomic fluid. More generally, our findings shed light on evolutionary mech- anisms giving rise to complex structures such as the placenta. We propose that although a choriovitelline placenta is never established physically in the human, the placental villi, exo- coelomic cavity, and secondary yolk sac function together as a physiological equivalent.	Co-expression
ERP020736	RNA-seq of human colorectal cancer cell line COLO320DM treated with the secretome of irradiated or control cancer-associated fibroblasts for 6 or 48 hours	Cancer-associated fibroblasts (CAFs) are an important component of the desmoplastic stroma in rectal cancer. Preoperative chemoradiotherapy plays a pivotal role in the management of locally advanced rectal cancer. Patient-derived CAFs were used to evaluate the response to radiotherapy and its consequent impact on colorectal cancer cells (COLO320DM). COLO320DM cells were seeded and 24 hours later 1.8Gy irradiated. Subsequently, 24h later COLO320DM cells were treated with the secretome of 10x 1.8Gy irradiated CAFs or sham treated CAFs in 0.5% of serum. RNA was isolated 6 hours or 48 hours later.	Co-expression
ERP020769	Phosphoglycerate dehydrogenase causes electron transport chain defect via impaired heme synthesis: RNA sequencing.	Given the prominent angiogenic impairment in PHGDHECKO mice and the proliferation defect of PHGDHKD ECs, which could not fully be explained by a decreased one carbon metabolism pool, together with the observed impairment of mitochondrial homeostasis and reduced respiration in PHGDHKD ECs, we performed an RNA-seq analysis of control   and PHGDHKD ECs.	Co-expression
ERP020771	RNA-seq analysis of neutrophils from CD40L-deficient patients and healthy controls, as well as HL-60 promielocytic cell line	We aim to characterize to effects of the absence of CD40L on neutrophil transcriptome and the effect of soluble CD40L on HL60 cells. For this purpose Total RNA of isolated neutrophils from three CD40L-deficient patients and three healthy controls as well as HL-60 cells from ATCC (HL-60 (ATCC® CCL-240™) were analyzed by RNAseq. Before RNA obtention, neutrophils were incubated for 2 hours in the presence or absence of 100 U/ml rhIFN-γ (Immukine, Boehringer Ingelheim), and HL-60 cells cultured for 6 days in the presence or absence of 500 ng/mL sCD40L and/or 1,0 % dimethyl sulfoxide (DMSO).	Co-expression
ERP020977	_Genetics_of_gene_expression_in_macrophage_immune_response_Open_access	We differentiated macrophages from induced pluripotent stem cells in 86 unrelated, healthy individuals derived by the Human Induced Pluripotent Stem Cells Initiative (HIPSCI), and profiled gene expression and chromatin accessibility in four experimental conditions: naive, interferon-gamma (IFNy) treatment, Salmonella infection and IFNy treatment followed by Salmonella infection. We detected gene expression QTLs (eQTLs) for 5,383 genes, and chromatin accessibility QTLs (caQTLs) for 32,918 accessible regions, including hundreds of long-range interactions. We show that profiling even a small number of additional cellular states substantially increases the number of eQTLs that we can confidently colocalise with a known disease association, with approximately 30% new disease-eQTL pairs discovered in each additional state. Furthermore, we show that approximately 50% of stimulus-specific effects on gene expression manifest in naïve cells where they alter chromatin accessibility alone. Our results suggest that many disease-associated genetic variants lie in regulatory elements in a ‘primed’ state waiting for an appropriate environmental signal before regulating gene expression.	Co-expression
ERP020994	Transcriptomic profiling of antigen-specific T cells at the single-cell level after clearance of hepatitis C virus	We used scRNA-seq data generated using Smart-seq2 to reconstruct the native TCRαβ from Ag-specific T cells and then to link these with the gene expression profile of individual cells. antigen specific CD8 T cells were obtained from a subject who had previously cleared hepatitis C virus (HCV) infection. A cell line was also generated from the same subject and included in the analysis with and without antigen stimulation.	Co-expression
ERP021140	Identification of heterogeneous senescence-associated transcriptional programs	We set out to characterize the transcriptional heterogeneity of the senescence program using a large number of whole-transcriptome sequencing datasets generated by us or publicly available.  We identify a number of senescence transcriptional signatures associated to specific stresses or cell types. We also merge all the studies to identify and validate the genes that are universally differentially regulated during senescence.	Co-expression
ERP021298	Functional and transcriptional heterogeneity of human hemopoietic lympho-myeloid progenitors	Cord blood (CB) samples from normal donors were obtained with informed consent. Fresh CB samples were processed within 18-34h after collection. Mononuclear cells were isolated and CD34+ fraction was separated. CB CD34+ enriched fraction was lineage depleted by staining with purified anti-human CD2, CD3, CD4, CD7, CD8a, CD11b, CD14, CD19, CD20, CD56, CD235a followed by Qdot 605 conjugated goat F(ab')2 anti-mouse IgG (H+L). Cells were also stained with anti-human CD38-FITC, CD45RA-PE or -BV650, CD123-PE Cy7, CD90-biotin, CD34- PerCP and CD10-APC. Finally, cells were incubated with streptavidin-conjugated APC-eF780 and Hoechst 33258 (Invitrogen, final concentration: 1 μg/ml). Populations were defined, as follows: HSC - Lin-CD34+CD38-CD90+CD45RA-CD10-, MPP - Lin-CD34+CD38-CD90-CD45RA-CD10-, LMPP - Lin-CD34+CD38-CD90-/loCD45RA+CD10-, MLP - Lin-CD34+CD38-CD90-/loCD45RA+CD10+, GMP - Lin-CD34+CD38+CD123+CD45RA+CD10-, CMP - Lin-CD34+CD38+CD123+CD45RA-CD10-, MEP - Lin-CD34+CD38+CD123-CD45RA-CD10-.	Co-expression
ERP021315	RNAseq analysis of human peritoneal dialysis effluent cells treated with or without alanyl-glutamine supplemented peritoneal dialysis fluid in a randomized controlled cross-over pilot study	The impact of PDF supplementation with alanyl-glutamine (AlaGln) on peritoneal immune-competence in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36) was tested by relating functional test results to transcriptome changes (RNAseq and miRNA analysis) in PD effluent cells.	Co-expression
ERP021415	RNA-Seq of purified P-bodies from HEK293 cells	To identify RNAs accumulating in P-bodies (cytoslic RNP granules), P-bodies were purified from HEK293 cell extracts using a Flow Activated Particle Sorting (FAPS) method. Sorted P-bodies were compared to the pre-sorted fraction to identify RNA enriched in P-bodies.	Co-expression
ERP021488	RNA-seq of human and mouse stem-cell derived neurons and mouse primary cortical neurons after KCl-induced membrane depolarization against controls.	This experiment comprises RNA-seq data used to study evolutionary differences between humans and mice in neuronal activity-dependent transcriptional responses. Activity-dependent transcriptional responses in developing human stem cell-derived cortical neurons were compared with those induced in developing primary- or stem cell-derived mouse cortical neurons 4 hours after KCl-induced membrane depolarisation. Activity-dependent transcriptional responses were also measured in aneuploid mouse neurons carrying human chromosome 21, allowing study of the regulation of Hsa21 genes, plus their mouse orthologs, side-by-side in the same cellular environment of a mouse primary neuron.	Co-expression
ERP021667	RNAseq of ovarian cancer ascites cells	mRNA from tumor celss, tumor associated macrophages and tumor associated T cells from high grade serous ovarian carcinoma patients was sequenced.	Co-expression
ERP021686	Mammary fat pad and intraductal xenografts with both DCIS.COM-lacZ and DCIS.COM-SOX11 cell lines to characterize the changes in mRNA expression in invasive cancers.	DCIS.COM-lacZ and DCIS.COM-SOX11 were injected intraductally into the mammary fat pad as nine replicates. At 6 week and 12 weeks post-injection, the mammary glands were collected. Similarly, DCIS.COM-lacZ and DCIS.COM-SOX11 were injected orthotopically into the mammary fat pad as five replicates. At 6 weeks post-injection, the mammary glands were collected. RNA-sequencing was utilised to analyse gene expression profiles from RNA isolated from these cells.	Co-expression
ERP021706	Transcriptome of self-reactive proliferating CD4+ T cells in multiple sclerosis	Multiple sclerosis (MS) is a T cell-mediated demyelinating autoimmune disease of the central nervous system causing neurological deficits with substantial disability. Our group demonstrated that self-reactive proliferation of peripheral lymphocytes is increased in MS patients, is associated genetic risk and is involved in the pathogenesis of MS. These observations are based on an established in vitro system, in which peripheral blood mononuclear cells (PBMC) were seeded out for 7 days in serum-free medium in the absence of an exogenous stimulus. In order to track the self-reactive proliferation, cells were labeled with the fluorescent proliferation marker CFSE. We further showed that in particular CD4+ T cells are increased in RRMS in remission and with HLA-DR15 serostatus, bear a pathogenic Th1 phenotype and are migrating preferentially to active brain lesions in MS.       In order to understand the biological relevance of the proliferating cells on a molecular level, we sorted CD4+ T cells from the self-reactive proliferating (gating: singlet+live+CD3+CD4+CFSEdim) and non- proliferating (gating: singlet+live+CD3+CD4+CFSEhi) compartment by flow cytometry based on CFSE-labeling of PBMCs after stimulus-free co-culture for 7 days. We performed RNA isolation and sequencing of these sorted cell subpopulations from 5 untreated RRMS patients in remission. The data compares differential expression of CD3+CD4+CFSEdim over CD3+CD4+CFSEhi​ cells.	Co-expression
ERP021828	RNA-seq of the human breast cancer ERα-suppressed MCF-7(MCF-7/SP10+) cells and of their internal control MCF-7 (MCF-7/C) cells	Estrogens receptor a (ERα) is essential for breast tumors,since about seventy percent of breast cancers are detected as ERα positive.Recent studies suggest that ERα is related with the epithelial cell morphology. Recently, it has demonstrated that the suppression of ERα induced epithelial-mesenchymal transition (EMT) in the MCF-7 breast cacner cells. Interestingly, the loss of ERa resulted in strong differences on the gene expression profile of a variety of genes. Therefore, the aim of the RNA-seq is to elucidate the effect of the silencing of ERα on the mRNA levels of a larger variety of genes, thus revealing possible target genes which may be implicated on the aggressive phenotype and behavior  of the ERα-suppresed MCF-7/SP10+ breast cancer cells. For this reason total RNA from both MCF-7/SP10+ cells and of their internal control MCF-7/C cells was extracted in 3 biological replicates and 3 technical replicates.	Co-expression
ERP022034	RNA sequencing of pancreatic adenocarcinoma (PDAC) xenograft samples	Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. this dataset, describe the RNA sequencing data used in the multiomics study.	Co-expression
ERP022060	RNA-seq of HEK293T cells treated with control b-globin siRNA and Pat1b siRNA	RNA-seq experiment to study the role of Pat1b in HEK293T cells. HEK293T cells were treated twice with siRNA with Lipofectamine 2000 then harvested after 48hours. Total RNA was extracted with TriReagent. Ribo-Zero TruSeq stranded mRNA libraries were prepared for each sample and sequenced on Illumina NextSeq 500 Sequencing System providing around 100 million reads per sample (around 75 bp paired-end reads).	Co-expression
ERP022084	RNAseq of primary human gallbladder cells, reprogrammed human gallbladder cells, and human pancreatic beta cells	We determined the global gene expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.	Co-expression
ERP022095	RNA-seq of human normal mammary gland cells FACS sorted into three populations: ALDH+, ALDH-CD44+CD24-, and ALDH-CD44-CD24+	The intent of this experiment was to determine the similarities and differences in expression signatures of normal breast cells that express markers associated with an epithelial-like (ALDH+) and mesenchymal-like (CD44+CD24-) stem cells in the normal human breast. Briefly, tissues were collected from women undergoing voluntary reduction mammoplasty. Tissues were dissociated using chemical and enzymatic methods to yield single cells. These cells were sorted by flow cytometry for aldehyde hydrogenase activity (ALDH+), CD44, and CD24, as well as viability, following depletion of hematopoeitc cells, endothelial cells, and fibroblasts.	Co-expression
ERP022206	Radiation tolerance mechanism of Crif1 in BMSC	do not decided yet	Co-expression
ERP022243	RNAseq of wild-type and giantin knockout retinal pigment epithelial cell lines	We generated a retinal pigment epithelial cell line with complete knockout of giantin using CRISPR. This experiment sought to define changes in the transcriptome of that cell line compared to the parental wild-type cells.	Co-expression
ERP022260	RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls	RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.	Co-expression
ERP022266	[RNA-seq] Simultaneous Isolation of DNA-RNA from a single-cell	The simultaneous sequencing of a single cell’s genome and transcriptome is powerful tools to understand the genomic and transcriptomic variations, and their correlative relationships. However, technical obstacles have prohibited the simultaneous analysis of both genome and transcriptome derived from a single cell. Here, we report a method for simultaneous isolation of DNA and total RNA (SIDR) from single cells, especially for parallel genome and transcriptome sequencing. The method adopts a strategy to physically separate genomic DNA and total RNA from single cells, based on hypotonic lysis and subsequent separation of cell lysate associated with magnetic microbeads. Systematic performance evaluation by quantitative real-time PCR and single-cell sequencing demonstrated that the method efficiency recovered genomic DNA and total RNA. We also validated that genomic DNA and total RNA simultaneously fractionated by SIDR method were suitable for the genome and transcriptome sequencing analysis of single cells, based on various aspects of sequencing data quality. By applying SIDR to integrated genome and transcriptome sequencing, this platform may be potentially an enabling tool to merge biological genetic and phenotypic information at the single cell scale.	Co-expression
ERP022329	Effect on gene expression after 4 days of a single, 15 Gy dose of ionizing X ray radiation on H522 human lung cancer, and FaDu, HSC2 and SCC4 human head and neck cancer cell-lines	H522 human lung cancer, and FaDu, HSC2 and SCC4 human head and neck cancer cells were grown adherent to 60%-80% confluence on 10-cm dishes in 8 ml RPMI-1640/+DMEM medium with 10% fetal bovine serum. Cells were irradiated with one dose of 15 Gy ionizing X rays in a Faxitron FX-650 machine; control cell culture dishes were not irradiated. After a day of radiation, adherent cells were detached by trypsinization and replated on 10-cm dishes in 8 ml RPMI-1640/+DMEM medium with 10% fetal bovine serum to reach 70%-90% confluence after three days, when adherent cells were harvested by scraping. Harvested cells were pelleted and kept frozen at -80 ºC. For each cell-line, three experiments were performed to obtain three pairs of control and irradiated cell pellets. One µg of total RNA isolated from each of the cell pellets using Norgen-Biotek Total RNA Isolation kit with an on-column DNAse I treatment step was used to prepare sequencing library for directional RNA sequencing to obtain paired 76 b reads on an Illumina NextSeq 500 instrument. Twenty-four libraries were sequenced in each flow lane, and each library was sequenced in four lanes of one flow cell. On-system software was used to demultiplex sequencing data.	Co-expression
ERP022368	RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis	Mycobacterium tuberculosis is an intracellular pathogen of macrophages which are key to controlling infection. Inflammatory lesions infected with M. tuberculosis have an acidic extracellular microenvironment which may influence macrophage function. In this study we performed RNA-seq on primary human monocyte derived macrophages from 4 healthy donors infected with virulent M. tuberculosis H37Rv for 24 hours. Cells were infected in media at physiological pH 7.4 or acidic media pH 7.0. Appropriate uninfected control cells at pH 7.4 and pH 7.0 were also included. We were thus able to identify the principal genes and pathways regulated by M. tuberculosis infection and the influence of extracellular acidosis on these pathways. Specifically, we show that acidosis enhances transcription of matrix metalloproteinase genes and increases tissue destruction pathways in tuberculosis. RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis	Co-expression
ERP022435	Unliganded Estrogen Receptor Beta cooperates with Argonaute 2 in the modulation of transcription rate and splicing of target genes in breast cancer cells. Part 4	Estrogen receptors (ERs) are primary targets for chemoprevention and endocrine therapy of breast cancer (BC) and provide prognostic and predictive information concerning tumor response to endocrine therapies. Expression of ERβ reduces cancer cell proliferation and tumor growth, pointing to an anti-proliferative action of this transcription factor and its positive prognostic value. Moreover, it has emerged that unliganded ERβ exhibits an active role in constitutive regulation of target genes transcription.  Indeed, gene expression profiling of hormone-deprived human BC cells expressing ERβ revealed a great impact of this ER subtype in the modulation of gene expression in absence of hormonal ligands. Starting from this observation, and to identify key nuclear factors acting in concert with ligand-free ERβ, Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) was applied to isolate nuclear protein complexes associated to unliganded ERβ in BC cells. Among the >300 proteins identified, we focused our attention on the functional significance of a complex comprising ERβ and AGO2, since this argonaute protein has been implicated in key biological processes in the cell nucleus. ERβ association with AGO2 and other known AGO2 interacting proteins was confirmed by co-immunoprecipitation in MCF-7 cells expressing tagged ERβ. ChIP-Seq allowed the identification of a number of ERβ- and AGO-binding sites to breast cancer cells genome, while AGO2 knock down resulted in significant changes in transcription rate and co-transcriptional mRNA splicing of a group of genes, comprising in particular a significant number of those modulated by unliganded ERβ. In conclusion, these experimental evidences suggest that AGO2 is a functional partner of ERβ involved in hormone-independent gene regulation in BC cells	Co-expression
ERP022441	Transcriptional profiling of activated CD4+ memory T cells exposed to anti-TNF and recombinant human TNF-alpha in vitro	We performed an RNA-seq analysis on FACS-sorted CD4+ memory T cells (Tmem, CD4+CD25-CD45RA-) stimulated in vitro with anti-CD3/CD28 coated beads (1:5), IL-2 (100 U/mL) in the presence of  a TNF-alpha inhibitor (Etanercept, ETN, 5 μg/mL) or recombinant human TNF-alpha (rhTNF-alpha, 50 ng/mL). The cells were cultured for three days at 37°C and 5% CO2. On day three Tmem were lysed (Buffer RLT supplemented with DTT, QIAGEN) and RNA extraction was performed (RNeasy Plus Micro kit), followed by sample preparation with TruSeq (polyA) mRNA kits (Illumina), RNA sequencing (carried out on an Illumina HiSeq2500), and the alignment of trimmed fastQ files to GRCh38 human reference genome. We also performed a Quality control (QC). This was done using the tool FastQC FastQC/0.11.3-Java-1.7.0_80. QC metrics were calculated for the aligned reads using Picard-tools picard/1.130-Java-1.7.0_80, CollectRnaSeqMetrics, MarkDuplicates, CollectInsertSize-Metrics and SAMtools/1.2-foss-2015b flagstat. Finally, we carried out a Differential expression gene (DEG) analysis using DESeq2, in order to evaluate the impact of ETN and rhTNF-alpha on Transcriptome profiling of stimulated CD4+ Tmem. Principal Component Analysis (PCA) was carried out to visualize the samples given their entire transcriptome and any remaining batch effects.	Co-expression
ERP022442	RNA-Seq of ALDH positive, ALDH negative and unsorted cells from patient-derived 3D in-vitro models of colon cancer	Fluorescence-activated cell sorting (FACS) was used to separate colon tumor samples into two fractions of ALDH Negative and ALDH Positive cells using the Aldefluor Assay. RNA samples were derived from FAC-sorted 3D in-vitro models of patient-derived colon tumors. Samples from unfractionated in vitro models are also included.	Co-expression
ERP022458	RNA-seq of H1299 cells stably transfected with empty vector or the p53 mutant R273H.	This experiment aimed to determine the genes that were upregulated when mutant p53 (R273H) was expressed.  We used H1299 lung cancer cells that are endogenously p53-null and overexpressed the p53 mutant.	Co-expression
ERP022527	Examination of the role of BMP signaling in patterning of human pluripotent stem cell derived mid/hindgut spheroids and maintenance of this patterning in organoids transplanted under mouse kidney capsules.	The goal of this study was to test the hypothesis that BMP signaling regulates patterning of human CDX2+ gut tube cultures (Spence et al 2011, Watson et al. 2014). The study is comprised of 2 separate experiments. The first experiment was to determine the immediate impact of BMP signaling on CDX2+ gut tube cultures. To do so we tested spheroids, spheroids after plating in Matrigel and exposed to 3 days of Noggin (100ng/mL), spheroids after plating in Matrigel and exposed to 3 days of EGF alone (100ng/mL, Control), and spheroids after plating in Matrigel and exposed to 3 days of BMP2 (100ng/mL). RNA was collected from spheroids and spheroids after 3 days of patterning. The second experiment examined if patterning was maintained after this initial 3 days of patterning and an addition 8-10 weeks following transplantation in vivo. To do this we grew all Matrigel plated spheroids for an additional 25 days in media containing EGF alone (Control media).  We then transplanted these organoids under the mouse kidney capsule and allowed them to mature for 8-10 weeks. We then collected RNA from the transplanted organoids.	Co-expression
ERP022538	RNA-seq of chemically reset human naive pluripotent stem cells	A simple method is presented to reset human pluripotent cells to a naive state via transient histone deacetylase inhibition and maintenance in chemically-defined naive stem cell culture media. Cells can be reset without transgenes and expanded continuously either on feeders or alternative substrates in feeder-free conditions. Multiple cell lines of varying origin were reset and characterised in parallel with conventionally cultured counterparts.	Co-expression
ERP022766	RNA-seq of HEK293T cell line	Two regulatory elements in chr8 (chr8:579137-581436) and chr20 (chr20:62115827-62119284) were deleted using CRISPR and the effects of their deletion were assessed using RNA-seq	Co-expression
ERP022800	RNAseq of ATO trial	Tumor samples from 22 patients enrolled in a phase I/II trial of Trisenox (ATO)	Co-expression
ERP022805	BATLAS: Deconvoluting brown adipose tissue	Recruitment and activation of classical brown and inducible brite/beige adipocytes has received increasing attention in recent years as a strategy to improve systemic metabolic control.Nevertheless, the origin and expression signatures of brown and brite/beige adipocytes are still under debate, mainly due to the complexity of tissue biopsies. To study different adipocyte types in detail, we generated pure samples of brown, brite/beige, and white mature adipocytes by fluorescence activated cell sorting. Using this resource, we could demonstrate that on a transcriptional level, brown and brite/beige mature adipocytes are identical. Employing a machine learning approach for paired analysis of transcriptional data of pure mouse brown,brite/beige and white adipocytes and human brown and white whole adipose tissue obtained by PET-CT-guided biopsies, we were concomitantly able to identify a gene signature that can classify brown and white adipose tissue depots. Using the newly developed algorithm, we were able to predict the brown adipocyte content in a mixed population of adipocytes from different human biopsies that can be used for in-depth characterization of complex tissue samples from adipose tissue and might therefore support the development strategies to increase brown adipocyte formation in humans.	Co-expression
ERP022839	RNAseq of human epithelial lung carcinoma cell line A549 exposed to ceria, silver or zinc ions, micron-sized particles or nanoparticles	The toxicity of silver and zinc oxide nanoparticles is hypothesised to be mediated by dissolved metal ions and cerium dioxide nanoparticles (CeO2 NPs) are hypothesised to induce toxicity specifically by oxidative stress dependant on their surface redox state. To test these hypotheses, RNAseq was applied to characterise the molecular responses of cells to metal nanoparticle and metal ion exposures. The human epithelial lung carcinoma cell line A549 was exposed to different CeO2 NPs with different surface charges, micron-sized and nano-sized silver particles and silver ions, micron-sized and nano-sized zinc oxide particles and zinc ions, or control conditions, for 1 hour, 6 hours and 24 hours. Concentrations were the lower of either  EC20 or 128 micrograms/mL. Transcriptional responses were characterised  by RNAseq transcriptomics using an Illumina HiSeq2500 .	Co-expression
ERP022909	Chracterization_of_iPSC_derived_macrophages___cardiovascular_pilot_Open_access	Atherosclerosis is characterized by the aggregation of low-density lipoprotein (LDL) cholesterol in arterial walls. The uptake of modified LDL by macrophages leading to foam cell formation is critical to the initiation and progression of atherosclerotic lesions. The gene expression programs driving foam cell formation as well as their genetic determinants have not been characterized on the genome-wide level to date. Here, we differentiated induced pluripotent stem cells (iPSCs) derived from 70 healthy individuals into macrophages, followed by stimulation of iPSC-derived macrophages with acetylated LDL (acLDL). Using strand-specific RNA-sequencing, we identified 1,726 differentially expressed genes between resting and acLDL-treated macrophages, mapping to pro-inflammatory signaling and cholesterol biosynthesis pathways. We found the expression and splicing of 1,817 and 1,276 genes to be modulated by local genetic variants under acLDL stimulation, respectively. In addition, we defined 66 response-specific expression quantitative trait loci (QTLs), including the FCER1A and FADS2 gene regions, which have previously been associated with the regulation of inflammatory biomarkers and major lipids, respectively. Further, we identified 39 response-specific splicing QTLs, including the ANKRD9, FCGR2A and SIRPA gene regions. In summary, we have developed an experimental framework to map genotype-dependent gene expression and splicing changes in iPSC-derived macrophages dependent on acLDL exposure, many of which underlie genetic risk regions of cardiovascular disease and related traits.	Co-expression
ERP022930	Transcriptome analysis of self-renewing human pancreatic progenitors derived from pluripotent stem cells	Human pluripotent stem cells were differentiated into PDX1+/NKX6-1+ Pancreatic Progenitors (PPd15 cells), which were subsequently captured and expanded in culture. These culture Pancreatic Progenitors (cPP cells) were capable of self-renewal and could be passaged up to 20 times. Furthermore, cPP cells were capable of differentiation into multiple pancreatic lineages, including c-peptide+ beta-like cells, both in vitro and in vivo.	Co-expression
ERP022968	RNAseq experiment of non-exposed skin, Actinic Keratosis, Intraepdimeral Carcinoma and Squamous Cell Carcinoma	The goal of the study is to compare the transcriptomic profile of patient-derived skin samples, Actinic Keratosis, Intraepidermal Carcinoma and Squamous Cell Carcinoma samples using next generation RNA Sequencing. We aim to identify perturbed pathways and similarities between the 4 conditions. Please note that detailed patients' information, such as gender and age, was withheld from this submission to protect the patients' identity.	Co-expression
ERP022982	RNA-seq of human testicular germ cell cancer	RNA-seq analysis of two Testicular Germ Cell Cancers (TGCC) of patients with chemotherapy-resistant disease. Purpose of the study was to resolve the early development and progression of the disease by whole genome sequencing, RNA-seq and methylation profiling of the primary tumor, and the targeted sequencing of purified tumor components (embryonal carcinoma (EC), teratoma (TE), and yolk sac tumor (YST), precursor lesion (Germ Cell Neoplasia In Situ (GCNIS)), and metastases.  Whole genome sequencing for the two patients, T6107 and T3209, have been deposited with the European Nucleotide Archive under project accession number PRJEB20644 / study accession ERP022815 ( http://www.ebi.ac.uk/ena/data/search?query=ERP022815 ).	Co-expression
ERP023007	RNASeq and ChIPSeq: Therapeutic Targeting of the CBP/P300 Bromodomain for the Treatment of Castration Resistant Prostate Cancer	Prostate cancer is a leading cause of cancer death in men. While patients initially respond well to anti-androgen therapies, resistance is common. Here we identify a requirement for the transcriptional co-activators CBP/P300 for prostate cancer cell growth, which is maintained in the context of resistance to current therapy. In order to take therapeutic advantage of this vulnerability, we have developed a novel small-molecule inhibitor of the CBP/P300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment reveals a critical role for CBP/P300 in the histone acetylation required for AR transcriptional activity and target-gene expression. These findings strongly support CBP/P300 bromodomain inhibition as a therapeutic strategy in the treatment of castration resistant prostate cancer.	Co-expression
ERP023066	Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression	Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and the number of neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, checkpoint immunotherapy is thought to be less effective in tumors with low mutation frequencies such as neuroblastoma, a neuroendocrine tumor of early childhood with poor outcome of the high-risk disease group. However, spontaneous regressions and paraneoplastic syndromes seen in neuroblastoma patients suggest substantial immunogenicity. N-Myc is the key oncogenic transcription factor amplified in high-risk neuroblastomas and associated with a poor outcome. New treatment approaches including immunotherapy are needed for this disease. To explore the role of N-Myc in interferon immune signaling, we depleted N-Myc by two independent siRNAs (siMYCN1, siMYCN2) in the human neuroblastoma cell line SK-N-BE as well as in the murine N-Myc transgenic (carrying a human MYCN transgene) neuroblastoma cell line mNB-A1 and exposed these cells to interferon gamma or TNF-alpha. Cells transfected with non-targeting control siRNAs (siNT) and cultured in regular medium served as experimental references for the respective stimulations. In addition we exposed the mouse neuroblastoma cell line mNB-A1 to the small molecule STING agonist DMXAA (25microM and 50microM) for targeted and cell intrinsic activation of the interferon system. We performed 3'mRNA-Seq transcriptome analyses on the Illumina HiSeq2500 sequencing platform.	Co-expression
ERP023082	Variation in RNA expression in a panel of 30 breast cancer cell lines	RNA expression was measured using RNA sequencing in 30 different breast cancer cell lines, under untreated, exponentially growing conditions.	Co-expression
ERP023222	Identification of driver genes in uterine leiomyosarcoma: RNA seq	RNA-sequencing was carried out on human leiomyosarcoma tissue. To uncover novel potential driver genes and recurrently affected pathways.	Co-expression
ERP023272	RNA-seq of formalin-fixed, paraffin-embedded uninvolved terminal ileal tissue obtained from ileo-colic resection surgeries of Crohn’s disease and control patients	The interpretation of transcriptional profiling studies of intestinal tissue from Crohn’s disease patients and control patients can be confounded by differing proportions of cell subsets (e.g. immune cells) present in these samples. In this study, we aimed to control for cellular composition using standard, archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens from Crohn’s patients (n=36) and controls (n=32) who underwent intestinal resection surgery. This approach allowed us to use the same tissue specimens for histological screening to select study samples with similar cellular composition and for RNA extraction for RNA-seq transcriptional profiling. We hypothesized that this approach would allow us to more clearly identify molecular signatures in ileal tissue that were associated with Crohn’s disease-associated pathological mechanisms.	Co-expression
ERP023317	RNA-seq of human tissues	RNA-seq was performed of tissue samples from human individuals representing different tissues in order to study the human tissue transcriptome. This submission contains 14 samples used in the paper "A proteogenomics workflow integrating discovery, curation and validation reveals human novel protein coding loci and single amino acid variants”.	Co-expression
ERP023321	The Long Noncoding RNA Landscape of Neuroendocrine Prostate Cancer and its Clinical Implications	BACKGROUND Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation. Long non-coding RNA (lncRNA) are implicated in cancer where they can control gene regulation. Until now the expression of lncRNAs during NEtD and their clinical associations were unexplored. RESULTS We implemented a next-generation sequence analysis pipeline that can detect transcripts at low expression levels and built a genome-wide catalogue (n=37,749) of lncRNAs. We applied this pipeline to 927 clinical samples and our high fidelity NEtD model LTL331 and identified 821 lncRNAs in NEPC. Among these are 122 lncRNAs that robustly distinguish NEPC from prostate adenocarcinoma (AD) patient tumours. The highest expressed lncRNAs within this signature are H19, LINC00617, and SSTR5-AS1. Another 742 are associated with the NEtD process and fall into four distinct patterns of expression (NEtD lncRNA Class I, II, III, and IV) in our PDX model and clinical samples. Each class has significant (z-scores>2) and unique enrichment for transcription factor binding site (TFBS) motifs in their sequences. Enriched TFBS include (1) TP53 and BRN1 in Class I, (2) ELF5, SPIC, and HOXD1 in Class II, (3) SPDEF in Class III, (4) HSF1 and FOXA1 in Class IV, and (5) TWIST1 when merging Class III with IV. Common TFBS in all NEtD lncRNA were also identified and include, E2F, REST, PAX5, PAX9, and STAF. Interrogation of the top deregulated candidates (n=100) in radical prostatectomy adenocarcinoma samples with long-term follow-up (median 18 years) revealed significant clinicopathological associations. Specifically, we identified 25 that are associated with rapid metastasis following androgen deprivation therapy (ADT). Two of these lncRNAs (SSTR5-AS1 and LINC00514) stratified patients undergoing ADT based on patient outcome. DISCUSSION To date, a comprehensive characterization of the dynamic landscape of lncRNAs during the NEtD process has not been performed. A temporal analysis of the PDX-based NEtD model has for the first time provided this dynamic landscape. TFBS analysis identified NEPC-related TF motifs present within the NEtD lncRNA sequences, suggesting functional roles for these lncRNAs in NEPC pathogenesis. Furthermore, select NEtD lncRNAs appear to be associated with metastasis and patients receiving ADT. Treatment-related metastasis is a clinical consequence of NEPC tumours. Top candidate lncRNAs FENDRR, H19, LINC00514, LINC00617, and SSTR5-AS1 identified in this study are implicated in the development of NEPC. We present here for the first time a genome-wide catalogue of NEtD lncRNAs that characterize the transdifferentiation process and a robust NEPC lncRNA patient expression signature. To accomplish this, we carried out the largest integrative study that applied a PDX NEtD model to clinical samples. These NEtD and NEPC lncRNAs are strong candidates for clinical biomarkers and therapeutic targets and warrant further investigation.	Co-expression
ERP023414	3' RNA-seq of CD142+/- human adipose stem and progenitor cells	To validate the anti-adipogenic effect of the newly discovered Areg cells in human, we used FACS to separate the CD142+ from the CD142- population within cultured (passage 1) adipogenic stem and progenitor cells (ASPCs) (CD31- CD45- stromal vascular fraction cells) that were derived from four individuals, and induced adipogenesis. We then performed 3’ RNA-seq expression profiling of the induced cells.	Co-expression
ERP023424	Transcriptional profiling of Th1, Th2, Th9, and Th17 T cell clones	We set out to explore whether "Th9" cells represent a distinct T-helper (Th) cell subset in humans by comprehensively characterizing the lineage-defining properties of human IL-9-producing Th cells. In particular, to investigate the transcription factor expression in Th9 clones as compared to Th1, Th17, and Th2 clones, we selected three to five representative T cell clones of each subset and performed gene expression analysis by using RNAseq . Peripheral Blood Mononuclear Cells (PBMC) were isolated by Ficoll-Plaque Plus (GE Healthcare, UK) density gradient centrifugation. Human CD4+ T cells were isolated from PBMC by EasySep positive selection kit (Stemcell Technologies) according to manufacturer’s instruction. Positively selected CD4+ T cells were washed with PBS and stained for subsequent Th cell subset sorting. Memory Th cell subsets were sorted to over 90% purity according to their expression of chemokine receptors from CD45RA-CD25-CD8-CD3+ cells: Th1(CXCR3+CCR8-CCR6-CCR4-), Th2 (CXCR3-CCR8-CCR6-CCR4+), Th17 (CXCR3-CCR8-CCR6+CCR4+), Th9 (CXCR3-CCR8+CCR6-CCR4+). Single cell Th subset clones were directly sorted into 96well plate according to their expression of chemokine receptors (see above). Single cell clones were expanded and maintained by periodic restimulation with PHA (phytohaemaglutinine, 1 µg/ml, Sigma-Chemicals) and irradiated allogenic feeder cells (5x104/well) in culture medium.	Co-expression
ERP023451	RNA seq of HGPS treated cells	Evaluation of transcript levels in HGPS cells upon treatment with proteasome inhibitor	Co-expression
ERP023550	RNA-seq of human intestinal organoids colonized with E. coli and other immature intestinal tissues	We performed RNA-seq to demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. RNA was isolated using the mirVana RNA isolation kit and following the \"Total RNA\" isolation protocol (Thermo-Fisher Scientific, Waltham MA). RNA library preparation and RNA-sequencing (single-end, 50 bp read length) were performed by the University of Michigan DNA Sequencing Core using the Illumina Hi-Seq 2500 platform. Transcriptional quantitation analysis was conducted using 64-bit Debian Linux stable version 7.10 (\"Wheezy\"). Pseudoalignment of RNA-seq data was computed using kallisto v0.43.0 and differential expression of pseudoaligned sequences was calculated using the R package DEseq2.	Co-expression
ERP023564	Enhanced energetic state and protection from oxidative stress in human myoblasts overexpressing BMI1	Three independently prepared normal and DMD myoblasts cell cultures infected with GFP and BMI1Over lentiviral particles and induced to differentiate for 2 days were analysed by illumina RNA sequencing	Co-expression
ERP023744	Neuroblastoma Wnt target gene signature identifies prognostic clusters and reveals complex interactions regulating differentiation and proliferation.	Neuroblastoma is one of the commonest and deadliest solid tumours of childhood. It is thought to arise as result of disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. One of the mechanisms by which this occurs is direct transcriptional repression of regulators of differentiation, such as nerve growth factor receptor (NGFR/p75NTR) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1) by the oncogenic transcription factor MYCN, which is over-expressed in approximately half of poor prognosis neuroblastomas as a result of genomic amplification. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues. However, our previous work demonstrated that Wnt signalling in neuroblastoma does not induce MYCN and c-MYC. This led us to define the neuroblastoma-specific Wnt-driven transcriptome using RNA sequencing, and characterise the accompanying changes in cell biology. We report the identification of novel Wnt targets likely to be involved in sympathetic nervous system differentiation, and show that Wnt signalling can drive differentiation of neuroblastoma cells. A subset of these differentiation genes are repressed by MYCN. Interrogation of primary tumour databases shows that our Wnt genes can (a) identify prognostic subgroups, and (b) reveal the complex interplay of signalling pathways contributing to the clinical and biological heterogeneity of neuroblastoma.	Co-expression
ERP023816	Time-series RNA-seq experiment performed on nine melanoma cell lines treated with BRAF inhibitor vemurafenib.	BRAF targeted drug vemurafenib have shown very good clinical benefit in melanoma patient containing BRAF V600E mutation. However, resistance always occurs in patient. Early stage of the resistance development require the tumor cell adapted to the targeted drug. We are trying to study the kinetic of melanoma cell adaptation towards vemurafenib. 10 melanoma cell lines with BRAF mutation are treated with targeted therapy vemurafenib. RNA-seq samples are collected after drug treatment for different time (day3 and day21) to compare with DMSO-treated control samples for each cell line. Except innate resistant cell line M381, all other cell lines shows inhibition of proliferation. However, a small cluster of cell lines (M397, M229 and M263) shows some other unique transcriptomic change. For cell line M397, M229 and M263, we also collected the RNA-seq data for long-term (73day/90day) drug treatment condition where the cells developed resistance to vemurafenib treatment. Dedifferentiation is enriched in these unique transcriptomic change within these 3 cell lines. Similar cell state dedifferentiation phenomenon is also reported to cause resistance towards immunotherpay where the resistant de-differentiated melanoma cells are induced by TNF which is secreted by tumor-infiltrating T cells. We also treat our cultured melanoma cells with TNF and collected the treated sample for RNA-seq experiment.	Co-expression
ERP023834	The signature of tamoxifen in the architecture of the tumor microenvironment	We did an initial QC on your samples using Bioanallyzer and Qubit. Sequencing libraries were prepared using a TruSeq Stranded mRNA Library Prep Kit from Illumina. All 6 samples were pooled together and run on Nextseq500 using 1x75bp read type	Co-expression
ERP023890	Intergenic Disease-associated Regions are Abundant in Novel Regulatory Transcripts	Analysis of transcriptomes from 21 tissues, 13 melanoma samples and 7 breast cancer cell lines, enriched for transcripts from haploblocks with intronic and intergenic GWAS SNPs using CaptureSeq.	Co-expression
ERP023908	Transcriptomics to study the role of Yy1 in melanoma	Transcriptomics to study the role of Yy1 in melanoma. MO1 and MO5 melanoma cells were treated with siCtrl and siYy1 for 72h and subsequently prepared for RNA-Seq.	Co-expression
ERP024004	RNA-seq of coding RNA from USP14 knockout human haploid (HAP1) cells	We performed a genome-scale screen for suppressors of interferon stimulated gene (ISG) expression in human haploid cells (HAP1). Ubiquitin specific peptidase 14 (USP14) was a significant hit. In order to validate USP14 as a regulator of ISG expression, we created knockouts of USP14 in HAP1 cells using CRISPR-Cas9 and performed RNA-seq on coding RNA from USP14 KO and WT cells. This data was used to determine if ISGs were upregulated in USP14 KO HAP1 cells.	Co-expression
ERP024006	RNA-seq of coding RNA from DDX6 knockout human haploid (HAP1) cells	We performed a genome-scale screen for suppressors of interferon stimulated gene (ISG) expression in human haploid cells (HAP1). DEAD-box helicase 6 (DDX6) was a significant hit. In order to validate DDX6 as a regulator of ISG expression, we created knockouts of DDX6 in HAP1 cells using CRISPR-Cas9 and performed RNA-seq on coding RNA from DDX6 KO and WT cells. This data was used to determine if ISGs were upregulated in DDX6 KO HAP1 cells.	Co-expression
ERP024091	lncRNA downregulation	lncRNA downregulation	Co-expression
ERP024098	Overexpression of human APOBEC3H in human HEK-293T cells	To identify transcriptome-wide effects of human APOBEC3H, human HEK-293T cells were transiently transfected with an expression construct for human APOBEC3H ORF cDNA.	Co-expression
ERP024278	Transcriptional_response_of_Kolf2_intestinal_organoids_to_IL_22	To produce whole transcriptome datasets from human organoids stimulated with IL-22	Co-expression
ERP024280	RNA-seq in a patient with idiopathic X-linked intellectual disability compared to healthy controls with normal mir222 expression	In the L020 family with idiopathic non-syndromic X-linked intellectual disability, one repeat expansion co-occurs with down-regulation of the neighboring MIR222 gene. RNA was sequenced in the proband and three controls to detect what other genes might be affected by the altered MIR222 expression.	Co-expression
ERP024336	RNA-seq of of dermal fibroblasts	Dermal fibroblasts from human, rhesus macaque, mouse and rat, stimulated with dsRNA (poly I:C), interferon and controls.<br>The innate immune response - the expression programme that is initiated once a pathogen is sensed - is known to be variable among responding cells, as well as to rapidly evolve in the course of mammal evolution. To study the transcriptional divergence and cell-to-cell variability of this response, we stimulated dermal fibroblast cells from two primates (human and macaque) and two rodents (mouse and rat) with dsRNA - a mimic of viral RNA that elicits a rapid innate immune response. Subsequently, we profiled the response using bulk RNA-seq, scRNA-seq and ChIP-seq across the four species and across different time points.	Co-expression
ERP024385	RNA-seq analysis of cytoplasmic RNAs extracted from human T Cells obtained from humanized mice infected with wild-type HTLV-1 and a mutant form lacking the PBM of Tax.	Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization.	Co-expression
ERP024526	Expression profiling of Jurkat cells infected with HIV-1 and treated with digoxin or DMSO	To determine changes of gene expression in human CD4+ T cells (Jurkat) infected with HIV-1 and treated with digoxin. Cells were infected (MOI 0.01) with a single cycle HIV-1 delta env expressing GFP and pseudotyoed with VSV-G in the presence of 400nM digoxin or DMSO. Cells were harvested 36 hours post-infection and processed for RNAseq	Co-expression
ERP024544	RNA-seq of Primary Human Hepatocytes (PHH) exposed to Valproic Acid (VPA) for 3 days daily and 3 days daily exposure followed by 3 days washout.	Primary Human Hepatocytes (PHH) were exposed daily for 3 days to 15 mM VPA after which RNA was isolated. After terminating the VPA treatment, part of the cells were kept with medium for 3 days in order to investigate the eventual persistence of VPA-induced methylome changes. Identification of differentially expressed regions in the RNA was carried out by the RNA-seq method.	Co-expression
ERP067388	PRC1.6 RNAseq	MGA was depleted via Crisper/Cas9 in HEK293 cells and the resulting gene expression changes were profiled.	Co-expression
ERP091820	Time line RNAseq of iPSC-derived neurons from ASD and control subjects.	To comprehensively profile early neurodevelopmental alterations in individuals with ASD, we harnessed a time series approach to monitor patient-derived induced pluripotent stem cells (iPSCs) throughout the recapitulation of cortical development. This dataset consists of patient derived neurons that go through all consecutive developmental stages (NSC-derived neurons) as well as a comparative set of iPSC-iNs (neurons generated from the same patients that bypass early NSC-like stages using an Ngn2-transgene approach). For this, we first used fluorescence-activated cell sorting (FACS) to purify a homogeneous population of NSCs based on the expression of the cell-surface markers CD184+/CD271-/CD44-/CD24-/CD15+. To trace ASD and control neurons over time, we performed a series of retroviral lineage-tracing experiments to trace the progenies of dividing NSCs using a retroviral vector expressing a membrane-tagged enhanced green fluorescent protein (eGFP) (CAG::LckN-eGFP). As differentiating neurons express PSA-NCAM on the cell surface, we established a FACS-based protocol for purification of defined subpopulations of retrovirally labeled eGFP+/PSA-NCAM+ double-positive neurons after 2, 4, 7 and 14 days of differentiation. IPSCs were sorted based on the expression of SSEA-4 and TRA1-81 and maturing iPSC-iNs were collected at the indicated days after induction by sorting for eGFP (indicative for the Ngn2 transgene)- and PSA-NCAM-positive cells.	Co-expression
ERP103984	Transcriptomes of inducible CD271 overexpression in the human melanoma cell line M010817. Part of p2352	The capacity of melanoma cells to dynamically switch between proliferative and invasive phenotypes is thought to underlie tumor progression, metastasis formation and therapy resistance in melanoma. In this study we identify the low affinity neurotrophin receptor CD271 to play a dual role as a mediator of phenotype switching, more precisely suppressing melanoma cell proliferation while concomitantly promoting metastasis formation in vivo. We therefore did a transcriptome analysis of genes dynamically controlled by CD271 in an experimental set-up mimicking reversible phenotype switching. We sequenced RNA of human melanoma cells before, during and after induced CD271 overexpression to find a transiently expressed gene set regulated by CD271 that could explain the phenotype switch observed upon temporal CD271 overexpression.	Co-expression
ERP104301	RNA-seq of transplanted pluripotent stem cells-derived human intestinal organoids upon mechanical lengthening and human jejunum tissues	Human Intestinal Organoids (HIOs) generated from embryonic and/or induced pluripotent stem cell lines offer an avenue to study both developmental and human specific disease states. Recently, progress has been made in scaling and maturing these inherently immature tissues through transplanting them in vivo. However, these resultant grafts best approximate fetal intestinal tissue thus limiting their utility. To induce growth and maturation of HIOs we used a nitinol spring device to mechanically induce enterogenesis of HIO in vivo. HIOs are cultured prior to implantation within the mesentery of immunodeficient mice. They are allowed to grow, vascularize, and mature before a second procedure is performed wherein a compressed nitinol spring is implanted within the lumen of the transplanted HIO (tHIO). Next Generation RNA sequencing was performed across transplanted samples as well as on human surgical samples to highlight the transcriptional similarities and differences between groups. Transcriptionally, the tHIO+S samples were more similar to human tissues than the tHIO. With these initial experiments, we concluded that the application of an intraluminal uniaxial force is a practical method to induce maturation of tHIOs in vivo without concomitant architectural disruptions. While our current system does lack certain complexities, we have demonstrated enterogenesis by means of mechanical manipulation.	Co-expression
ERP104309	SRPK1_is_a_therapeutic_vulnerability_in_acute_myeloid_leukemia_through_its_effects_on_isoform_choice_of_epigenetic_regulators__	Acute myeloid leukemia (AML) is an aggressive cancer of hematopoietic stem cells that remains lethal for most sufferers. Having recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of AML, here we investigate the molecular basis and therapeutic potential of this finding. First, we show that genetic or pharmacological inhibition of SRPK1 induces cell cycle arrest, leukemic cell differentiation and prolongation of survival of immunocompromised mice transplanted with AML cells. We go on to show that SRPK1 inhibition led to  altered isoform levels of many genes including several with roles in leukemogenesis such as MYB and MED24. Collectively our findings reveal that SRPK1 is required for normal splicing of key epigenetic regulators and forms a novel a therapeutic vulnerability in AML.	Co-expression
ERP104371	RNA-seq of LPS- and palmitate-stimulated THP-1 macrophages	In this study we performed an RNA-seq analysis of lipopolysaccharide (LPS) and palmitate (PAL) stimulated THP-1 macrophages to study the gene regulatory mechanisms underlying classical innnate immune response and chronical inflammatory response caused by metabolic stress. This analysis was done to complement single-cell transcriptome analyses of the same cell models.	Co-expression
ERP104463	RNA-seq of isolated human foetal and hiPSC L/M-opsin cone photoreceptor populations labelled using the AAV2/9.pR2.1.GFP reporter	The loss of cone photoreceptor cells, which are critical for optimal daylight vision, have the great impact on vision during retinal degenerations. Retinal differentiation of human induced pluripotent stem cell (hiPSC) sources could provide a renewable source of cone photoreceptors towards developing a cone cell replacement therapy to treat blindness. Demonstration of comparable gene expression profiles between human foetal and stem cell-derived cones at equivalent stages is required to progress the cell transplantation approach into the patient, as it is hypothesised stem cell-derived cones are required to show high levels of developmental recapitulation of the in vivo generated cones. In this study, the AAV2/9.pR2.1.GFP reporter was used to specifically label L/M-opsin cone photoreceptors in human foetal retinal samples, obtained from the MRC-Wellcome Trust Human Developmental Biology Resource, at a range of developmental stages. The L/M-opsin cone population represent the majority cone cell types in the adult human retina and are the only photoreceptors present within the fovea. Using fluorescence activated cell sorting, L/M-opsin GFP+ cones and GFP- retinal populations, alongside total foetal retinal samples containing all retinal cell tytpes, were isolated and processed for bulk RNA sequencing and downstream comparative analysis. Using DESeq2 differential gene expression analyses, statistically significant genes enriched within the GFP+ human foetal LM-opsin cone populations were determined which led to the identification of a cone enriched gene signature of human L/M-opsin cone photoreceptors. The AAV2/9.pR2.1.GFP reporter was applied to hiPSC-derived retinal cultures to isolate and process cone-like cell populations for RNA sequencing using the same strategy developed within the human foetal retina. Applying the cone enriched gene signature to the transcriptome of hiPSC-derived GFP+ samples at equivalent developmental stages revealed some expression similarities in genes found to be enriched within the late foetal L/M-opsin cone photoreceptors. This analysis overall revealed an intermediate stage of cone differentiation was achieved within the hiPSC-derived samples and the comparison to human foetal L/M-opsin gene express profiles suggesting further differentiation of hiPSC-derived sample is required.	Co-expression
ERP104519	Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release	RNASeq was performed to study transcriptomic abundancy in four human metastatic melanoma cell lines. Samples correspond to: JM1: MEL-XY1 cell line; JM2: MEL-XY2 cell line; JM3: MEL-XY3 cell line; JM4: MEL-XX4 cell line (von Euw et al, J Transl Med. 2007 Apr 20;5:19.)	Co-expression
ERP104537	Transcriptome of CBX7 and CBX8 overexpressing CD34+ HSPCs	Transcriptome of CBX7 and CBX8 overexpressing CD34+ HSPCs	Co-expression
ERP104602	RNAseq analysis of fibroblasts, iPSC, iPSC derived RPE and retinal cells from retinitis pigmentosa type 11 patients.	Mutations in pre-mRNA processing factors (PRPFs) account for 40% of autosomal dominant retinitis pigmentosa (RP). It is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To understand the molecular basis of this phenotype, we have generated PRPF31 patient-specific optic cups and retinal pigmented epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing of pre-mRNA splicing, ciliogenesis and cell-to-substrate adherens junction genes was observed in patient-specific retinal cells, but not fibroblasts and iPSCs, providing mechanistic insights into retinal-specific phenotypes of PRPF31-related RP type 11. RPE was the most affected, characterised by loss of apical-basal polarity, reduced trans-epithelial resistance, phagocytic capacity, microvilli, and cilia length and incidence. Disrupted cilia morphology was observed in patient-specific- photoreceptors that progressively displayed features associated with degeneration and cell stress. In situ gene-editing of the patient mutation rescued key structural and functional phenotypes in RPE and photoreceptors, providing conceptual proof for future therapeutic strategies.	Co-expression
ERP104782	RNA-seq of whole blood samples from patients with visceral leishmaniasis.	To ascertain which molecular pathways underlying the pathogenesis of human visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, we performed modular co-expression gene networks analysis using CEMiTool R package and the transcriptional profile of whole blood samples from patients diagnosed with active VL compared to VL-treated condition (cured patients) and to healthy control samples.	Co-expression
ERP104860	Functionally-relevant splicing of resident pre-mRNAs in anucleate platelets upon activation by physiological stimuli	Platelet activation is the key event triggering thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies using antiaggregants still fail to prevent thrombotic coronary events in a significant number of patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how the activity of megakaryocyte-derived mRNAs is regulated in these anucleate cell fragments. We applied a combined multi-omics approach to investigate this phenomenon in platelets from healthy donors activated in vitro with Collagen or Thrombin Receptor Activating Peptide. Combining HiRIEF LC-MS to transcriptome analysis by RNA-Seq allowed platelet proteome characterization at deep coverage, revealing a significant effect of either stimulus on proteome composition. In silico intron retention analysis was then applied to search for splicing events induced by platelet activation, coupled to unbiased proteogenomics, to correlate intron retention in resting platelets to intron removal by RNA splicing during activation. This allowed identification of a set of transcripts, specifically involved in platelet shape changes, showing reduced intron retention and high peptide representation at exon-exon junctions in activated vs resting platelets.  These results indicate that RNA splicing events takes place in platelets during activation and that pre-mRNA maturation of specific transcripts is part of the activation cascade and could therefore provide novel molecular markers of platelet activation status in acute coronary syndromes and other pathological conditions.	Co-expression
ERP104864	Comprehensive transcriptome analysis of synovium and peripheral blood reveals major disease heterogeneity early in the RA disease process prior to therapeutic intervention	We report the first comparative analysis between histology, RNA-seq of synovium and matched peripheral blood, and clinico-radiological parameters in early rheumatoid arthritis (RA). Using a novel modular approach, we describe underlying pathways associated with three pre-dominant RA pathotypes. Myeloid was associated with macrophages, lymphoid with B and plasma cells, and fibroid with minimal inflammatory cell infiltration. Synovium RNA-seq was better correlated with the pathotypes than blood RNA-seq, but peripheral blood signatures, including type I interferon, were detected as associated with particular myeloid or lymphoid pathotypes. This study describes the molecular heterogeneity of RA and provides major new insights into the cross compartmental molecular pathways that underlie RA.	Co-expression
ERP104876	Transcriptome of self-reactive proliferating CD19+ B cells in multiple sclerosis	Multiple sclerosis (MS) is a T cell-mediated demyelinating autoimmune disease of the central nervous system causing neurological deficits with substantial disability. Our group demonstrated that self-reactive proliferation of peripheral lymphocytes is increased in MS patients, is associated genetic risk and is involved in the pathogenesis of MS. These observations are based on an established in vitro system, in which peripheral blood mononuclear cells (PBMC) were seeded out for 7 days in serum-free medium in the absence of an exogenous stimulus. In order to track the self-reactive proliferation, cells were labeled with the fluorescent proliferation marker CFSE. We showed that memory CD19+ B cells are enriched in the self-reactive proliferating compartment in RRMS in remission and that these cells are important to interact with and to induce proliferation of brain-homing CD4+ T cells in a HLA-DR-dependent manner.In order to understand the biological relevance of the proliferating cells on a molecular level, we sorted CD19+ B cells from the self-reactive proliferating (gating: singlet+live+CD19+CFSEdim) and non-proliferating (gating: singlet+live+CD19+CFSEhi) compartment by flow cytometry based on CFSE-labeling of PBMCs after stimulus-free co-culture for 7 days. We performed RNA isolation and sequencing of these sorted cell subpopulations from 5 untreated RRMS patients in remission. The data shows expression of CD19+CFSEdim and CD19+CFSEhi cells.	Co-expression
ERP104908	RNA seq experiment of Treg cells isolated from peripheral blood of patients with pulmonary sarcoidosis compared to Treg cells from peripheral blood of healthy individuals	Sarcoidosis is manifested by an exaggerated Th1 response on one hand, combined with high numbers of dysfunctional Treg cells on the other3. Moreover, it has been shown that Treg cells in patients with pulmonary sarcoidosis (PS) have impaired immunosuppressive function, survival and enhanced apoptotic susceptibility towards Fas ligand (CD95L)4.  However, the molecular background for the impairment of the Treg function in PS has not been elucidated.	Co-expression
ERP104977	A unique spliced varicella-zoster virus latency transcript represses expression of the viral transactivator gene 61	During primary infection, neurotropic alphaherpesviruses (αHVs) gain access to neurons in sensory and cranial ganglia establishing lifelong latent infection from which they can later reactivate to cause debilitating disease. For most αHVs, including the best-studied herpes simplex type 1 ( HSV-1), viral latency is characterized by expression of a single or restricted set of transcripts that map antisense to the open reading frame (ORF) homologous to the major HSV immediate early viral transactivator, ICP0. These latency transcripts, either directly or through encoded miRNAs or proteins, repress expression of the ICP0 orthologues. The exception is varicella-zoster virus (VZV), an αHV which infects over 90% of adults and for which neither a canonical latency transcript1, nor a putative mechanism for repressing lytic transcription during latency have been identified. Here, we describe the discovery and functional characterization of a VZV latency transcript (VLT), that maps antisense to VZV ORF 61 (the VZV ICP0 homologue9,10), and which is consistently expressed in neurons of latently infected human trigeminal ganglia (TG). VLT encodes a protein with late kinetics during lytic VZV infection in vitro and in zoster skin lesions. Whereas multiple alternatively spliced VLT isoforms are expressed during lytic VZV infection, a single unique VLT isoform that specifically suppresses ORF61 gene expression predominates in latently VZV-infected human TG. The discovery of VLT directly unifies the latent VZV transcription program with those of better-characterized αHVs, removing longstanding barriers to understanding VZV latency and paving the way for research into the development of vaccines that do not establish latency or reactivate, and drugs that eradicate latent VZV.	Co-expression
ERP105014	Inhibition of mevalonate pathway prevents adipocyte browning in mouse and men by affecting protein prenylation	Research in recent years focusing on brown adipose tissue functionality emphasizes an important role of this organ in energy homeostasis. Utilizing a transcriptome analysis of human brown and white adipose tissue, we identified an enrichment of the mevalonate pathway in BAT suggesting its importance in regulating BAT function. By inhibiting different intermediate steps of the mevalonate pathway, using pharmacological and genetic approaches in vitro and in vivo, we show that mevalonate pathway controls brown adipocyte functionality in mouse and men by providing geranylgeranyl pyrophosphate, the substrate for protein prenylation of small GTP-binding proteins. Taken together, our study demonstrates the importance of the mevalonate pathway for brown fat functionality in mouse and men.	Co-expression
ERP105032	Electrophysiological properties of human β-cell lines EndoC-βH1 and  βH2 conform with human β-cells	We have characterized the electrophysiological properties of the human β-cell lines EndoC-βH1 and EndoC-βH2. Both cell lines respond to glucose (6-20mM) with 2- to 3-fold stimulation of insulin secretion, an effect that was mimicked by tolbutamide (0.2mM) and reversed by diazoxide (0.5mM). Glucose-induced insulin release correlated with an elevation of [Ca2+]i, membrane depolarization and increased action potential firing. KATP channel activity at 1mM glucose is low and increasing glucose to 6 or 20mM glucose reduced KATP channel activity to the same extent as the KATP channel blocker tolbutamide (0.2mM). The upstroke of the action potentials in EndoC-βH1 and –βH2 cells observed at high glucose principally reflects activation of L- and P/Q-type Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. Action potential repolarization involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis (measured by measurements of membrane capacitance) was triggered by membrane depolarizations >10ms to membrane potentials above -30mV. Both cell lines were well-granulated (6,000-15,000 granules/cell) and granules consisted of a central insulin core surrounded by a clear halo. We conclude that the EndoC-βH1 and –βH2 cells share many features of primary human β-cells and that they represent a valuable addition to the experimental ‘tool box’.	Co-expression
ERP105150	Ribosome profiling of CLL patient samples	The functional consequences of many of the genetic changes, or combinations of genetic changes, in chronic lymphocytic leukaemia (CLL) are not known, but it is essential to discover these in order to understand the biology of the disease and the causes of individual variation in response to novel and conventional treatments.   In this proof-of-principle study the translational landscape of CLL was determined for the first time by ribosome profiling.   Individual variation in response to stimuli from the tumour microenvironment has not been systematically explored previously, but is likely to influence response to treatment and survival.	Co-expression
ERP105194	Transcriptome profiling by high throughput sequencing of HeLa cells depleted of MATR3, PTBP1/2 individually or in combination by siRNA.	We performed RNA-seq experiments on three biological replicates of HeLa cells depleted of MATR3, PTBP1/2, controls, or combined depletion of MATR3/PTBP1/2. Cells were fractionated into cytoplasmic and nuclear RNA. Library preparation was done with the TruSeq stranded RNAseq library kit (Illumina) according to manufacturer’s recommendations; RNA was depleted of rRNA using the RiboZero kit (Epicentre). All libraries were sequenced on Illumina HiSeq2 machines in a single-end manner with a read length of 100 nt.	Co-expression
ERP105312	Expression profiling of DDX3X and DDX54 knockdown in MCF7 cells	We performed RNA-seq to observe the gene expression changes in cells following siRNA-mediated knockdown of DDX3X and DDX54 RNA helicases in human breast cancer MCF7 cells. Two siRNAs were used to target each RNA helicase and scramble siRNA-treated MCF7 cells were used as controls.	Co-expression
ERP105393	RNA-seq of human U2OS cells depleted of NUAK1 by shRNA compared to control	Aim: To determine the impact of NUAK1 depletion on the transcriptome of U2OS cells.	Co-expression
ERP105460	Comparison of the transcriptomic impact of NRF2 depletion with that of NUAK1 depletion in SW480 colorectal cancer cells	The intent of the experiment is to determine how much of NRF2 (NFE2L2)-dependent transcription requires NUAK1 upstream.  SW480 cells were transfected with siRNA targeting either NRF2, NUAK1 or non-targeting control, and harvested for analysis by RNA-SEQ 48hrs after transfection.  mRNA was analysed by Illumina paired-end RNA-SEQ	Co-expression
ERP105461	Using mitoribosomal profiling to investigate human mitochondrial translation	Human 143B.206 Rho+ cells (depleted mitochondrial DNA) and cytoplasts (derived from mitochondrial patient fibroblast containing C1624T mutation in mitochondrial tRNAVal ) were previously used to generated transmitochondrial cybrid lines. Hek293T cells,143B cells and cybrid cells were cultured in DMEM supplemented with 10% FCS in 5% CO2 at 37 °C. Cells were treated with Chloramphenicol (100 μg/ ml) for 15 min before harvest. Cells were then lysed and RNase I digested. Lysates were then loaded on a sucrose gradient (7%-47%). Fractions containing mito-monosomes were used to isolated RNA which were used to generate the library for deep sequencing. Mitoribosomal profiling were generated for both control (143B and Hek293T) and cybrid cells to reveal aspects of mitoribosome behaviour.	Co-expression
ERP105482	Biomarkers of response and resistance to checkpoint blockade immunotherapy in metastatic melanoma	Identifying the mechanistic features that determine a cancer patient's response to immune checkpoint inhibitors is a critical step towards improving the efficacy of current therapies and optimising the design of clinical trials for next-generation drugs. Here, we investigated the transcriptomic and immunophenotypic profiles of metastatic melanoma patients treated with anti-PD-1 alone or combined anti-PD-1 and anti-CTLA-4 immunotherapy. Effector T-cells are essential for increased anti-cancer activity, favouring better survival outcomes in patients treated with anti-PD-1 monotherapy. In contrast, response to combined anti-PD-1 and anti-CTLA-4 immunotherapy relied upon memory cytotoxic and helper T-cell populations. Patients with resistance to immune checkpoint blockade exploited the metabolic and hypoxia-mediated pathways to alter tumour microenvironment causing impairment of T-cell trafficking and function. Our findings provide a strong rationale for stratifying patients based on molecular profiles that determine response and resistance to anti-PD1 alone or in combination with anti-CTLA-4 immunotherapy.	Co-expression
ERP105501	RNA-Seq analysis of human osteoarthritic intact cartilage following total knee replacement	Large scale RNA-Seq analysis was performed to investigate the transcriptomic response to osteoarthritis in cartilage and investigate potential subgroups of patients. Data were collected from intact knee cartilage (posterior lateral condyle) from at total of 60 patients with osteoarthritis (OA) following total knee replacement and 10 control non-OA patients following amputation.	Co-expression
ERP105640	RNA-seq of human ovarian adenocarcinoma cell line SKOV3 treated with bisphenol A (10 or 100 nM) against untreated controls	Human ovarian adenocarcinoma SKOV3 cells were exposed to BPA (10 or 100 nM) or 0.1% DMSO for 24 h,and then total RNA was extracted from cells using Trizol reagent. Sequencing libraries were generated using NEBNext UltraTM RNA Library Prep Kit for Illumina (NEB) following manufacturer’s recommendations and index codes were added to attribute sequences to each sample. Then, the index-coded samples were clustered on a cBot Cluster Generation System using TruSeq PE Cluster Kit v3-cBot-HS (Illumina) according to the manufacturer’s instructions. After cluster generation, the library preparations were sequenced on an Illumina Hisreq 4000 platform with 150 bp paired-end reads.	Co-expression
ERP105662	T helper type 2 and type 0 RNA-seq time course	CD4+ T cells were extracted from mouse and human. They were activated in vitro with CD3/28 and cultured with Il4	Co-expression
ERP105778	RNA-Seq of 293T cells depleted of U2AF-related proteins	Characterization of RNA processing events dependent on U2AF-related proteins PUF60 and RBM39.  PUF60 (poly-U-binding factor 60 kDa, also known as FIR, Hfp or Ro-bp1) is a splicing factor homologous to the 65 kD subunit of the auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF65). PUF60 has two central RNA recognition motifs and a C-terminal U2AF homology motif (UHM), but lacks the N terminal arginine/serine-rich (RS) and UHM ligand motif (ULM) domains present in U2AF65.  PUF60 activity, in conjunction with U2AF, facilitates the association of U2 snRNP with the pre-mRNA. PUF60 and U2AF65 can bind SF3b155 ULMs simultaneously and noncompetitively.  RBM39 (also known as CAPERα, HCC1, FSAP59 or RNPC2) is an RNA processing factor and a hormone-dependent transcriptional coactivator. RBM39 domain structure is similar to PUF60, except for the extra N-terminal RS domain with unknown function.  To understand function of the two proteins on a genome-wide scale, each protein was individually depleted from human embryonic kidney cell line 293 using RNAi to systematically characterize the PUF60- and RBM39-dependent exon usage.	Co-expression
ERP105867	Bulk RNA-seq validation experiments for "High dimensional single cell analysis predicts response to anti-PD-1 immunotherapy"	Immune checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) is effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable response. Therefore, predictive biomarkers of clinical response are urgently needed. Here, we employed high-dimensional single cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of  metastatic melanoma patients before and after anti-PD-1 immunotherapy. During therapy, we observed a clear treatment response to immunotherapy in the T cell compartment. However, prior to commending therapy a strong predictor of progression free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. We could confirm this by conventional flow cytometry in an independent validation cohort and propose this as a novel predictive biomarker for therapy decisions in the clinic.  In order to determine whether there are cell intrinsic changes in the monocyte signature, we performed RNA sequencing on sorted CD14+CD16-HLA-DRhi cells from HD, NR and R at baseline.  Representative samples (n=4, each) of responders/non responders/ and healthy donors were selected from archival samples stored in the dermatology biobank according to the same clinical criteria used in the discovery and validation cohorts for CyTOF and FACS analysis. CD14+CD16-HLA-DRhiLin- (CD3, CD4, CD19, CD45RO) monocytes were sorted from frozen PBMC form blood samples from HD, R and NR at baseline.	Co-expression
ERP105873	CCR8 expression defines tissue-resident memory T cells in human skin	Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is under strict control of T cell antigen receptor (TCR)-engagement and the skin tissue microenvironment. We here examined the relationship between CCR8+ and CCR8− T cells. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T (TRM) cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue-localization (CD103) and -retention (CD69) markers, low levels of inhibitory receptors (PD-1, Tim-3, LAG-3), and a lack of senescence markers (CD57, KLRG1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (PD-1+), senescent (CD57+, KLRG1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput analyses of expressed T cell receptor beta-chain (TRB) gene rearrangement sequences showed that the two skin memory T cell compartments distinguished by CCR8 expression are clonotypically distinct, suggesting that they are produced in response to separate antigenic challenges and distinct stimulatory conditions. Moreover, the phenotypic profiles of these populations were stable in vitro and the presence of similar levels of telomere erosion excludes the possibility of a linear differentiation pathway. In conclusion, CCR8 marks skin-specific, long-lived memory T cells. Therefore, we propose that CCR8+ T cells should be targeted in future skin vaccination research.	Co-expression
ERP106152	Human primary adipose-derived stem cells (hpASC) differentiated to white adipocytes stimulated with norepinephrine 3h	We investigated the early transcriptional responses of human white adipocytes to NE. Already after 3 h of NE stimulation we revealed a wide transcriptional response and a wide range of pathways.	Co-expression
ERP106168	Korean Complex Karyotype Sarcoma Patients (RNA-seq)	To identify mutation and transcriptome profile in Complex Karyotype Sarcoma Patients, Whole exome sequencing and RNA sequencing analyses were performed using frozen cancer tissue. Adjacent normal tissue of the same patients were used for somatic molecular landscape.	Co-expression
ERP106228	FXR activation inhibits CAF tumor-promoting features	Cancer-associated fibroblasts (CAFs), the principal components of tumor microenvironment, play multiple roles in breast cancer onset and progression. While their impact is widely accepted, treatment options to target CAFs in clinical practice were not yet well established.  The nuclear receptor superfamily encompasses a druggable class of molecules, expressed in various stroma and parenchymal cell types, with the interesting therapeutic potential to modulate the reactive microenvironment. Having already addressed the oncosuppressive role of the nuclear Farnesoid X Receptor (FXR) in mammary epithelial cancer cells, the present study is aimed to assess the function of FXR in CAFs and evaluate whether its activation may affect their tumor-promoting features.	Co-expression
ERP106298	mRNA-seq of human cells lines derived from Papillary thyroid carcinoma (TPC1) transfected with siRNA against BHLHE40 (DEC1) or with scramble control siRNA	The goal of this experiment was to identify genes under the regulation of the bHLh transcription factor Dec1 in thyroid cancer. To this end silencing of Dec1 by siRna transfection in TPC1 cells was performed and changes in gene expression analyzed by mRNA-seq	Co-expression
ERP106451	Dual RNA-seq of peripheral blood from Gambian children with severe or uncomplicated Plasmodium falciparum malaria	This study examined the differences in human and parasite gene expression pattern between children with severe malaria and those with uncomplicated malaria through a dual RNA-seq approach. Peripheral blood samples were collected which contained substantial numbers of parasites that required no RNA enrichment prior to library preparation and sequencing.	Co-expression
ERP106487	RNA sequencing of purified intestinal epithelial cells from paediatric biopsies including Inflammatory Bowel Disease and healthy controls	This study investigated alterations in the transcriptomic profiles of intestinal epithelial cells in Inflammatory Bowel Diseases (IBD), i.e. Crohn's Disease and Ulcerative Colitis.  Biopsies were taken from treatment-naive paediatric patients at diagnostic endoscopy from terminal ileum (TI), ascending colon (AC) and sigmoid colon (SC). Intestinal epithelial cells were purified using enzyme digestion and magnetic bead separation. RNA extraction was performed on EpCAM-positive cells, using AllPrep DNA/RNA mini kit.  An Agilent Bioanalyzer was used to check RNA integrity following the manufacturer’s guidelines. mRNA was sequenced at the University of Kiel, Germany.	Co-expression
ERP106519	RNA-seq as a global measure of the similarity between human pluripotent stem cell and fetal liver derived B cell hierarchies	Evidence suggests childhood acute lymphoblastic leukemia (cALL) arises in early human development. Existing models of pre-leukemic initiation using the ETV6-RUNX1 fusion do not recapitulate human disease, highlighting the need for a developmentally relevant human model system. A human pluripotent stem cell (hPSC) model genome was engineered to express ETV6-RUNX1 from the endogenous ETV6 promoter. RNA-seq data from sorted hematopoietic progenitors identified according to surface markers.	Co-expression
ERP106532	RNA-seq of human skin lesions diagnosed as actinic keratosis, intraepidermal carcinoma or squamous cell carcinoma	We report whole tissue RNA-seq data captured from 25 AK, IEC or SCC lesions obtained from the skin of 17 individuals. We used RNA-seq to detect and measure HPV E7 transcription.	Co-expression
ERP106556	RNA-seq analysis of the effect of BSA and NaOH added to standard culturing medium on THP-1 macrophages	The data is supplementary to the RNA-seq analysis of LPS and palmitate stimulation of THP-1 macrophages (E-MTAB-6064), where palmitate for the cell treatment was dissolved in sodium hydroxide and coupled with BSA at a molar ratio 7.5:1. Here we stimulated THP-1 macrophages with the corresponding concentration of BSA (4%) and NaOH (0.4 mM) in the presence of 10 nM phorbol 12-myristate 13-acetate (PMA) for 24 hours added to the standard RPMI 1640 medium with 10% fetal bovine serum (FBS) to estimate the effects and compared them with unstimulated THP-1 macrophages cultured in RPMI 1640 medium with 10% FBS and 10nM PMA.	Co-expression
ERP106765	RNA-seq to investigate impact of treatment of KRAS mutant A549 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib	KRAS mutation is widely presumed to confer independence from upstream RTK signalling, however emerging evidence from mouse models of lung cancer suggests that ERBB RTKs may amplify signalling through RAS isoforms and participate in mutant RAS-driven lung cancer.  This is one of 3 datasets where we examined the transcriptional impact of treatment of KRAS mutant human lung cancer cell lines with the multi-ERBB inhibitor Neratinib	Co-expression
ERP106922	miR-200 and miR-375 control widespread epithelial plasticity-associated alternative splicing by controlling Quaking	Members of the miR-200 family are critical gatekeepers of the epithelial state, restraining expression of pro-mesenchymal genes that drive epithelial-mesenchymal transition (EMT) and contribute to metastatic cancer progression. Here, we show that miR-200c and another epithelial-enriched miRNA, miR-375, exert widespread control of alternative splicing in cancer cells. This is achieved by strong suppression of the RNA binding protein Quaking (QKI). QKI directly regulates hundreds of EMT alternative splicing events converging on targets within the actin cytoskeleton regulatory network without appreciably affecting mRNA levels, resulting in pleiotropic effects such as increased cell migration and invasion. QKI-driven alternative splicing signatures are broadly conserved across many cancer types. Importantly, actin-associated genes are directly targeted by both miR-200c/miR-375 and QKI, revealing coordinated control of mRNA abundance and alternative splicing during EMT. These findings demonstrate the existence of a miR-200/miR-375/QKI axis that controls alternative splicing and critically impacts on cancer-associated epithelial cell plasticity.	Co-expression
ERP106942	Accessory replicates, produced alongside the data for the circRNA study PRJEB8225.	The polyA-depleted RNA-seq data in this study was produced to provide additional replicates and accessory samples for the samples in study PRJEB8225. These samples were used in combination with the samples in PRJEB8225 for other projects.Data in the current study are:  - 1 replicate of HMLE cells  - 2 replicates of MesHMLE cells (HMLE cells after TGF-beta treatment), transformed with a negative siRNA (i.e. controls for siRNA knockdown in MesHMLE cells).Samples were produced as described in Conn et al., (2015), Cell. (DOI: 10.1016/j.cell.2015.02.014).	Co-expression
ERP106996	RNA-seq comparison of gene expression in enteroids derived of fresh or frozen human intestinal biopsies	Background & Aims Patient-derived gastrointestinal organoids are powerful tools for studying human physiology and disease. However, generating organoids requires prompt isolation and culture of fresh tissue, which is labor and time intensive, placing restraints on basic and clinical research. For example organoid biobanking efforts, or the ability to obtain specimens from distant locations that lack the expertise to culture organoids, is limited by current approaches. We sought to develop a method by which tissue biopsies from patients could be cryo-preserved, stored, or shipped, and later thawed in order to establish live organoid cultures. Methods A method for freezing and recovery, along with straightforward isolation methods using readily available materials were developed. Epithelial isolation and culture conditions were optimized to promote cell survival and the establishment of long-term culture post-thawing. Results Patient biopsies from stomach, duodenum, ileum, colon and from adenomateous colonic polyps  were frozen, subsequently thawed and used to successfully establish patient-specific epithelium-only organoid cultures with 100% efficiency (n=31 independent patient biopsies from different regions of the GI tract). Frozen tissue could be shipped internationally and across the United States and used to establish successful organoid cultures.  Organoid cultures could be expanded, passaged and frozen down for long-term storage. RNA-sequencing demonstrates that organoids derived from fresh tissue or from frozen biopsies are >99% transcriptionally identical. Conclusions Cryo-preservation of human tissue biopsies followed by the establishment of long-term, expandable cultures has negligible effect on transcription when compared to freshly prepared organoids, and will be of immense benefit to research and for clinical applications. This technique will allow for the establishment of biobanks of human tissues that can be revived and cultured in the future as well as transported across the globe for research, therapeutic or diagnostic use in remote labs and/or clinics.	Co-expression
ERP107079	tbd	tbd	Co-expression
ERP107143	Cytokine-mediated modulation of the hepatic miRNome: IL-6-mediated up-regulation of miR-146b-5p	IL-6-type cytokines play important roles in the (patho-)biology of the liver. For instance, they induce the important acute phase response to inflammatory signals and they are involved in hepatocarcinogenesis. Much is known about the regulation of protein-coding genes by cytokine whereas their effect on the miRNome is less well understood. Here, we performed a microarray screen to identify microRNAs (miRNAs) in human hepatocytes which are subject to regulation by IL-6-type cytokines. Using samples of two donors, 27 and 68 miRNAs (out of 1,733) were found to be differentially expressed upon incubation with hyper-IL-6 (HIL-6) for up to 72 h, with an overlap of 15 commonly regulated miRNAs. qPCR validation revealed that miR-146b-5p was also consistently up-regulated in hepatocytes derived from two other donors. Interestingly, miR-146b-5p (but not miR-146a-5p) were induced by HIL-6 and the IL-6-type cytokine OSM but also by IFNγ in non-transformed liver-derived PH5CH8 and THLE-2 cells and in Huh-7 hepatoma cells. We did not find evidence for a regulation of miR-146b-5p expression by promoter methylation, also when analyzing the TCGA data set on liver cancer samples. Inducible overexpression of miR-146b-5p in PH5CH8 cells followed by RNA-Seq revealed effects on multiple mRNAs. The differentially regulated mRNAs include those encoding IRAK1 and TRAF6 crucial for Toll-like receptor signaling. Indeed, LPS, but not TNF -mediated up-regulation of MCP-1 and IL-6 mRNAs was attenuated upon overexpression of miR-146b-5p, suggesting a possible negative regulatory loop to switch off inflammatory signaling in hepatocytes.	Co-expression
ERP107276	Gene expression profiling by RNA-seq of human iPSC and iPSC-derived cardiomyocytes from an Yoruban individual (NA19101)	We generated triplicate iPSC and iPSC-derived cardiomyocytes for analysis of differential expression paired with Hi-C data	Co-expression
ERP107288	GBM12 flank or intracranial study	This study was designed to investigate the distribution of and cellular response to erlotinib, an EGFR inhibitor, in a patient-derived xenograft model of GBM. Mice were injected with GBM12 cells in either the flank or orthotopic region (intracranial). Mice were dosed with vehicle (placebo) or Erlotinib (a single dose of 5, 33 or 100 mg/kg via oral gavage) and sacrificed after two hours post-dose. mRNA sequencing data were obtained to correlate transcriptional response.	Co-expression
ERP107424	RNA-sequencing of human embryonic and fetal urinary bladder and genital tissues	The general aim is to provide knowledge of transcriptomic profiles of the developing urinary bladder in order to shed light on gene expression important in the mechanisms behind the developmental defects of bladder exstrophy. Human bladder tissues and gential tissues, as control samples, were surgically removed from terminated fetuses after informed consent and ethical approval. Gene expression data were extracted and analysed after high throughput sequencing of paired-end mRNA libraries (Illumina).	Co-expression
ERP107544	RNA-Seq of human aortic endothelial cells with lysophosphatidylinositol against untreated controls	Vascular Innate immune cells, such as macrophages, elicit long-term T cell-, and B cell- immune responses, by expressing danger-associated molecular pattern (DAMP) receptors, T cell co-stimulation receptors and presenting antigens to the adaptive system through major histocompatibility complex (MHC)-II.  Here, we investigated whether human aortic endothelial cells (HAECs) could also be “transdifferentiated” into innate immune cells after treatment of hyperlipidemia-upregulated DAMP molecules, lysophosphatidylinositol (LPI).  HAECs were treated with vehicle control or lysophosphatidylinositol (16:0) (10µM) for 18 hours.	Co-expression
ERP107545	RNA-Seq of human aortic endothelial cells with lysophosphatidylcholine against untreated controls	Vascular Innate immune cells, such as macrophages, elicit long-term T cell-, and B cell- immune responses, by expressing danger-associated molecular pattern (DAMP) receptors, T cell co-stimulation receptors and presenting antigens to the adaptive system through major histocompatibility complex (MHC)-II.  Here, we investigated whether human aortic endothelial cells (HAECs) could also be "transdifferentiated" into innate immune cells after treatment of lysophosphatidylcholine (LPC).  LPC specifically upregulated genes that are involved in cholesterol biosynthesis, presumably through sterol regulatory element-binding protein 2 (SREBP2).  In addition, we found that both LPC induced adhesion molecules, cytokines, and chemokines in HAECs, which are classical markers for endothelial activation.  Moreover, LPC transdifferentiated HAECs into innate immune cells including induction of potent DAMP receptors, such as CD36, T cell co-stimulation receptors and MHC-II molecules.	Co-expression
ERP107715	RNA-seq of PBMCs to investigate peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas	Low-grade gliomas (LGGs) are the most common brain tumor of childhood. Children with LGGs are ideal candidates for immunotherapy due to slow tumor growth, and as these children are otherwise healthy, and often have intact immune systems. We recently reported in an early phase clinical trial that vaccine treatment elicited strong biologic responses in LGG patients, compared with our experience in adult and pediatric high-grade brain-stem and non-brain stem gliomas. Additionally, we observed radiographic responses of stable disease (n=7), partial response (n=3), and complete response (n=2) following therapy. These remarkable results prompted us to initiate a phase II trial utilizing this strategy in pediatric LGGs. In order to identify potential peripheral response patterns in each response group, we performed Illumina RNA-sequencing on PBMCs samples (n=54), collected either prior to treatment or at multiple time points following treatment.	Co-expression
ERP107744	RNA-seq of HeLa-MZ cells treated with Wnt3a conditioned media for 0, 2 and 6 hours	Transcriptional profiling of HeLa cells treated with Wnt3a at 0, 2 and 6 hours to identify transcriptional regulators controlling lipid homeostasis. Cells were treated with control or Wnt3a conditioned media for the indicated times before RNA extraction and sequencing.	Co-expression
ERP107752	10 Pancreatic cancer cell lines with or without KRAS knock down RNA sequencing	10 Pancreatic cancer cell lines were treated with KRAS knock down or control with no KRAS knowdown. Then RNA was extracted and sequenced.	Co-expression
ERP107762	time-course RNAseq of 7 Pancreatic cell lines with ERK inhibitor treatment	7 Pancreatic cell lines were treated with ERK inhibitor. RNA was collected at different time points (0h, 1h, 4h, 12h, 24h) and then sequenced.	Co-expression
ERP107783	RNA-seq to investigate gene expression profile associated with long-non coding RNA RAIN  in TPC1 cells	We used RNA-seq analysis to identify gene expression profile in TPC1 cells transfected with LNA gapmers against RAIN vs control	Co-expression
ERP107802	RNA-seq of primary human M2-polarized macrophages cultured in either high-concentration or low-concentration type I collagen.	M2-polarized macrophages have been shown to adapt their migration mode to physical properties of the surrounding extracellular matrix. They migrate in the integrin-mediated adhesion and proteolytic activity-dependent mesenchymal mode in stiff matrices, and in the integrin- and protease-independent amoeboid mode in low density, porous environments. To find out what impact has the switching between the migration modes on expression of both protein-coding and non-coding genes we employed RNA sequencing of total RNA depleted of ribosomal RNA isolated from M2 macrophages migrating in three-dimensional collagen gels of high or low concentration for 48 hours.	Co-expression
ERP107923	RNA sequencing of human, IDH2-mutated, acute myeloid leukemia samples from patients before or during treatment with Enasidenib	Mutations in isocitrate dehydrogenase 2 (IDH2) occur in many cancers including Acute Myeloid Leukemia (AML). Recently, we showed that single agent Enasidenib, a first-in-class, selective mutant IDH2 inhibitor, produces a 40% response in relapsed/refractory AML patients by promoting differentiation of leukaemic cells. In this current study, we describe two patients who responded to Enasidenib treatment but subsequently relapsed with an IDH2-mutant subclone which had acquired mutations in DHX15 and DDX1 genes.  These genes have putative functions in regulating splicing.  We have studied the alternative splicing events using RNASeq in the sample pre-relapse (before acquisition of DHX15 and DDX1 mutations) and at relapse (after acquisition of DHX15 and DDX1 mutations).	Co-expression
ERP108322	Transcriptomic profiling of human neuromesodermal-like cells and spinal cord progenitors derived in vitro from H9 ES cell line	Human ES (H9) cells were directed towards a neuromesodermal progenitor-like cell state and these cells were then subsequently differentiated towards a neural cell fate. Human ES cells (H9) were differentiated into neuromesodermal progenitor-like cells by culturing in Neurobasal/1x N2/1x B27 medium (N2/B27) supplemented with 20 ng/ml bFgf and 3 μM CHIR99021 for 3 days and exposure to dual SMAD inhibition (dSMADi) (Noggin 50 ng/ml and the TGFb receptor type 1 inhibitor SB431542 10 μM) during day 3 (D3). Transcriptome analysis was then carried out following a selection procedure to enrich for NMP-like cells (sD3/NMP-like). This involved use of a hES (H9) cell line engineered with CRISPR-Cas9 to express GFP under the control of the endogenous Nkx1.2 promoter. At the end of day 3 cells were selected for high GFP expression, as high Nkx1.2 transcription is characteristic of NMP cell populations in mouse and chick embryos. These cells were then lysed and RNA extracted for RNASeq.   Humans ES cells (H9) differentiated into NMP-like cells as above (without selection) were also allowed to develop further on day 4 (in the presence of dSMADi and Retinoic acid (RA) 100nM, in N2/B27) and then in RA alone until end of day 8 (D8). These cells were then lysed and RNA extracted for RNASeq.	Co-expression
ERP108370	RNA-seq of Glioma Neural Stem (GNS) cell line G144 after MEK inhibition in wild type (WT) and CIC (Capicua) depleted cells.	We identified genome-wide binding patterns of CIC in several different cell types and find that CIC target genes are enriched for MAPK effector genes involved in cell cycle regulation and proliferation. CIC binding to its target genes is abolished by high MAPK activity, which leads to hyperacetylation and their transcriptional activation. Inhibition of MAPK signaling via MEK inhibition leads to recruitment of CIC to its target genes.  ChIP-seq data of G144 cells after MEK inhibition and CIC knockout is available under accession E-MTAB-6682	Co-expression
ERP108428	"RNA-Seq Comparing TRIZOL and XRNAX Extracted RNA"	For interrogating the RNA content of UV254nm XRNAX extracts MCF7 cells were UV254nm crosslinked and extracted with XRNAX. For comparison non-crosslinked cells were extracted with conventional TRIZOL. Both extracts were digested with proteinase K and cleaned up with silica spin columns. Resulting RNA was prepared into sequencing libraries before and after RiboZero rRNA depletion using the TruSeq RNA Library Prep Kit v2 (Illumina, not stranded). For interrogating the RNA content of UV365nm XRNAX extracts MCF7 cells were grown in the presence of 100 µM 4-thiouridine (4-SU) for 16 hours before crosslinking at UV365nm and extraction with XRNAX. For comparison identically treated but non-crosslinked cells were extracted with conventional TRIZOL. Both extracts were digested with proteinase K and cleaned up with silica spin columns. Resulting RNA was prepared into sequencing libraries after RiboZero rRNA depletion using the TruSeq Stranded Total RNA kit (Illumina, stranded).	Co-expression
ERP108439	Transcriptomic profiling of three different neuroblastoma cell lines (CLB-BAR, CLB-GE and SK-N-AS) in response to ALK inhibition	Anaplastic Lymphoma Kinase (ALK) is a tyrosine kinase receptor which is a clinical target of major interest in cancer, including neuroblastoma. To better understand ALK signaling, three different neuroblastoma cell lines (CLB-BAR, CLB-GE and SK-N-AS) were cultured for 1hr and 24hrs in control conditions or after treatment with the ALK inhibitors crizotinib or lorlatinib. RNA-Seq experiments were performed to determine the expression changes resulting from ALK inhibition. Together with parallel phosphoproteomic experiments, these data unveil several important conserved oncogenic pathways in neuroblastoma.	Co-expression
ERP108451	RNA sequencing of CD57+ and CD57- effector memory CD8 T cells in patients with type 1 diabetes	Type 1 diabetes is an autoimmune disease in which insulin-secreting β cells of the pancreatic islets are selectively destroyed. CD8 T cells are regarded as critical players in mediating β cell destruction and as a result, considerable effort has been expended to define CD8 T cell behaviour in this disease. The overarching aim of the experiment is to characterize a recently identified autoreactive CD57-positive CD8 T cell subset which is associated with loss of function of islet beta cells in type 1 diabetes, to compare the phenotype of the CD57-positive effector memory CD8 T cells versus the CD57-negative compartment, and provide an insight into the function of these cells in the disease process. To that aim, HLA-A*24 positive patients with T1D -within 2 years of diagnosis- were asked to provide a blood, and following consent, and PBMC were isolated. CD57-positive and CD57-negative CD8 T cell populations were sorted by FACS, and finally, RNA was extracted. Amplified cDNA was obtained and used for the library preparation.	Co-expression
ERP108475	RNA-seq in GR18 cell line to identify genes regulated by the Glucocorticoid Receptor	To identify the genes regulated by the Glucocorticoid Receptor (GR), we performed RNA-seq in GR18 cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for GR), upon glucocorticoid (dexamethasone) or vehicle (ethanol) treatment.	Co-expression
ERP108490	RNA-seq of Plasmodium vivax derived from clinical isolates	This project contains RNA-sequencing reads of Plasmodium vivax derived directly from clinical patients. Here, we aim to characterize the gene expression patterns in patients with various parasite compositions. Patients (n=10) were recruited from two malaria endemic areas in Thailand. Ten RNA samples were treated with DNase, followed by Epicentre Globin-Zero Gold kit to deplete rRNA and globin transcript. The RNA-seq libraries were sequenced on an Illumina HiSeq4000 platform to generate approximately 60 million paired-end reads of 150 bp for each sample.	Co-expression
ERP108557	Total RNA-seq of human oesophageal adenocarcinoma cell line OE19 treated with siNT, siHNF4A, siGATA6 and siHNF4A+siGATA6 for 72 hours	To investigate the role of transcription factors in oesophageal adenocarcinoma, transcription factors were knocked down using siRNA and RNA was extracted and sequenced to identify target genes.	Co-expression
ERP108602	BCL-2 levels do not predict azathioprine treatment response in inflammatory bowel disease, but inhibition induces lymphocyte apoptosis and ameliorates colitis in mice.	Background: Inducing apoptosis of autoreactive lymphocytes is part of the therapeutic strategy for Crohn’s disease (CD) patients. Failure to respond to medical therapies upon inflammatory bowel disease could result from insufficient apoptosis. To date there are no useful molecular factors for the prediction of clinical relapse.  Study Aims: Characterization of the BCL-2 family-related risk of therapy resistance and verifying its usefulness as parameter for the prediction of clinical relapse could be helpful in deciding which medical therapy to recommend. The project is directly targeted to develop rapidly therapeutic improvement for patients with IBD. A long-term goal is the development of new therapeutic options for the treatment of IBD via a physiologic homeostasis and turnover of lymphocytes. Study Design: We propose to characterize the BCL-2 family-related risk of therapy resistance and its usefulness as parameter for the prediction of clinical relapse upon medical therapy. Samples will be used for next generation sequencing, qPCR, WB, immunohistochemistry and immunofluorescence. The hypothesis is considered confirmed if expression of BCL-2 family members in human peripheral blood is significantly changed between patient groups and correlates with the number of lymphocyte subpopulations.	Co-expression
ERP108679	Xenogeneic graft-versus-host disease in humanized NSG and NSG-HLA-A2/HHD mice	Despite the increasing use of humanized mouse models to study new approaches of graft-versus-host disease (GVHD) prevention, the pathogenesis of xenogeneic GVHD (xGVHD) in these models remains misunderstood. The aim of this study is to describe this pathogenesis in NOD/LtSz-PrkdcscidIL2rγtm1Wjl (NSG) mice infused with human PBMCs and to assess the impact of the expression of HLA-A0201 by NSG mice cells (NSG-HLA-A2/HHD mice) on xGVHD and graft-versus-leukemia (GvL) effects, by taking advantage of next-generation technologies. We found that T cells recovered from NSG mice after transplantation had upregulated expression of genes involved in cell proliferation, as well as in TCR, co-stimulatory, IL-2/STAT5, mTOR and Aurora kinase A pathways. T cells had mainly an effector memory or an effector phenotype and exhibited a Th1/Tc1-skewed differentiation. TCRbeta repertoire diversity was markedly lower both in the spleen and lungs (a xGVHD target organ) than at infusion. There was no correlation between the frequencies of specific clonotypes at baseline and in transplanted mice. Finally, expression of HLA-A0201 by NSG mice led to more severe xGVHD and enhanced GvL effects toward HLA-A2+ leukemic cells. Altogether our data demonstrate that the pathogenesis of xGVHD shares important features with human GVHD and that NSG-HLA-A2/HHD mice could serve as better model to study GVHD and GvL effects.	Co-expression
ERP108746	Comprehensive identification of RNA–protein interactions in any organism using orthogonal organic phase separation (OOPS)s	Existing high-throughput methods to identify RNA-binding proteins (RBPs) are based on capture of polyadenylated RNAs and cannot recover proteins that interact with nonadenylated RNAs, including long noncoding RNA, pre-mRNAs and bacterial RNAs. We present orthogonal organic phase separation (OOPS), which does not require molecular tagging or capture of poly-adenylated RNA, and apply it to recover cross-linked protein–RNA and free protein, or protein-bound RNA and free RNA, in an unbiased way. We validated OOPS in HEK293, U2OS and MCF10A human cell lines, and show that 96% of proteins recovered were bound to RNA. We show that all long RNAs can be cross-linked to proteins, and recovered 1,838 RBPs, including 926 putative novel RBPs. OOPS is approximately 100-fold more efficient than existing methods and can enable analyses of dynamic RNA–protein interactions. We also characterize dynamic changes in RNA–protein interactions in mammalian cells following nocodazole arrest, and present a bacterial RNA-interactome for Escherichia coli. OOPS is compatible with downstream proteomics and RNA sequencing, and can be applied in any organism	Co-expression
ERP108747	pheno-seq – linking 3D phenotypes of clonal tumor spheroids to gene expression	3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Transcriptional heterogeneity can be dissected by single-cell RNA-sequencing, but these technologies suffer from low RNA-input and fail to directly correlate gene expression with contextual cellular phenotypes. Here we present ‘pheno-seq’ for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids derived from 3D models of breast and colorectal cancer. Specifically, we identify characteristic expression signatures that are associated with heterogeneous invasive and proliferative behavior including a rare cell subtype. Furthermore, we identify functionally relevant transcriptional regulators missed by single-cell RNA-seq, link visual phenotypes defined by heterogenous expression to inhibitor response and infer single-cell regulatory states by deconvolution. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently prove to be useful for translational research.	Co-expression
ERP108822	Expression changes in BRCA1-deficient breast cancer PDX models treated with PARP-inhibitors.	BRCA1 deficiencies cause breast, ovarian and other cancers, and render tumours hypersensitive to PARP-inhibitors. To understand resistance mechanisms, we conducted explored expression changes in BRCA1-deficient breast cancer PDX models treated with PARP-inhibitors.	Co-expression
ERP109073	RNAseq of Human Umbilical Vein Endothelial Cells treated with Insulin in the presence or absence of TGF-beta kinase inhibitor SB431542 for 90 minute.	Endothelial cells play many important role during development and development of diseases. Endothelial dysfunction which is commonly seen in diabetes patients is thought to be one of the first step that leads to adverse events such as retinopathy, nephropathy, and atherosclerosis. To examine to which extent TGF-beta signaling contributes to insulin-induced transcriptional responses we performed this RNAseq on Human umbilical vein endothelial cells.	Co-expression
ERP109084	RNA-sequencing of human dermal fibroblasts (wild-type, overexpressing FoxM1, and with FoxM1 knock-down).	Aneuploidy, a condition in which the number of chromosomes in a cell is not an exact multiple of the haploid set, has been linked to aging and age-associated diseases. This association has been well-documented for oocytes and is the main cause of miscarriage and birth defects in humans. Aneuploidy has been also reported for elderly somatic cells, but the molecular mechanisms remain unknown. Here, we show that aneuploidy increases with natural aging due to transcriptional downregulation of several mitotic genes leading to cumulative dysfunction of the mitotic machinery. Live cell imaging of mitosis in primary dermal fibroblasts isolated from young, middle-aged and old-aged humans and mice revealed that mitotic duration increases with advancing age alongside with chromosome segregation defects. This age-associated loss of mitotic fidelity correlated with the steady repression of Forkhead box M1 (FoxM1), the transcription factor that drives the expression of many G2/M cell cycle genes. Indeed, expression of a constitutively active form of FoxM1 restored mitotic gene levels in old cells and, importantly, prevented both aneuploidy and cellular senescence. Finally, we found that the majority of senescent elderly fibroblasts were aneuploid, suggesting cellular senescence as the major outcome of age-associated aneuploidy. Thus, our work opens up the possibility of modulating mitotic efficiency through FoxM1 to delay aging.	Co-expression
ERP109255	RNA-seq of hepatic biopsies taken from patients with chronic liver disease presenting with different aetiologies (HCV, FLD) and fibrosis stages.	To determine gene signatures associated with advanced liver fibrosis, we undertook RNA-sequencing of liver biopsies from patients presenting with different aetiologies (HCV or FLD) and fibrosis stages (n=69 patients).	Co-expression
ERP109257	RNA-seq analysis of two common T cell models, HUT78 and JURKAT E6.1: Project 5 of Open Targets - Epigenomes of Cell Lines	The aim of this experiment was to characterize the gene expression of two common immortalized T cell lines (HUT78 and JURKAT E6.1) with and without activating stimuli. Two independent cultures were carried out for each of the cell lines. Cells were cultured according to supplier recommendations and either left untreated or stimulated with Dynabeads human T-activator CD4/CD28 beads (Invitrogen, UK) at a ratio of 1 bead:3 cells for 48 hours.  This RNA-seq experiment is being carried out as part of the Open Targets project to identify a gene expression signature of common immortalised cell lines/models. This signature will be used in combination with data from ChIP-seq experiments from the same cell lines against primary cells and tissues. The overall aim of the Open Targets Cell Line Epigenome project is to establish a systematic approach for the determination of human biological and disease relevance through the generation of transcriptomic and epigenomic data in cell lines of interest. Comparison of cell line mRNA expression and epigenome data with existing and newly generated reference data from human tissue and cell types will identify assay systems that will provide greater confidence in translating target biology and compound pharmacology to patients.	Co-expression
ERP109263	RNA-seq of blood taken from patients suffering from sleeping sickness and infected with Trypanosoma brucei rhodesiense	Shotgun sequencing of sleeping sickness patient blood. WARNING: these results cannot be compared with those from trypanosome poly(A)+ mRNA, because the poly(A) selection introduces substantial bias, including loss of long mRNAs. Details will appear in the publication. These are additional sequencing runs that match some from E-MTAB-5293	Co-expression
ERP109267	RNA-seq analysis of several in vitro models of hepatocyte function: Project 4 of Open Targets - Epigenomes of Cell Lines	The aim of this experiment was to characterize the gene expression of several in vitro cellular models of hepatocyte function: primary hepatocytes and common immortalized liver cell lines (HepG2, Hep3B and Huh7), cultured in parallel in both 2D and 3D configurations.  Two independent cultures were carried out for each of the cell lines. For primary cultures, cells were obtained from three independent donors and cultured in parallel in both conditions. For the 2D culture, cell lines were grown using standard culture methods and harvested sub-confluence in exponential growth phase. For the 2D culture of primary hepatocytes, cells were grown in sandwich configuration between two layers of extracellular matrix (collagen coated plates and medium containing 0.25mg/ml Matrigel) and harvested at day 9 post seeding. For 3D cultures, cells were seeded at 1500 cells per well in ultra-low adherence multi-well plates to facilitate cellular aggregation and spheroid formation. Cell line spheroids aggregated rapidly and were harvested 4-5 days post seeding. Primary cell spheroids formed more slowly and were harvested 14-17 days post seeding.  This RNA-seq experiment is being carried out as part of the Open Targets project to identify a gene expression signature of common immortalized cell lines/models. This signature will be used in combination with data from ChIP-seq experiments from the same cell lines against primary cells and tissues. The overall aim of the Open Targets Cell Line Epigenome project is to establish a systematic approach for the determination of human biological and disease relevance through the generation of transcriptomic and epigenomic data in cell lines of interest. Comparison of cell line mRNA expression and epigenome data with existing and newly generated reference data from human tissue and cell types will identify assay systems that will provide greater confidence in translating target biology and compound pharmacology to patients.	Co-expression
ERP109295	RNASeq of human breast cancer cells MCF7 and LCC2 treated with Tamoxifen or DMSO	RNASeq of human breast cancer cells MCF7 and LCC2 treated with Tamoxifen and DMSO	Co-expression
ERP109432	Comparative proteomic and RNA-seq analyses identify glypican-3 as a hepatocyte host cell receptor for Plasmodium falciparum sporozoite invasion	Understanding the liver stage invasion and development of Plasmodium falciparum parasites is difficult due to limitations in current methodologies, namely, a hepatocyte cell line that supports the invasion of sporozoites. In this work we seek to develop and characterize a subclone of the HC-04 cell line that supports higher invasion rates than the parental line. We make use of both RNA-seq and LC-MS/MS proteomics to characterize cells grown in two different mediums. Finally, we identify and validate a surface protein, glypican-3, which is deferentially expressed between parental and subclone cell lines, when compared to HepG2 cells, and demonstrate that antibodies against glypican-3 decrease parasite invasion.	Co-expression
ERP109451	RNA-seq of hepatocytes obtained through step-wise differentiation of hIPSCs from a patient with A1AT deficiency and its point mutation-corrected isogenic hIPSC line. Comparison to primary hepatocytes from a healthy donor and an A1AT-deficient patient.	A1AT deficiency is an autosomal not recessive disorder caused by mutations in the SERPINA1 gene. Individuals with the Z variant retain polymerised protein in the endoplasmic reticulum of hepatocytes, predisposing them to liver disease. This study primarily aimed to uncover the molecular mechanisms that link protein misfolding to liver injury. To that end, RNA was extracted from hepatocytes differentiated from hIPSCs carrying the Z variant and mutation-corrected hIPSCs (control). The second objective of the study was to benchmark the gene expression profile of both hIPSC-derived hepatocytes types to primary hepatocytes of wild type and a Z variant A1AT genotype.	Co-expression
ERP109583	The histone chaperone HIRA cooperates with PML-NBs to activate host innate immune defences in response to HSV-1 infection	Host innate immune defences play critical roles in restricting the propagation and pathogenesis of invading viral pathogens. Here we show that the histone H3.3 chaperone HIRA (histone cell cycle regulator) cooperates with promyelocytic leukaemia nuclear bodies (PML-NBs) to mediate the induction of innate immune defences in response to herpes simplex virus 1 (HSV-1) infection. Under conditions that activate innate immune signalling, HIRA relocalized from the nuclear matrix to PML-NBs in a Janus-Associated Kinase (JAK), Cyclin Dependent Kinase (CDK), and Sp100-dependent manner. RNA-seq analysis revealed that HIRA was required to promote the transcription induction of a broad repertoire of host genes implicated in the regulation of innate immunity to HSV-1 infection, including MHC-I antigen presentation, cytokine signalling, and interferon stimulated gene (ISG) products. ChIP-seq analysis revealed that PML, the principle scaffolding protein of PML-NBs, was required for the efficient enrichment of HIRA directly onto ISGs, identifying a role for PML in the HIRA-dependent regulation of innate immune defences to virus infection. Our data identifies independent roles for HIRA to mediate both the intrinsic repression of viral gene expression and induction of innate immune defences that restrict the initiation and propagation of HSV-1, respectively. These intracellular host defences are antagonized by the HSV-1 ubiquitin ligase ICP0, which mediates the disruption of PML-NBs from the outset of nuclear infection. Our study highlights the importance of histone chaperones to regulate multiple phases of host immunity to virus infection, findings that are likely to be highly pertinent in the cellular restriction of many clinically important viral pathogens.	Co-expression
ERP109626	RNA-seq to investigate the proto CpG island methylator phenotype of sessile serrated adenoma/polyps	BACKGROUND & AIM: Sessile serrated adenoma/polyps (SSA/Ps) are the likely culprit of ~20% colon cancers but they are molecularly poorly understood. We investigated their epigenetic phenotype using high-throughput analysis of DNA methylation and gene expression.  METHODS: 17 SSA/Ps and, as a comparative group, 15 conventional adenomas (all with matched samples of normal mucosa) were prospectively collected during colonoscopy. DNA from the 64 tissues was analyzed, via bisulfite next generation sequencing, for methylation at ~2.7 million CpG sites located prevalently in gene regulatory regions spanning 80.5Mb (~2.5% of the genome). The transcriptome of these samples was also investigated using RNA sequencing. An independent series of 61 archival lesions was used for targeted verification of DNA methylation.  RESULTS: Both SSA/Ps and conventional adenomas showed a profound remodelling of their methylome. Cytosine hypermethylation was more pervasive in SSA/Ps than adenomas, in terms of number of hypermethylated regions (22,147 vs 15,965, respectively) and genes (4938 vs 3443, respectively). In addition, the extent of hypermethylation in a given region was higher in SSA/Ps than adenomas. This methylation pattern of SSA/Ps was reminiscent of the CpG island methylator phenotype (CIMP) of their descendant cancers. We have called this phenotype proto-CIMP since most of the hypermethylation occurred in CpG islands and shores. SSA/Ps were also protected from a wave of demethylation that instead occurred in adenomas outside of CpG islands/shores (4288 vs 18,417 hypomethylated regions in SSAPs vs adenomas). Verification studies of six hypermethylated regions demonstrated the high potential of DNA methylation markers for predicting the diagnosis of SSA/Ps and/or adenomas. Proto-CIMP of SSA/Ps was surprisingly associated with a higher number of up- (618) than downregulated (349) genes, while adenomas showed the opposite trend (516 up- vs 712 downregulated genes). CONCLUSIONS: The epigenetic landscape of SSA/Ps differs substantially from that of conventional adenomas. This huge amount of epigenetic variation represents a rich source of promising diagnostic tools, such as novel DNA markers or histologic stainings, for the tailored management of the two most frequent colon cancer precursors.	Co-expression
ERP109703	RNA-seq analysis of Chronic Lymphocytic Leukemia patients belonging to stereotyped subsets #6 and #8	Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Yet, subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter’s transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on their gene expression profiling and performed RNA-seq.	Co-expression
ERP109789	RNA-seq of human neurons derived from H9 embryonic stem cell lines treated with BDNF, TrkB agonist ZEB 85 or NT4 against untreated controls	As a result of a large number of in vitro as well as in vivo experiments with rodents, brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB are now widely appreciated to play major roles in brain function. There is also a growing appreciation that decreased BDNF signalling may be a significant component in a wide range of brain dysfunction in humans based on the discovery of mutations and polymorphisms in the corresponding genes. Human neurons generated in vitro had been shown to be responsive to TrkB phosphorylation upon treatment with BNDF, TrkB agonist ZEB85, the related factor neurotrophin-4 (NT4). In order to compare the transcriptional changes upon treatment with the three TrkB ligands RNA-seq analysis was deployed. Cultures had been treated in triplicates with BDNF, ZEB85 or NT4 for 30 minutes, 2 hours, 12 hours and 24 hours, while non treated controls were lysed at each time-point.	Co-expression
ERP109857	Pre-existing functional heterogeneity of tumorigenic compartment as the origin of chemoresistance in pancreatic tumors	Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution of tumor cells derived from human pancreatic tumors, we demonstrate that in vitro cultures and in vivo tumors are maintained by a common set of tumorigenic cells that can be used to establish clonal replica tumors (CRTs), large cohorts of animals bearing human tumors with identical clonal composition. Using CRTs to conduct quantitative assessments of adaptive responses to therapeutics, we uncovered a multitude of functionally heterogeneous subpopulations of cells with differential degrees of drug sensitivity. High-throughput isolation and deep characterization of unique clonal lineages showed genetic and transcriptomic diversity underlying functionally diverse subpopulations. Molecular annotation of gemcitabine-naïve clonal lineages with distinct responses to treatment in the context of CRTs generated signatures that can predict the response to chemotherapy, representing a potential biomarker to stratify patients with pancreatic cancer.  WEX data for the study is available at: EGAS00001003442	Co-expression
ERP109918	Bulk RNA-seq of of human dermal fibroblasts from up to 66 individuals (supplementary)	Dermal fibroblasts from up to 66 human donors, stimulated with dsRNA (poly I:C) in a time course of 0, 2, 6 hours, profiled using the Smart-seq2 protocol. Donor fibroblast samples were supplied by the Hipsci consortium.	Co-expression
ERP109940	RNA-Seq of human fetal hearts at 9, 12 and 16 weeks of gestation	RNA-Seq was used to study alterations in gene expression in the developing human heart across three gestational ages in the first and early second trimester. All tissue was acquired following elective termination of pregnancy and informed parental consent. Storage and use of tissue was in premises licensed by the 2004 Human Tissues Act (UK) and all protocols had ethical committee approval. All samples were found to be morphologically normal during regular checks with the midwife and upon medical termination of pregnancy as certified by the physician. RNA was extracted using BioRad Aurum Total RNA Fatty and Fibrous Tissue Kit (cat no. 732-6830) following manufacturers instructions. Illumina compatible barcoded mRNA sequencing libraries were made from 100 ng of total RNA after polyA selection for mature mRNAs using the TruSeq Stranded mRNA Sample Preparation Kit’s high sample protocol (Illumina). Sequencing was performed on a single HiSeq 3000 150 bp paired end lane with the data exported as a pair of fastq formatted data files for each sample. Sample quality was assessed prior to sequencing.	Co-expression
ERP109941	Epithelium-only cultured stem cells isolated from human pluripotent stem cell derived intestinal organoids grown in matrigel and alginate	Human intestinal organoids were grown in a typical 3D matrigel culture environment, or in an alginate gel, then a subset from each condition were xenotransplanted to vascularized and mature in vivo. Epithelium was isolated and epithelial only organoids (enteroids) were then grown from each condition prior to sequencing bulk RNA-sequencing.	Co-expression
ERP109983	RNA-seq of human pancreatic cell lines, L3.6pl and BxPC-3, upon knockdown of p63 for 48 hours compared to siControl	Investigation of gene expression profile changes upon down regulation of p63 in L3.6pl and BxPC-3 cell lines which are representative of the squamous molecular subtype in pancreatic cancer	Co-expression
ERP109990	TCF/LEF dependent and independent regulation of Wnt/beta-catenin transcription	During canonical Wnt signalling the activity of nuclear beta-catenin is largely mediated by the TCF/LEF family of transcription factors. To challenge this view we used the CRISPR/Cas9 genome editing approach to generate HEK 293T cell clones simultaneously carrying loss-of-function alleles of all four TCF/LEF genes. Exploiting unbiased whole transcriptome sequencing studies, we found that a subset of beta-catenin transcriptional targets did not require TCF/LEF factors for their regulation. Consistent with this finding, we observed in a genome-wide analysis that beta-catenin occupied specific genomic regions in the absence of TCF/LEF. Finally, we revealed the existence of a transcriptional activity of beta-catenin that specifically appears when TCF/LEF factors are absent, and refer to this as beta-catenin-GHOST response. Collectively, this study uncovers a previously neglected modus operandi of beta-catenin that bypasses the TCF/LEF transcription factors.	Co-expression
ERP109999	RNAseq of isolated mitotic HeLa cells treated with Actinomycin D	The goal of this experiment was to assess whether transcription happens during mitosis. For this, we isolated mitotic HeLa cells and treated them with a transcription inhibitor, ActD.	Co-expression
ERP110052	Transcriptome profiling of Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975	Further to our previous study (E-MTAB-5997), here we performed transcriptome profiling on Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975, and would like to understand the effects of Anlotinib on Anlotinib-resistant NCI-H1975 cell, compare the different transcriptome profiling on NCI-H1975 cells and Anlotinib-resistant NCI-H1975 cells, sought to find the biomarker for explaining Anlotinib resistance.	Co-expression
ERP110083	RNA-seq analysis of PROX1 overexpression and knockdown in glioblastoma cell lines	Glioblastoma represents the most common and aggressive primary brain tumor type in adults. Stem cell regulatory pathways have been shown to be activated in gliomas supporting self-renewal, tumor maintenance and survival under stress. Glioblastoma stem-like phenotype, cell motility and tumor cell heterogeneity are considered significant hurdles to overcome for developing new treatment against these tumors. Transcription factor PROX1 has been associated with stem-like-phenotypes. Here, we overexpressed and suppressed PROX1 in glioma cell lines in order understand the gene expression regulated by this transcription factor.	Co-expression
ERP110099	Reverse transcriptase inhibitors in Aicardi-Goutières syndrome	Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous encephalopathy whose pathology is linked to an abnormal type I interferon response induced by self-derived nucleic acids. Data indicate that endogenous retroelements represent one source of interferon-stimulatory self-nucleic acid. No effective therapies are available for this disorder. In this pilot study involving patients with AGS due to mutations in TREX1, RNASEH2A, RNASEH2B or SAMHD1 three nucleoside analogue reverse transcriptase inhibitors (RTIs) were administered over 12 months. Transcription profiling was done by RNA-seq.	Co-expression
ERP110106	RNA-seq of blood from donors with connective tissue diseases in the Lupus Extended Phenotype Cohort	The connective tissue diseases (CTDs) are group of inflammatory disorders with overlapping clinical and serological manifestations. We have undertaken Lupus Extended Phenotype (LEAP) study in of a cohort of adult patients with CTDs, namely systemic lupus erythematosus, Sjogren's syndrome, mixed and undifferentiated CTD, limited and diffuse cutaneous systemic sclerosis and dermatomyositis.   RNAseq was undertaken in 12 participants from 4 ‘cohorts’ based on interferon stimulated gene and autoantibodies analyses: 3 ISG positive and anti-Smith positive participants; 3 ISG positive and anti-Smith negative participants; 3 ISG negative and anti-Smith positive participants and 3 ISG negative and anti-Smith negative participants.	Co-expression
ERP110138	RNA-Seq of human micro- and macrovascular endothelial cells	Background: If the majority of antibody mediated rejections (AMRs) of the renal allograft are due to anti-HLA antibodies, non anti-HLA antibodies have also been suspected. The occurrence of non anti-HLA-associated AMRs remains associated with unresolved diagnostic and therapeutic issues.  Methods: To better understand the pathomechanisms of these rejections, we identified, though a nation-wide study, kidney transplant recipients (KTRs), without anti-HLA donor specific antibodies, experiencing acute graft dysfunction within the first 3 months after transplantation and severe microvascular injury on biopsy (called acute microvascular rejections, AMVR).	Co-expression
ERP110145	RNA-seq analysis of MES-MM 98 and REN mesothelioma cell lines modulated for miR-24-3p expression	Identification of relevant miR-24-3p target mRNAs in human mesothelioma cell lines in order to characterize novel therapeutical targets in Mesothelioma disease	Co-expression
ERP110314	RNA-seq of human ASCs expanded with 10% FBS and in FBS-deprived condition.	In this experiment we determined the effects of FBS supplementation and subsequent deprivation (after second passage) on the whole transcriptome, including comprehensive mRNA and miRNA profiling.	Co-expression
ERP110318	RNA-seq of human melanoma cell line A375 treated with the tetracycline analogs Col-3 or doxycycline against untreated controls	Apart from their antibacterial activity, tetracyclines have demonstrated diverse and beneficial “off-target” biological activities in human disease, spurring interest in their development as non-antimicrobial therapeutics in diseases such as cancer. To better define biological pathways modified by the tetracyclines in human cancer, we sought to determine differential gene expression in the A375 cancer cell line treated with the tetracyclines, Col-3 and doxycycline, relative to control (vehicle-treated) cells. A375 cells were treated with either 10 μM Col-3, 10 μM doxycycline, or vehicle (DMSO) for 6 h, and changes to gene expression were assessed by RNA-Seq.	Co-expression
ERP110376	RNA-seq expression profiling of humain MAIT cells in blood and liver as compared to mainstream TCD4+ and TCD8+ cells.	At variance with what is observed in mice, no distinct MAIT1 or MAIT17 subsets exist in human blood, as all MAIT cells express a variety of transcription factors such as Rorgt, Tbet, Eomes and Helios. However, they are also found in tissues in which they have specific effector functions. To determine these tissue programs, we analyzed the transcription pattern of MAIT cells as compared to mainstream memory (CD45RA-CD27+) CD4+ and CD8+ T cells from human blood and liver. The paired samples of blood and liver cells were obtained from patients operated for metastatic uveal melanoma (liver samples from a “healthy” liver fragment), and from the blood of healthy controls.	Co-expression
ERP110448	RNA-Seq of A375 cells treated with tetracycline-based crosslinking probes to identify binding sites for the tetracycline analogs Col-3 and doxycycline on the human ribosome	Following the identification of the 80S ribosome as a putative target of the tetracycline analogs Col3 and doxycycline, we next sought to identify the precise binding sites for these tetracyclines within the ribonucleoprotein complex. We incorporated dual bioorthogonal handles into tetracycline-based probes, containing both a photoactive diazirine to enable direct probe crosslinking to the human ribosome and an azide handle to allow selective enrichment of crosslinked biomolecules via copper-free click chemistry. The Col-3 and doxycycline probes were each incubated with A375 cells, followed by irradiation at 365 nm to induce photolysis of the diazirine moiety and subsequent crosslinking to adjacent ribosomal components. Pulldown and RNA-Seq of the crosslinked RNAs from our experiments were used to identify enrichment of reverse transcription (RT) stops at ribosomal RNA sites caused by local crosslinking of our probes. This RNA-Seq based RT stop enrichment analysis was compared to results using an non-specific aniline control probe and untreated controls.	Co-expression
ERP110482	RNA-Seq of A375 cells treated with tetracycline-based crosslinking probes, with and without competition by parent tetracyclines, to show specific binding of the tetracycline analogs Col-3 and doxycycline on rRNA substructures of the human ribosome	Upon finding that the tetracyclines COL-3 and doxycycline target unique rRNA substructures of the 80S ribosome (E-MTAB-7147), we confirmed these putative ribosomal binding sites by showing that tetracycline-based crosslinking probes are specifically competed from these rRNA structures by their parent drugs. In short, we incorporated dual bioorthogonal handles into tetracycline-based probes, containing both a photoactive diazirine to enable direct probe crosslinking to the human ribosome and an azide handle to allow selective enrichment of crosslinked biomolecules via copper-free ‘click’ chemistry. The COL-3 and doxycycline probes were each incubated with A375 cells, followed by irradiation at 365 nm to induce photolysis of the diazirine moiety and subsequent crosslinking to adjacent ribosomal components. Pulldown and RNA-Seq of the crosslinked RNAs from our experiments were used to identify enrichment of reverse transcription (RT) stops at ribosomal RNA sites caused by local crosslinking of our probes. In these experiments, UV crosslinking was preformed with the COL-3 and doxycycline probe compounds in the presence and absence of free COL-3 and doxycycline (i.e., parent tetracycline molecules lacking the bifunctional diazirine-azide moiety), which were used as competitors to specifically diminish crosslinking to the ribosomal RNA. Crosslinking to ribosomal RNA was determined using RNA-Seq based RT stop enrichment, which was was also compared to inactive tetracycline probes containing a modified bifunctional linker, a non-specific aniline probe, and untreated controls.	Co-expression
ERP110628	MDA-MB-231/1833 bone-metastatic breast cancer cell gene expression after conditioning in conditioned medium from HUVECs conditioned in conditioned medium from static and flow-stimulated MLO-Y4 osteocytes	Bone metastases is a common severe complication for breast cancer. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced breast cancer cell extravasation across endothelial monolayers. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. Therefore, we used RNA sequencing to show that CM from endothelial cells conditioned in CM from flow-stimulated osteocytes significantly altered gene expression in bone-metastatic breast cancer cells. This This provides insights into the capability of bone-loading activity in preventing bone metastases.	Co-expression
ERP110773	mRNA-seq of HCT116 RNF40 knockdown cells upon TNF-alpha stimulation	This analysis identifies genes which are affected upon RNF40 knockdown cells and/or TNF-alpha stimulation	Co-expression
ERP110814	RNA-sequencing of the mRNA transcriptome in blood, across three time-points in severe psoriasis patients treated with the tumor necrosis factor (TNF) inhibitor, etanercept	Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the mRNA transcriptome in blood	Co-expression
ERP110816	RNA-sequencing of the mRNA transcriptome in lesional and non-lesional skin, across three time-points in severe psoriasis patients treated with the tumor necrosis factor (TNF) inhibitor, etanercept	Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the small-RNA transcriptome in blood	Co-expression
ERP111019	Herbal formula YYJD induces lung cancer cell apoptosis via activation of EGR1 (RNA-seq)	In this study,we demonstrated the transcription factor EGR1 is activated by TCM YYJD and such activation mediated YYJD-induced apoptosis in lung cancer cells and provided a novel insight to understand the anti-tumor mechanism of Chinese herb YYJD.	Co-expression
ERP111064	RNAseq analysis of IKKbeta knockdown EDC4 knockdown irradiated and untreated	U2OS cells expressing DOX inducible pTRIPZ shRNA against IKKbeta or EDC4 were irradiated or left untreated. RNA stability was determined as through actinomycin D chase experiment.	Co-expression
ERP111116	RNA-seq of JAK2VF and DNMT3A mutant Myelofibrosis patients	Determination of differentially expressed genes from peripheral blood of Myelofibrosis patients with JAK2VF and JAK2VF and DNMT3A mutations	Co-expression
ERP111307	PRPF8 iCLIP on HeLa cells in response to eIF4A3 Knockdown	This experiment uses iCLIP to identify the binding pattern of the spliceosomal protein PRPF8 on RNA. The data shows that PRPF8 binds strongly and specifically in the region 12 to 14nt upstream of 5' splice sites (5ss). Due to PRPF8's role in the formation of the catalytically active spliceosome, this data can be used as a readout of 5ss selection. Here, we performed iCLIP on HeLa cells treated with control or EIF4A3 siRNA, with 4 replicate samples per condition and eIF4A3 protein levels reduced ~50% in knockdown. We investigated the role of the exon junction complex (EJC) in suppressing 5ss that are reconstituted at the junction of two canonical exons (RS-5ss) - selection of these splice sites would result in recursive splicing of canonical exons. We plotted the crosslink sites of reads that span an exon-exon junction, seperating reads that span RS-5ss from those that do not. We found that reads that span an RS-5ss are enriched at the 12-14nt window associated with 5ss selection, while reads that span other exon-exon junctions are not enriched. This effect is magnified greatly by knockdown of eIF4A3. The results indicate that RS-5ss can be used by the spliceosome, but that this process is usually repressed by the EJC. This data is evidence of recursive splicing of canonical exons and the role of the EJC in repressing recursive splicing.	Co-expression
ERP111405	RNA-seq of human cancer cell line OVCA420* following TIGAR knockdown with shRNA	To identify differentially expressed genes following TIGAR knockdown, OVCA420* was transduced with TIGAR-targeting or non-targeting (control) shRNAs. 54 hours after the transduction, RNA was extracted and Illumina TruSeq RNA Sample Preparation Kit v2 was used to prepare the libraries. Each group contains 3 replicates. NextSeq 500 was used for sequencing.	Co-expression
ERP111437	Generation of progesterone-responsive endometrial fibroblasts from human induced pluripotent stem cells: role of the WNT/CTNNB1 pathway	Defective endometrial stromal fibroblasts (EMSF) contribute to uterine factor infertility, endometriosis and endometrial cancer. Induced pluripotent stem cells (iPSC) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSF is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSC to EMSF is unknown. The uterus differentiates from the intermediate mesoderm (IM) to form coelomic epithelium (CE) followed by the Müllerian duct (MD). Here, we successfully directed the differentiation of human iPSC (hiPSC) through IM, CE and MD to EMSF under molecularly defined embryoid body culture conditions using specific hormonal treatments. Activation of CTNNB1 was essential for expression of progesterone receptor that mediated the final differentiation step of EMSF before implantation. These hiPSC-derived tissues illustrated the potential for iPSC-based endometrial regeneration for future cell-based treatments.	Co-expression
ERP111521	RNA-sequencing of human induced pluripotent stem cell-derived intestinal epithelial organoids	The purpose of this study was to characterise iPSC-derived human intestinal epithelial organoids (iPSCo) by comparing these cultures with primary purified intestinal epithelial cells (IEC).  Intestinal epithelial organoid (IEO) cultures were derived from at least three different lines of iPSCs, RNA was extracted and gene expression was profiled using RNA-sequencing. We compared these profiles with datasets we have previously derived from purified IEC from mature terminal ileum (TI) and sigmoid colon (SC) as well as human fetal proximal gut (FPG) and fetal distal gut (FDG).	Co-expression
ERP111852	RNA-seq comparison of fetal lung and cultured fetal lung derived organoids with pluripotent stem cell derived lung organoids	Underdeveloped lungs are the primary cause of death in premature infants, however, little is known about stem and progenitor cell maintenance during human lung development. In this study, we have identified that FGF7, Retinoic Acid and CHIR-99021, a small molecule that inhibits GSK3 to activate Wnt signaling, support in vitro maintenance of primary human fetal lung bud tip progenitor cells in a progenitor state. Furthermore, these factors are sufficient to derive a population of human bud tip-like progenitor cells in 3D organoid structures from human pluripotent stem cells (hPSC). Functional studies showed that hPSC-derived bud tip progenitor organoids do not contain any mesenchymal cell types, maintain multilineage potential in vitro and are able to engraft into the airways of injured mice and respond to systemic factors.   We performed RNA-sequencing to assess the degree of similarity in global gene expression profiles between the full human fetal lung (59-127 days gestation), isolated human fetal bud tip progenitors, organoids grown from primary fetal bud tip progenitors, and hPSC-derived bud tip organoids. Results showed that hPSC-derived organoids have molecular profiles similar to organoids generated from primary human fetal lung tissue. Gene expression differences between hPSC-derived bud tip organoids and fetal progenitor organoids may be related to the presence of contaminating mesenchymal cells in primary cultures. hPSC-derived bud tip organoids are generated from a well-defined human cell sources, offering a distinct advantage over rare primary tissue as a means to study human specific lung development, homeostasis and disease.<br>Sample Nomenclature - Description<br>                                                                                                                                                                                                                                                      -------------------------------------------------------------------------<br>  Peripheral fetal lung                 the distal/peripheral portion of the fetal lung (i.e., distal 0.5 cm) was excised from the rest of the lung using a scalpel. This includes all components of the lung (e.g., epithelial, mesenchymal, vascular).                                                 <br>Isolated fetal bud tip                the bud peripheral portion of the fetal lung was excised with a scalpel and subjected to enzymatic digestion and microdissection. The epithelium was dissected and separated from the mesenchyme, but a small amount of associated mesenchyme likely remained.   <br>Fetal progenitor organoid         3D organoid structures that arose from culturing isolated fetal epithelial bud tips.                                                                                                                                                                            <br>Foregut spheroid                     3D foregut endoderm structure as described in Dye et al. (2015). Gives rise to patterned lung organoid (PLO) when grown in 3F medium.            <br> Patterned lung organoid (PLO)  lung organoids that were generated by differentiating hPSCs, as described throughout the manuscript.    <br> Bud tip organoid                      organoids derived from PLOs, enriched for SOX2/SOX9 co-expressing cells, and grown/passaged in 3F medium.	Co-expression
ERP111913	RNA-seq from knee and hip osteoarthritis cartilage	In total, 70 samples on macroscopically preserved and lesioned OA cartilage from the same patient was taken for RNA-seq. Subsequently, paired-end 2×100 bp RNA library sequencing (Illumina TruSeq RNA Library Prep Kit, Illumina HiSeq 2000 and TruSeq Stranded Total RNA LT Sample Prep Kit, Illumina HiSeq 4000) was performed.	Co-expression
ERP111914	Transcriptome comparison of human Extra-thymic AIRE expressing cells to medullary thymic epithelial cells and conventional antigen presenting dendritic cells.	The provenance of eTACs is unknown, and their characterisation in humans is currently absent.  Using bulk RNA sequencing we compare the endogenous expression capacity for self-antigens between eTACs, mTECs and cDCs.	Co-expression
ERP112241	RNA-seq of human breast cancer cell lines: CAL120; MDAMB468 and BT549 incubated in DMEM-F12 and Plasmax in normoxia (21%O2) and hypoxia (0.1% O2)	To compare the effect of different culture media on gene expression in multiple cell lines under different oxygen availability.	Co-expression
ERP112291	RNA seq. of lung cancer tumors	Gene expression in treatment-naive pathologic stage I non-small cell lung cancer tumors that were resected from patients was examined by RNA sequencing.	Co-expression
ERP112312	RNA-seq of HER2-positive breast cancer BT474 cell line in response to KDM5 ihibition	Alterations in the histone methylation profiles are observed in various types of cancer and targeting of this epigenetic process has therapeutic potential. Here we provide proof-of-principle that pharmacological targeting of KDM5 histone-demethylases is a new strategy for the personalized treatment of HER2-positive breast cancer.  This analysis demonstrates that cells characterized by HER2-positivity are particularly sensitive to KDM5 inhibition. The results are confirmed in an appropriate in vivo model with a close structural analogue (KDM5-inh1A). In selected HER2-positive breast cancer cells, we demonstrate synergistic interactions between KDM5-inh1 and HER2-targeting agents (trastuzumab and lapatinib). In addition, HER2-positive cell lines showing innate/acquired resistance to trastuzumab show sensitivity to KDM5-inh1. The levels of KDM5A/B/C proteins, which are selectively targeted by the agent, have no significant association with KDM5-inh1 responsiveness across our panel of breast cancer cell lines, suggesting the existence of other determinants of sensitivity. Using RNA-sequencing data of the breast cancer cell lines, we generate a gene-expression model, consisting of fifteen genes, which is a robust predictor of KDM5-inh1 sensitivity. In a test set of breast cancers, this model correctly predicts sensitivity to the compound in a large fraction of HER2+ tumors. In conclusion, KDM5 inhibition has potential in the treatment of HER2+ breast cancer and our gene-expression model can be developed into a diagnostic tool to select patients who may benefit from treatments based on KDM5-inhibitors.	Co-expression
ERP112500	RNA-seq of TCF4 silencing in A431 cells	TCF4 was silenced in cutaneous squamous cell carcinoma of A431 cells, and detected the mRNA profiles compared to the negative control and blank control.	Co-expression
ERP112503	RNA-seq profiling of NSCLC cell lines exposed to the PARP inhibitor talazoparib.	An isogenic model of ERCC1-deficiency derived from the A549 NSCLC cell line was used for this study; this model consists of an ERCC1-wildtype parental cell line and an ERCC1-knockout cell line  that was generated by zinc-finger targeting of ERCC1 gene. Both cell lines were exposed to the PARPi talazoparib or DMSO (vehicle) for 48h in culture. For each condition, RNA was extracted from cells and subsequently sequenced on a HiSeq 2500 platform (Illumina).	Co-expression
ERP112510	Transcriptome analysis of AML samples at diagnosis and relapse after Hematopoietic Stem Cell Transplantation (HSCT)	Transcriptome profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.	Co-expression
ERP112751	The LL-100 panel: 100 DSMZ cell lines for blood cancer studies; RNA-Seq	For many years, immortalized cell lines have been used as model systems for cancer research. Cell line panels were established for basic research and drug development, but did not cover the full spectrum of leukemia and lymphoma. Therefore, we now developed a novel panel (LL-100), 100 cell lines covering 22 entities of human leukemia and lymphoma including T-cell, B-cell and myeloid malignancies. Importantly, all cell lines are unequivocally authenticated and assigned to the correct tissue. Cell line samples were proven to be free of mycoplasma and virus contamination. Whole exome sequencing (WES) and RNA sequencing (RNA-seq) of the hundred authenticated leukemia-lymphoma cell lines were conducted with a uniform methodology to complement existing data on these publicly available cell lines. This part captures RNA-Seq. This data set will be useful for understanding the function of oncogenes and tumor suppressor genes and to develop targeted therapies.	Co-expression
ERP112773	A single agent induces apoptosis of AML blasts and prolongs survival in AML xenograft models.	To improve outcomes for pediatric AML, identifying novel agents with tolerable side effect profiles is critical. Recently, an agent has been shown to reduce signaling of myeloid lineage cells. This FDA-approved drug is well tolerated and has known pediatric dosing that achieves plasma concentrations of 40-80µM. We conducted pre-clinical testing of this agent with AML cell lines and pediatric patient samples. Cell lines demonstrated time and dose-dependent induction of apoptosis.	Co-expression
ERP112787	Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair	The melanocytic lineage, which is prominently exposed to ultraviolet-radiation (UVR) and radiation-independent oxidative damage, requires specific DNA-damage response mechanisms to maintain genomic and transcriptional homeostasis. The coordinate lineage-specific regulation of intricately intertwined DNA repair and transcription is incompletely understood. Here we demonstrate that the Microphthalmia-associated transcription factor (MITF) directly controls general transcription and UVR-induced nucleotide excision repair by transactivation of GTF2H1 as a core element of TFIIH. Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. Moreover, MITF controls c-MYC implicated in general transcription by transactivation of far upstream binding protein 2 (FUBP2/KSHRP), which induces c-MYC pulse regulation through TFIIH, and experimental depletion of MITF results in consecutive loss of CDK7 in the TFIIH-CAK subcomplex. Targeted for proteasomal degradation, CDK7 is dependent on transactivation by MITF or c-MYC to maintain a steady state. The dependence of TFIIH-CAK on sequence-specific MITF and c-MYC constitutes a previously unrecognized mechanism feeding into super-enhancer-driven or other oncogenic transcriptional circuitries, which supports the concept of a transcription-directed therapeutic intervention in melanoma.	Co-expression
ERP112912	Recurrent activating STAT5B N642H mutations in myeloid neoplasms with eosinophilia	Whole transcriptome sequencing (RNAseq) of 14 cases with suspected primary eosinophilia was performed to identify recurrent mutations which could be used as new diagnostic and prognostic markers as well as potential targets for therapy.	Co-expression
ERP113092	Variation in RNA expression in a panel of 30 breast cancer cell lines	RNA expression was measured using RNA sequencing in 30 different breast cancer cell lines, under untreated, exponentially growing conditions.	Co-expression
ERP113133	Placenta transcriptome profiling in Intrauterine Growth Restriction (IUGR)	The aim of the  current research was to broaden the knowledge about the transcriptomic complexity of the human placenta by identifying genes potentially involved in IUGR pathophysiology.	Co-expression
ERP113252	Regional differences in human biliary tissues and corresponding in vitro derived organoids	RNA-Sequencing was performed on mechanically dissociated, epithelial-enriched samples, of human extrahepatic biliary tissue from Gallbladder, Common Bile Duct, and Pancreatic Duct tissues. Sequencing was also performed on in vitro cultures of Organoid cell lines at passage 5 that were derived from human Gallbladder, Common Bile Duct, Pancreatic Duct, or Intrahepatic Bile Ducts.	Co-expression
ERP113396	RNA-sequencing of inflamed intestinal mucosa of inflammatory bowel disease patients	Studying differences in responders and non-responders to therapy in inflammatory bowel disease (IBD) patients (crohn's disease and ulcerative colitis)	Co-expression
ERP113438	RNAseq of proneural glioblastoma stem-like cells 72 hours after infection with human cytomegalovirus (CMV) Towne strain	This study was performed in order to determine the gene expression changes associated with CMV infection of glioblastoma cells. CMV has been associated with gliobalstoma but its effects are not well characterized.	Co-expression
ERP113498	Population RNA-seq of human ESC-derived cardiac derivatives	In vitro cardiac differentiation of human ESCs recapitulates in vivo embryonic heart development, and thus, serves as an excellent tool to investigate human cardiac development. Identification of molecular signatures during cardiac differentiation of human ESCs is instrumental for advancing our understanding of human cardiogenesis. We, as well as others have improved cardiac differentiation protocols significantly in recent years; however, detailed molecular mechanisms involved in cardiac lineage commitment have not yet been clearly defined. Based on this, we tried to identify the cellular hierarchies and molecular signatures of each of the in vitro human ESC-differentiating cardiac cell lineages through the well-established cardiac differentiatio protocol by Wnt signaling modulation and the FACS-sorted population RNA-seq analyses.	Co-expression
ERP113593	RNA-seq of human cardiovascular endothelial cell line HUVEC, treated with different media	Human cardiovascular endothelial cells were treated with different media for seven days. Subsequently, total RNA was isolated and purified. After rRNA removal, the samples were sequenced using HiSeq3000 (Illumina).	Co-expression
ERP113770	Establishment of Porcine and Human Expanded Potential Stem Cells (bulk RNA-seq)	Despite intensive efforts, establishing porcine embryonic stem cells has been challenging. We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the activity of critical molecular pathways that predisposes lineage differentiation in the mouse preimplantation embryo. EPSCs had enriched molecular signatures of blastomeres and possessed the developmental potency to all embryonic and extraembryonic cell lineages. In this study, we report the derivation of porcine EPSC (pEPSC) lines either directly from preimplantation embryos or by reprogramming fetal fibroblasts. Under similar culture conditions, human ESCs and iPSCs can be converted, or somatic cells are directly reprogrammed, to EPSCs (hEPSCs) that display the molecular and functional attributes reminiscent of pEPSCs. Here, we performed RNA-seq experiments to characterise the transcriptional signatures of the EPSCs.	Co-expression
ERP113862	Extracellular proteins from Lactobacillus acidophilus are essential immunomodulatory players in Crohn Disease	In this study, the response of human immune cells to the extracellular proteins secreted by L. acidophilus is adressed. RNASeq is used to show how these proteins are able to shift the global immune response in Monocyte-derived dendritic cells.	Co-expression
ERP113881	Transcriptome profiling of primary skin fibroblasts reveal distinct molecular features between PLOD1- and FKBP14-kyphoscoliotic Ehlers-Danlos Syndrome	Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS) is a rare heritable disease characterised by congenital muscle hypotonia, kyphoscoliosis and joint hypermobility. Pathogenic variants of kEDS include mutations in PLOD1 or FKBP14 genes. PLOD1 encodes lysyl hydroxylase 1 enzyme which hydroxylates lysine residues in the collagen helix, allowing glycosylation and crosslinking that contribute to fibril strength, while FKBP14 encodes a peptidyl-prolyl cis-trans isomerase that catalyses collagen folding and acts as a chaperone for types III, VI and X collagen. We aim to better characterise the pathology of kEDS in order to distinguish the molecular features underlying PLOD1-kEDS and FKBP14-kEDS despite overlapping phenotypes to facilitate diagnosis, and to identify novel molecular targets that may expand treatment strategies. Transcriptome profiling by RNA-sequencing of patient-derived skin fibroblasts revealed differential expression of genes encoding extracellular matrix components that are unique between PLOD1-kEDS and FKBP14-kEDS. Furthermore, we identified genes involved in inner ear development, vascular remodelling, ER stress and protein trafficking that were differentially expressed in patient fibroblasts compared to controls. Overall, our study presents the first transcriptomics data in kEDS revealing distinct molecular features between PLOD1-kEDS and FKBP14-kEDS and serves as a tool to better understand the disease pathology.	Co-expression
ERP113943	Elucidation of purine-9 methylation in human nucleo-cytoplasmic tRNAs	The TRM10 family of methyltransferases is responsible for the methylation of position 9 in tRNAs in Archaea and Eukarya. The human genome encodes three enzymes of the family, of which only the mitochondrial form TRMT10C was previously characterized, whereas the function and the targets of TRMT10A and TRMT10B were not investigated so far. Here we show that TRMT10A and TRMT10B methylate a subset of nuclear-encoded tRNAs in human cells; the two enzymes have a completely distinct repertoire of targets, and show no functional redundancy. Remarkably, TRMT10A is guanosine-9 specific and methylates 11 distinct tRNAs, whilst TRMT10B is the first identified adenosine-9-specific tRNA methyltransferase in eukaryotes and methylates a single tRNA. Furthermore, we show that the lack of G9 methylation causes a decrease in the steady-state levels of the initiator tRNAiMet‑CAT, and an alteration in its further post-transcriptional modification. In conclusion, our work sheds light on the function in vivo of the members of the TRM10 family, and provides evidence that the loss of TRMT10A can affect the cellular translation machinery.	Co-expression
ERP114104	Altered Gene Expression in Antipsychotic Induced Weight Gain	We sequenced the transcriptome of two cohorts of first episode schizophrenia patients before and after three months of treatment with antipsychotics. The first cohort, or the “weight gain” group, included 18 individuals who gained more than 1.5 points of BMI after the treatment. The second cohort, the “no weight gain” group, also included  18 individuals with a change in BMI after the treatment between 1.0 and -1.0 points.	Co-expression
ERP114122	Variation and genetic control of chromatin architecture in humans (RNAseq)	This data set comprises population (46 samples) measurements of RNA expression levels for a subset of the 1000 Genomes Project CEPH samples. This data was generated as part of the following study: - Population Variation and Genetic Control of Modular Chromatin Architecture in Humans. Cell. 2015 Aug 27;162(5):1039-50. doi: 10.1016/j.cell.2015.08.001. Epub 2015 Aug 20.  An additional set of 111 samples from the 1000 Genomes Project (GBR and TSI populations) were also assayed using RNA-seq. This data was generated as part of the following study: - Chromatin 3D interactions mediate genetic effects on regulatory networks.	Co-expression
ERP114127	RNAseq of human cell line RPCI-WM1 comparing artificial PRDM1-targeting miRNA to non-targeting control, and comparing Tazemetostat treatment to DMSO. ChIPseq for the factors BLIMP1 and H3K27me3 in the RPCI-WM1, OPM-2 and NCI-H929 cell lines, along with ChIPseq for EZH2 in the NCI-H929 cell line.	To identify the role of BLIMP1 in Waldenström's macroglobulinemia, the PRDM1 transcript was targeted using an artificial miRNA. RNAseq was used to compare it to a non-targeting control in the RPCI-WM1 cell line. To determine the role of EZH2 in Waldenström's macroglobulinemia, the RPCI-WM1 cell line was treated with 0.3µM of the EZH2 inhibitor Tazemetostat, compared to DMSO vehicle control by RNAseq. ChIPseq was performed for the factors BLIMP1 and H3K27me3 in the RPCI-WM1, OPM-2 and NCI-H929 cell lines, along with ChIPseq for EZH2 in the NCI-H929 cell line.	Co-expression
ERP114128	RNA-seq in GR18 cell line to identify genes regulated by the Glucocorticoid Receptor (24h treatment)	To identify the genes regulated by the Glucocorticoid Receptor (GR), we performed RNA-seq in GR18 cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for GR), upon glucocorticoid (dexamethasone) or vehicle (ethanol) treatment for 24 hours.	Co-expression
ERP114243	Illumina RNA-seq of polyA+ RNA from HAP1 cells	Illumina RNA-seq was performed on polyA+ RNA isolated from the human HAP1 cell line	Co-expression
ERP114262	Transcriptomic analysis by AmpliSeq Ion Torrent to explore the effects of the long non-coding RNA TGFB2-AS1 on gene expression in human keratinocytes	TGFB2-AS1 is a long non-coding RNA which is induced by ΤGFβ signaling. In order to assess the importance of TGFB2-AS1 on the regulation of gene expression, we performed an AmpliSeq transcriptomic array in human keratinocytes (HaCaT), which stably over-express TGFB2-AS1 or control pcDNA3 empty vector. In addition, cells were stimulated with TGFβ1 for 24 hours, in order to observe the effects of TGFB2-AS1 on gene expression, downstream of TGFβ signaling. RNA from the following four conditions was used in this experiment: 1) pcDNA3, 2) pcDNA3+TGFβ1, 3) pcDNA3-TGFB2-AS1, 4) pcDNA3-TGFB2-AS1+TGFβ1. Biological triplicates were used per condition.	Co-expression
ERP114365	RNA-Seq of human U87MG-GFP cells from sub-cutan xenografts as a function of distance from blood vessels	We devised a novel methodology for sorting stroma-free tumor cells according to their relative distance from BVs by injecting a vascular perfusion marker (Hoechst 33342). Briefly, post 4 weeks of sub cutaneous implantation of U87MG-GFP cell line into dorsal flank of NOD-SCID mice, the mice were injected i.v. with Hoechst dye. Mice sacrificed, tumors retrieved, single cell dissociated and FACS sorted to isolate cells located at progressive distance from blood vessels based on perfusion dye intake. Three fractions namely - Hh (close to BVs), Hm (intermediate) and Hl (farther from BVs) were FACS sorted. RNA was extracted from the sorted cells and RNA-Sequencing performed.	Co-expression
ERP114370	mRNA-seq for HCT116 Parental and ARID1A knockdown cells, mRNA-seq for DLD1 Parental, ARID1A knockdown and ARID1A knockout cells, mRNA-seq for COLO320DM Parental and ARID1A knockdown and ARID1A knockout cells	The study identifies genes that are regulated by the loss of the chromatin remodeller subunit ARID1A in colorectal cancer cell lines. This gene is  frequently mutated in colorectal cancer.	Co-expression
ERP114386	Fractionation RNAseq in conjunction with Illumina TRUseq method	H9 human ESCs (H9 line) were cultured in BMP4 cultured medium on Matrigel-coated plates. Colonies were passaged for maintanence by Gentle Cell Dissociation Reagent	Co-expression
ERP114387	RNAseq libraries to study early developmental progenitors (24hrs differentiation vs hESCs)	Illumina TRUseq method to generate highly strand-specific next-generation sequencing (NGS) libraries	Co-expression
ERP114425	Integrative analysis of single-cell expression data reveals distinct regulatory states in bidirectional promoters.	Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs.We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles.Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.	Co-expression
ERP114435	Infection of naïve primary human B-lymphocytes with Epstein-Barr virus (EBV) – time course transcriptomic analysis in the pre-latent phase of viral infection	B cells from anonymous adenoid donors were isolated and sorted for naïve B cells, which were subsequently infected with a reference EBV strain (2089_B95-8) using a defined multiplicity of infection. Infection of resting B cells with EBV induces their activation, their proliferation, and subsequent immortalization giving rise to lymphoblastoid cell lines (LCL) in vitro. Non-infected primary B-lymphocytes immediately after preparation (day 0) and at early time points post infection (day 1, 2, 3, 4, 5, 8, and 14) were collected and total RNAs were prepared. We performed time course RNA-seq experiments and assessed the expression kinetics of viral (EBV_2089) and cellular genes (Hg19) in these cells that show impressive phenotypic alterations over time.  The experiment revealed the very dynamic regulation of viral and cellular genes that could be grouped into six clusters of transcriptional regulation documenting the cellular response to viral infection and the virally induced cell reprogramming and transformation.	Co-expression
ERP114480	RNA-seq in Raji cells with inducible BZLF1 prior to and after induction of EBV's lytic cycle by doxycycline	(i) RNA transcripts of Raji iBZLF1 cells (https://www.biorxiv.org/content/10.1101/573659v1) were compared between non-induced cells and cells induced with doxycycline (100 ng/ ml) for 6 h. Human (Hg19) as well as viral (EBV, Raji KF717093.1) transcripts were analyzed. Artificial ERCC Spike-ins (Thermo Scientific) were added to selected samples to control for global changes of RNA levels.  (ii) For control purposes, the RNA transcripts in Raji cells equipped with a doxycycline-controlled truncated BZLF1 allele lacking its transactivation domain (Raji iBZLF1 AD-truncated) were prior to and after induction for 6 h. (iii) For another control, the RNA transcripts of parental, unmodified Raji cells were analyzed prior to and after doxycycline induction for 6 h.  All experiments were performed as triplicates.	Co-expression
ERP114921	RNA-seq of H1N1 infected monocyte-derived dendritic cells (MoDC), stimulated with single-stranded oligonucleotides (ssON) and/or Poly I:C.	Evaluation of modulation of the innate immune response during H1N1 infection. The modulatory effect of Single-stranded oligonucleotides (ssON) on monocyte-derived dendritic cells (MoDCs) are evaluated. RNAseq data are used to study the effect on the transcriptome of MoDCs, during infection with simultaneous addition of ssON. Further mechanistic information are added via RNAseq data on poly I:C stimulated MoDCs (Toll-Like Receptor 3 agonist). Control samples are included to perform differential expression analysis.  Provided are the fastq files, obtained in the following manner: The RNA sequencing was performed with the TruSeq RiboZero kit from Illumina, 25 M reads per sample and 2x125bp. Read quality were assessed using FastQC (Version 0.11.5) Trim Galore (Version 0.3.6) was used for adapter removal and quality trimming with a quality threshold of 20 on the Phred scale.   Count files was created out of the trimmed  fastq by mapping high-quality reads to Homo sapiens UCSC hg38 (GRCh38.77) reference genome using STAR aligner (version 2.5) with default values and the parameter out Reads Unmapped set to Fastx in order to extract the unmapped reads. After STAR alignment, the count data for the aligned reads were generated with HTSeq-count (version 0.6.1). The-m parameter was set to union.	Co-expression
ERP114936	RNA-Seq of human lymph node stromal cells during the earliest phases of rheumatoid arthritis	Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially expressed genes between RA at risk or RA versus healthy using RNA sequencing in order to identify new therapeutic targets.	Co-expression
ERP115010	Blood RNAseq of TB contacts samples	Blood RNAseq data of tuberculosis contact samples. Contacts of patients with active pulmonary and extrapulmonary TB, with a cumulative duration of exposure of greater than eight hours in a confined space to the index case prior to initiation of treatment, were invited to participate from multiple UK TB clinics. At enrolment, IGRAs were done using the QuantiFERON-TB Plus assay (Qiagen, Hilden, Germany), and peripheral blood RNA was collected into TempusTM tubes for genomewide transcriptional profiling by RNA sequencing.	Co-expression
ERP115027	RNA-seq analyses of OCI-Ly10 cell lines transduced by doxycycline-inducible lentiviral vectors expressing SPI1 WT or mutant proteins	To characterize the functional consequences of mutant or WT binding	Co-expression
ERP115046	RNASeq of human mesenchymal stem cells (6 donors) with and without treatment with 1 hour of cyclic tensile strain (2.6 – 6.2% strain, 5.0 Hz).	Understanding how cells respond to and cope with high levels of mechanical stress is important to gain a better understanding of mechano-biology, both in health and disease. The experiment was designed to assess the total mRNA levels in mechanically stimulated cells and was used, in conjunction with mass spectrometry data, to gain an insight into the systemic response to high-intensity mechanical strain.  Here, total RNA was extracted from human mesenchymal stem cells (n=6) following 1 hour of cyclic tensile strain (2.6 – 6.2% strain, 5.0 Hz) using a Flexcell Tension Plus device. RNA from unstrained cells was used as control. The protein coding RNAs were then sequenced with Illumina HiSeq technology.	Co-expression
ERP115185	RNA-seq to investigate YBX3 siRNA knockdown in HeLa cells	This study identifies the transcriptomic effects of YBX3 depletion after 2 days of siRNA knockdown. Unspecific siRNA and untreated cells were used as controls. The cells were grown in SILAC media and the effects on protein levels were measured by mass spectrometry. Also an eCLIP (E-MTAB-5888) experiment was performed to identify RNA targets of YBX3.	Co-expression
ERP115228	RNA-seq of circulating Tfh like cells at day zero and seven relative to seasonal influenza vaccination	RNA sequencing of 200 ICOS+CD38+CXCR5+PD-1+ cTfh cells immediately prior to, and seven days after influenza vaccination in four individuals	Co-expression
ERP115250	Timeline RNAseq of fibroblast to neuron direction conversion	Timeline RNAseq to identify gene expression dynamics over the course of conversion of fibroblasts into induced neurons.	Co-expression
ERP115406	RNA-seq timeline of fibroblast to neuron conversion using traditional NC media and NC+ZPAK media	Bulk RNA was extracted via trizol at Fibroblasts stage, 5 days, 10 days, 15 days, and 20 days of fibroblast to neuron conversion using traditional NC media, or NC media supplemented with ZM336372, pyrintegrin, AZ960, and KC7F2	Co-expression
ERP115551	Transcriptome analysis of human brain microvascular endothelial cells response to Neisseria meningitidis and its antigen MafA using RNA-seq	Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with Neisseria meningitidis or its ligand MafA .	Co-expression
ERP115758	Transcriptome analysis of human brain microvascular endothelial cells response to Borrelia burgdorferi and its antigen Erp23 using RNA-seq	Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with Borrelia burgdorferi   or its ligand Erp23.	Co-expression
ERP115772	Transcriptome analysis of human brain microvascular endothelial cells response to Streptococcus pneumoniae and its antigen Adhesion lipoprotein using RNA-seq	Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with Streptococcus pneumoniae or its ligand Adhesion lipoprotein.	Co-expression
ERP115774	Transcriptome analysis of human brain microvascular endothelial cells response to interactive DIII domain of protein E of WNV and interactive DIII domain of protein E of TBEV using RNA-seq	Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with DIII domain of protein E of WNV and  DIII domain of protein E of TBEV.	Co-expression
GDS1012	Idiopathic and scleroderma-associated pulmonary fibrosis derived fibroblasts response to TGFbeta	Analysis of adult lung fibroblasts treated with 4 ng/ml TGFbeta cytokine for 4 hours. Fibroblasts obtained from patients with idiopathic or scleroderma-associated pulmonary fibrosis. Results provide insight into the role of TGFbeta in pulmonary fibrosis.	Co-expression
GDS1020	Post-traumatic stress disorder development	Expression profiling of peripheral mononuclear blood cells (PMBC) from patients with post-traumatic stress disorder. PMBC samples obtained from patients a few hours and 4 months after exposure to psychological stress.	Co-expression
GDS1022	Lung pneumocyte response to Pseudomonas aeruginosa type III secretion system mutants	Analysis of A549 lung pneumocytes after infection with Pseudomonas aeruginosa (PA) PAK mutants deleted for various components of the type III secretion system (TTSS).  Mutants in TTSS effectors and translocators studied.  PA causes serious respiratory infections in cystic fibrosis patients.	Co-expression
GDS1023	Hematopoietic stem cell engraftment in goat	Human-goat chimerism achieved by transplanting human CD34+Lin- cord blood cells into fetal goats. Markers indicate human genes expressed in goat liver and blood. Human/goat hematopoietic stem cell (HSC) xenogeneic model allows analysis of HSC transplantation, expansion and differentiation in vivo.	Co-expression
GDS1028	Severe acute respiratory syndrome expression profile	Expression profiling of peripheral blood mononuclear cells (PBMC) from 10 adult patients with severe acute respiratory syndrome (SARS). Results provide insight into the host immune response to the SARS coronavirus.	Co-expression
GDS1036	Microglial cell response to interferon-gamma: time course	Expression profiling of microglial cells obtained from 4 different samples following treatment with 200 u/ml interferon-gamma (IFN-gamma).  Cells examined 1, 6, and 4 hours after treatment.  Results provide insight into the regulation of immune functions in microglia by IFN-gamma.	Co-expression
GDS1048	Lymphoblastoid cell lines from CEPH/Utah families	Expression profiling of lymphoblastoid cell lines from 15 CEPH/Utah families.  Cell lines from 3 generations examined.  Results provide insight into the heritability of gene expression traits in segregating human populations.	Co-expression
GDS1050	Valproic acid effect on theca cells (HG-U133A)	Analysis of normal theca cells treated with 500 uM valproic acid (VPA), an anti-epilipetic that induces polycystic ovary syndrome (PCOS)-like symptoms. Theca cells from PCOS patients also examined. Results provide insight into the underlying mechanisms contributing to VPA-induced PCOS-like symptoms.	Co-expression
GDS1051	Valproic acid effect on theca cells (HG-U133B)	Analysis of normal theca cells treated with 500 uM valproic acid (VPA), an anti-epilipetic that induces polycystic ovary syndrome (PCOS)-like symptoms. Theca cells from PCOS patients also examined. Results provide insight into the underlying mechanisms contributing to VPA-induced PCOS-like symptoms.	Co-expression
GDS1059	Acute myeloid leukemia response to chemotherapy	Analysis of mononuclear cells from 54 chemotherapy treated patients less than 15 years of age with acute myeloid leukemia (AML). Mononuclear cells taken from peripheral blood or bone marrow. Results identify expression patterns associated with complete remission and relapse with resistant disease.	Co-expression
GDS1062	Squamous cell carcinoma of the oral cavity with lymph node metastasis	Expression profiling of 18 primary squamous cell carcinomas of the oral cavity with or without lymph node metastasis. Expression in lymph node metastasis also examined. Results used to identify gene expression signature in primary tumors that indicates the presence of lymph node metastasis.	Co-expression
GDS1063	Primary effusion lymphomas and associated viral infections	Analysis of Kaposi's sarcoma-associated herpesvirus (KSHV) positive mononuclear cells from 3 patients with primary effusion lymphoma (PEL), 9 KSHV positive PEL cell lines, and 3 KSHV negative cell lines from lymphomatous effusions.  Effect of concomittant Epstein-Barr virus infection also examined.	Co-expression
GDS1064	Acute myeloid leukemia subclasses	Expression profiling of bone marrow from 43 patients with various forms of acute myeloid leukemia (AML): 10 promyelocytic leukemias with t(15;17), 4 AMLs with inv(16), 7 monocytic leukemias, and 22 nonmonocytic leukemias.  Results identify expression signatures unique to each AML subclass.	Co-expression
GDS1065	Mitochondrial encephalomyopathies associated with mitochondrial DNA mutations	Analysis of muscle from 12 patients with various forms of mitochondrial encephalomyopathies associated with mitochondrial DNA mutations: 8 patients with a A3243G mutation, and 4 patients with a 4977 base pair deletion. Results identify possible expression signature for mitochondrial disorders.	Co-expression
GDS1067	Plasma cell dyscrasias	Expression profiling of plasma cells from patients with plasma cell dyscrasias: 7 with monoclonal gammopathy of undetermined significance, 39 with multiple myeloma (MM), and 6 with plasma cell leukemia.  Results provide insight into the neoplastic transformation of plasma cells in MM.	Co-expression
GDS1074	AML1-ETO fusion protein effect on CD34+ hematopoietic cells	Analysis of CD34+ hematopoietic cells expressing the AML1-ETO fusion protein which is formed in acute myeloid leukemia (AML) from translocation t(8;21). CD34+ cells isolated from peripheral blood progenitor and cord blood cells. Results provide insight into the role of AML1-ETO in leukemogenesis.	Co-expression
GDS1078	E2F-1 overexpression effect on melanoma cells	Expression profiling of SKMEL-2 melanoma cells overexpressing the transcription factor E2F-1. E2F-1 overexpression induces apoptosis in many tumor cells. Results provide insight into the mechanisms underlying E2F-1 induced apoptosis in melanoma cells.	Co-expression
GDS1085	Normal tissues of diverse types (SHBW)	Expression profiling of 115 samples from 35 different types of normal tissues. Samples obtained by surgery or autopsy, and evaluated by pathologists. Results provide insight into the molecular organization of diverse cell types, and provide a baseline for comparison to diseased tissues.	Co-expression
GDS1088	Normal tissues of diverse types (SHDP)	Expression profiling of 115 samples from 35 different types of normal tissues. Samples obtained by surgery or autopsy, and evaluated by pathologists. Results provide insight into the molecular organization of diverse cell types, and provide a baseline for comparison to diseased tissues.	Co-expression
GDS1094	Estrogen receptor alpha/beta heterodimer action in response to estrogen and tamoxifen	Expression profiling of U2OS osteosarcoma cell line expressing estrogen receptor/alpha heterodimer after treatment with 10 nM 17beta-estradiol (E2) or 10 nM 4-OH tamoxifen (4HT) for 24 hours. Results provide insight into the role of estrogen receptor/alpha heterodimer in gene regulation.	Co-expression
GDS1095	Hematopoeitic stem cells of various types	Expression profiling of Lin-CD34-, Lin-CD34+, and Lin+CD34+ peripheral blood hematopoeitic stem cells (HSCs). Results provide insight into the molecular basis of the association of CD34 expression with self-renewal and lineage commitment in HSCs.	Co-expression
GDS1096	Normal tissues of various types	Expression profiling of 36 types of normal tissue. Each RNA tissue sample pooled from several donors.  Results identify tissue specific genes and provide baselines for interpreting gene expression in cancer.	Co-expression
GDS1112	Glaucomatous astrocytes from the optic nerve head	Expression profiling of astrocytes taken from the optic nerve head (ONH) of patients with glaucoma. The ONH is the site of damage in glaucomatous optic neuropathy. Studies suggest that damage in glaucoma is mediated by reactive astrocytes.	Co-expression
GDS12	Bone marrow stromal cell lines	Examination of two functionally distinct human bone marrow stromal cell lines, HS-27a and HS-5. Four independent RNA samples from each cell line analyzed.	Co-expression
GDS1204	Lung cancer cell line response to motexafin gadolinium: time course	Expression profiling of lung cancer cell line A549 following treatment with 50 uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd). Cells examined at 4, 12, and 24 hours following treatment. Results provide insight into the mechanism of action of MGd.	Co-expression
GDS1209	Sarcoma and hypoxia	Expression profiling of soft tissue sarcoma samples. Hypoxic regions often develop in tumors as they increase in size. Results provide insight into the expression of hypoxia-related genes in sarcomas.	Co-expression
GDS1210	Gastric cancer	Expression profiling of 22 primary advanced gastric cancer tissues. Whole gastric cancer tissues examined in the presence of metastasis and according to histological type. Results provide insight into the progression and diversity of gastric cancer.	Co-expression
GDS1212	Tumor necrosis factor effect in the absence of NF-kappaB activity: time course	Temporal analysis of the effect of tumor necrosis factor (TNF)  on gene expression in HeLa cells with NF-kappaB inactivated. NF-kappaB inactivated with 2 ug/ml doxycycline. Cells examined at various time points following stimulation with 25 ng/ml TNF. Results identify potential targets of NF-kappaB.	Co-expression
GDS1215	Acute myeloblastic leukemia cells response to all trans retinoic acid and valproic acid	Analysis of acute myeloblastic leukemia (AML) cell line, OCI/AML-2, following treatment with valproic acid (VPA) and all trans retinoic acid (ATRA). VPA inhibits histone deacetylase. Results provide insight into the responsiveness of AML cells to ATRA when VPA is present.	Co-expression
GDS1220	Malignant pleural mesothelioma	Expression profiling of malignant pleural mesothelioma (MPM) tumors. MPM is a highly lethal malignancy associated with asbestos exposure. Results provide insight into the pathogenesis of MPM.	Co-expression
GDS1221	Chronic myelogenous leukemia response to imatinib	Analysis of peripheral blood and bone marrow of chronic myelogenous leukemia (CML) patients prior to imatinib (Gleevec) treatment. Imatinib induces complete cytogenetic response (CCR) in most CML patients. This study attempts to determine transcriptional signature of imatinib non-responders.	Co-expression
GDS1230	Hematopoietic stem cell and progenitor cell comparison (HG-U133A)	Comparison of CD34+CD33-CD38-Rho(lo)c-kit+ cells, enriched for hematopoietic stem/progenitor cells (HSC), to CD34+CD33-CD38-Rho(hi) cells, enriched for committed hematopoietic progenitor cells (HPC). Cells obtained from umbilical cord blood and bone marrow. Provides insight into control of HSC fate.	Co-expression
GDS1231	Hematopoietic stem cell and progenitor cell comparison (HG-U133B)	Comparison of CD34+CD33-CD38-Rho(lo)c-kit+ cells, enriched for hematopoietic stem/progenitor cells (HSC), to CD34+CD33-CD38-Rho(hi) cells, enriched for committed hematopoietic progenitor cells (HPC). Cells obtained from umbilical cord blood and bone marrow. Provides insight into control of HSC fate.	Co-expression
GDS1235	Pediatric acute lymphoblastic leukemia subtypes	Expression profiling of bone marrow from pediatric patients with acute lymphoblastic leukemia (ALL). 10 B-cell ALL, 5 T-cell ALL, and 3 B-cell ALL, with the MLL/AF4 chromosomal rearrangement, patients examined. Results provide insight into the pathogenesis of childhood ALL.	Co-expression
GDS1237	Promyelocytic cell response to Anaplasma phagocytophilum infection	Expression profiling of NB4 promyelocytic leukemic cells infected with Anaplasma phagocytophilum, an obligate intracellular bacterium that causes granulocytic anaplasmosis. NB4 is a model for neutrophil maturation. Results provide insight into host cellular pathways affected by A. phagocytophilum.	Co-expression
GDS1249	Toll-like receptor agonists synergistic effect on dendritic cells: time course	Temporal analysis of monocyte-derived dendritic cells (DCs) treated with lipopolysaccharide (LPS), an agonist for toll-like receptor (TLR) 4, the synthetic imidazoquinoline resiquimod R848, an agonist for TLR8, or both. Provides insight into the synergistic effect of TLR agonists in activating DCs.	Co-expression
GDS1250	Atypical ductal hyperplasia and breast cancer	Comparison of atypical ductal hyperplasia (ADH) tissues from patients with and without a history of breast cancer. Incidence of invasive breast cancer is high in ADH patients. Results identify putative markers of invasive breast cancer.	Co-expression
GDS1252	Idiopathic pulmonary fibrosis	Expression profiling of lung tissues from patients with idiopathic pulmonary fibrosis (IPF), a progressive and lethal disorder characterized by the abnormal formation of fibrous scar tissue in the lungs. Results provide insight into the pathogenesis of IPF.	Co-expression
GDS1253	Pituitary adenoma subtypes	Expression profiling of 4 pituitary adenoma subtypes. Growth hormone (GH), prolactin (PRL), and adrenocorticotrophin (ACTH) secreting pituitary adenomas, and non-functioning pituitary adenoma examined. 5 specimens pooled and examined for each subtype. Results provide insight into tumor pathogenesis.	Co-expression
GDS1256	IFN-gamma inflammatory effect on bronchial epithelial cells modulated by dexamethasone: time course	Analysis of bronchial epithelial cells treated with interferon (IFN) gamma, or dexamethasone (dex), or both. IFN-gamma plays a role in lung inflammatory responses and corticosteroids such as dex are used as treatments for inflammation. Cells examined 8 or 24 hours after treatment.	Co-expression
GDS1257	Sickle cell plasma effect on pulmonary artery endothelial cells (HG-U133A)	Expression profiling of pulmonary artery endothelial cells exposed to plasma from sickle cell disease (SCD) patients with sickle acute chest syndrome or from SCD patients at steady state. Results provide insight into the role of extra-erythrocytic factors in sickle cell vasoocclusion.	Co-expression
GDS1258	Sickle cell plasma effect on pulmonary artery endothelial cells (HG-U133B)	Expression profiling of pulmonary artery endothelial cells exposed to plasma from sickle cell disease (SCD) patients with sickle acute chest syndrome or from SCD patients at steady state. Results provide insight into the role of extra-erythrocytic factors in sickle cell vasoocclusion.	Co-expression
GDS1263	Dukes B colon cancer recurrence	Expression profiling of previously resected frozen primary tumors from patients with Dukes' stage B colon cancer that recurred in 5 years. Results identify potential prognostic markers for tumor relapse.	Co-expression
GDS1269	Cigarette smoking effect on alveolar macrophage	Analysis of alveolar macrophages from 15 cigarette smokers, 15 non-smokers and 15 asthmatics. Results suggest that alveolar macrophage activation induced by smoking contributes to emphysema.	Co-expression
GDS1282	Clear cell sarcoma of the kidney	Expression profiling of clear cell sarcoma of the kidney (CCSK). Wilms' tumors and fetal kidney control samples also examined. Objective is to reveal diagnostic markers and insight into the pathogenesis of CCSK.	Co-expression
GDS1284	Multiple myeloma molecular classification	Analysis of CD138+ plasma cells purified from bone marrow of multiple myeloma (MM) patients. Results used to classify MM cases into translocation/cyclin (TC) groups based on cyclin D expression and presence of translocations in the immunoglobulin heavy chain locus at 14q32.	Co-expression
GDS1286	Esophageal cell response to low pH: time course	Analysis of esophageal cell line SKGT4 following exposure to low pH 6.5. Cells examined at various time points up to 2 hours following exposure. Results provide insight into role of gastric acid in pathogenesis of gastro-esophageal reflux disease (GORD) and esophagus adenocarcinoma.	Co-expression
GDS1287	Bone mineral density and circulating monocytes	Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis.	Co-expression
GDS1288	Mesenchymal precursor cells derived from embryonic stem cells	Comparison of mesenchymal stem cells (MSC) and undifferentiated embryonic stem cells (ESC). ESC plated on a monolayer of OP9 stromal cells in the presence of 20% heat inactivated fetal bovine serum in alpha MEM medium to induce differentiation into MSC.	Co-expression
GDS1289	TNFalpha effect on epidermal keratinocytes in the presence of NF-kappa B inhibitor: time course	Analysis of epidermal keratinocytes treated with TNFalpha in the presence of 10 uM parthenolide, an NF-kappa B inhibitor. Cells examined at various time points up to 48 hours following TNFalpha treatment. Results identify NF-kappa B-dependent subset of TNFalpha-regulated genes.	Co-expression
GDS1290	CD4+ lymphocyte polarization into Th1 and Th2 cells in the presence of TGFbeta: time course (HG-U95A)	Analysis of CD4+ lymphocyte induced to differentiate into Th1 and Th2 by treatment with IL-12 and IL-4 respectively in the presence of TGFbeta. Cells examined at various time points up to 48 hours after treatment. Results provide insight into the mechanisms regulating CD4+ cell polarization.	Co-expression
GDS1295	Lethal congenital contracture syndrome	Analysis of spinal cord from fetuses with lethal congenital contracture syndrome (LCCS). LCCS is autosomal recessive, causes death in 32nd gestational week, and involves degeneration of anterior horn motor neurons in spinal cord. Results provide insight into pathways active in motoneuron disease.	Co-expression
GDS1304	Cigarette smoking effect on small airway epithelium	Analysis of phenotypically normal 10th to 12th order small airway bronchial epithelia from cigarette smokers. Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD). Results provide insight into the early pathogenesis of COPD.	Co-expression
GDS1310	Neonatal mononuclear cell response to lipopolysaccharide	Analysis of neonatal mononuclear cells from cord blood incubated with 5 ug/ml lipopolysaccharide (LPS). Effect of LPS on adult mononuclear cells from peripheral blood compared. Results provide insight into the molecular basis for increased susceptibility of neonates to sepsis.	Co-expression
GDS1312	Squamous lung cancer	Expression profiling of squamous lung cancer biopsy specimens and paired normal specimens from 5 patients. Differentially expressed genes integrated with protein interaction maps. Results suggest that differentially expressed genes are highly connected through protein interactions.	Co-expression
GDS1313	GFAP-negative lamina cribrosa cell response to TGF-beta1	Analysis of glial fibrillary acidic acid (GFAP)-negative lamina cribrosa (LC) glial cell response to 10 ng/ml TGF-beta1 for 24 hours. This is a model for primary open-angle glaucoma (POAG) in which TGF-beta levels are elevated in human LC tissue.	Co-expression
GDS1314	Malignant melanoma cell lines	Expression profiling of MelJUSO, A375, 607B, 518A2, and Skmel 28 malignant melanoma cell lines. Results correlated with regions of chromosomal breakpoints, and indicate an association between chromosomal breakpoints and altered gene expression.	Co-expression
GDS1317	Umbilical vein endothelial cell response to shear stress and intraluminal pressure	Analysis of endothelial cells (HUVEC) isolated from umbilical veins subjected to high shear stress or high intraluminal pressure. Umbilical veins exposed to each stimuli using a vascular ex vivo perfusion system. Results suggests that response to shear stress differs from response to pressure.	Co-expression
GDS1320	Scott syndrome B lymphoblast response to calcium ionophore	Analysis of Scott B lymphoblasts after calcium ionophore A23187 treatment. Lymphoblasts derived from a patient with Scott syndrome, a hemorrhagic disease. Results provide insight into the mechanisms underlying the apoptotic effect of A23187, and susceptibility of Scott B lymphoblasts to apoptosis.	Co-expression
GDS1321	Barrett's metaplasia progression to adenocarcinoma	Expression profiling of normal esophageal epithelium, premalignant Barrett's metaplasia, and esophageal adenocarcinoma samples. Tissue samples of each type obtained from 8 patients by transhiatal esophagectomy. Results identify potential markers of disease progression.	Co-expression
GDS1324	T-cell acute lymphoblastic leukemia with CALM-AF10 fusion	Analysis of T-cell acute lymphoblastic leukemia (ALL) samples containing t(10;11)(p13;q14-21) translocation that fuses the clathrin-assembly protein-like lymphoid-myeloid leukemia gene CALM to the transcription factor AF10. Results provide insight into the consequences of CALM-AF10 expression.	Co-expression
GDS1325	Telomerase reverse transcriptase overexpression effect on CD4+ lymphocytes	Analysis of CD4+ T cells overexpressing green fluorescent protein telomerase reverse transcriptase fusion protein (GFP-hTERT). hTERT encodes catalytic reverse transcriptase subunit of telomerase. Provides insight into long-term consequences of hTERT overexpression in T lymphocytes.	Co-expression
GDS1326	Breast cancer cells reexpressing estrogen receptor alpha response to 17beta-estradiol	Analysis of the response of estrogen receptor (ER) negative MDA-MB-231 breast cancer cells infected with full-length ER alpha adenoviral constructs to treatment with 17beta-estradiol (E2). Results provide insight into the anti-proliferative effect of E2 on breast cancer cells reexpressing ER.	Co-expression
GDS1327	Lens epithelial and lens cortical fiber cell comparison	Comparison of lens epithelial cells to lens cortical fiber cells. Cells microdissected from lenses of post mortem donors. Results identify genes that may play roles in maintaining the specialized functions of each cell type and provides insight into potential mechanisms of lens cell differentiation.	Co-expression
GDS1329	Molecular apocrine breast tumors	Analysis of tumors of 49 breast cancer patients. Tumors classified into luminal and basal classes, and a novel molecular apocrine class. Apocrine tumors are estrogen receptor negative (ER-) and androgen receptor positive (AR+), while luminal tumors are ER+ and AR+, and basal tumors are ER- and AR-.	Co-expression
GDS1330	Crohn disease and ulcerative colitis comparison	Expression profiling of mucosal biopsy samples from sigmoid colons of 10 patients with Crohn disease (CD) and 10 patients with ulcerative colitis (UC). CD and UC are two forms of inflammatory bowel disease. Results provide insight into the pathogenesis of CD and UC.	Co-expression
GDS1331	Huntington's disease: peripheral blood expression profile (HG-U133A)	Analysis of blood samples of 5 presymptomatic and 12 symptomatic Huntington's disease (HD) patients. Studies suggest that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Results identify potential markers for HD.	Co-expression
GDS1332	Huntington's disease: peripheral blood expression profile (Codelink Uniset 20K)	Analysis of blood samples of 5 presymptomatic and 12 symptomatic Huntington's disease (HD) patients. Studies suggest that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Results identify potential markers for HD.	Co-expression
GDS1333	Duchenne Muscular Dystrophy response to oxandrolone (HG-U133A)	Analysis of gastrocnemius muscle biopsy specimens from Duchenne muscular dystrophy (DMD) patients before and after 3 months of treatment with 0.1mg/kg/day oxandrolone, a synthetic anabolic steroid. Results provide insight into mechanisms underlying the beneficial effect of oxandrolone in DMD.	Co-expression
GDS1334	Duchenne Muscular Dystrophy response to oxandrolone (HG-U133B)	Analysis of gastrocnemius muscle biopsy specimens from Duchenne muscular dystrophy (DMD) patients before and after 3 months of treatment with 0.1mg/kg/day oxandrolone, a synthetic anabolic steroid. Results provide insight into mechanisms underlying the beneficial effect of oxandrolone in DMD.	Co-expression
GDS1340	Exercise effect on aged muscle	Expression profiling of vastus lateralis muscles from 6 healthy, elderly, sedentary males after 3 months of exercise at 80% of maximal capacity.  Results provide insight into the molecular changes induced by exercise in sedentary skeletal muscles.	Co-expression
GDS1344	Papillary renal cell carcinoma classification	Analysis of renal tumors from 34 papillary renal cell carcinoma (PRCC) cases. Results identify 2 molecular signatures that correlate with the morphologic classification of PRCC. Molecular class type 1 tumors correlate with excellent survival, while type 2 tumors correlate with poor survival.	Co-expression
GDS1347	Neurogenic potential of mesenchymal stem cells	Comparison of mesenchymal stem cells (MSC) treated with  dimethylsulphoxide and butylated hydroxyanisole (DMSO/BHA) for 6 or 48 hours to fetal brain (positive control) or adult liver (negative control). Results raise doubts about the DMSO/BHA protocol for generating neural cells from MSCs.	Co-expression
GDS1348	Cigarette smoke effect on bronchial epithelial cells: time course	Analysis of cultured normal bronchial epithelial cells 4 and 24 hours after exposure to 15 minutes of cigarette smoke in order to better understand molecular impact of tobacco exposure.	Co-expression
GDS1353	Glucocorticoid effect on lens epithelial cells: time course	Analysis of cultured immortalized lens epithelial cells (LEC) 4 and 16 hours after treatment with 1 uM dexamethasone, a glucocorticoid steroid hormone. Long-term glucocorticoid use can induce cataract formation. Results identify glucocorticoid targets and short-term effects of glucocorticoid on LECs	Co-expression
GDS1362	Ischemic and nonischemic cardiomyopathy comparison	Analysis of myocardial tissues from nonischemic (NICM) and ischemic cardiomyopathy (ICM) patients. NICM and ICM, major forms of dilated cardiomyopathy leading to congestive heart failure, have similar presentations but differ in pathophysiology, prognosis, and response to therapy.	Co-expression
GDS1365	IFN-gamma primed macrophage response to IFN-gamma restimulation: time course	Analysis of CD14+ monocytes primed with 3 U/ml (subactivating dose) IFN-gamma for 48 hours and restimulated with 100 U/ml (saturating dose) IFN-gamma for various time point up to 24 hours. Results provide insight into the influence of IFN-gamma priming on IFN-gamma induced transcriptional responses.	Co-expression
GDS1369	Autophagy effect on the MHC class II antigenic peptide repertoire	Analysis of Awells B-lymphoblastoid cell line after 6 and 24 hours of starvation-induced autophagy. Results identify the influence of autophagy on the MHC-II ligandome, in promoting MHC-II presentation of antigens from intracellular source proteins, and on the MHC-II antigen-processing machinery.	Co-expression
GDS1372	Bone morphogenic protein 2 effect on idiopathic pulmonary arterial hypertension	Analysis of pulmonary artery smooth muscle cells (PASMC) from patients with idiopathic pulmonary arterial hypertension (IPAH). PASMC treated with 200 nM bone morphogenic protein 2 (BMP-2) for 24 hours. BMP signaling dysfunction has been implicated in IPAH.	Co-expression
GDS1373	Peroxisome proliferator-activated receptor subtype activation effect on liver cell	Analysis of HepG2 cells expressing peroxisome proliferator-activated receptor (PPAR) alpha, beta/delta, gamma 1, or gamma 2. Cells expressing PPARs treated with fenofibric acid, GW501516, or ciglitizone to activate alpha, beta/delta, or gamma subtypes respectively. PPARs regulate lipid homeostasis.	Co-expression
GDS1375	Cutaneous malignant melanoma	Expression profiling of primary malignant melanoma, benign skin nevi, and normal skin samples. Results identify potential molecular markers for lymph node staging assays, and provide insight into melanoma tumorigenesis.	Co-expression
GDS1376	Essential thrombocythemia	Analysis of platelets from patients with essential thrombocythemia (ET). ET is a myeloproliferative disorder resulting in an abnormal increase in the number of blood platelets. Results indicate that distinct expression patterns of 17beta-hydroxysteroid dehydrogenases are associated with ET.	Co-expression
GDS1380	Glioblastoma pseudopalisading cells	Analysis of pseudopalisading cells obtained by laser capture microdissection from glioblastoma tumors. The presence of pseudopalisading cells is associated with aggressive malignant gliomas. Results identify putative prognostic markers for glioblastoma.	Co-expression
GDS1381	Carboplatin sensitive and resistant ovarian carcinoma	Comparison of carboplatin sensitive and resistant ovarian cancer cells. Carboplatin is a chemotherapy drug. Cancer cells prepared from primary cultures of ovarian papillary serous adenocarcinomas. Results identify potential markers for carboplatin responsiveness in ovarian carcinoma.	Co-expression
GDS1384	c-Myb and its oncogenic variant v-Myb	Analysis of transcriptional activity in MCF7 cells infected with control adenovirus versus adenovirus expressing c-Myb, oncogenic variant v-Myb, or a 3MutC hybrid construct. Results indicate that v-Myb is a distinct transcriptional regulator with a unique set of activities.	Co-expression
GDS1388	B-cell chronic lymphocytic leukemia progression	Analysis of primary lymphocytes from B-cell chronic lymphocytic leukemia (B-CLL) patients. Lymphocytes from patients with indolent B-CLL compared to those with progressive B-CLL. Results identify putative gene markers of B-CLL progression from a stable to an aggressive state.	Co-expression
GDS1390	Prostate cancer progression after androgen ablation	Analysis of prostate cancer progression following androgen ablation treatment. 10 treated androgen-independent primary prostate tumors compared to 10 untreated androgen-dependent primary  prostate tumors. Results provide insight into progression of prostate cancer to aggressive androgen-independent	Co-expression
GDS1392	Myelodysplastic syndrome	Analysis of bone marrow CD34+ progenitor cells from normal-karyotype, low-blast-count, early, low-risk myelodysplastic syndrome (MDS) patients, age-matched controls, and patients with non-MDS anemia. Results provide insight into pathogenesis of MDS and identify putative markers of MDS.	Co-expression
GDS1397	T cells infected with an HIV-based vector	Analysis of Jurkat T cells infected with an HIV-based vector transducing green fluorescent protein. Expression of genes hosting HIV integration events examined. Results provide insight into how expression from the HIV type 1 promoter is affected by the integration site of the provirus.	Co-expression
GDS1401	CD34+ hematopoietic cells expanded in artificial matrix of fibrillar collagen I	Analysis of CD34+ hematopoietic stem/progenitor cells (HSC) expanded for 7 days in an artificial matrix of fibrillar collagen I, the major matrix component of bone. Results provide insight into the limitations of ex vivo expansion to increase the number of transplantable HSCs from cord blood.	Co-expression
GDS1402	Various normal pure cell cultures	Expression profiling of various pure normal epithelial, endothelial, fibroblast, stromal, and muscle cell cultures. Data provide baseline for understanding cellular mechanisms for maintenance of stable cell types and for studying pathways to terminally differentiated state.	Co-expression
GDS1405	Pulmonary type II cell differentiation	Analysis of epithelial cells isolated from 13 fetal lungs (13-20 wks old) and cultured in dexamethasone/cyclic AMP/isobutylmethylxanthine (DCI) for 72 hrs to promote type II cell differentiation. Mature alveolar type II cells that produce surfactant are critical for adaptation to extrauterine life.	Co-expression
GDS1407	Leukocyte inflammatory responses to lipopolysaccharide	Analysis of whole blood following 4 hour treatment with lipolysaccharide (LPS). Leukocytes from individuals with high and low responses to LPS examined. LPS response assessed by measuring cytokine production. Results provide insight into the variability of LPS responses between individuals.	Co-expression
GDS1411	HCaRG overexpression in kidney cells	Analysis of HCaRG9, a stably-transfected HEK293 embryonal kidney cell line over-expressing the hypertension-related, calcium-regulated gene (HCaRG). Results identify a role for HCaRG in kidney repair involving increased renal cell migration and transforming growth factor-alpha (TGF-α) expression.	Co-expression
GDS1412	Hormone replacement therapy effect on whole blood	Comparison of whole blood samples from 42 postmenopausal women on hormone replacement therapy (HRT) to those of 47 postmenopausal women not on HRT. Subjects are part of the Norwegian Women and Cancer Study (NOWAC).	Co-expression
GDS1413	Lipid peroxidation product 4-hydroxy-2-nonenal effect on cells: time course	Analysis of RKO colorectal carcinoma cell line at 6 and 24 hours following exposure to subcytotoxic and cytotoxic amounts of 4-hydroxy-2-nonenal (HNE). HNE is an abundant product of polyunsaturated fatty acid oxidation and decomposition and reacts extensively with DNA and proteins.	Co-expression
GDS1414	Candoxin effect on glial cells: time course	Analysis of glial cell line Hs683 at various time points up to 48 hours following exposure to 300 nM of candoxin (CDX) snake venom. CDX is a neurotoxin that inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and delays cell death in glial cells.	Co-expression
GDS1419	Classical Hodgkin's lymphoma: T cell expression profile	Expression profiling of CD3+ T cells isolated from peripheral blood samples of untreated patients with classical Hodgkin's lymphoma. CD3+ T cells from healthy donors and patients with sarcoidosis also examined.	Co-expression
GDS1423	Lunasin effect on prostate epithelial cells	Expression profiling of normal prostate epithelial RWPE1 cells and tumorigenic prostate cancer RWPE2 cells treated with 2 uM lunasin for 24 hours. Lunasin is a soybean peptide shown to suppress carcinogenesis. Results provide insight into the chemopreventive properties of lunasin.	Co-expression
GDS1424	Folic acid deficiency effect on colon cancer cells	Analysis of HT-29 colon cancer cells cultured in pteroylglutamic acid or methyl-tetrahydrofolate at concentrations of 10 or 100 ng/ml each. Studies suggest that folate deficiency can have an inhibitory effect on the progression of established colonic tumor cells.	Co-expression
GDS1436	Cigarette smoking effect on alveolar macrophages	Anlaysis of alveolar macrophages of 5 phenotypically normal smokers who consume ~20 packs cigarettes/year. Smoking is the leading cause of respiratory diseases collectively known as chronic obstructive pulmonary disease (COPD). Provides insight into early events in molecular pathogenesis of COPD.	Co-expression
GDS1438	Kidneys removed by laparoscopic donor nephrectomy	Analysis of kidneys removed by laparoscopic donor nephrectomy (LDN), a minimally invasive procedure that involves several hours of carbon dioxide pneumoperitoneum. Renal cortices of kidneys recovered by LDN compared to those removed by open donor nephrectomy.	Co-expression
GDS1439	Prostate cancer progression	Expression profiling of prostate cancer tumors that are benign, clinically localized, or metastatic and refractory to hormones. Results compared to those obtained from immunoblotting to identify concordant changes in mRNA and protein levels.	Co-expression
GDS1440	Melanoma cell lines treated with a DNA methylase inhibitor	Analysis of a poorly tumorigenic melanoma cell line and its 3 highly aggressive derivative lines after treatment with 2'-deoxy-5-azacytidine (DAC), a DNA methyltransferase inhibitor. Results suggest multiple markers for melanoma progression that are regulated by DNA methylation.	Co-expression
GDS1442	PPARα  agonist ciprofibrate effect on liver	Analysis of primate livers exposed to ciprofibrate at various doses for 4 or 15 days. Peroxisome proliferator-activated receptor-α (PPARα) agonists such as ciprofibrate cause hepatocarcinogenesis in rodents but not in primates. Results identify species differences in response to PPARα agonist.	Co-expression
GDS1447	Bronchial epithelial cell response to vanadium and zinc	Analysis of bronchial epithelial cells after 4 hours of exposure to 50 uM vanadium (V) or zinc (Zn). Excessive V and Zn in the air can arise from the burning of heavy fuel and during welding and smelting operations, respectively. Results identify biomarkers that distinguish V from Zn exposure.	Co-expression
GDS1449	HIV-1 infection effect on peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells from HIV-1 seropositive and seronegative individuals. Results used to identify a 10-gene signature used for determining HIV-1 serostatus, and a 6-gene signature to identify seropositive individuals exhibiting changes in CD4+ T cell counts.	Co-expression
GDS145	Serum stimulation with cycloheximide time course	Analysis of the transcriptional program in the response of human fibroblasts to serum. Serum added to fibroblasts in the presence of cycloheximide and samples taken at 0, 0.5, 2 and 4 hours.	Co-expression
GDS1453	Camptothecin effect on renal epithelial cell line and HIV transduction	Analysis of renal epithelial cell line 293T following treatment with 2 uM camptothecin, which boosts transduction of cells by HIV. Camptothecin induces DNA damage and arrests cell cycle at G2/M. Results provide insight into the mechanisms underlying HIV transduction boost induced by camptothecin.	Co-expression
GDS1476	Uterine fibroids with fumarate hydratase mutations	Analysis of 7 uterine fibroids carrying fumarate hydratase (FH) mutations. FH catalyzes hydration of fumarate in the Krebs tricarboxylic acid cycle. Results provide insight into the connection between the disruption of mitochondrial metabolic pathways and neoplasia.	Co-expression
GDS1477	Transcription factor FoxM1 inactivation effect on breast cancer cell	Expression profiling of BT-20 breast cancer cells 48 hours after transfection with FoxM1 siRNA. Elevated expression of FoxM1 has been observed in hepatocellular carcinoma, basal cell carcinoma, and breast cancer. Results provide insight into the role of FoxM1 in cancer cell growth.	Co-expression
GDS1478	Intestinal epithelial cell response to probiotic Escherichia coli strain Nissle 1917	Analysis of Caco-2 intestinal epithelial cells cocultured for 6 hours with the probiotic Escherichia coli strain Nissle 1917 (EcN). A controlled clinical trial suggests that EcN is effective in remission maintenance of ulcerative colitis. Results provide insight into EcN-host interactions.	Co-expression
GDS1479	Carcinoma in situ lesions of the urinary bladder	Analysis of bladder biopsies of superficial transitional cell carcinomas with or without surrounding carcinoma in situ (CIS) lesions and muscle invasive carcinomas (mTCC). CIS is a common mTCC precursor. Results provide insight into which tumors in early stage bladder cancer are likely to progress.	Co-expression
GDS1480	Obesity: preadipocyte expression profile (HG-U133A)	Analysis of cultured abdominal subcutaneous preadipocytes from 7 male and 7 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of preadipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1481	Obesity: preadipocyte expression profile (HG-U133B)	Analysis of cultured abdominal subcutaneous preadipocytes from 7 male and 7 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of preadipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1495	Obesity: adipocyte expression profile (HG-U95B)	Analysis of cultured abdominal subcutaneous mature adipocytes from 9 male and 10 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1496	Obesity: adipocyte expression profile (HG-U95C)	Analysis of cultured abdominal subcutaneous mature adipocytes from 9 male and 10 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1497	Obesity: adipocyte expression profile (HG-U95D)	Analysis of cultured abdominal subcutaneous mature adipocytes from 9 male and 10 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1498	Obesity: adipocyte expression profile (HG-U95E)	Analysis of cultured abdominal subcutaneous mature adipocytes from 9 male and 10 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS1499	Hepatocyte nuclear factor 1beta mutant overexpression effect on embryonic kidney cells	Analysis of HEK293 embryonic kidney cells overexpressing wild type hepatocyte nuclear factor (HNF) 1beta or HNF1alpha, or the HNF1beta A263insGG mutant. Results identify gene targets of HNF1 beta, and provide insight into the functional differences between HNF1beta and HNF1alpha.	Co-expression
GDS1503	Hutchinson-Gilford progeria syndrome: fibroblast (HG-U133A)	Expression profiling of three fibroblast cell lines derived from Hutchinson-Gilford progeria syndrome (HGPS) patients. Identified changes in gene expression may provide clues to potential risk factors or factors influencing disease progression.	Co-expression
GDS1504	Hutchinson-Gilford progeria syndrome: fibroblast  (HG-U133B)	Expression profiling of three fibroblast cell lines derived from Hutchinson-Gilford progeria syndrome (HGPS) patients. Identified changes in gene expression may provide clues to potential risk factors or factors influencing disease progression.	Co-expression
GDS1505	Cultured skin substitute	Comparison of cultured skin substitute (CSS), cultured keratinocytes, cultured fibroblasts, and native skin. CSS contains fibroblasts and keratinocytes, and can facilitate wound healing. Results provide insight into physiological and molecular differences between CSS and native skin.	Co-expression
GDS1510	Tamoxifen effect on normal endometrial epithelium	Analysis of normal endometrial epithelial cells following treatment with oestrogen or tamoxifen (TMX).  Results provide insight into the molecular basis of the association of TMX treatment of breast cancer with an increased incidence of endometrial cancer.	Co-expression
GDS1520	Mast cell activation via the Fc(epsilon)RI	Analysis of umbilical cord blood-derived mast cells 2 hours post stimulation by high-affinity IgE receptor (FcεRI). Cells incubated with myeloma IgE and IL-4 prior to stimulation. Cells activated via FcεRI with anti-IgE antibody to induce release of antihistamines and other inflammation mediators.	Co-expression
GDS1523	Ovarian cancer cell lines	Analysis of 10 ovarian cancer cell lines: 4 ovarian serous adenocarcinomas, 1 paclitaxel/cisplatin resistant ovarian adenocarcinoma cell line derivative, 5 ovarian clear cell adenocarcinomas. Expression profile of each cell line compared to its sensitivity to paclitaxel and cisplatin.	Co-expression
GDS1530	Fibroblast response to cytomegalovirus infection: time course	Analysis of fibroblasts infected with cytomegalovirus (CMV) AD169 strain or a derivative lacking the CMV chemokine receptor US28. Cells examined at 50, 72, and 98 hours post-infection. Results identify pathways affected by CMV and provide insight into the role of US28 in the late phase of infection.	Co-expression
GDS1542	Tumor necrosis factor effect on macrovascular umbilical vein endothelial cells	Analysis of macrovascular umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor (TNF)-alpha for 5 hours. TNF is a potent inflammatory stimulus. Results provide insight into the relevance of the diversity of endothelial cell subtypes for the response to inflammatory stimuli.	Co-expression
GDS1543	Tumor necrosis factor effect on microvascular endothelial cells	Analysis of microvascular endothelial cells (HMEC) stimulated with tumor necrosis factor (TNF)-alpha for 5 hours. TNF is a potent inflammatory stimulus. Results provide insight into the relevance of the diversity of endothelial cell subtypes for the response to inflammatory stimuli.	Co-expression
GDS1548	Neuroblastoma cell lines	Analysis of four cell lines initially established as neuroblastomas. Results indicate that the SK-N-MC cell line expresses all of the Ewing Family Tumor (EFT) signature genes. EFTs are small round blue cell tumors that show features of neuroectodermal differentiation.	Co-expression
GDS1549	Estrogen effect on estrogen receptor alpha positive breast cancer cell lines	Expression profiling of estrogen receptor positive breast cancer cell lines treated with estradiol for 24 hours. MCF-7, T47-D, and BT-474 breast cancer cell lines examined. Results identify candidate genes involved in estrogen stimulated breast cancer growth.	Co-expression
GDS1553	Fullerene effect on vascular endothelial cells	Analysis of umbilical vein endothelial cells (ECs) treated with hydroxyl fullerene, a major nanomaterial. Nanomaterials are known to translocate into the circulation and may thus directly affect vascular ECs. Results provide insight into the effects of fullerenes on endothelial injury and toxicity.	Co-expression
GDS1557	Atrial and ventricular myocardium comparison (HG-U133B)	Analysis of right atria and left ventricles of hearts. While both the ventricle and atrium contract, the atrium is also a source and target for neurohumoral signals. Results provide insight into the molecular basis for the ultrastructural and functional differences between the atrium and ventricle.	Co-expression
GDS1559	Permanent atrial fibrillation (HG-U133B)	Analysis of atrium from patients with permanent atrial fibrillation (AF). AF is associated with extensive structural, contractile, and electrophysiological remodeling. Results identify adoption of a ventricular-like genomic signature as a general feature of the fibrillating atrium.	Co-expression
GDS156	Muscle function and aging (HG-U95A)	Comparison of gene expression in vastus lateralis skeletal muscle biopsies in healthy young (21-31 year old) and older (62-77 year old) men. Sample RNAs isolated from individuals and pooled into groups of 8.	Co-expression
GDS1562	Alveolar rhabdomyosarcoma	Analysis of 14 tumor biopsies from children affected by alveolar rhabdomyosarcoma (ARMS). Seven patients were positive for the PAX3-FKHR fusion gene, which indicates an unfavorable prognosis. Results identify expression signatures that differentiate PAX3-FKHR positive from PAX3-FKHR negative ARMS.	Co-expression
GDS1563	Host response to malaria	Analysis of whole blood from Kenyan children with acute malaria or other febrile illnesses, both at hospital admission and after recovery. Samples collected during July September 2002. Results provide a perspective of the host response to malaria and further insight into processes of pathogenesis.	Co-expression
GDS1568	Fibroblast response to serum: time course	Analysis of fibroblasts at various time points up to 36 hours after serum stimulation. The fibroblast serum response represents a wound healing program; cancer progression is likened to wound healing gone awry. Results provide insight into the significance of the wound healing process in cancer.	Co-expression
GDS157	Type 2 diabetes and insulin resistance (HuGeneFL)	Analysis of gene expression in pooled vastus lateralis muscle samples from insulin-sensitive and insulin-resistant equally obese, non-diabetic Pima Indians. A search for susceptibility genes for type 2 diabetes.	Co-expression
GDS1579	Endotoxin effect on leukocytes: time course (U133 2.0)	Analysis of leukocytes from 6 healthy subjects intravenously administered bacterial endotoxin. Leukocytes examined at various time points up to 6 hours post-infusion. Results provide insight into the molecular mechanisms involved in the propagation and resolution of the inflammatory response.	Co-expression
GDS158	Type 2 diabetes and insulin resistance (Hu35k-A)	Analysis of gene expression in pooled vastus lateralis muscle samples from insulin-sensitive and insulin-resistant equally obese, non-diabetic Pima Indians. A search for susceptibility genes for type 2 diabetes.	Co-expression
GDS1580	Lens epithelium-derived growth factor knockdown	Expression profiling of 293T cells depleted for lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 binds to HIV integrase. Results identify LEDGF/p75 regulated genes, which may be preferential targets of HIV integration.	Co-expression
GDS1597	Coronary artery atherosclerosis	Analysis of 51 coronary artery segments from the explanted hearts of 22 cardiac patients. Results provide insight into the pathogenesis and progression of atherosclerotic disease.	Co-expression
GDS160	Type 2 diabetes and insulin resistance (Hu35k-B)	Analysis of gene expression in pooled vastus lateralis muscle samples from insulin-sensitive and insulin-resistant equally obese, non-diabetic Pima Indians. A search for susceptibility genes for type 2 diabetes.	Co-expression
GDS1604	Ionizing radiation effect on monocytic leukemia cells	Analysis of leukemia THP-1 moncytes exposed to ionizing radiation (IR). IR exposure is associated with thrombotic vascular occlusion. Thrombosis in cancer is associated with poor prognosis. Results provide insight into the effect of IR on the expression of tissue factor, an activator of coagulation.	Co-expression
GDS161	Type 2 diabetes and insulin resistance (Hu35k-C)	Analysis of gene expression in pooled vastus lateralis muscle samples from insulin-sensitive and insulin-resistant equally obese, non-diabetic Pima Indians. A search for susceptibility genes for type 2 diabetes.	Co-expression
GDS1615	Ulcerative colitis and Crohn's disease comparison: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells (PBMCs) from Crohn's disease (CD) and ulcerative colitis (UC) patients. Results identify a PBMC expression signature that distinguishes between CD and UC, suggesting that diagnosis of these two inflammatory bowel diseases (IBD) using PBMCs is possible.	Co-expression
GDS1617	Motexafin gadolinium and zinc effect on Ramos B-cell lymphoma line	Analysis of Ramos B-cell lymphoma cultures following 4 hour treatment with anticancer agent motexafin gadolinium (MGd), zinc acetate (25 or 50 uM), or combinations of MGd and zinc. Results provide insight into the molecular changes that accompany the disruption of intracellular zinc homeostasis.	Co-expression
GDS1618	Lymph node and tonsil comparison	Analysis of lymph node (sinuses) and tonsil (no sinuses), highly similar secondary lymphoid organs. Metastatic tumor cells are preferentially arrested in the lymph node sinuses. Results identify signature genes that are prime candidates for mediating adhesion of tumor cells to sinusoidal cells.	Co-expression
GDS162	Type 2 diabetes and insulin resistance (Hu35k-D)	Analysis of gene expression in pooled vastus lateralis muscle samples from insulin-sensitive and insulin-resistant equally obese, non-diabetic Pima Indians. A search for susceptibility genes for type 2 diabetes.	Co-expression
GDS1627	Breast cancer cell lines response to chemotherapeutic drugs: time course	Analysis of 4 breast cell lines treated for up to 36 hrs with the chemotherapeutic agents 5-fluorouracil (5FU), doxorubicin (DOX), or etoposide (ETOP), a drug mechanistically similar to DOX. Expression profiles for DOX- and 5FU-treated cells were used to successfully predict the response to ETOP.	Co-expression
GDS1630	Immortalized endothelial cell line response to atorvastatin	Analysis of EA.hy926, an immortalized umbilical vein endothelial cell (HUVEC) line, and its primary cell counterpart following treatment with HMG-CoA reductase inhibitor atorvastatin to inhibit the mevalonate pathway. Results suggest EA.hy926 cells have retained endothelial cell-specific features.	Co-expression
GDS1637	Oncogene-induced sensescence in vitro model	Analysis of transformed cell lines that either exhibit oncogene-induced senescence (OIS) triggered by MEK activation or bypass OIS. Senescent cells exist in premalignant tumors but not in malignant ones. Results provide insight into the molecular basis of OIS.	Co-expression
GDS1645	Nitric oxide effect on soluble guanylate cyclase deficient cells	Analysis of soluble guanylate cyclase-deficient U937 cells exposed to the nitric oxide (NO) donor S-nitrosoglutathione. Cells treated in the presence of dibutyryl-cAMP (Bt2cAMP) to block signaling due to NO-induced decreases in cAMP. Results provide insight into the cGMP-independent effects of NO.	Co-expression
GDS1646	HIV-1 burden effect on mononuclear cell response to co-infection with Neisseria gonorrhoeae	Analysis of peripheral blood mononuclear cells infected with various titers of HIV-1 and exposed to a single infectious dose of Neisseria gonorrhoeae (Gc). Results provide insight into the role of viral burden in defining the cellular contribution to host immune response to co-infection with Gc.	Co-expression
GDS1650	Pulmonary adenocarcinoma	Analysis of pulmonary adenocarcinomas (AC). Carcinogen exposure is responsible for the majority of ACs. Results compared with those obtained from a urethane-induced lung tumor model in the mouse (GDS1649), and provide insight into the conserved pathways underlying the development of AC.	Co-expression
GDS1663	Expression data from different research centers	Comparison of expression data from the Translational Genomics Research Institute to that from the Children's National Medical Center in Washington, DC. Data consists of normal kidney, liver, and spleen expression profiles.	Co-expression
GDS1664	Parathyroid hormone-related protein knockdown effect on breast cancer cells	Analysis of MDA-MB-231 breast cancer cells depleted for parathyroid hormone-related protein (PTHrP) using siRNA. PTHrP affects the proliferative and invasive activities of breast cancer cells and regulates their sensitivity to apoptotic stimuli. Results identify PTHrP-regulated tumor-relevant genes.	Co-expression
GDS1665	Papillary thyroid carcinoma	Analysis of papillary thyroid carcinoma (PTC) tumors from 9 patients. PTC accounts for about 80% of all thyroid cancers. These results, together with those obtained from custom miRNA chips, indicate the involvement of several miRNAs and the receptor tyrosine kinase KIT in PTC pathogenesis.	Co-expression
GDS1667	Head and neck squamous cell carcinoma tumors harboring human papillomavirus	Analysis of 8 head and neck squamous cell carcinoma (HNSCC) tumors positive for human papilloma virus (HPV). 28 HNSCC HPV negative tumors examined. Between 15% and 35% of HNSCCs harbor HPV DNA. Results provide insight into the effect of HPV infection in HNSCC.	Co-expression
GDS1672	Keratinocyte stem cell–enriched hair follicle bulge cells	Comparison of outer root sheath (ORS) cells of the hair follicle bulge with other defined ORS cell subpopulations within the follicle. Results provide insight into the biological distinctiveness of hair follicle bulge cells, suggesting the bulge is a repository for keratinocyte stem cells (KSCs).	Co-expression
GDS1673	Non-diseased lung tissue	Analysis of non-diseased lungs from 23 multi-organ donors.  Upper and lower lobe peripheral sections of the lung were examined. Donors varied in age, sex, smoking history, and ethnicity. Results provide a reference for microarray studies of pulmonary disease.	Co-expression
GDS1676	T cell leukemia cell response to human herpesvirus 6 infection: time course	Analysis of an adult T cell leukemia cell line (TaY) following infection with human herpesvirus type 6B strain OK. Cells examined up to 5 days post-infection. Chronically-infected TaY cells were also examined. Results identify candidate genes that regulate the immune response during viral infection.	Co-expression
GDS1679	Exhaustive endurance exercise effect on skeletal muscle: time course	Expression profiling of vastus lateralis muscles 3 and 48 hours after a 75-minute bout of high-intensity cycling. Results identify transcriptional pathways activated in skeletal muscles recovering from endurance exercise.	Co-expression
GDS1681	Dendritic cell response to measles virus infection: time course	Analysis of dendritic cells (DCs) for up to 24 hours after infection with measles virus (MV). MV induces immunosuppression followed by lasting immunity. DCs appear to play a role in this effect. Results provide insight into MV-DC interactions and suggest mechanisms for MV-modulated immune response.	Co-expression
GDS1684	Cardiac allograft rejection: time course	Expression profiling of endomyocardial tissues from 3 subjects before, during, and after a rejection episode.  Cardiac allograft rejection is a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy.	Co-expression
GDS1685	Hereditary gingival fibromatosis	Analysis of gingival tissues from a patient with hereditary gingival fibromatosis (HGF). HGF is a benign disorder characterized by a slow progressive enlargement of the gingiva. This hypertrophic overgrowth of the gingiva may completely cover the teeth.	Co-expression
GDS1688	Various lung cancer cell lines	Expression profiling of a set of 29 lung cancer cell lines consisting of 10 non-small cell adenocarcinoma, 10 small cell cancer, and 9 squamous cell cancer lines.  Gene expression results analyzed in relation to the sensitivity of each cell line to commonly used anti-cancer agents.	Co-expression
GDS1696	Nanosecond pulsed electric fields effect: time course	Expression profiling of Jurkat cells 30min and 60min after exposure to nanosecond pulsed electric fields (nsPEFs) for two consecutive 10 ns pulses at 280kV/cm. Results provide insight into the early response genes to DNA damage caused by electric field radiation.	Co-expression
GDS1697	DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine effect on prostate cancer cell lines	Analysis of prostate cancer cell lines after treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-aza-dC). Aberrant DNA methylation is an early event in the development of prostate cancer. Results identify hypermethylated genes whose expression is induced by 5-aza-dC.	Co-expression
GDS1699	Androgen sensitive and insensitive prostate cancer cell lines: expression profiles	Analysis of androgen sensitive (AS) and insensitive (AI) prostate cancer cell lines. Despite the wide use of these cell lines as model systems, a global genotypic characterization of these cell lines is currently lacking. Results identify differences in gene expression profiles.	Co-expression
GDS170	Tumor suppressor protein p53 gene dosage effects	Analysis of tumor suppressor protein p53 gene dosage effects in HCT116 colorectal carcinoma-derived cell lines p53 -/-, +/- and +/+ at 0 and 12 hours. Cells with different numbers of functional TP53 alleles can be distinguished by gene expression profile.	Co-expression
GDS1700	Anemia induced by acute renal rejection: peripheral blood lymphocytes	Analysis of peripheral blood lymphocytes from 4 renal allograft recipients with acute rejection and concurrent anemia. Compromised renal function after renal allograft transplantation often results in anemia. Results provide insight into the molecular events underlying anemia in acute rejection.	Co-expression
GDS171	HIV viral infection time course	Gene expression profile of proliferating normal peripheral blood mononuclear cells (PBMC) infected with HIV type 1 RF. Assessed at 0, 12, 24, 48, and 72 hours postinfection and compared with those of matched uninfected PBMC.	Co-expression
GDS1710	bHLH transcription factor MyoD knockdown effect on myoblast differentiation	Analysis of C2C12 myoblast cell line following RNAi knockdown of the bHLH transcription factor MyoD. RNA prepared from cells after 1, 3, and 6 days of myogenic differentiation in DMEM medium supplemented with 2% horse serum. Results identify targets of MyoD.	Co-expression
GDS1712	2,4-dibencilaminoquinazoline effect on various cancer cell lines	Analysis of breast HTB26, colon HT29, and bladder T24 cancer cell lines after treatment with 2,4-dibencilaminoquinazoline, which exhibits cytostatic and apoptotic effects. Gene expression examined after 2,4-dibencilaminoquinazoline induces caspase activation or DNA fragmentation.	Co-expression
GDS1713	Ewing family tumor and neuroblastoma comparison	Analysis of Ewing family tumor (EFT) and neuroblastoma (NB) samples. Distinguishing EFTs from other small round blue cell tumors (SRBCTs), such as NBs, by histologic methods is often difficult. Results identify EF-associated genes that enable molecular discrimination between EFTs and other SRBCTs.	Co-expression
GDS1714	Bleomycin effect on mutagen-sensitive lymphoblastoid cell lines	Analysis of mutagen-sensitive lymphoblastoid cell lines after exposure to bleomycin. Mutagen-sensitive cells exhibit a high number of bleomycin-induced chromatid breaks. Mutagen sensitivity (MS) reflects an individual's susceptibility to sporadic cancers. Results identify genes involved in MS.	Co-expression
GDS172	SIV disease progression	Analysis of SIV MAC 251 disease progression in Rhesus Macaque peripheral blood mononuclear cells (PBMC). Slow, typical and fast progression groups examined at baseline, 3 and 7 weeks post-infection.	Co-expression
GDS1726	HIV encephalitis: brain frontal cortex	Analysis of brain frontal cortex of HIV-seropositive patients with HIV encephalitis (HIVE). HIVE affects >40% of AIDS patients, promoting neurodegeneration and cognitive impairment. Results suggest HIV-mediated dysregulation of genes involved in neuronal maintenance might play an important role.	Co-expression
GDS1730	Autocrine platelet-derived growth factor inhibition effect on malignant gliomas	Analysis of U87 glioblastoma (GBM) cell clones overexpressing a dominant-negative form of platelet-derived growth factor (PDGF) A subunit to inactive the PDGF autocrine signaling loop. The autocrine PDGF loop is a hallmark of GBM. Results identify genes regulated by oncogenic PDGF signaling.	Co-expression
GDS1732	Papillary thyroid cancer	Expression profiling of 7 papillary thyroid carcinoma (PTC) samples. PTC is the most common type of thyroid cancer, representing up to 80% of all malignant thyroid tumors. Results provide insight into potential molecular markers for PTC.	Co-expression
GDS1733	Heat shock transcription factor HSF1 depleted cells response to heat shock: time course	Analysis of HSF1-depleted HeLa cells at various time points up to 24 hours following heat shock treatment at 43 degrees C. Heat shock transcription factor HSF1 silenced using RNA interference (siHSF1_1, siHSF1_2). Results provide insight into the structure and function of the HSF1 signaling network.	Co-expression
GDS1735	Vdelta1 and Vdelta2 gamma delta T cells response to non-TCR agonist  stimulation	Analysis of Vdelta1 (Vd1) and Vdelta2 (Vd2) gamma delta (gd) T cells following stimulation with a non-TCR mediated agonist, PMA/ionomycin. Vd1 and Vd2 cells differ in tissue tropism, TCR usage, and agonist response. Results provide insight into the functional differences between Vd1 and Vd2 cells.	Co-expression
GDS1736	Arachidonic acid effect on prostate cancer cells	Analysis of PC-3 prostate cancer cells incubated with arachidonic acid (AA).  AA is an omega-6 fatty acid shown to induce cancer cell proliferation. Results suggest AA plays an important role in stimulation of growth-related genes and proliferation via phosphatidylinositol 3-kinase (PI3K) signaling.	Co-expression
GDS1746	Primary epithelial cell cultures from prostate tumors	Analysis of epithelial cell cultures from prostate tumor explants. Results identify an epithelial-restricted transcription profile that can be integrated with tumor grade and clinical information with the aim of discriminating indolent and aggressive prostate tumors that are histologically similar.	Co-expression
GDS1750	Mantle cell lymphoma cell lines (HG-U133A)	Expression profiling of 4 mantle cell lymphoma (MCL) cell lines. MCL has the worst prognosis among B-cell lymphomas. Gene expression results combine with genomic profiling results to identify genes that are relevant to MCL pathogenesis and that could also represent possible therapeutic targets.	Co-expression
GDS1753	Colchicine anti-inflammatory effect: time course and dose response	Analysis of umbilical vein endothelial cell line HUVEC at various time points up to 24 hours following treatment with 100 ng/ml or 1 ug/ml of colchicine. Colchicine is an alkaloid used to alleviate rheumatic complaints like gout and to prevent acute attacks of familial Mediterranean fever.	Co-expression
GDS1758	Pterygium	Expression profiling of primary pterygium tissue. Pterygium, a common ocular surface disorder, is a fibrovascular overgrowth from the conjunctiva onto the cornea. Results provide insight into pterygium pathogenesis.	Co-expression
GDS1760	Telomerase reverse transcriptase immortalizing effect on fibroblasts and endothelial cells: time-course	Analysis of normal fibroblasts and endothelial cells, at various population doubling levels (PDLs), following human telomerase reverse transcriptase (hTERT) transfection. hTERT mediates cellular immortalization. Results identify cell-type specific transcriptional responses during immortalization.	Co-expression
GDS1761	NCI60 cancer cell lines	Analysis of 60 cell lines (the NCI60) derived from tumors from a variety of tissues and organs. Such cell lines are used extensively as experimental models of neoplastic disease. Results identify variation in gene expression patterns in the cell lines and their relationships to tumors in vivo.	Co-expression
GDS1768	Platelet-derived growth factor effect on fibroblasts: time course	Expression profiling of AG01518 foreskin fibroblasts at various time points up to 24 hours following stimulation with 10 ng/ml platelet-derived growth factor (PDGF). PDGF is a potent mitogen for fibroblasts and other cells of mesenchymal origin. Results identify genes regulated by PDGF.	Co-expression
GDS177	Cytomegalovirus strain comparison	Human foreskin fibroblasts (HFF) infected with cytomegalovirus strains fhCMV-H (rapid spread in vitro) and fhCMV-T (slow spread in vitro). UV-inactivated viruses also examined to control for response to coat glycoprotein B and active viral infection.	Co-expression
GDS1772	Hypoxia effect on vhl and p53 null mutants	Analysis of cell lines lacking VHL or p53 following exposure to hypoxia. VHL is the gene responsible for degrading transcription factor HIF-1. p53 null mutants examined to identify genes whose expression under hypoxia depends on p53. Results identify genes regulated by HIF-1.	Co-expression
GDS1774	Chronic hepatitis C infection response to Agaricus blazei medicinal extract: peripheral blood cells	Analysis of peripheral blood cells from chronic hepatitis patients following oral administration of Agaricus blazei Murill (AbM) extract 3 times daily for 1 week. AbM extracts are used as a non-prescription remedy for cancer and infections, including hepatitis.	Co-expression
GDS1777	Colon tubular adenoma and carcinoma cells	Analysis of colon tubular adenoma and carcinoma cells microdissected from formalin-fixed paraffin-embedded sections of colon tubular adenomas containing focal adenocarcinomas. Results provide insight into the progression of colon cancers from pre-existing adenomas.	Co-expression
GDS1779	Hypoxia effect on astrocytes	Analysis of purified primary astrocytes exposed to hypoxia for 24 hours. Gene expression in HeLa cells also examined. Astrocytes play critical roles in the proper functioning of the brain. Results provide insight into the molecular events underlying the astrocytic responses to hypoxia.	Co-expression
GDS1780	Colorectal cancer progression: polysomal mRNA profiles	Comparison of polysomal RNA from isogenic cell lines established from a colorectal cancer (CRC) patient. SW480 and SW620 cells derived from the primary tumor and a lymph node metastasis, respectively. The cell lines constitute a cellular model of CRC transition from invasive carcinoma to metastasis.	Co-expression
GDS1783	Vascular smooth muscle response to voltage-dependent and store-operated calcium channel activation	Analysis of cerebral vascular smooth muscle cells after activation of voltage-dependent (VDCCs) or store-operated calcium channels (SOCCs). VDCCs activated by K+ depolarization and SOCCs by thapsigargin. Results provide insight into the effect of different calcium signals on gene expression.	Co-expression
GDS1791	Wilms' tumor	Expression profiling of Wilms' tumor tissue after pre-operative chemotherapy. Stratagene Universal Reference RNA also examined. Results are part of a cross-platform evaluation and compared to data generated from Serial Analysis of Gene Expression.	Co-expression
GDS1792	Gastric tubular adenoma and carcinoma	Analysis of gastric tubular adenoma and carcinoma cells microdissected from formalin-fixed paraffin-embedded sections of gastric biopsies. Early lesions are small and detectable only with a microscope. Results indicate that routinely processed biopsy specimens may be useful in expression profiling.	Co-expression
GDS1806	Modeled microgravity effect on activated T lymphocytes	Analysis of activated T-cells subjected to modeled microgravity. The study seeks to identify microgravity sensitive genes involved in apoptosis and the immune response. Microgravity is an environment of little net gravitational force that is experienced in spaceflight and by free-falling objects.	Co-expression
GDS1807	Hypoxia effect on B lymphocyte cell line	Expression profiling of B lymphocyte P493-6 cells subjected to hypoxia. Cells incubated in 0.1% oxygen for 29 hours, the point of highest expression of hypoxia-inducible factor 1 (HIF-1).  Results identify hypoxia responsive genes in P493-6 cells.	Co-expression
GDS181	Large-scale analysis of the human transcriptome (HG-U95A)	Gene expression profiles from a diverse array of tissues, organs, and cell lines, from the normal physiological state. Represents a preliminary description of the normal mammalian transcriptome.	Co-expression
GDS1812	HPV16 integration and episomal loss effect on cervical keratinocytes	Analysis of high-risk human papillomavirus (HRHPV) HPV16-containing cervical keratinocyte W12 cells selected for integrated HPV16. Results show that HRHPV integration and episome loss are key events in cervical neoplastic progression.	Co-expression
GDS1813	Glial brain tumors	Analysis of 50 glial brain tumors of various histogenesis. Results provide insight into the molecular mechanisms underlying gliomagenesis and define biological pathway maps associated with gliomagenesis as well as distinct glioma subtypes.	Co-expression
GDS1815	High-grade gliomas (HG-U133A)	Analysis of high-grade glioma (HGGs) samples from cases of WHO grade III and IV astrocytomas. Results classify HGGs into molecular subclasses with prognostic value that predict survival and disease progression. The molecular subclasses resemble key stages of neurogenesis.	Co-expression
GDS1816	High-grade gliomas (HG-U133B)	Analysis of high-grade glioma (HGGs) samples from cases of WHO grade III and IV astrocytomas. Results classify HGGs into molecular subclasses with prognostic value that predict survival and disease progression. The molecular subclasses resemble key stages of neurogenesis.	Co-expression
GDS183	Bladder tumor stage classification	Identification of clinically relevant subclasses of bladder carcinoma. Three major stages identified, Ta, T1 and T2-4. Ta tumors further classified into subgroups. A 32-gene molecular classifier was built.	Co-expression
GDS1830	Chemoresistant glioblastomas: expression profile	Expression analysis of cell lines derived from primary and recurrent glioblastomas with resistance to O6-alkylating agents, BCNU and TMZ. Chemoresistance to these widely-used drugs is a major obstacle to tumor treatment. Results identify a transcriptomic signature of resistance to alkylating agents.	Co-expression
GDS1835	Various cell lines and Universal Reference RNA (II)	Analysis of individual cell lines representing different tissues against a Universal Reference RNA (URR). URR prepared from pooled RNA from the individual cell lines. Results indicate the individual cell lines contribute their own unique set of genes, thereby diversifying gene representation in URR.	Co-expression
GDS1839	Follicular lymphomas and response to rituximab	Analysis of lymph node biopsies from 24 follicular lymphoma patients. Biopsies obtained before any systemic therapy. Results analyzed together with the subsequent response of patients to rituximab, a monoclonal antibody directed against the B cell antigen, CD20.	Co-expression
GDS1841	Chronic endoplasmic reticulum stress imposed by misfolded surfactant protein C (HG-U133A)	Analysis of cells that constitutively express misfolded surfactant protein C, which induces chronic endoplasmic reticulum (ER) stress and cytotoxicity. Results provide evidence for an NF-kB-dependent adaptive response to the chronic ER stress imposed by the misfolded protein.	Co-expression
GDS1846	Interferon gamma effect on keratinocytes: time course	Analysis of keratinocytes treated with interferon gamma (IFN-gamma) for up to 48 hours. IFN-gamma is a multifunctional, immunomodulatory cytokine with cell type-specific antiviral activities. Results provide insight into molecular processes regulated by IFN-gamma in keratinocytes.	Co-expression
GDS1847	Vitamin D effect on intestinal epithelial cells	Analysis of intestinal epithelial Caco-2 cells following treatment with 1,25-dihydroxyvitamin D3 for 24 hours. 1,25-dihydroxyvitamin D3 stimulated calcium absorption in the intestine. Results provide insight into the additional effects of vitamin D on intestinal epithelial cells.	Co-expression
GDS1850	Carious pulpal tissue	Expression profiling of core pulpal tissue from carious teeth. RNA pooled from 11 carious teeth. Results provide insight into the molecular events that occur during the progression of dental caries.	Co-expression
GDS1852	siRNA knockdown and transcriptional response to DNA damage	Analysis of HEK293 cells following siRNA knockdown of p53, RelA, or ATM, and subsequent treatment with neocarzinostatin, a radiomimetic drug that induces DNA double-strand breaks. Results indicate RNAi combined with expression profiling is a powerful method for dissecting transcriptional networks.	Co-expression
GDS1854	Glycoconjugate expression profiling in mouse postnatal cerebellar development	We used a custom Affymetrix GeneChip, the "GLYCOv2" array, to measure differences in gene expression patterns from adult and postnatal day 7 (P7) mouse cerebellum RNA. Keywords = Cerebellum, microarray, development, glycoconjugates, glycosyltransferases, proteoglycans, gene expression Keywords: other	Co-expression
GDS1857	Rheumatoid arthritis: synovial tissues	Expression profiling of synovial tissues of patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease characterized by pain, stiffness, swelling, and destruction of joints. Results provide insight into the pathogenesis of RA.	Co-expression
GDS1858	Various miRNA transfections: time course	Analysis of HeLa cells at 12 or 24 hours after transfection with wild type or mutant miR-1 or miR-124. miR-1 is preferentially expressed in heart and skeletal muscle, while miR-124 is preferentially expressed in brain. Results suggest that metazoan miRNAs can reduce the levels of target transcripts.	Co-expression
GDS1869	Heregulin and forskolin mitogenic effect on cultured Schwann cells	Analysis of passage 1 and passage 3 Schwann cell cultures obtained from four donors and maintained in the presence of the heregulin and forskolin. Heregulin and forskolin synergistically drive Schwann cell proliferation in vitro.	Co-expression
GDS1873	Antiestrogen and aromatase inhibitor effect on breast cancer cells	Analysis of estrogen receptor positive, aromatase transfected MCF-7 cells after treatment with an antiestrogen (AE) or an aromatase inhibitor (AI). AEs and AIs are used to treat estrogen-dependent breast cancer. Cells also treated with androgen which is converted to estrogen by aromatase.	Co-expression
GDS1875	Host cell response to HIV-1 Vpr-induced cell cycle arrest: time course	Analysis of cell lines expressing wild-type or mutant HIV-1 Vpr protein at various timepoints following doxycycline induction. Vpr advances HIV pathogenesis by inhibiting the cell cycle at G2/M. Results identify changes in cellular gene expression associated with Vpr-mediated cell cycle arrest.	Co-expression
GDS1886	Moderate hypothermia effect in vitro	Analysis of acute monocytic leukemia THP-1 cells exposed to moderate hypothermia (MH) at 32 degrees C for 24 hours. THP-1 cell line is an in vitro system for analyzing the effects of hypothermia. MH has therapeutic applications. Results show substantial changes in gene expression in response to MH.	Co-expression
GDS1887	Rectal cancer cells and radiotherapy response	Analysis of rectal cancer cells from patients prior to preoperative radiotherapy. Response to radiotherapy determined by histopathologic examination of resected specimens. Results identify gene markers for the characterization and prediction of the response to radiotherapy in rectal cancer.	Co-expression
GDS1902	Cyanobacterial metabolite apratoxin A cytotoxic effect on colon adenocarcinoma cells: time course and dose response	Analysis of colon adenocarcinoma HT29 cells at various time points up to 12 hours following treatment with 2 or 10 nM of the cyanobacterial metabolite apratoxin A. Results provide insight into the molecular mechanisms underlying the cytotoxic effect of apratoxin A on tumor cells.	Co-expression
GDS1904	A Focused Microarray Approach to Functional Glycomics: Transcriptional Regulation of the Glycome	Glycosylation is the most common post-translational modification of proteins, yet genes relevant to the synthesis of glycan structure and function are incompletely represented and poorly annotated on the commercially available arrays.  To fill the need for expression analysis of such genes we employed the Affymetrix technology to develop a focused and highly annotated glycogene chip representing human and murine glycogenes, including glycosyltranferases, nucleotide sugar transporters, glycosidases, proteoglycans and glycan-binding proteins. In this report the array has been used to generate glycogene expression profiles of nine murine tissues.  Global analysis with a hierarchical clustering algorithm, reveals that expression profiles in immune tissues (thymus, spleen, lymph node and bone marrow) are more closely related, relative to those of non-immune tissues (kidney, liver, brain and testes). Of the biosynthetic enzymes, those responsible for synthesis of the core regions of N-and O-linked oligosaccharides are ubiquitously expressed, while glycosyltransferase that elaborate terminal structures are expressed in a highly tissue-specific manner, accounting for tissue and ultimately cell type-specific glycosylation.  Comparison of gene expression profiles with MALDI-TOF profiling of N-linked oligosaccharides suggested that the alpha-1-3 fucosyltransferase IX, Fut9, is the enzyme responsible for terminal fucosylation in kidney and brain, a finding validated by analysis of Fut9 knockout mice. Two families of glycan-binding proteins, C-type lectins and siglecs, are predominately expressed in the immune tissues, consistent with their emerging functions in both innate and acquired immunity. The glycogene chip reported in this study is available to the scientific community through the Consortium for Functional Glycomics (http://www.functionalglycomics.org). Keywords: Glycogenes, Glycomics, Glycosyltransferase, Lectin, Glycosylation, Glycome, Microarray, Kidney, Fut9	Co-expression
GDS1912	X-linked recessive dystonia-parkinsonism	Expression profiling of the caudate nucleus and nucleus accumbens from the brain of a patient with X-linked recessive dystonia-parkinsonism (XDP). XDP is an adult onset disorder characterized by dystonia and parkinsonism. Result provide insight into the pathogenesis of XDP.	Co-expression
GDS1917	Cerebellar cortex in schizophrenia	Analysis of cortical samples corresponding to the crus I/VIIa area of the cerebellum from schizophrenia patients. A study indicates that targets of the RNA-binding ELAV-like protein HuD are overexpressed in the prefrontal cortex of patients with schizophrenia.	Co-expression
GDS1925	Estrogen receptor alpha positive breast cancer cells response to hyperactivation of MAPK pathway	Analysis of estrogen receptor (ER) alpha positive MCF-7 breast cancer cells overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR. Results indicate that increased MAPK activation results in loss of ER-alpha expression.	Co-expression
GDS1926	Leukotriene D4 and thrombin effect on endothelial cells: time course	Temporal analysis of umbilical vein endothelial cells (HUVEC) treated with leukotriene D4 (LTD4) and/or thrombin. LTD4 activates the cysteinyl leukotriene receptor cysLT2-R. Thrombin activates the protease-activated receptor PAR-1. cysLT2-R and PAR-1 may cooperate to augment vascular injury.	Co-expression
GDS1940	Eccentric exercise effect on skeletal muscle: time course	Analysis of vastus lateralis muscles of healthy subjects 3 and 48 hrs after a bout of resistance (RES) exercise of 300 single-leg maximal eccentric contractions (EC). EC is the lengthening of a muscle due to an external force while that muscle is contracting. EC commonly results in muscle damage.	Co-expression
GDS1942	Transgenic Krüppel-like factor 4 induction: time course	Analysis of RKO colon cancer cell line treated for up to 24 hours with ponasterone A to induce expression of a full-length, transgenic Krüppel-like factor 4 (KLF4). KLF4 is an epithelially-enriched, zinc finger transcription factor. Results provide insight into the biochemical function of KLF4.	Co-expression
GDS1954	Various T7 RNA polymerase-based RNA amplification/labeling methods	Comparison of expression profiles generated using various T7 RNA polymerase-based in vitro transcription (IVT) RNA labeling methods. The length of the IVT reactions ranged from 4 to 16 hours. Results provide evidence for amplification method-dependent biases in gene expression data.	Co-expression
GDS1956	Various muscle diseases (HG-U133A)	Analysis of muscle biopsy specimens from patients with various muscle diseases. Results provide insight into the diagnosis and pathogenesis of muscle diseases.	Co-expression
GDS1960	Testicular diffuse large B cell lymphoma	Analysis of testicular diffuse large B cell lymphoma (DLBCL) tissues with small homozygous HLA-DQ/HLA-DR deletions, larger hemizygous MHC complex deletions, or without deletions. Results provide insight into the significance of the downregulation of HLA class II expression in testicular DLBCL.	Co-expression
GDS1962	Glioma-derived stem cell factor effect on angiogenesis in the brain	Analysis of gliomas of different grades. Stem cell factor (SCF) is overexpressed by glioma cells but its role in gliomagenesis has been unclear. Results identify a positive correlation of SCF expression with increasing glioma grade which supports a role for SCF in tumor angiogenesis in the brain.	Co-expression
GDS1965	Melanocyte to melanoma transformation	Expression profiling of normal melanocytes, primary melanoma cells, and metastatic melanoma cells. Results provide insight into changes in advanced melanoma relative to normal melanocytes and reveal new targets that can be used in assessing prognosis, staging, and therapy of melanoma patients.	Co-expression
GDS1968	Endothelial cell response to hypoxia and subsequent reoxygenation	Expression profiling of umbilical vein endothelial cells (HUVECs) subjected to hypoxia for 1 hour and subsequent reoxygenation for various lengths of time up to 24 hours.	Co-expression
GDS1972	RNAlater preservative effect on uterine myometrium: time course	Analysis of uterine myometrial tissue specimens stored in RNAlater preservative for 24 or 74 hours at room temperature. Results indicate RNALater did not contribute any systematic shift in quantitative RNA expression results relative to alternative tissue processing methods (fresh, snap-frozen).	Co-expression
GDS1973	Various prostate cell types	Analysis of basal, luminal secretory, stromal fibromuscular, and endothelial cells of the prostate. Cell types separated with magnetic cell sorting (MACS) based on cell-type specific cluster designation (CD) antigens. Results identify gene expression signatures at the level of individual cell types.	Co-expression
GDS1974	Keratinocyte response to GLI1 and GLI2 induction: time course	Analysis of keratinocyte HaCaT cells at 24 and 72 hours following induction of GLI1 or a constitutively active form of GLI2 from a tetracycline inducible promoter. GLI transcription factors mediate the hedgehog signal in development and carcinogenesis.	Co-expression
GDS1975	Gliomas of grades III and IV (HG-U133A)	Analysis of grades III and IV gliomas of various histologic types. Results used to develop a gene-expression based, histology independent-classification scheme, and provide insight into the biology of gliomas.	Co-expression
GDS1976	Gliomas of grades III and IV (HG-U133B)	Analysis of grades III and IV gliomas of various histologic types. Results used to develop a gene-expression based, histology independent-classification scheme, and provide insight into the biology of gliomas.	Co-expression
GDS1979	Amyloid precursor protein intracellular domain effect on neural cells	Analysis of neural cells induced to express amyloid precursor protein (APP) intracellular domain (AICD) or the combination of AICD and its co-activator Fe65. Secretase processing of APP produces beta-amyloid, the main constituent of Alzheimer plaques, and AICD. Results identify target genes of AICD.	Co-expression
GDS198	Inflammatory myopathy	Molecular profiles of muscle tissue in patients with inflammatory myopathies.	Co-expression
GDS1989	Melanoma progression	Analysis of tissue specimens representing benign nevus, atypical nevus, melanoma in situ, vertical growth phase (VGP) melanoma, and metastatic growth phase (MGP) melanoma. Results identify expression signatures that distinguish benign and atypical nevi and melanomas in situ from VGPs and MGPs.	Co-expression
GDS1993	Colon carcinoma cell line differentiation: transporter and ion channel expression profile	Analysis of colon carcinoma Caco-2 cells cultured for various lengths of time up to 3 weeks in flasks or on filters. An array focusing on transporters and ion channels was used. Results provide insight into the influence of cell differentiation on the mRNA expression of transporters and channels.	Co-expression
GDS2007	Fibrosarcoma cell line response to various cytostatic drugs	Analysis of fibrosarcoma HT1080 cells following exposure to the cytostatic chemotherapeutic agents actinomycin D or vincristine for 24 hours, or doxorubicin for 6 and 24 hours. Results provide insight into the molecular mechanisms underlying the cell death in response to cytotoxic therapies.	Co-expression
GDS2008	Sustained EGR1 expression in endothelial cells: time course (HG-U133A)	Analysis of umbilical vein endothelial cells (HUVEC) at various time points up to 48 hours following transfection with a recombinant adenovirus expressing early growth response-1 (EGR1). EGR1 is implicated in cell growth, apoptosis, and differentiation. Results identify potential EGR1 target genes.	Co-expression
GDS2009	Sustained EGR1 expression in endothelial cells: time course (HG-U133B)	Analysis of umbilical vein endothelial cells (HUVEC) at various time points up to 48 hours following transfection with a recombinant adenovirus expressing early growth response-1 (EGR1). EGR1 is implicated in cell growth, apoptosis, and differentiation. Results identify potential EGR1 target genes.	Co-expression
GDS201	Interferon induction by small hairpin RNA	Embryonic lung fibroblasts (HLF) infected with control lentivirus, or lentivirus expressing MRG15 and MRGX small hairpin RNAs from the H1 polIII promoter. The MRG15 shRNA induces an interferon response that is unrelated to silencing of MRG15.	Co-expression
GDS2010	Wilms' tumor 1-associating protein knockdown	Analysis of umbilical vein endothelial cells (HUVEC) following siRNA knockdown of Wilms' tumor 1-associating protein, WTAP. WTAP interacts with Wilms' tumor 1 (WT1). The Wilms' tumor suppressor gene WT1 is important in the development of the genitourinary system.	Co-expression
GDS2014	Ulcerative colitis	Expression profiling of colonic mucosa from patients with ulcerative colitis, a chronic inflammatory bowel disease of the colon. Colonic mucosa from patients with irritable bowel syndrome used as controls. Biopsies obtained during colonoscopy from region with macroscopically normal appearing mucosa.	Co-expression
GDS2018	Hypoxia-inducible factors-1 and -2 overexpression effect on embryonic kidney cells	Analysis of HEK293T embryonic kidney cells subjected to hypoxia or overexpressing hypoxia-inducible factor (HIF)-1, degradation resistant HIF-1, or HIF-2. Results provide insight into the respective roles of HIF-1 and HIF-2 in the cellular response to hypoxia.	Co-expression
GDS2021	Coronary smooth muscle cell response to beta-1 receptor blockers metoprolol and nebivolol	Expression profiling of coronary smooth muscle cells treated with metoprolol or nebivolol. Metoprolol and nebivolol are beta 1-receptor blockers. In a study of 155 patients with hypertension, adverse effects of metoprolol were higher than nebivolol (Uhlir et al. 1991).	Co-expression
GDS2023	Bronchial epithelial cell response to respiratory syncytial virus infection: time course	Expression profiling of bronchial epithelial cells at 4 and 24 hours following treatment with respiratory syncytial virus (RSV) at 1.0 MOI. RSV is the most common cause of bronchiolitis and pneumonia among infants.	Co-expression
GDS2034	Prostate cancer cell line LNCaP response to synthetic androgen R1881: time course	Expression profiling of prostate cancer cell line LNCaP treated for up to 8 hours with the synthetic androgen R1881. LNCaP cells grow slowly in medium devoid of steroids but resume growth upon the addition of androgens. The study aims to identify direct targets of the androgen receptor.	Co-expression
GDS2035	Vectorless gravity effect on T cell activation	Analysis of T cells costimulated with concanavalin A and anti-CD28 antibody in a vectorless gravity environment, which approximates true freefall or microgravity experienced in spaceflight. Results provide insight into the molecular basis of the altered immune function experienced by astronauts.	Co-expression
GDS2036	Macrophage response to hypoxia	Expression profiling of cultured macrophages subjected to hypoxia for 24 hours. Macrophages were derived from the mononuclear cells of 4 healthy donors.	Co-expression
GDS2038	Epstein-Barr virus nuclear antigen 2 activation	Analysis of Epstein-Barr virus (EBV) negative B-cell lines BL41K3 and BJABK3 following activation of EBV nuclear antigen 2 (EBNA-2). EBNA-2 fused to the hormone-binding domain of the estrogen receptor, and EBNA-2 activated upon estrogen binding. Results identify EBNA-2 target genes.	Co-expression
GDS2039	Endothelial cell morphogenesis (HG-U133A)	Analysis of microvascular endothelial cells stimulated to either proliferate or undergo tubulogenesis in vitro. Results provide insight into the molecular mechanisms underlying the regulation of endothelial cell morphogenesis.	Co-expression
GDS2040	Endothelial cell morphogenesis (HG-U133B)	Analysis of microvascular endothelial cells stimulated to either proliferate or undergo tubulogenesis in vitro. Results provide insight into the molecular mechanisms underlying the regulation of endothelial cell morphogenesis.	Co-expression
GDS2042	Celiac disease: intraepithelial cytotoxic T lymphocytes	Analysis of intraepithelial cytotoxic T lymphocytes (IE-CTLs), aberrantly expressing the cytolytic natural killer (NK) cell lineage receptor NKG2C, from celiac disease patients. Results provide insight into the role of IE-CTLs reprogrammed into NK-like cells in the pathogenesis of celiac disease.	Co-expression
GDS2045	Ductal carcinoma in situ to invasive ductal carcinoma progression (HG-U133A)	Analysis of preinvasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) tumors. Pairs of patient-matched DCIS and IDC tumor specimens analyzed. Results provide insight into the mechanisms underlying the progression of DCIS to IDC.	Co-expression
GDS2046	Ductal carcinoma in situ to invasive ductal carcinoma progression (HG-U133 2.0)	Analysis of preinvasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) tumors. Pairs of patient-matched DCIS and IDC tumor specimens analyzed. Results provide insight into the mechanisms underlying the progression of DCIS to IDC.	Co-expression
GDS2048	Acute rotavirus infection: peripheral blood mononuclear cells	Expression profiling of peripheral blood mononuclear cells (PBMCs) from children with acute rotavirus diarrhea. Rotavirus is the most common cause of severe diarrhea in children.	Co-expression
GDS2049	Glycosylphosphatidylinositol-specific phospholipase D overexpression effect on hepatoma cells: time course	Analysis of hepatoma HepG2 cells 6 and 12 hours following transduction with a recombinant adenovirus expressing glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). Results provide insight into the role of GPI-PLD in hepatic lipid metabolism.	Co-expression
GDS2052	Endometrium throughout the menstrual cycle	Analysis of the normal endometrium at distinct phases of the menstrual cycle. Results provide insight into whether molecular profiles of the endometrium can distinguish the different phases of the menstrual cycle.	Co-expression
GDS2054	Chronic endoplasmic reticulum stress imposed by misfolded surfactant protein C (HG-U133B)	Analysis of cells that constitutively express misfolded surfactant protein C, which induces chronic endoplasmic reticulum (ER) stress and cytotoxicity. Results provide evidence for an NF-kB-dependent adaptive response to the chronic ER stress imposed by the misfolded protein.	Co-expression
GDS2055	Skeletal muscle types (HG-U133A)	Analysis of tibialis anterior, deltoid, quadriceps, and gastrocnemius muscles obtained at autopsy from pediatric and geriatric subjects unaffected by neuromuscular disease. Results provide insight into the molecular basis of the selective involvement of different muscles in muscular dystrophies.	Co-expression
GDS2056	Skeletal muscle types (HG-U133B)	Analysis of tibialis anterior, deltoid, quadriceps, and gastrocnemius muscles obtained at autopsy from pediatric and geriatric subjects unaffected by neuromuscular disease. Results provide insight into the molecular basis of the selective involvement of different muscles in muscular dystrophies.	Co-expression
GDS2057	Androgen receptor modulator effect: time course (HG-U133A)	Analysis of LNCaP cells treated for 6 and 24 hours with RTI-018, an androgen receptor (AR) ligand with a mechanism of action different from that of canonical agonists. Results provide insight into the link between RTI-018 induced AR conformational changes and its ability to regulate gene expression.	Co-expression
GDS2058	Androgen receptor modulator effect: time course (HG-U133B)	Analysis of LNCaP cells treated for 6 and 24 hours with RTI-018, an androgen receptor (AR) ligand with a mechanism of action different from that of canonical agonists. Results provide insight into the link between RTI-018 induced AR conformational changes and its ability to regulate gene expression.	Co-expression
GDS2080	Early and late onset severe preeclampsia: placenta	Analysis of placentas from patients with early or late onset severe preeclampsia. Preeclampsia is a serious pregnancy-associated disorder characterized by hypertension and proteinuria. Results provide insight into the pathogenesis of preeclampsia.	Co-expression
GDS2081	Jun kinase inhibition effect on keratinocytes: time course	Analysis of keratinocytes at various time points up to 48 hours following treatment with the Jun kinase (JNK) inhibitor SP600125. SP600125 is a reversible ATP-competitive inhibitor specific for the three isoforms of JNK. Results identify JNK-regulated genes in epidermal keratinocytes.	Co-expression
GDS2083	Limb immobilization effect on skeletal muscle	Analysis of vastus lateralis muscle after knee immobilization for 48 hours. Limbs immobilized due to injury or illness experience significant muscle atrophy within 1 or 2 weeks. Results provide insight into the mechanisms regulating the rapid protein degradation in immobilized skeletal muscles.	Co-expression
GDS2084	Polycystic ovary syndrome: adipose tissue	Analysis of omental adipose tissues of morbidly obese patients with polycystic ovary syndrome (PCOS). PCOS is a common hormonal disorder among women of reproductive age, and is characterized by hyperandrogenism and chronic anovulation. PCOS is associated with obesity.	Co-expression
GDS2086	Transcription factor p63 inactivation effect on squamous cells (HG-U133A)	Analysis of squamous cells following siRNA knockdown of the transcription factor p63, a homolog of the tumor suppressor p53. p63 encodes multiple isoforms that activate or repress transcription, and is critical for the development and maintenance of squamous epithelia.	Co-expression
GDS2087	Transcription factor p63 inactivation effect on squamous cells (HG-U133B)	Analysis of squamous cells following siRNA knockdown of the transcription factor p63, a homolog of the tumor suppressor p53. p63 encodes multiple isoforms that activate or repress transcription, and is critical for the development and maintenance of squamous epithelia.	Co-expression
GDS2088	Transcription factor p63 inactivation effect on squamous cells (HG-U133 2.0)	Analysis of squamous cell lines following siRNA knockdown of the transcription factor p63, a homolog of the tumor suppressor p53. p63 encodes multiple isoforms that activate or repress transcription, and is critical for the development and maintenance of squamous epithelia.	Co-expression
GDS2089	Skeletal muscle response to weight loss	Analysis of vastus lateralis muscles of morbidly obese patients before and after gastric bypass surgery. Surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight. Results provide insight into the pathogenesis of obesity.	Co-expression
GDS2090	Sphingosine 1-phosphate effect on glioblastoma cells	Analysis of glioblastoma cells treated with sphingosine 1-phosphate (S1P). S1P is a lysophospholipid involved in various cellular processes such as migration, proliferation, and survival. Results provide insight into the effect of S1P on glioblastoma angiogenesis and invasion.	Co-expression
GDS2095	Glucocorticoid receptor activation effect on breast cancer cells: time course (series 1)	Analysis of breast cancer MCF10A-Myc cells at various time points up to 24 hours following treatment with dexamethasone to activate the glucocorticoid receptor (GR). GR activation is critical in the stress response of virtually all cell types.	Co-expression
GDS2096	Glucocorticoid receptor activation effect on breast cancer cells: time course (series 2)	Analysis of breast cancer MCF10A-Myc cells at various time points up to 24 hours following treatment with dexamethasone to activate the glucocorticoid receptor (GR). GR activation is critical in the stress response of virtually all cell types.	Co-expression
GDS2097	Glucocorticoid receptor activation effect on breast cancer cells: time course (series 3)	Analysis of breast cancer MCF10A-Myc cells at various time points up to 24 hours following treatment with dexamethasone to activate the glucocorticoid receptor (GR). GR activation is critical in the stress response of virtually all cell types.	Co-expression
GDS2104	Prostaglandin J2 effect on neuroblastoma cell line: time course	Analysis of neuroblastoma SK-N-SH cells at various time points up to 24 hours following treatment with prostaglandin J2 (PGJ2), a neurotoxic product of inflammation. Results provide insight into mechanisms of PGJ2-induced accumulation/aggregation of ubiquitinated proteins and to neuronal cell death.	Co-expression
GDS2106	Lymphoblastoid cell lines from various CEPH pedigrees	Analysis of lymphoblastoid cell lines of 57 unrelated CEPH individuals from the International HapMap Project. Results used to find association between the expression phenotypes and SNP markers across the genome genotyped on the 57 individuals that belong to various CEPH pedigrees.	Co-expression
GDS2110	Adrenal gland across a 24-hour period	Analysis of whole adrenal glands collected at 4-hour intervals across a 24-hour period from adult females acclimated to a 12hr light, 12hr dark photoperiod. Results provide insight into the nature of oscillatory patterns of gene expression in the adrenal gland.	Co-expression
GDS2113	Pheochromocytomas of various genetic origins	Analysis of 76 adrenal and extra-adrenal pheochromocytomas. These neural crest-derived tumors of uniform phenotype arise from inherited or sporadic mutations in at least six independent genes. Results provide insight into the molecular pathogenesis of pheochromocytomas.	Co-expression
GDS2118	Myelodysplastic syndromes: CD34+ cells	Analysis of CD34+ cells from 55 patients with myelodysplastic syndromes (MDSs). MDSs are a heterogeneous group of hematopoietic malignancies, characterized by blood cytopenias, ineffective hematopoiesis, and a hypercellular bone marrow. Results provide insight into the pathophysiology of MDS.	Co-expression
GDS2125	Methyl-CpG-binding protein 2 binding disruption during neuronal maturation	Analysis of SH-SY5Y cells undergoing PMA-induced neuronal maturational differentiation after transfection with a MeCP2 decoy to disrupt binding of MeCP2 to endogenous targets. Results provide insight into the pathogenesis of Rett syndrome, a neurodevelopmental disorder caused by mutations in MeCP2.	Co-expression
GDS2126	Rheumatoid arthritis: synovial tissues	Analysis of synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis. RA is a chronic, inflammatory joint disease with pronounced inter-patient heterogeneity. Results provide insight into the pathogenesis of RA.	Co-expression
GDS213	Congestive heart failure	Analysis of canine tachycardia-induced cardiomyopathy caused by several weeks of rapid ventricular pacing.  Left ventricular free wall samples from control dogs and dogs with pacing-induced heart failure compared.	Co-expression
GDS214	Duchenne muscular dystrophy (MuscleChip)	Examination of muscle biopsies from Duchenne muscular dystrophy patients and normal subjects of various age groups.  Both mixed groups of patients (5 patient biopsies per group) and individual biopsies analyzed.	Co-expression
GDS2142	Cystic fibrosis patients with mild and severe lung disease: nasal respiratory epithelium (HG-U133A)	Analysis of the nasal respiratory epithelium of cystic fibrosis (CF) patients with mild or severe lung disease. CF patients have identical homozygous deltaF508 CFTR genotypes but exhibit variability in pulmonary disease severity. Results provide insight into the basis of the phenotypic difference.	Co-expression
GDS2143	Cystic fibrosis patients with mild and severe lung disease: nasal respiratory epithelium (HG-U133B)	Analysis of the nasal respiratory epithelium of cystic fibrosis (CF) patients with mild or severe lung disease. CF patients have identical homozygous deltaF508 CFTR genotypes but exhibit variability in pulmonary disease severity. Results provide insight into the basis of the phenotypic difference.	Co-expression
GDS215	Juvenile dermatomyositis muscle profile (MuscleChip)	Examination of skeletal muscle from juvenile dermatomyositis (JDM) patients, a common pediatric inflammatory myopathy. Muscle biopsies processed singly or in mixed groups of two. Patients genotyped for TNFalpha which is associated with prolonged disease.	Co-expression
GDS2153	Dermatomyositis	Analysis of skeletal muscle biopsies of 5 patients with dermatomyositis (DM). DM is an idiopathic inflammatory myopathy characterized by muscle weakness and skin lesions. Results provide insight into the pathogenic pathways responsible for muscle fiber damage and dysfunction in myositis.	Co-expression
GDS2154	Inflammatory dilated cardiomyopathy	Analysis of parvovirus B19 positive endomyocardial biopsy (EMB) specimens from patients with inflammatory dilated cardiomyopathy (DCMi). Results report on a distinctive cardiac expression pattern in DCMi thereby providing insight into the pathogenesis of this DCM subtype.	Co-expression
GDS2164	Simian immune deficiency virus Nef protein expression effect on CD4+ T cells	Analysis of Jurkat CD4+ T cells following induction of simian immune deficiency virus (SIV) Nef from an inducible promoter. The Nef protein is expressed early in HIV and SIV infections and plays a crucial role in disease progression. Results identify Nef-mediated changes in T cell gene expression.	Co-expression
GDS2168	HIV viremia effect on monocytes	Analysis of CD14+ monocytes from 8 HIV patients at the aviremic state during highly active antiretroviral therapy (HAART) and at the viremic state after the cessation of HAART. Results provide insight into the impact of HIV infection and high-level HIV viremia on the function of monocytes.	Co-expression
GDS2170	Transcription factor IIF cofactor GAS41 overexpression	Analysis of SaoS2 cells overexpressing GAS41, a cofactor of the general transcription factor IIF. GAS41 expression from a tet-off vector was suppressed by the addition of doxycycline. Results provide insight into the role of GAS41 in eukaryotic transcription initiation.	Co-expression
GDS2171	Prostate adenocarcinomas of various Gleason patterns	Analysis of prostate adenocarcinoma specimens with Gleason patterns 3, 4, or 5. Adenocarcinoma specimens obtained by radical prostatectomy. Results identify molecular alterations underlying prostate cancer grades.	Co-expression
GDS2175	Cockayne syndrome group B protein-null fibroblast rescue (HG-U133A)	Analysis of Cockayne syndrome group B (CSB) protein-null fibroblasts rescued by expression of CSB cDNA. CS, a neurodegenerative disorder, arises mostly from CSB defects. Results provide insight into how CSB defects cause CS.	Co-expression
GDS2176	Cockayne syndrome group B protein-null fibroblast rescue  (HG-U133B)	Analysis of Cockayne syndrome group B (CSB) protein-null fibroblasts rescued by expression of CSB cDNA. CS, a neurodegenerative disorder, arises mostly from CSB defects. Results provide insight into how CSB defects cause CS.	Co-expression
GDS2180	M-CSF and GM-CSF differentiated macrophages response to bacillus Calmette-Guerin (Subset A)	Analysis of granulocyte-macrophage colony-stimulating factor (CSF) or macrophage-CSF differentiated macrophages stimulated with bacillus Calmette-Guerin. The two macrophage types differ in their resistance to mycobacterial infection. Results identify host resistance or susceptibility genes.	Co-expression
GDS2182	M-CSF and GM-CSF differentiated macrophages response to bacillus Calmette-Guerin (Subset B)	Analysis of granulocyte-macrophage colony-stimulating factor (CSF) or macrophage-CSF differentiated macrophages stimulated with bacillus Calmette-Guerin. The two macrophage types differ in their resistance to mycobacterial infection. Results identify host resistance or susceptibility genes.	Co-expression
GDS2183	M-CSF and GM-CSF differentiated macrophages response to bacillus Calmette-Guerin (Subset C)	Analysis of granulocyte-macrophage colony-stimulating factor (CSF) or macrophage-CSF differentiated macrophages stimulated with bacillus Calmette-Guerin. The two macrophage types differ in their resistance to mycobacterial infection. Results identify host resistance or susceptibility genes.	Co-expression
GDS2189	BRCA1/CtIP/ZBRK1 repressor complex depletion effect on mammary epithelial cells	Analysis of MCF10A mammary epithelial cells (MECs) in 3D culture following depletion of the BRCA1/CtIP/ZBRK1 repressor complex using BRCA1 or CtIP RNAi. Results provide insight into the molecular mechanisms underlying the accelerated mammary tumor growth correlated with impaired BRCA1 function.	Co-expression
GDS2190	Bipolar disorder: dorsolateral prefrontal cortex	Analysis of postmortem dorsolateral prefrontal cortex from 30 adults with bipolar disorder. Results provide insight into the pathophysiology of the disease.	Co-expression
GDS2191	Bipolar disorder: orbitofrontal cortex	Analysis of postmortem orbitofrontal cortex from 10 adults with bipolar disorder. Results provide insight into the pathophysiology of the disease.	Co-expression
GDS2193	Sry-related high mobility group box 4 knockdown effect on adenoid cystic carcinoma cells	Analysis of adenoid cystic carcinoma (ACC) derived cells (ACC3) following RNAi knockdown of Sry-related high mobility group box 4 (Sox4). Sox4 is one of the most upregulated genes in ACC. Results provide insight into the role of Sox4 in the pathogenesis of ACC.	Co-expression
GDS2200	Non-melanoma skin cancer	Analysis of normal skin, actinic keratotic (AK) lesion, and squamous cell carcinoma (SCC) tumor biopsies from 5 patients with non-melanoma skin cancer (NMSC). Results provide insight into the molecular pathogenesis of NMSC.	Co-expression
GDS2201	Serrated and conventional adenocarcinomas	Comparison of serrated and conventional colorectal adenocarcinoma tumor samples. Results differentiate serrated from conventional colorectal carcinomas (CRC) and provide insight into the molecular pathogenesis of serrated CRC.	Co-expression
GDS2204	Universal reference RNA in various amounts	Analysis of 1, 2, 5 or 10 ug of Stratagene universal human reference RNA as starting material. Results provide insight into the influence of starting RNA quantity on the subsequent gene expression signal measured from a microarray.	Co-expression
GDS2205	Dilated cardiomyopathy: left ventricle	Comparison of subendocardial left ventricular tissue samples from 7 patients with dilated cardiomyopathy (DCM) to those from 5 patients with non-failing (NF) hearts. DCM is a common cause of heart failure. Results contribute to the identification of a gene expression signature for DCM.	Co-expression
GDS2206	Dilated cardiomyopathy: septum	Comparison of septal myocardial tissue samples from 13 patients with dilated cardiomyopathy (DCM) to those from 15 patients with non-failing (NF) hearts. DCM is a common cause of heart failure. Results contribute to the identification of a gene expression signature for DCM.	Co-expression
GDS2213	Hepatoma cell response to inhibition of DNA methylation and histone deacetylation	Analysis of HepG2 hepatoma cells following treatment with 5-aza-2'-deoxycytidine (5-aza-dC) to inhibit DNA methylation, or trichostatin A (TSA) to inhibit histone deacetylation, or both. Results identify epigentically regulated genes in hepatoma cells.	Co-expression
GDS2214	Septic neutrophil response to lipopolysaccharide and high mobility group box 1 protein	Analysis of septic neutrophils treated with lipopolysaccharide or high mobility group box 1 (HMGB1) protein. Neutrophils isolated from patients with sepsis-induced acute lung injury (ALI). HMGB1 is a late mediator of endotoxin lethality, and neutrophils play a role in endotoxemia-associated ALI.	Co-expression
GDS2215	Insecticides chlorpyrifos and cyfluthrin effect on primary fetal astrocytes	Analysis of primary fetal astrocytes following exposure to the insecticide chlorpyrifos, an organophosphate, or cyfluthrin, a pyrethroid. Results provide insight into the neurotoxicity of cyfluthrin compared to chlorpyrifos and the mechanisms underlying the neurotoxicity of both insecticides.	Co-expression
GDS2216	Lipopolysaccharide antagonist effect on lipopolysaccharide-stimulated dendritic cells: time course	Analysis of monocyte-derived dendritic cells treated with cyanobacterial product (CyP) for 1 or 3 hours, or with lipopolysaccharide (LPS) in the presence or absence of CyP for 3 hours. Results provide insight into the extent of the antagonistic activity of CyP on LPS-induced responses.	Co-expression
GDS2219	Gene expression analysis of testicular DLBCL: ABC or GCB subtype?	Diffuse large B cell lymphomas (DLBCL) constitute a heterogeneous group of lymphomas in which germinal center B cell-like and activated B cell-like subtypes can be discerned based on pathology, clinical presentation and gene expression patterns. Testicular DLBCL form an immune-privileged site-related subgroup of DLBCL with an unfavorable prognosis. We used cDNA microarray analysis, immunohistochemistry for CD10, Bcl6 and MUM1, and somatic hypermutation analysis of the immunoglobulin heavy chain gene rearrangements to determine the subtype of primary testicular DLBCL. Immunohistochemistry revealed 14/22 testicular DLBCL with an activated B cell-like immunophenotype and 8/22 with an ambiguous immunophenotype co-expressing CD10 and high levels of MUM1. cDNA microarray analysis of these 22 and 4 additional cases showed a uniform activated B cell-like gene expression pattern in both immunophenotypes. Somatic hypermutation analysis showed a very high mutation load in 7 cases tested, but intraclonal heterogeneity was found at low level in only one of these cases. We conclude that primary testicular DLBCL have uniform activated B cell-like subtype characteristics despite a number of cases showing an ambiguous immunophenotype. Keywords: Gene expression	Co-expression
GDS222	Microarray technology comparison (3OPHs version 1)	Part of a comparison of spotted long oligonucleotide arrays with in situ synthesized 25-mer arrays. Examination of amplified and unamplified K562 erythroleukemia RNA and Stratagene Universal Human Reference RNA.	Co-expression
GDS2221	Galectin-1 maturative effect on monocyte-derived dendritic cells	Analysis of monocyte-derived dendritic cells induced to mature with galectin-1, a member of the beta-galactoside-binding lectin family that binds to cell surface glyconjugates. Results provide insight into the role of galectin-1 in the immunobiology of dendritic cells.	Co-expression
GDS223	Microarray technology comparison (HG-U95A)	Part of a comparison of spotted long oligonucleotide arrays with in situ synthesized 25-mer arrays. Examination of amplified and unamplified K562 erythroleukemia RNA and Stratagene Universal Human Reference RNA.	Co-expression
GDS2230	Intestinal absorptive cell model response to iron deficiency and overload	Analysis of intestinal CaCo-2 cell line grown in medium free of iron or supplemented with hemin to mimic iron overload. Intestinal iron absorption is crucial for systemic iron homeostasis. Results provide insight into molecular mechanisms regulating iron metabolism.	Co-expression
GDS2234	Skeletal muscle response to endurance exercise training	Comparison of vastus lateralis muscles of previously sedentary individuals with improved insulin sensitivity (SI) after 20 weeks of exercise to those with no change in SI. Results provide insight into the mechanisms involved in the improvement in SI induced by regular exercise.	Co-expression
GDS2239	Hepatitis C virus core protein effect on hepatocyte cell line	Analysis of HepG2 hepatocytes following induction of hepatitis C virus (HCV) core protein expression. HCV core protein is implicated in the development of hepatocellular carcinoma (HCC). Results provide insight into the molecular processes affected by the HCV core protein.	Co-expression
GDS2240	Ileocecal epithelial cell line response to Cryptosporidium parvum infection: time course	Analysis of HCT-8 ileocecal epithelial cells at various time points up to 72 hours after infection with Cryptosporidium parvum, an obligate intracellular protozoan that is a major cause of gastrointestinal diseases. Results provide insight into the interaction between the host cell and C. parvum.	Co-expression
GDS2241	Trophoblast cell lines	Comparison of BeWo and JEG3 trophoblast cell lines. Trophoblast cell lines are used as surrogates for primary trophoblast cells in the study of placental function. Results provide insight into the differences between the two cell lines.	Co-expression
GDS2242	Acute promyelocytic leukemia	Analysis of bone marrow samples from 18 patients with acute promyelocytic leukemia (APL). Fms-like tyrosine kinase 3 (Flt3) is mutated in 35 to 40% of APL cases. Results provide insight into the role of Flt3 mutations in the pathogenesis of APL.	Co-expression
GDS2244	Melanoma cell line response to E2F-1 overexpression and doxorubicin treatment	Analysis of E2F-1 overexpressing SK-MEL-2 melanoma cells treated with the anti-cancer drug doxorubicin (dox). Results provide insight into the molecular mechanisms underlying the synergistic effect on melanoma cell apoptosis observed when E2F-1 overexpression is combined with dox treatment	Co-expression
GDS2245	Uterine fibroids with mutated fumarate hydratase (I)	Analysis of uterine fibroids with mutations in the fumarate hydratase (FH) gene. FH  catalyzes the hydration of fumarate in the TCA cycle. Heterozygous germline mutations in FH cause uterine fibroids and renal cell cancer. Results provide insight into the pathogenesis of TCA cycle-related tumors.	Co-expression
GDS2246	Uterine fibroids with mutated fumarate hydratase (II)	Analysis of uterine fibroids with mutations in the fumarate hydratase (FH) gene. FH  catalyzes the hydration of fumarate in the TCA cycle. Heterozygous germline mutations in FH cause uterine fibroids and renal cell cancer. Results provide insight into the pathogenesis of TCA cycle-related tumors.	Co-expression
GDS2250	Basal-like breast cancer tumors	Analysis of sporadic basal-like cancer (BLC), BRCA-associated breast cancer, and non-BLC tumors. Sporadic BLC are phenotypically similar to BRCA1-associated cancers. Results provide insight into the molecular pathogenesis of BLC and BRCA1-associated breast cancer.	Co-expression
GDS2251	Myeloid leukemia cell lines	Comparison of myeloid leukemia cells to normal monocytes. Transcriptional status of each gene compared to its CpG methylation state. The methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes.	Co-expression
GDS2255	Transmigrated neutrophils in the alveolar space of endotoxin-exposed lung	Analysis of neutrophils that transmigrate to the alveolar space. Transmigration induced by bronchoscopic instillation of volunteers with endotoxin (LPS). Results identify differences between pulmonary and circulating neutrophils that occur early in endotoxin-induced lung inflammation.	Co-expression
GDS2287	Airway epithelial cell response to Pseudomonas aeruginosa rsmA mutant infection	Analysis of airway epithelial cells infected with Pseudomonas aeruginosa PAO1 or the rsmA mutant. RsmA is a small RNA-binding protein that plays a role in the regulation of virulence-related genes in P. aeruginosa. Results provide insight into the influence of RsmA-regulated functions on the host.	Co-expression
GDS2295	Aplidin and cytarabine effect on diffuse large B cell lymphoma cell line	Analysis of diffuse large B cell lymphoma SKI-DLCL cells treated with Aplidin, cytarabine (AraC), or both anticancer drugs. The effect of the drugs on animals with SKI-DLCL cell-derived tumors also examined. Results provide insight into the action of Aplidin alone and in combination with AraC.	Co-expression
GDS2297	Gefitinib effect on various non-small cell lung cancer cell lines (HG-U133A)	Analysis of baseline non-small cell lung cancer (NSCLC) cell lines with a broad range of sensitivity to the anticancer drug gefitinib. Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Results used to define a gene expression signature of gefitinib sensitivity.	Co-expression
GDS2298	Gefitinib effect on various non-small cell lung cancer cell lines (HG-U133B)	Analysis of baseline non-small cell lung cancer (NSCLC) cell lines with a broad range of sensitivity to the anticancer drug gefitinib. Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Results used to define a gene expression signature of gefitinib sensitivity.	Co-expression
GDS2307	Oxidatively modified LDL effect on retinal pigment epithelial cell line	Analysis of retinal pigment epithelial ARPE-19 cells following treatment with LDL or oxidatively modified LDL (ox-LDL) for 48 hours. Results provide insight into the role of ox-LDLs in the development of age-related macular degeneration.	Co-expression
GDS2310	Exercise effect on white blood cells	Analysis of white blood cells (WBCs) from 5 males following exhaustive or moderate exercise. Results provide insight into the effects of exercise at the molecular level and the feasibility of using gene expression profiles of WBCs to monitor exercise and training load.	Co-expression
GDS232	Medulloblastoma metastasis	Identification of genes causing medulloblastoma tumors to metastasize. Analyzed 23 primary medulloblastomas clinically designated as either metastatic or non-metastatic.	Co-expression
GDS2321	Polyethylene glycol-conjugated G-CSF mobilized CD34+ cells	Analysis of granulocyte colony stimulating factor (G-CSF) or polyethylene glycol-conjugated (pegylated) G-CSF mobilized CD34+ hematopoietic stem and progenitor cells from multiple myeloma patients undergoing chemotherapy. Pegylated G-CSF has a longer half-life than unconjugated G-CSF.	Co-expression
GDS2323	Estrogen-starved breast cancer cell line: time course	Analysis of breast cancer MCF7/BUS cells starved of estrogen for up to 2 days. Results compared to that from an experiment (GDS2324) examining the response to low concentrations of 17beta-estradiol (E2). Results provide insight into the E2 sensitivity of E2 inducible or suppressible genes.	Co-expression
GDS2324	Low concentrations of 17beta-estradiol effect on breast cancer cell line	Analysis of breast cancer MCF7/BUS cells treated with 17beta-estradiol (E2) at concentrations up to 100 pM. Results compared to that from an experiment examining the response to hormone starvation (GDS2323). Results provide insight into the E2 sensitivity of E2 inducible or suppressible genes.	Co-expression
GDS2332	Neisseria meningitidis non-adherent mutant infected umbilical vein endothelial cells	Analysis of umbilical vein endothelial cells 4 hours following infection with adherent wild type, frpC-deficient mutant, or the non-adherent (delta pilD) mutant form of Neisseria meningitidis. Results provide insight into the role of adherence-mediated signaling in N. meningitidis infections.	Co-expression
GDS2333	Neisseria meningitidis non-adherent mutant infected umbilical vein endothelial cells: time course	Analysis of umbilical vein endothelial cells 1 and 6 hours following infection with adherent wild type or the non-adherent (delta pilD) mutant form of Neisseria meningitidis. Results provide insight into the role of adherence-mediated signaling in N. meningitidis infections.	Co-expression
GDS2339	Hepatitis B surface antigen effect on hepatoma cell line	Analysis of hepatoma HepG2 cells secreting the hepatitis B surface antigen (HBsAg). Transfected cells examined 4 and 8 days after seeding. Results provide insight into the effect of persistently secreting HBsAg on the host cell.	Co-expression
GDS2341	Type I and Type II interferons effect on lung epithelial cell line: time course	Analysis of lung epithelial A549 cells 6 and 24 hours following treatment with type I interferon (IFN), type II IFN, or both. Results provide insight into the molecular basis of the synergistic antiviral and antiproliferative effects observed when type I and type II IFNs are combined.	Co-expression
GDS2342	Chronic phase chronic myelogenous leukemia: CD34+ hematopoietic stem and progenitor cells	Analysis of CD34+ hematopoietic stem and progenitor cells from the bone marrow of untreated patients with chronic myelogenous leukemia (CML) in first chronic phase. Results provide insight into the pathogenesis of chronic phase CML.	Co-expression
GDS2352	T cell receptor-independent basal signaling in unstimulated Jurkat T cells	Analysis of resting Jurkat T cells and derived mutants lacking T cell receptor (TCR) signaling proteins. Even without TCR engagement, the signaling pathways normally responsive to TCR are not inert. Results provide insight into the transcriptional consequences of the constitutive signaling pathway.	Co-expression
GDS2356	Hair follicles from males and females	Analysis of unstaged hair follicles from males and females. Results provide insight into the feasibility of extracting intact RNA, from a small number of hair follicles, in sufficient quantities for expression profiling.	Co-expression
GDS2358	DJ-1 knockdown effect on lung carcinoma cell line	Analysis of non-small-cell lung carcinoma H157 cells following DJ-1 siRNA knockdown. DJ-1, a cancer- and Parkinson's disease-associated protein, protects cells from toxic stresses.	Co-expression
GDS2362	Presymptomatic and symptomatic malaria: peripheral blood mononuclear cells	Comparison of peripheral blood mononuclear cells of subjects with early, presymptomatic, experimentally acquired malaria to those with acute, uncomplicated, naturally acquired malaria. Results provide insight into the immune response to malaria in these two stages of infection.	Co-expression
GDS2366	Preadipocytes from anatomically separate fat depots (HG-U133A)	Analysis of undifferentiated and differentiated preadipocytes from abdominal subcutaneous, mesenteric, and greater omental regions. Separate fat depots differ in size, function, and contribution to pathological states. Results provide insight into the contribution of preadipocytes to this variation.	Co-expression
GDS2367	Tamoxifen effect on breast cancer cell line expressing estrogen receptor alpha and beta	Analysis of estrogen receptor alpha (ERalpha)-positive MCF-7 breast cancer (BC) cells infected with adenovirus-ERbeta and treated with tamoxifen (Tam). Tam is a selective ER modulator used in BC prevention and treatment. Results provide insight into Tam activity in the presence of both ERs.	Co-expression
GDS2368	Preadipocytes from anatomically separate fat depots (HG-U133B)	Analysis of undifferentiated and differentiated preadipocytes from abdominal subcutaneous, mesenteric, and greater omental regions. Separate fat depots differ in size, function, and contribution to pathological states. Results provide insight into the contribution of preadipocytes to this variation.	Co-expression
GDS2373	Squamous cell lung carcinomas	Analysis of primary squamous cell lung carcinomas (SCCs) from 129 patients. SCCs and adenocarcinomas compose the majority of non small cell lung cancers. Gene expression profiles were compared to clinical outcome.	Co-expression
GDS2374	Glucose-dependent insulinotropic peptide-dependent adrenal hyperplasia	Analysis of hyperplastic adrenal glands from patients with glucose-dependent insulinotropic peptide (GIP)-dependent Cushing's Syndrome (CS) or ACTH-dependent CS. Results provide insight into the molecular basis of the ectopic adrenal expression of GIPR in GIP-dependent CS.	Co-expression
GDS2378	UTP and alpha-chemokine CXCL12 effect on CD34+ hematopoietic stem cells	Analysis of CD34+ hematopoietic stem cells (HSCs) treated with UTP, alpha-chemokine CXCL12, or both. CXCL12 is a HSC chemoattractant secreted by the bone marrow. Results provide insight into the molecular mechanisms underlying the enhancement of CXCL12-dependent HSC migration by UTP.	Co-expression
GDS2381	Atopic dermatitis (HG-U133A)	Analysis of lesional and non-lesional skin biopsy specimens from adult patients with atopic dermatitis (AD). Results provide insight into the molecular changes associated with early AD inflammation.	Co-expression
GDS2382	Atopic dermatitis (HG-U133B)	Analysis of lesional and non-lesional skin biopsy specimens from adult patients with atopic dermatitis (AD). Results provide insight into the molecular changes associated with early AD inflammation.	Co-expression
GDS2384	Xenograft model of prostate carcinoma progression	Analysis of prostate cancer (PC) xenografts collected from male mice up to 14 days after castration. The androgen receptor (AR) plays a pivotal role in the growth and survival of prostate carcinoma.  Results provide insight into the role of selective adaptations of the AR pathway in PC progression.	Co-expression
GDS2386	Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression	BACKGROUND: Assessment of gene expression in peripheral blood may provide a noninvasive screening test for allograft rejection. We hypothesized that changes in peripheral blood expression profiles would correlate with biopsy-proven rejection and would resolve after treatment of rejection episodes. METHODS AND RESULTS: We performed a case-control study nested within a cohort of 189 cardiac transplant patients who had blood samples obtained during endomyocardial biopsy (EMB). Using Affymetrix HU133A microarrays, we analyzed whole-blood expression profiles from 3 groups: (1) control samples with negative EMB (n=7); (2) samples obtained during rejection (at least International Society for Heart and Lung Transplantation grade 3A; n=7); and (3) samples obtained after rejection, after treatment and normalization of the EMB (n=7). We identified 91 transcripts differentially expressed in rejection compared with control (false discovery rate <0.10). In postrejection samples, 98% of transcripts returned toward control levels, displaying an intermediate expression profile for patients with treated rejection (P<0.0001). Cluster analysis of the 40 transcripts with >25% change in expression levels during rejection demonstrated good discrimination between control and rejection samples and verified the intermediate expression profile of postrejection samples. Quantitative real-time polymerase chain reaction confirmed significant differential expression for the predictive markers CFLAR and SOD2 (UniGene ID No. 355724 and No. 384944). CONCLUSIONS: These data demonstrate that peripheral blood expression profiles correlate with biopsy-proven allograft rejection. Intermediate expression profiles of treated rejection suggest persistent immune activation despite normalization of the EMB. If validated in larger studies, expression profiling may prove to be a more sensitive screening test for allograft rejection than EMB. Keywords: human, peripheral blood, before and after therpay, untreated control	Co-expression
GDS2395	Epidermal stem cell and transit-amplifying cell (HG-U133A)	Analysis of cDNA libraries each generated from a single cultured epidermal stem cell (SC) or transit-amplifying (TA) cell. TA cells are SC progenies that are destined to terminally differentiate. Single cell expression profiling avoids the problem of potentially masking cellular heterogeneity.	Co-expression
GDS2396	Epidermal stem cell and transit-amplifying cell (HG-U133B)	Analysis of cDNA libraries each generated from a single cultured epidermal stem cell (SC) or transit-amplifying (TA) cell. TA cells are SC progenies that are destined to terminally differentiate. Single cell expression profiling avoids the problem of potentially masking cellular heterogeneity.	Co-expression
GDS2397	Idiopathic myelofibrosis: hematopoietic CD34+ stem cells	Analysis of pooled hematopoietic CD34+ stem cells from peripheral blood of patients with idiopathic myelofibrosis (IM), a rare chronic myeloproliferative disorder. Results provide insight into the molecular pathogenesis of IM.	Co-expression
GDS2414	Decidual stromal cell response to trophoblast conditioned medium: time course	Analysis of decidualized endometrial stromal cells at various time points up to 12 hours following treatment with conditioned media from trophoblasts. Results provide insight into the paracrine signaling between the trophoblast and the decidua.	Co-expression
GDS2415	Breast carcinomas and local recurrence	Analysis of primary breast carcinoma tumors from 50 patients who received breast-conserving therapy (BCT). 19 patients subsequently developed a local recurrence of the carcinoma. 9 recurrent tumors also examined. Compared to mastectomy, BCT is associated with a higher rate of local recurrence.	Co-expression
GDS2416	Different areas of cervical cancer tumors	Analysis of 33 biopsies from 11 cervical cancer patients. Biopsies were obtained from 2 to 5 different areas of each tumor. Results provide insight into the extent of intratumor heterogeneity in gene expression in cervical cancer patients.	Co-expression
GDS2417	Exercise effect on white blood cells	Analysis of whole white blood cells (WBC), peripheral blood mononuclear cells, and T lymphocytes following exhaustive exercise. Results provide insight into the improvements in reliability and sensitivity attained using WBC subtypes to monitor physiological states.	Co-expression
GDS2418	Vulvar intraepithelial neoplasia	Analysis of vulvar intraepithelial neoplasia (VIN) lesions. VIN is a premalignant disorder caused by human papillomaviruses. Results provide insight into the pathogenesis of VIN.	Co-expression
GDS2419	Multiple sclerosis response to interferon beta-1a therapy: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis (MS) patients 1 day before, 1 day after, and up to 12 months after the initiation of interferon beta-1a (IFN-beta-1a) therapy. Results identify biomarkers for beta-IFN responsiveness.	Co-expression
GDS2422	Fibroblast growth factor 2 restimulation effect on embryonic fibroblast	Analysis of embryonic fibroblasts starved of fibroblast growth factor 2 (FGF2) for 2 days and subsequently restimulated with FGF2. FGF2 promotes the self-renewal of embryonic stem cells (ESCs) . Results provide insight into the molecular mechanisms underlying ESC self-renewal in response to FGF2.	Co-expression
GDS2423	Embryonic fibroblast-like differentiated cell	Analysis of embryonic fibroblast-like (EF) differentiated cells derived from H9 embryonic stem cells. Foreskin fibroblasts, and undifferentiated H9 and embryonic carcinoma cells also examined. Results provide insight into the differences between EF cells and fibroblasts at the molecular level.	Co-expression
GDS2426	Hypertension-related calcium-regulated gene overexpression effect on kidney cell line	Analysis of HEK293 kidney cells overexpressing the hypertension-related calcium-regulated gene (HCaRG). HCaRG is involved in the control of renal cell proliferation and differentiation. Results provide insight into the role of HCaRG in kidney repair after injury.	Co-expression
GDS2428	DNA demethylation effect on glioblastoma cultures	Analysis of short-term cultured glioblastoma cells treated with 5-aza-dC to induce DNA demethylation. Glioblastoma cells derived from 3 independent primary glioblastomas. Results provide insight into the role of epigenetic alterations in glioblastoma gene inactivation.	Co-expression
GDS2429	Monocyte differentiation to macrophage and subsequent polarization (HG-U133A)	Analysis of monocytes (MCs) treated with M-CSF to induce differentiation into macrophages (MPs), and mature MPs treated with either IFN-gamma and LPS or IL-4 to induce polarization to M1 or M2 cells, respectively. Results provide insight into MC to MP differentiation and polarized activation.	Co-expression
GDS2430	Monocyte differentiation to macrophage and subsequent polarization (HG-U133B)	Analysis of monocytes (MCs) treated with M-CSF to induce differentiation into macrophages (MPs), and mature MPs treated with either IFN-gamma and LPS or IL-4 to induce polarization to M1 or M2 cells, respectively. Results provide insight into MC to MP differentiation and polarized activation.	Co-expression
GDS2431	Erythroid differentiation in vitro: time course	Analysis of adult differentiating CD34+ hematopoietic progenitor cells at various time points up to 11 days of growth in serum-free medium containing erythropoietin, interleukin-3 and stem cell factor. Results provide insight into the molecular basis of erythropoiesis.	Co-expression
GDS2432	Pituitary adenoma predisposition: whole blood	Analysis of whole blood from individuals with pituitary adenoma predisposition. Pituitary adenomas are common benign neoplasms characterized by oversecretion of growth hormone, leading to acromegaly. Results provide insight into the molecular basis of pituitary adenomas.	Co-expression
GDS2444	Dichloroacetate effect on cultured lung carcinoma and glioblastoma cells	Analysis of A549 lung carcinoma and M059K glioblastoma cells treated with dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase. DCA shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential in cancer cells.	Co-expression
GDS2445	Polycomb group protein depletion effect on embryonic fibroblasts	Analysis of embryonic fibroblasts depleted of the polycomb group (PcG) proteins EZH2, EED, SUZ12, or BMI-1. PcG proteins form complexes that regulate the expression of homeotic genes during development. Results provide insight into the mechanisms employed by PcGs to control development.	Co-expression
GDS2446	PTEN deletion mutation effect on colon cancer cells	Analysis of HCT116 colon cancer cells in which tumor suppressor gene PTEN had been deleted by gene targeting. Activation of PI3K signaling by PTEN mutations can lead to activation of p53-mediated cell growth suppression. Results provide insight into the role of PTEN in cancer pathogenesis.	Co-expression
GDS2447	Transcriptional profiling of tobacco smokers versus controls	Analysis of lymphoblast cell lines derived from six subjects with active nicotine dependence. Depression susceptibility, nicotine dependence, alcohol dependence, and cannabis dependence have correlated genetic and environmental diatheses. Results provide insight into complex behaviour disorders.	Co-expression
GDS2448	Erythropoietin effect on early erythroid progenitor cells	Analysis of CD34+ erythroid progenitors stimulated with erythropoietin (Epo) with or without LY294002, a PI3K inhibitor. Epo promotes differentiation and proliferation of early progenitors via activation of PI3K. Results provide insight into molecular mechanisms underlying the effects of Epo.	Co-expression
GDS2452	Histone deacetylase inhibitor effect on endothelial cells	Analysis of umbilical vein endothelial cells treated with 500 nM trichostatin A (TSA) for 24 hours. TSA is a histone deacetylase inhibitor. TSA treatment results in decreased endothelial nitric oxide synthase expression.	Co-expression
GDS2453	PPAR-gamma activation and RAR-alpha inhibition effect on dendritic cells	Analysis of dendritic cells (DCs) treated with the PPAR-gamma ligand rosiglitazone alone or with the RAR-alpha antagonist AGN193109. DCs treated with the RAR-alpha agonist AM580 also examined. Results provide insight into the contribution of retinoid signaling to the PPAR-gamma response.	Co-expression
GDS2470	Neural tube defect: amniotic fluid	Analysis of amniotic fluid samples from pregnant women carrying fetuses with neural tube defects (NTDs) diagnosed during ultrasound examination. Results provide insight into the feasibility of using amniotic fluid samples to characterize polygenic disorders, such as NTD, at the molecular level.	Co-expression
GDS2471	Serum amyloid A effect on endothelial cells: time course	Analysis of umbilical vein endothelial (HUVEC) cells stimulated with serum amyloid A (SAA) for up to 48 hours. SAA is an acute phase protein.	Co-expression
GDS2478	Inflammatory acne	Analysis of inflammatory papules and normal skin from six patients with acne. Results provide insight into the molecular pathogenesis of acne.	Co-expression
GDS2484	Dermal lymphatic endothelial cell response to tumor necrosis factor alpha	Analysis of dermal lymphatic endothelial cells treated with tumor necrosis factor alpha to define inflammation-induced changes. Results provide insight into the mechanisms regulating the transmigration of leukocytes from inflamed skin across the lymphatic vessel endothelium into lymph nodes.	Co-expression
GDS2486	Small airway epithelium response to cigarette smoking	Analysis of small airway epithelial cells of phenotypically normal smokers. The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. Results provide insight into how smoking modifies small airway structure and function.	Co-expression
GDS2489	Large airway epithelium response to cigarette smoking (HuGeneFL)	Analysis of large airway epithelial cells of phenotypically normal smokers. Lung cancer tumors exhibit neuroendocrine properties, and chronic smokers have increased numbers of neuroendocrine cells. Results provide insight into the effect of cigarette smoking on neuroendocrine cells.	Co-expression
GDS2490	Large airway epithelium response to cigarette smoking (HG-133A)	Analysis of large airway epithelial cells of phenotypically normal smokers. Lung cancer tumors exhibit neuroendocrine properties, and chronic smokers have increased numbers of neuroendocrine cells. Results provide insight into the effect of cigarette smoking on neuroendocrine cells.	Co-expression
GDS2491	Large airway epithelium response to cigarette smoking (HG-U133 2.0)	Analysis of large airway epithelial cells of phenotypically normal smokers. Lung cancer tumors exhibit neuroendocrine properties, and chronic smokers have increased numbers of neuroendocrine cells. Results provide insight into the effect of cigarette smoking on neuroendocrine cells.	Co-expression
GDS2493	Glucocorticoid sensitive and resistant acute lymphoblastic leukemia samples	Analysis of pretreatment acute lymphoblastic leukemia samples that are either sensitive or resistant to glucocorticoid (GC)-induced apoptosis in vitro. Results used to search a database of expression profiles of pharmacologic treatment of cells for small molecules that reverse the resistance to GCs.	Co-expression
GDS2494	Rapamycin effect on a glucorticoid-resistant T cell lymphoblastic leukemia cell line: time course	Analysis of the glucocorticoid (GC) resistant T cell lymphoblastic leukemia cell line CEM-c1 following treatment with rapamycin for 3 or 24 hours. Results compared to a GC sensitivity expression signature. Results provide insight into the feasibility of using rapamycin to reverse GC resistance.	Co-expression
GDS2495	Airway epithelium response to injury: time course	Analysis of airway epithelia from healthy individuals 7 and 14 days following injury by epithelial denudation. Results provide insight into the molecular mechanisms underlying airway epithelial repair.	Co-expression
GDS2499	Anti-cancer agent sapphyrin PCI-2050 effect on lung cancer cell line: dose response	Analysis of A549 lung cancer cells following treatment with anti-cancer agent sapphyrin PCI-2050 or transcription inhibitor actinomycin D. Hydrophilic sapphyrins localize to tumors, generate oxidative stress, and inhibit gene expression.	Co-expression
GDS2501	B-cell chronic lymphocytic leukemia cell type and prognosis	Analysis of B-cell chronic lymphocytic leukemia (B-CLL) cells that express or do not express zeta-associated protein (ZAP-70) and CD38. The prognosis of patients with ZAP-70-CD38- B-CLL cells is good, those with ZAP-70+CD38+ B-CLL cells is poor.	Co-expression
GDS2513	Nicotinamide effect on thrombopoietin-induced megakaryocyte differentiation in vitro	Analysis of thrombopoietin-cultured CD34+ cells at various time points up to 5 days following treatment with nicotinamide. Thrombopoietin induces CD34+ cells to differentiate into megakaryocytes. Results provide insight into the effect of nicotinamide on megakaryocyte differentiation.	Co-expression
GDS2516	Interferons effect on endothelial cells	Analysis of endothelial cells treated with interferon (IFN) alpha, beta, or gamma for 5 hours.  The effect of IFNs on fibroblasts was also examined.  Results provide insight into the molecular basis of the antiangiogenic activity exhibited by IFNs.	Co-expression
GDS2518	Psoriatic plaques	Analysis of uninvolved and lesional skin of 13 patients with plaque-type psoriasis. Psoriasis vulgaris is characterized by hyperproliferation and incomplete terminal differentiation of epidermal keratinocytes. Results provide insight into the molecular pathogenesis of psoriasis.	Co-expression
GDS2519	Early-stage Parkinson's disease: whole blood	Analysis of blood of 50 patients predominantly with early-stage Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the cellular blood of patients with early-stage PD.	Co-expression
GDS2520	Head and neck squamous cell carcinoma	Analysis of paired normal tissues and tumor samples from patients with head and neck squamous cell carcinoma (HNSCC).  Results used to assess the effectiveness of using a combinatorial approach to analyze microarray data in identifying differentially expressed genes.	Co-expression
GDS2528	Basal plate of the placenta from midgestation to term (HG-U133A)	Analysis of the basal plate of the placenta from midgestation to term. The basal plate is the region where maternal and fetal cells coexist. Its proper formation is required for pregnancy. Results provide insight into the molecular basis of the unique cell-cell interactions in the basal plate.	Co-expression
GDS2529	Basal plate of the placenta from midgestation to term (HG-U133B)	Analysis of the basal plate of the placenta from midgestation to term. The basal plate is the region where maternal and fetal cells coexist. Its proper formation is required for pregnancy. Results provide insight into the molecular basis of the unique cell-cell interactions in the basal plate.	Co-expression
GDS2530	Retinoblastomas with loss of heterozygosity at chromosome 16q	Analysis of 4 retinoblastomas with loss of heterozygosity (LOH) at chromosome 16q. In addition to RB1 gene mutations, retinoblastomas frequently show gains of 1q and 6p and losses of 16q. Results identify candidate tumor suppressors on 16q in retinoblastoma.	Co-expression
GDS2534	p63 depletion effect	Analysis of ME180 cervical carcinoma cells depleted for p63 isoforms by expression of a small hairpin RNA targeting the p63 oligomerization domain. p63 is a p53 homolog essential for stratified epithelial development. Results provide insight into the function of p63 in transcriptional regulation.	Co-expression
GDS2535	Vanadium pentoxide effect on lung fibroblasts: time course	Analysis of lung fibroblasts for up to 24 hours following exposure to vanadium pentoxide (V2O5). Exposure to V2O5 is a cause of occupational bronchitis. Results provide insight into the molecular mechanisms that contribute to airway remodeling associated with V2O5-induced bronchitis.	Co-expression
GDS2536	Nickel effect on endothelial cells	Analysis of human umbilical vein endothelial cells treated with nickel chloride. Nickel compounds, important carcinogens and inducers of contact allergy reactions, are activators of endothelial cells. Results provide insight into the signaling pathways mediating the cellular responses to nickel.	Co-expression
GDS2545	Metastatic prostate cancer (HG-U95A)	Analysis of metastatic prostate tumors and primary prostate tumors.  Normal tissue adjacent to the tumor and normal donor tissue also examined. Metastasis reflects the most adverse clinical outcome. Results provide insight into the molecular mechanisms underlying the metastatic process.	Co-expression
GDS2546	Metastatic prostate cancer (HG-U95B)	Analysis of metastatic prostate tumors and primary prostate tumors.  Normal tissue adjacent to the tumor and normal donor tissue also examined. Metastasis reflects the most adverse clinical outcome. Results provide insight into the molecular mechanisms underlying the metastatic process.	Co-expression
GDS2547	Metastatic prostate cancer (HG-U95C)	Analysis of metastatic prostate tumors and primary prostate tumors.  Normal tissue adjacent to the tumor and normal donor tissue also examined. Metastasis reflects the most adverse clinical outcome. Results provide insight into the molecular mechanisms underlying the metastatic process.	Co-expression
GDS2548	Preeclampsia: uteroplacental tissues	Analysis of the deciduas, placentas, and fat tissues of preeclamptic women. The decidua and the placenta are two tissues of the uteroplacental unit. Results provide insight into the role of the uteroplacental renin-angiotensin system in the pathogenesis of preeclampsia.	Co-expression
GDS2563	Cigarette smoking effect on T lymphocytes	Analysis of T lymphocytes of 3 male heavy smokers. Results provide insight into sensitivity of T lymphocytes to cigarette smoking.	Co-expression
GDS2565	Endothelial cell response to ultrafine particles	Analysis of pulmonary artery endothelial cells HPAEC exposed to ultrafine particles for 4 hours. Results provide insight into the molecular basis of the association of pollutant particle exposure to increased cardiovascular mortality and morbidity.	Co-expression
GDS2573	Far-upstream element binding protein inactivation	Analysis of primary skin fibroblasts (Hs68) following siRNA knockdown of far-upstream element binding protein (FBP) 1, 2, or 3. Results provide insight into the function of each member of the FBP transactivator family.	Co-expression
GDS258	Juvenile dermatomyositis muscle profile (HuGeneFL)	Examination of skeletal muscle from juvenile dermatomyositis (JDM) patients, a common pediatric inflammatory myopathy. Muscle biopsies processed singly or in mixed groups of two. Patients genotyped for TNFalpha which is associated with prolonged disease.	Co-expression
GDS2601	Alzheimer blood mononuclear cells	Analysis of blood mononuclear cells of sporadic Alzheimer disease (AD) and age- gender-matched normal controls. Results reveal insights into systemic nature of gene dys-regulation in sporadic AD and suggest novel pathways of beta-amyloid deposition.	Co-expression
GDS2603	Arsenite and p53 effect on G2 synchronized fibroblasts	Analysis of p53-expressing or p53-deficient fibroblasts exposed to arsenite (As) after release from G2 phase synchrony. p53 is activated in response to mitotic disruption by arsenic. Results provide insight into the role of p53 in the As-induced disruption of G2/M phase progression.	Co-expression
GDS2604	Asbestos effect on epithelial and mesothelial lung cell lines: time course	Analysis of epithelial and mesothelial lung cell lines at various time points up to 7 days after exposure to asbestos. Asbestos exposure causes lung diseases such as asbestosis, malignant mesothelioma, and lung cancer. Results provide insight into the pathogenesis of asbestos-associated diseases.	Co-expression
GDS2606	Bronchial epithelial cell line response to various airway pathogens	Analysis of bronchial epithelial BEAS-2B cells exposed to UV-inactivated Staphylococcus aureus, Pseudomonas aeruginosa, or respiratory syncytial virus. Results provide insight into the common and specific molecular responses of bronchial epithelial cells to various airway pathogens.	Co-expression
GDS2609	Early onset colorectal cancer: normal-appearing colonic mucosa	Analysis of normal-appearing colonic mucosa of early onset colorectal cancer (CRC) patients without a prior family history of CRC. Results provide insight into the molecular pathogenesis of early onset CRC.	Co-expression
GDS261	Asthma exacerbatory factors	Comparison of epithelial cells derived from asthmatic and normal bronchial airways, and examination of factors that enhance inflammatory and immunologic responses which exacerbate asthma. Effects of ozone and rhinovirus examined.	Co-expression
GDS2611	Interleukin-20 subfamily cytokines effect on epidermal keratinocytes	Analysis of cultured epidermal keratinocytes treated with various cytokines of the interleukin-20 (IL-20) subfamily. IL-20 cytokines are up-regulated in psoriatic skin. Results provide insight into the role of IL-20 cytokines in the pathogenesis of psoriasis.	Co-expression
GDS2613	Rett syndrome: brain frontal cortex	Analysis of brain frontal cortices of individuals with Rett syndrome (RTT). RTT is an X-linked neurodevelopmental disorder linked to heterozygous de novo mutations in MECP2, a gene encoding methyl-CpG-binding protein 2. Results provide insight into molecular pathogenesis of RTT.	Co-expression
GDS2615	Mucociliary differentiation of airway epithelial cells	Analysis of primary airway epithelial cells cultured at an air-liquid interface for up to 28 days to induce their differentiation into polarized, pseudostratified epithelia of ciliated and mucus-secreting cells. Results provide insight into the mechanisms underlying mucociliary differentiation.	Co-expression
GDS2617	Tumorigenic breast cancer cells (HG-U133A)	Analysis of breast cancer cells that have high tumorigenic capacity.  These cells express CD44 and low or undetectable levels of CD24. Results used to define a gene expression signature associated with metastasis.	Co-expression
GDS2618	Tumorigenic breast cancer cells (HG-U133B)	Analysis of breast cancer cells that have high tumorigenic capacity.  These cells express CD44 and low or undetectable levels of CD24. Results used to define a gene expression signature associated with metastasis.	Co-expression
GDS262	Duchenne muscular dystrophy (HG-U95A)	Examination of muscle biopsies from Duchenne muscular dystrophy patients and normal subjects of various age groups. Both mixed groups of patients (5 patient biopsies per group) and individual biopsies analyzed.	Co-expression
GDS2622	Epidermal growth factor effect on mammary epithelial cell line: time course	Analysis of mammary epithelial MCF10A cells following treatment with epidermal growth factor for various time points up to 480 minutes. Results provide insight into the dynamics of growth factor signaling.	Co-expression
GDS2623	Epidermal growth factor effect on cervical carcinoma cell line: time course	Analysis of cervical carcinoma HeLa cells following treatment with epidermal growth factor for various time points up to 480 minutes. Results provide insight into the dynamics of growth factor signaling.	Co-expression
GDS2626	Epidermal growth factor and heregulin effect on breast cancer cell line: dose response and time course	Analysis of MCF-7 breast cancer cells treated with various doses of epidermal growth factor (EGF) or heregulin (HRG) for up to 90 minutes. EGF and HRG induce distinct kinase kinetics and phenotypes of MCF-7 cells. Results provide insight into the linkage between signaling dynamics and cell fate.	Co-expression
GDS2628	Vitamin D effect on bronchial smooth muscle cells	Analysis of bronchial muscle cells treated with 1alpha,25-dihydroxy-vitamin D3, the ligand for the vitamin D receptor (VDR). Genetic variants in VDR are associated with asthma. Results provide insight into the molecular basis of this association.	Co-expression
GDS2635	Invasive ductal and lobular breast carcinomas	Analysis of invasive ductal carcinoma (IDC) cells, invasive lobular carcinoma (ILC) cells, and their normal counterparts. Cells obtained from postmenopausal breast cancer patients.  Results provide insight into the molecular differences between IDC and ILC.	Co-expression
GDS264	Duchenne muscular dystrophy (HG-U95D)	Examination of muscle biopsies from Duchenne muscular dystrophy patients and normal subjects of various age groups. Both mixed groups of patients (5 patient biopsies per group) and individual biopsies analyzed.	Co-expression
GDS2642	Crohn's disease and ulcerative colitis	Analysis of colonoscopic biopsies from patients with Crohn’s disease (CD) or ulcerative colitis (UC). CD and UC are inflammatory bowel diseases with variable, overlapping clinical features and complex pathophysiologies. Results provide insight into the pathogenesis of CD and UC.	Co-expression
GDS2643	Waldenstrom's macroglobulinemia: B lymphocytes and plasma cells	Analysis of B lymphocytes (BL) and plasma cells (PC) from patients with Waldenstrom's macroglobulinemia (WM), a B-lymphoproliferative disorder (BLPD). Results provide insight into differences between PC and BL from WM and their cell counterpart in chronic lymphocytic leukemia and multiple myeloma.	Co-expression
GDS2649	HIV infection effect on CD4+ and CD8+ T cells	Analysis of CD4+ and CD8+ T cells from HIV patients at different clinical stages and rates of disease progression. Changes in T-cell function are a hallmark of HIV infection. Results provide insight into the pathogenic mechanisms in HIV infections that lead to these changes in T-cell function.	Co-expression
GDS265	Duchenne muscular dystrophy (HG-U95E)	Examination of muscle biopsies from Duchenne muscular dystrophy patients and normal subjects of various age groups. Both mixed groups of patients (5 patient biopsies per group) and individual biopsies analyzed.	Co-expression
GDS2652	Neonatal brain response to docosahexaenoic acid supplemented formulas	Analysis of precentral gyri from neonates fed for 12 weeks with either a formula containing both 0.33% docosahexaenoic acid (DHA) and 0.67% arachidonic acid (ARA) or one with 1.0% DHA and 0.67% ARA. DHA and AHA are the major long chain polyunsaturated fatty acids of the central nervous system.	Co-expression
GDS2653	Sequestosome 1 and dipeptidylpeptidase III overexpression effect on neuroblastoma cell line	Analysis of IMR-32 neuroblastoma cells overexpressing sequestosome 1 (SQSTM1) or dipeptidylpeptidase III (DPP3). SQSTM1 and DPP3 activate the antioxidant response element (ARE). Results provide insight into mechanisms regulating the activation of the ARE.	Co-expression
GDS2655	Fetal and adult reticulocytes (HG-U133A)	Analysis of circulating blood reticulocytes from umbilical cords and normal adults. Reticulocytes are immature red blood cells containing residual RNA. Results provide insight into the molecular basis of terminal erythroid differentiation.	Co-expression
GDS2656	Fetal and adult reticulocytes (HG-U133B)	Analysis of circulating blood reticulocytes from umbilical cords and normal adults. Reticulocytes are immature red blood cells containing residual RNA. Results provide insight into the molecular basis of terminal erythroid differentiation.	Co-expression
GDS2657	miR-124 overexpression: time course	Analysis of HepG2 cells overexpressing miR-124 for up to 120 hours. Results combined with a computational method for predicting miRNA targets to identify targets of miR-124.	Co-expression
GDS266	Asthma and atopy (HG-U133A)	Investigation of CD4+ lymphocytes from patients with and without atopy, in combination with asthma.	Co-expression
GDS267	Asthma and atopy (HG-U133B)	Investigation of CD4+ lymphocytes from patients with and without atopy, in combination with asthma.	Co-expression
GDS2676	CD38-positive and CD38-negative chronic lymphocytic leukemia cells	Analysis of paired CD38(+) and CD38(-) chronic lymphocytic leukemia (CLL) cells from six patients. CD38 expression is an important prognostic marker in CLL with high levels of CD38 antigen associated with shorter overall survival. Results provide insight into the molecular basis of this association.	Co-expression
GDS2678	Brain regions of humans and chimpanzees	Comparison of various human and chimpanzee brain regions. Results provide insight into the genetic basis of human specializations in brain organization and cognition.	Co-expression
GDS268	Obesity and fatty acid oxidation	Identification of proteins involved in fatty acid oxidation in skeletal muscle. Fat oxidation may be reduced in morbidly obese individuals. Provides understanding of how obesity contributes to cardiovascular disease via insulin resistance.	Co-expression
GDS2682	Conjunctiva and cornea comparison	Analysis of conjunctival (Cnj) and corneal (Co) epithelia, the main cellular components of the ocular surface. Cnj and Co epithelia are embryologically related but phenotypically and functionally disparate. Results provide insight into the molecular basis of these differences.	Co-expression
GDS2695	Teratozoospermia (HumanRef-8 BeadChip)	Analysis of sperm cells from males with consistent and severe teratozoospermia, a condition in which less than 4 percent of sperm cells are morphologically normal. Results provide insight into the molecular basis of a range of teratozoospermic presentations.	Co-expression
GDS2696	Teratozoospermia (Human-6 BeadChip)	Analysis of sperm cells from males with consistent and severe teratozoospermia, a condition in which less than 4 percent of sperm cells are morphologically normal. Results provide insight into the molecular basis of a range of teratozoospermic presentations.	Co-expression
GDS2697	Teratozoospermia (HG-U133 2.0 )	Analysis of sperm cells from males with consistent and severe teratozoospermia, a condition in which less than 4 percent of sperm cells are morphologically normal. Results provide insight into the molecular basis of a range of teratozoospermic presentations.	Co-expression
GDS270	Duchenne muscular dystrophy (HG-U95B)	Examination of muscle biopsies from Duchenne muscular dystrophy patients and normal subjects of various age groups. Both mixed groups of patients (5 patient biopsies per group) and individual biopsies analyzed.	Co-expression
GDS2705	PPARgamma agonist and platinum-based drug effect on adenocarcinoma cell line	Analysis of NSCLC adenocarcinoma cells treated with rosiglitazone, carboplatin, or both. Rosiglitazone is an agonist of the nuclear receptor PPARgamma. Results provide insight into the molecular basis of the synergy observed between rosiglitazone and platinum-based drugs in cancer models.	Co-expression
GDS2706	Philadelphia chromosome positive acute lymphoblastic leukemia cell lines response to imatinib mesylate	Analysis of Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia cell lines BV173 and SUP-B15 treated with the anticancer drug imatinib mesylate (STI571). Ph encodes the oncogenic BCR-ABL1 kinase. Results provide insight into molecular basis of the transforming activity of BCR-ABL1.	Co-expression
GDS2723	Primary immunodeficiency syndrome: B cells	Analysis of immortalized B cells from 2 children with a primary immunodeficiency syndrome that is characterized by neutropenia, partial albinism, short stature, and B-cell and cytotoxic T-cell deficiencies. Results provide insight into the genetic basis of this syndrome.	Co-expression
GDS2724	Transcriptional regulators Bmi-1 and Mel-18 depletion effect on medulloblastoma cell line	Analysis of DAOY medulloblastoma cells following RNAi knockdown of Bmi-1, Mel-18, or both. Bmi-1 and Mel-18 belong to the Polycomb group (PcG) of transcriptional regulators. Results provide insight into the role of Bmi-1 and Mel-18 in the pathogenesis of medulloblastoma.	Co-expression
GDS2728	CD133+ and CD133- glioblastoma-derived cancer stem cell lines	Comparison of CD133+ and CD133- glioblastoma-derived cancer stem cells (CSC). Both CSC subpopulations were derived from primary glioblastomas. Results provide insight into the role of CD133+ and CD133- CSCs in the pathogenesis of glioblastoma.	Co-expression
GDS2729	Cyclophosphamide-resistant chronic myelogenous leukemia cell line	Analysis of chronic myelogenous leukemia (CML) cells resistant to cyclophosphamide (CP), an alkylating anticancer drug. Results provide insight into the molecular basis of CP resistance in CML.	Co-expression
GDS2732	2-(3,4,5-trimethoxyphenylamino)-pyrrolo[2,3-d]pyrimidine effect on epidermal keratinocytes: time course	Analysis of epidermal keratinocytes at various time points up to 48 hours following treatment with 2-(3,4,5-trimethoxyphenylamino)-pyrrolo[2,3-d]pyrimidine (PP). PP induces the terminal differentiation of epidermal keratinocytes. Results provide insight into the mechanism of action of PP.	Co-expression
GDS2733	Cytosine arabinoside effect on Ewing's sarcoma cell line: time course and dose response	Analysis of Ewing’s sarcoma A673 cells for up to 5 days after treatment with cytosine arabinoside (ARA-C) at EC50 or twice the EC50. ARA-C identified as a modulator of the Ewing’s sarcoma EWS/FLI fusion protein. Results provide insight into the specificity of the response of A673 cells to ARA-C.	Co-expression
GDS2735	Metastatic melanoma: peripheral blood lymphocytes	Analysis of sorted peripheral blood lymphocytes (CD8 T cells, CD4 T cells, B cells, NK cells) from patients with melanoma. These subpopulations are involved in antitumor responses and negatively impacted by cancer. Results provide insight into molecular mechanisms of immune dysfunction in cancer.	Co-expression
GDS2736	Malignant fibrous histiocytoma and various soft tissue sarcomas	Analysis of malignant fibrous histiocytoma (MFH) tumors and various soft tissue sarcomas (STSs). MFH is characterized by non-recurrent complex chromosomal aberrations, and overlapping histological and immunohistochemical phenotypes. Results provide insight into the similarities between MFH and STSs.	Co-expression
GDS2737	Endometriosis	Analysis of endometrial specimens from women with endometriosis. Endometrial gene expression examined at various phases of the menstrual cycle. Results provide insight into the molecular pathogenesis of endometriosis.	Co-expression
GDS2739	Hyperplastic enlarged lobular units: epithelial cells	Analysis of epithelial cells isolated from hyperplastic enlarged lobular units (HELUs). HELUs arise from the enlargement of normal terminal duct lobular units by hyperplastic columnar epithelial cells and are the earliest histologically identifiable precursor of breast cancer.	Co-expression
GDS274	Hepatocellular carcinoma metastasis	Generation of a molecular signature for metastatic hepatocellular carcinoma (HCC) and identification of genes relevant to metastasis and patient survival. Osteopontin identified as molecular marker for defining metastatic potential.	Co-expression
GDS2740	Lengthening and shortening contractions effect on the muscle: time course	Analysis of skeletal muscles at various time points up to 24 hours after acute bouts of either lengthening (LCs) or shortening contractions (SCs). Resistance training using LCs results in greater increases in muscle size than SCs. Results provide insight into the molecular basis of this difference.	Co-expression
GDS2744	Dioxin effect on breast cancer cell line (HG-U133A)	Analysis of MCF-7 breast cancer cells treated with 100 nM dioxin. Although dioxin is causative for many types of cancers, low exposure to dioxin is associated with a decreased incidence of breast carcinoma. Results provide insight into the molecular basis of this protective effect.	Co-expression
GDS2745	Dioxin effect on breast cancer cell line (HG-U133B)	Analysis of MCF-7 breast cancer cells treated with 100 nM dioxin. Although dioxin is causative for many types of cancers, low exposure to dioxin is associated with a decreased incidence of breast carcinoma. Results provide insight into the molecular basis of this protective effect.	Co-expression
GDS2749	Immature dendritic cell response to Aspergillus fumigatus infection in vitro	Analysis of dendritic cells (DCs) infected with Aspergillus fumigatus (AF) in vitro. DCs obtained from two healthy donors. AF is a ubiquitous mold and a common cause of invasive aspergillosis (IA) in immunocompromised patients. Results provide insight into DC involvement in antifungal defense.	Co-expression
GDS2750	Immature dendritic cell response to hypoxia in vitro	Analysis of immature dendritic cells (DCs) differentiated from monocytes under hypoxia for 4 days. DCs are antigen presenting cells whose development is influenced by the microenvironment. Hypoxia is an important constituent of the microenvironment of inflamed tissues.	Co-expression
GDS2754	Exhaustive exercise effect on peripheral blood mononuclear cells and T lymphocytes	Analysis of peripheral blood mononuclear cells and T lymphocytes from individuals before and after a bout of acute exhaustive exercise. White blood cell (WBC) subpopulations shift during physical activities. Results provide insight into the response of sorted WBC subpopulations to acute exercise.	Co-expression
GDS2755	miR-34 overexpression	Analysis of HCT116 cells overexpressing miR-34, a microRNA. miR-34 is commonly deleted in human cancers. Results provide insight into the function of miR-34.	Co-expression
GDS2756	Measles: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells (PBMCs) from measles patients. PBMCs collected upon hospital admission, at discharge, and one month after discharge. Results provide insight into the immunological changes that occur during measles infections.	Co-expression
GDS2758	Hypoxia and 2-oxoglutrate-dependent dioxygenase inhibition (HG-U133A)	Analysis of MCF-7 breast cancer cells exposed to hypoxia or treated with the non-specific 2-oxoglutarate (2-OG) dependent dioxygenase inhibitor dimethyloxalylglycine. Results provide insight into the role of 2-OG dioxygenases in the regulation of gene expression during hypoxia.	Co-expression
GDS2759	Hypoxia and 2-oxoglutrate-dependent dioxygenase inhibition (Human-6 BeadChip)	Analysis of MCF-7 breast cancer cells exposed to hypoxia or treated with the non-specific 2-oxoglutarate (2-OG) dependent dioxygenase inhibitor dimethyloxalylglycine. Results provide insight into the role of 2-OG dioxygenases in the regulation of gene expression during hypoxia.	Co-expression
GDS2760	Hypoxia-inducible factor depletion  (HG-U133 2.0)	Analysis of hypoxic MCF-7 breast cancer cells depleted for hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, or both HIF alpha subunits. Results provide insight into the extent of the role of HIF-1alpha and HIF-2alpha in the regulation of gene expression during hypoxia.	Co-expression
GDS2761	Hypoxia-inducible factor depletion (Human-6 BeadChip)	Analysis of hypoxic MCF-7 breast cancer cells depleted for hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, or both HIF alpha subunits. Results provide insight into the extent of the role of HIF-1alpha and HIF-2alpha in the regulation of gene expression during hypoxia.	Co-expression
GDS2763	Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy: dendritic cells	Analysis of in vitro differentiated dendritic cells (DCs) from patients with PLOSL, an early onset dementia with bone cysts caused by mutations in DAP12 and TREM2 genes which encode important signaling molecules in DCs. Results provide further insight into mechanisms underlying PLOSL pathogenesis.	Co-expression
GDS2767	Blood response to various beverages: time course	Analysis of blood samples from 6 individuals at various time points up to 12 hours following the intake of water, ethanol, grape juice, or red wine. Results may contribute to elucidating the mechanisms underlying the cardioprotective effects of red wine.	Co-expression
GDS2770	Estrogen effect on breast cancer cell line coexpressing estrogen receptors alpha and beta	Analysis of estrogen receptor (ER) alpha positive MCF-7 breast cancer cells following introduction of ERbeta and treatment with estrogen. The majority of breast cancers express both ERalpha and ERbeta. Results provide insight into the comodulatory effects of these two ERs.	Co-expression
GDS2771	Large airway epithelial cells from cigarette smokers with suspect lung cancer	Analysis of large airway epithelial cells from cigarette smokers without cancer, with cancer, and with suspect lung cancer. Results provide insight into the feasibility of using gene expression to detect early stage lung cancer in smokers.	Co-expression
GDS2772	Sevoflurane and propofol effect on the heart during off-pump coronary artery bypass graft surgery	Analysis of atrial biopsies from patients receiving the anesthetic gas sevoflurane or the intravenous anesthetic propofol during off-pump coronary artery bypass graft surgery. Anesthetic gases protect against myocardial ischemia. Results provide insight into the basis of this protective effect.	Co-expression
GDS2777	Bexarotene effect on gemcitabine resistant non-small lung cancer cell line	Analysis of gemcitabine (Gem)-resistant non-small lung cancer Calu3 cells treated with bexarotene (Bex). Acquired drug resistance is a major obstacle in cancer therapy. Results provide insight into molecular mechanisms underlying the ability of bexarotene to overcome Gem-resistance in Calu3 cells.	Co-expression
GDS2778	1,2,4-benzenetriol effect on peripheral blood mononuclear cells in vitro	Analysis of cultured peripheral blood mononuclear cells treated with the benzene metabolite 1,2,4-benzenetriol. Benzene is an air pollutant and carcinogen. Results provide insight into the molecular basis of benzene cytotoxicity.	Co-expression
GDS2779	Lymphoblastoid cell lines from monozygotic twin pairs discordant for bipolar disorder	Analysis of lymphoblastoid cell lines derived from 3 monozygotic twin pairs discordant for bipolar disorder. Results provide insight into the molecular pathogenesis of bipolar disorder.	Co-expression
GDS2780	Heavy metals effect on liver cell line	Analysis of liver carcinoma HepG2 cells exposed to various heavy metals. Results provide insight into the molecular basis of heavy metal cytotoxicity.	Co-expression
GDS2781	Nonsense mediated decay factor UPF1 depletion	Analysis of HeLa cells depleted for the nonsense-mediated decay (NMD)-keys factor UPF1. NMD represents a key mechanism to control the expression of wild-type and aberrant mRNAs. Results provide insight into the extent of gene regulation mediated by UPF1 activity.	Co-expression
GDS2782	Androgen response element specific DNA-binding polyamide effect on dihydrotestoterone-stimulated prostate cell line	Analysis of DHT-stimulated LNCaP prostate cells treated with an androgen response (AR) element (ARE) specific DNA binding polyamide. Polyamide designed to target the sequence 5'-WGWWCW-3' and disrupt AR-mediated gene expression. Effects of the synthetic antiandrogen bicalutamide also examined.	Co-expression
GDS2785	Ovarian cancer tumors after neo-adjuvant chemotherapy	Analysis of malignant ovarian cancer tumors from patients receiving neo-adjuvant chemotherapy. Ovarian adenomas and untreated ovarian carcinomas also examined.  Results used to define gene expression signatures associated with clinical responses to chemotherapy.	Co-expression
GDS2787	LIM-only protein 4 induction effect on breast cancer cell line (HG-U133A)	Analysis of breast cancer MCF-7 cells following the induction of expression of nuclear LIM-only protein 4 (LMO4). LMO4 is upregulated in breast cancer. Results provide insight into the role of LMO4 in promoting tumor formation.	Co-expression
GDS2788	LIM-only protein 4 induction effect on breast cancer cell line (HG-U133B)	Analysis of breast cancer MCF-7 cells following the induction of expression of nuclear LIM-only protein 4 (LMO4). LMO4 is upregulated in breast cancer. Results provide insight into the role of LMO4 in promoting tumor formation.	Co-expression
GDS2789	LIM homeobox protein cofactor dominant negative form effect on breast cancer cell line	Analysis of breast cancer MCF-7 cells after the induction of expression of a dominant negative form of the cofactor of LIM domains (CLIM), a co-regulator of the nuclear LIM only protein 4 (LMO4). LMO4 is upregulated in breast cancer. Results provide insight into the role of LMO4 in tumor formation.	Co-expression
GDS2790	Skeletal muscle response to insulin infusion (HuGeneFL)	Analysis of skeletal muscles from non-diabetics after a 3 hour infusion of insulin. Glucose uptake by skeletal muscles in response to insulin is impaired in type 2 diabetes. Results provide insight into the molecular mechanisms regulating glucose homeostasis in response to insulin.	Co-expression
GDS2791	Skeletal muscle response to insulin infusion (HG-U133A)	Analysis of skeletal muscles from non-diabetics after a 2 hour infusion of insulin. Glucose uptake by skeletal muscles in response to insulin is impaired in type 2 diabetes. Results provide insight into the molecular mechanisms regulating glucose homeostasis in response to insulin.	Co-expression
GDS2794	T-cell acute lymphoblastic leukemia cell line response to Notch receptor inhibition	Analysis of T-cell acute lymphoblast leukemia (T-ALL) MOLT4 cells following gamma-secretase inhibitor (GSI) DAPT treatment. Gamma-secretase activity is required for Notch 1 receptor signaling. Results provide insight into the role of Notch signaling in T-ALL development.	Co-expression
GDS2795	Alzheimer's disease: neurofibrillary tangles	Analysis of entorhinal cortex neurons containing neurofibrillary tangles (NFT) from 10 mid-stage Alzheimer's disease (AD) patients. Comparison with histopathologically normal neurons from the same patients and brain region. Results provide insight into the formation of NFTs in AD.	Co-expression
GDS2808	Sepsis: neutrophils	Analysis of neutrophils from critically ill patients with sepsis. Results used to define a gene expression signature for sepsis and provides insight into the host response to sepsis.	Co-expression
GDS2810	Organized and growth-arrested mammary acini: time course	Temporal analysis of two nonmalignant mammary epithelial cells (HMEC) grown in a laminin-rich extracellular matrix. Both HMECs transit from a disorganized to an organized state to form polarized acini. Results identify gene signatures with potential value for breast cancer prognosis prediction.	Co-expression
GDS2819	Leukemic white blood cells and various RNA preparation protocols	Analysis of RNA samples prepared from leukemic white blood cells using 3 different protocols. Samples obtained from 27 pediatric patients with various subtypes of acute leukemia. Results provide insight into the impact of RNA preparation methods on the variation in gene expression data.	Co-expression
GDS2821	Parkinson's disease: substantia nigra	Analysis of substantia nigrae from postmortem brains of patients with Parkinson’s disease (PD). Neurons in the substantia nigra, which produces dopamine, degenerate in PD. Results provide insight into the molecular pathogenesis of PD.	Co-expression
GDS2822	Placental malaria	Analysis of inflamed placentas from patients with chronic placental malaria (PM). Chronic inflammation during PM is frequent in first time mothers and is associated with poor maternal and fetal outcomes. Results provide insight into the pathogenesis of chronic PM.	Co-expression
GDS2824	Autism, fragile X syndrome, and 15q11-q13 duplication: lymphoblastoid cells	Analysis of lymphoblastoid cells from males with autism due to a fragile X mutation or a 15q11-q13 duplication. Results provide insight into the pathogenesis of autism spectrum disorders.	Co-expression
GDS2827	ERalpha-negative ERbeta-positive breast carcinoma response to tamoxifen	Analysis of estrogen receptor (ER) alpha negative ERbeta-positive breast cancer tumors from patients treated with tamoxifen for 2 years. Unlike ERalpha-negative ERbeta-negative breast cancers, ERalpha-negative ERbeta-positive cancers respond favorably to tamoxifen treatment.	Co-expression
GDS2831	Primary graft dysfunction after lung transplantation	Analysis of donor lung biopsies from recipients that developed primary graft dysfunction after lung transplantation. Results provide insight into the pathogenesis of primary lung graft dysfunction.	Co-expression
GDS2832	Sphingosine-1-phosphate effect on embryonic stem cells	Analysis of embryonic stem cells (ESCs) after treatment with sphingosine-1-phosphate (S1P) which plays a role in regulation of fate in many cell types. ESCs grown on mouse embryo fibroblast feeder cells and under feeder-free conditions. Results provide insight into the role of S1P in ESC renewal.	Co-expression
GDS2833	Polyomavirus JCV resistant glial cell line (HG-U133A)	Analysis of SVGR2 glial cells resistant to the human polyomavirus JCV, the causative agent of progressive multifocal leukoencephalopathy. SVGR2 cells are derived from susceptible glial cells (SVG-A). Results provide insight into the molecular mechanisms underlying susceptibility to JCV infection.	Co-expression
GDS2834	Polyomavirus JCV resistant glial cell line (HG-U133B)	Analysis of SVGR2 glial cells resistant to the human polyomavirus JCV, the causative agent of progressive multifocal leukoencephalopathy. SVGR2 cells are derived from susceptible glial cells (SVG-A). Results provide insight into the molecular mechanisms underlying susceptibility to JCV infection.	Co-expression
GDS2835	Ovarian endometriosis	Comparison of endometriosis lesions to normal endometrial tissues obtained from the same patient at the same time. Results provide insight into the pathogenesis of endometriosis.	Co-expression
GDS2838	Abdominal aortic aneurysm	Analysis of aneurysmal abdominal aortas (AAAs). Abdominal aortic aneurysms are a common disorder and mortality from ruptured AAAs is high. Results provide insight into the pathogenesis of abdominal aortic aneurysm.	Co-expression
GDS2842	Testicular seminoma progression	Analysis of testicular seminoma tumors at various stages of progression (pT1, pT2, pT3). Results provide insight into the pathogenesis of testicular seminoma.	Co-expression
GDS2847	Anisomycin effect on leukemia cell line: time course	Analysis of myeloid leukemia U937 cells treated with anisomycin for various time points up to 6 hours. Anisomycin is a potent inducer of apoptosis. Results provide insight into the mechanism of action of anisomycin in inducing apoptosis.	Co-expression
GDS2852	Interleukin 13 effect on bronchial cell line: time course	Analysis of bronchial A549 cells at various time points up to 24 hours following treatment with the cytokine interleukin 13 (IL-13). IL-13 contributes to the pathogenesis of asthma.	Co-expression
GDS2853	Low and high grade astrocytomas	Comparison of low and high grade astrocytoma brain tumors. Results provide insight into the molecular differences between the two types of tumors.	Co-expression
GDS2855	Various muscle diseases (HG-U133B)	Analysis of muscle biopsy specimens from patients with various muscle diseases.  Results provide insight into the diagnosis and pathogenesis of muscle diseases.	Co-expression
GDS2856	Peripheral blood-derived monocytes response to lipopolysaccharide: time course	Analysis of peripheral blood-derived monocytes at various time points up to 24 hours following treatment with lipopolysaccharide. Results compared with those obtained from Massively Parallel Signature Sequencing.	Co-expression
GDS2858	Myeloid-related protein 8 and 14 effect on microvascular endothelial cells	Analysis of microvascular endothelial cells (ECs) treated with the myeloid-related protein 8 (MRP8) and 14 (MRP14), proteins that form heterodimers secreted by phagocytes at inflammatory sites. Results provide insight into the role of MRP8 and MRP14 in EC cell death during inflammation.	Co-expression
GDS2860	Aldosterone-producing adeonoma	Analysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism (PA). The source of aldosterone in many patients with PA is unilateral APA. Results provide insight into the mechanisms causing elevated aldosterone production in APA.	Co-expression
GDS2861	X-Box binding protein overexpression effect on breast cancer cell line	Analysis of MCF7 breast cancer (BC) cells overexpressing spliced X-box binding protein-1 (XBP1), a transcription factor that participates in the unfolded protein response (UPR). Results provide insight into the role of XBP1 and the UPR in estrogen and antiestrogen responsiveness in breast cancer.	Co-expression
GDS2864	RhoGDIbeta depletion effect on breast cancer cell line	Analysis of MDA-MB-231 breast cancer cells following RhoGDIbeta knockdown. RhoGDIbeta is a Rho guanine nucleotide dissociation inhibitor (RhoGDI) expressed in tumor cells. RhoGDIs negatively regulate the activity of Rho GTPases.	Co-expression
GDS2865	Metastatic prostate tumor model	Comparison of poorly and highly metastatic prostate subcutaneous tumors derived from xenotransplanted human PC-3 prostate cancer cells. Results provide insight into the molecular mechanisms contributing to prostate cancer metastasis.	Co-expression
GDS2866	Monocyte-derived macrophages of chronic obstructive pulmonary disease patients response to fine and ultrafine particles	Analysis of monocyte-derived macrophages from chronic obstructive pulmonary disease (COPD) patients after in vitro treatment with a mix of fine titanium dioxide (TiO2) and ultrafine Printex 90 particles, or lipopolysaccharide (LPS). TiO2 and Printex 90 are used in the manufacture of many products.	Co-expression
GDS2867	TAp63alpha-Q540L mutant protein expression	Analysis of H1299 cells expressing the TAp63alpha-Q540L mutant protein. TAp63alpha-Q540L is a form of p63 that contains a missense mutation in the SAM domain. Mutations in the SAM domain of p63 are associated with Hay-Wells syndrome.	Co-expression
GDS2868	Inadequate dietary protein intake effect on the skeletal muscle	Analysis of vastus lateralis skeletal muscle biopsies from older males and females (aged 55-80 years) before and during a diet inadequate in proteins. Results provide insight into the molecular changes in skeletal muscles brought about by inadequate dietary protein intake.	Co-expression
GDS287	Muscle function and aging - male (HG-U133A)	Comparison of gene expression in vastus lateralis skeletal muscle biopsies in healthy young (21-27 year old) and older (67-75 year old) men	Co-expression
GDS288	Muscle function and aging - male (HG-U133B)	Comparison of gene expression in vastus lateralis skeletal muscle biopsies in healthy young (21-27 year old) and older (67-75 year old) men.	Co-expression
GDS2880	Clear cell renal cell carcinoma (HG-U133A)	Analysis of patient matched normal and stage 1 or stage 2 clear cell renal cell carcinoma (cRCC) tumors. Results provide insight into the molecular pathogenesis of cRCC.	Co-expression
GDS2881	Clear cell renal cell carcinoma (HB-U133B)	Analysis of patient matched normal and stage 1 or stage 2 clear cell renal cell carcinoma (cRCC) tumors. Results provide insight into the molecular pathogenesis of cRCC.	Co-expression
GDS2883	LEDGF/p75 transcription factor deficiency effect on T-cell line	Analysis of Jurkat T-cells depleted for the LEDGF/p75 transcription factor. LEDGF/p75 is involved in targeting HIV DNA integration. Results provide insight into the mechanisms controlling HIV integration.	Co-expression
GDS2887	Moderate stage Huntington's disease lymphocytes	Analysis of lymphocytes from patients with moderate stage Huntington's disease (HD). Results provide insight into the feasibility of using gene expression to identify biomarkers for moderate stage HD.	Co-expression
GDS2889	Air pollutant and oxidized lipid effect on microvascular endothelial cells: dose response	Analysis of microvascular endothelial cells treated at various concentrations of the model air pollutant diesel exhaust particles (DEP), an oxidized phospholipid (ox-PAPC), or both. Results provide insight into the synergistic effect of DEP and ox-PAPC in promoting vascular inflammation.	Co-expression
GDS289	Chronic obstructive pulmonary disease	Study of the signaling mechanisms responsible for diaphragm muscle transformation from fast-to-slow fiber type in chronic obstructive pulmonary disease (COPD) patients.	Co-expression
GDS2892	Optineurin depletion	Analysis of HeLa cells depleted for optineurin using RNAi knockdown. Mutations in the gene for optineurin are associated with open-angle glaucoma. Results provide insight into the function of optineurin and its role in the pathogenesis of open-angle glaucoma.	Co-expression
GDS2902	Hypoxia and lymphathic endothelial cells	Analysis of lymphatic endothelial cells (LECs) subjected to hypoxia or treated with conditioned media from lung carcinoma cells grown under hypoxic conditions. LECs contribute to tumor metastasis.	Co-expression
GDS2904	Hematopoietic stem cell response to uridine triphosphate: time course	Analysis of CD34+ hematopoietic stem cells treated for up to 24 hours with uridine triphosphate.	Co-expression
GDS2908	T-cell prolymphocytic leukemia with inv(14)(q11q32)	Analysis of T-cell prolymphocytic leukemia (T-PLL) cells with the cytogenetic abnormality inv(14)(q11q32). T-PLL is a rare aggressive lymphoma derived from mature T cells. Results provide insight into the pathogenesis of T-PLL.	Co-expression
GDS2918	Colorectal cancer markers in plasma	Analysis of blood plasma from patients with colorectal cancer. Results used to identify gene markers for colorectal cancer.	Co-expression
GDS2919	Tremorogenic chemical harmane effect on astrocytes	Analysis of astrocytes treated with the tremorogenic chemical harmane. Increased blood harmane concentration is associated with an increased risk of essential tremor. Astrocyte dysfunction is associated with neurodegenerative diseases.	Co-expression
GDS2920	Testosterone effect on skeletal muscles of HIV-infected males experiencing weight loss	Analysis of skeletal muscles of HIV-infected males experiencing weight loss after treatment with testosterone. HIV-associated wasting and weight loss are clinically significant concerns. Results provide insight into androgen action and the potential of anabolic therapies for wasting and sarcopenia.	Co-expression
GDS2921	Wilms' tumor suppressor (WT1) targets: time course	Analysis of U2OS osteosarcoma cells at various time points up to 12 hours following induction of a tetracycline-repressible Wilms' tumor 1 (WT1) gene encoding the -KTS isoform. WT1 encodes a zinc finger transcription factor that is involved in organ development.	Co-expression
GDS2922	Ascending aortic aneurysms	Analysis of aneurysmal tissue from ascending aortas of patients with normal tricuspid aortic valves or abnormal bicuspid aortic valves (BAVs). BAV is a congenital anomaly associated with an increased risk for ascending aortic aneurysm (AscAAs). Results provide insight into the pathogenesis of AscAA.	Co-expression
GDS2926	Megakaryocytic differentiation: time course	Temporal analysis of phorbol ester-treated CHRF-288-11 megakaryoblastic cells induced to undergo megakaryocytic (Mk) differentiation and primary Mk (PriMk) cells derived from cytokine-treated CD34+ peripheral blood cells. Results provide insight into molecular mechanisms underlying megakaryopoiesis.	Co-expression
GDS2930	Cis-urocanic acid effect on keratinocytes	Analysis of keratinocytes treated with cis-urocanic acid (UCA). UCA is an epidermal chromophore that undergoes trans to cis photoisomerization following ultraviolet radiation exposure. Results provide insight into the effect of cis-UCA on the cell-mediated immune response in the skin.	Co-expression
GDS2931	Rheumatoid arthritis and osteoarthritis: synovial fibroblasts	Comparison of synovial fibroblasts from patients with rheumatoid arthritis (RA) to those with osteoarthritis (OA). RA is characterized by chronic inflammation and destruction of multiple joints. OA is a degenerative disease resulting from the breakdown of cartilage.	Co-expression
GDS2932	TGF-beta effect on normal and tumor cell lines: time course	Analysis of normal lung epithelial HPL1D cells and lung adenocarcinoma A549 cells treated with TGF-beta for up to 12 hours. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells but acts as a pro-tumor cytokine by promoting tumour angiogenesis, immune-escape, and metastasis.	Co-expression
GDS2933	Gingival epithelial cell line response to commensal and opportunistic oral microbial species	Analysis of gingival epithelial HIGK cells co-cultured with the the oral commensal Streptococcus gordonii or the opportunistic commensal Fusobacterium nucleatum. Results provide insight into the mechanisms underlying the adaptation of hosts to commensals.	Co-expression
GDS2935	Allergic contact dermatitis: time course	Analysis of skin biopsies from nickel-allergic patients whose skins were exposed to nickel, a sensitizing hapten, for up to 96 hours to elicit allergic contact dermatitis (ACD). Results provide insight into molecular mechanisms underlying the pathogenesis of ACD.	Co-expression
GDS2938	IFN-gamma and IL-1beta effect on thyroid epithelial cells (HG-U133A)	Analysis of thyroid epithelial cells (TECs) treated with IFN-gamma, IL-1beta, or both. Fas-mediated apoptosis plays a role in the pathogenesis of autoimmune thyroid diseases. TECs are resistant to Fas-mediated apoptosis, but the resistance is overcome by pretreatment with IFN-gamma and IL-1beta.	Co-expression
GDS2939	IFN-gamma and IL-1beta effect on thyroid epithelial cells (HG-U133A 2.0)	Analysis of thyroid epithelial cells (TECs) treated with IFN-gamma, IL-1beta, or both. Fas-mediated apoptosis plays a role in the pathogenesis of autoimmune thyroid diseases. TECs are resistant to Fas-mediated apoptosis, but the resistance is overcome by pretreatment with IFN-gamma and IL-1beta.	Co-expression
GDS2940	Dendritic cell response to TGF-beta1: time course	Analysis of dendritic cells (DCs) at various time points up to 36 hours following treatment with TGF-beta1. DCs derived from CD34+ hematopoietic progenitor cells induced to differentiate in vitro. Results provide insight into the role of TGF-beta1 in DC development.	Co-expression
GDS2941	Down syndrome: brain	Analysis of postmortem brains of individuals with Down syndrome. Results provide insight into the pathogenesis of Down syndrome.	Co-expression
GDS2947	Colorectal adenoma formation	Analysis of colorectal adenomas and normal mucosas from 32 patients. Results provide insight into the molecular mechanisms underlying the formation of colorectal adenomas.	Co-expression
GDS2951	Hypoxia effect on peripheral blood lymphocytes	Analysis of peripheral blood lymphocytes (PBL) subjected to hypoxia in vitro. PBL were grown at 1% or 20% ambient oxygen.	Co-expression
GDS2952	Rheumatoid arthritis response to anti-tumor necrosis factor treatment: whole blood	Analysis of whole blood samples from rheumatoid arthritis (RA) patients following anti-tumor necrosis factor therapy. Results provide insight into the pathogenesis of RA and the molecular mechanisms associated with the response to anti-TNF treatment.	Co-expression
GDS2954	Mycobacterium tuberculosis-derived lipopeptide effect on monocytes and dendritic cells: time course	Analysis of monocytes (MOs) and MO-derived dendritic cells (DCs) for up to 24 hours following Mycobacterium tuberculosis-derived lipopeptide treatment. Toll-like receptor activation by bacterial lipopeptides reduced the viability of M. tuberculosis in MOs and macrophages but not MO-derived DCs.	Co-expression
GDS2958	Tumor suppressor PTEN depletion effect on various cell lines	Analysis of A431, HCC827, and SKBR-3 carcinoma cell lines depleted for the tumor suppressor PTEN. Inactivation of PTEN is a common genetic lesion in cancer. Results provide insight into the molecular basis of the oncogenic phenotypes resulting from PTEN deficiency.	Co-expression
GDS2959	Granulocyte colony-stimulating factor mobilized leukocytes	Analysis of leukocytes from individuals before and after the administration of granulocyte colony-stimulating factor (G-CSF). G-CSF is used to boost granulocyte counts in immunocompromised patients. Results provide insight into the effect of G-CSF on the immune system.	Co-expression
GDS2960	Marfan syndrome: cultured skin fibroblasts	Analysis of cultured skin fibroblasts prepared from patients with Marfan syndrome (MFS). MFS is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. Results provide insight into the molecular pathogenesis of MFS.	Co-expression
GDS2963	Vincristine-sensitive and resistant ovarian carcinoma cell lines	Analysis of the vincristine-sensitive SKOV3 ovarian carcinoma cell line and its vincristine-resistant derivative. Vincristine is a chemotherapeutic agent used for the treatment of cancer. Results provide insight into the molecular mechanisms underlying the emergence of multidrug resistance.	Co-expression
GDS2966	Resveratrol effect on lung carcinoma cell line	Analysis of lung carcinoma A549 cells treated with resveratrol. Resveratrol is a phytoestrogen found in red wine. Results provide insight into protective effect of resveratrol against lung cancer.	Co-expression
GDS2970	Polyamide-chlorambucil conjugate 1R-Chl effect on leukemia cell line	Analysis of leukemia K562 cells treated with the polyamide-chlorambucil conjugate 1R-Chl. 1R-Chl down-regulates transcription of the human histone H4c gene and inhibits the growth of several cancer cell lines in vitro.	Co-expression
GDS2971	Hemiasterlin analog HTI-286 effect on docetaxel-resistant prostate cancer cell line	Analysis of prostate cancer LNCaP cells treated with the chemotherapeutic agent docetaxel or the hemiasterlin analog HTI-286. Like docetaxel, HTI-286 disrupts microtubule dynamics. But unlike docetaxel, HT-286 exhibits reduced multidrug resistance.	Co-expression
GDS2975	TGF-beta 1 effect on immortalized ovarian surface epithelial cell line: time course	Analysis of immortalized ovarian surface epithelial (IOSE) cells treated for up to 12 hours with transforming growth factor beta 1 (TGFb1). IOSE cells are derived from normal ovarian epithelial cells which, unlike ovarian cancer, respond to TGFb1-induced growth inhibition.	Co-expression
GDS2978	Multiple sclerosis: brain	Analysis of brains of individuals afflicted with multiple sclerosis (MS), a primary demyelinating disease of the central nervous system. Results provide insight into the molecular mechanisms underlying MS pathogenesis.	Co-expression
GDS2987	Comparison of Rho kinase inhibitor and atorvastatin effects on primary cell lines	Analysis of three primary cell lines treated with Rho kinase (ROCK) 2 inhibitor SLx-2119 or with atorvastatin. Effects of ROCK inhibitors overlap to some extent with the pleiotropic (nonlipid lowering) effects of statins. Results suggest possible synergistic effects between the two classes of drugs.	Co-expression
GDS2988	Paeoniflorin effect on lymphoma cell line: time course	Analysis of U937 lymphoma cells at various time points up to 6 hours following treatment with paeoniflorin (PF). PF, isolated from paeony roots, causes apoptosis and is a chemical heat shock protein (HSP) inducer. Results provide insight into the molecular mechanisms of action of this compound.	Co-expression
GDS2990	Cigarette smoking effect on full-term placenta	Analysis of full-term placentas exposed to maternal cigarette smoke. The placenta produces and metabolizes steroids and xenobiotics. Results provide insight into the effects of maternal cigarette smoking on the placenta at term, with a focus on xenobiotic- and steroid-metabolizing genes.	Co-expression
GDS3003	House dust mite extract effect on a bronchial epithelial cell line	Analysis of H292 bronchial epithelial cells exposed to house dust mite (HDM) extract. More than just a physical barrier, epithelium can produce mediators in response to pathogens and allergens. Results provide insight into the nature of the response of bronchial epithelial cells to HDM allergen.	Co-expression
GDS3004	Heat stress effect on an epithelial cell line	Analysis of HEp2 epithelial cells subjected to heat stress at temperatures of 37 to 40 degrees C. Results provide insight into the regulatory pathways that control the response to heat stress.	Co-expression
GDS3005	Macrophage response to interleukins 1 and 6	Analysis of cultured monocyte-derived macrophages (MDM) stimulated with interleukin (IL) 1 or IL-6 for 4 hours. Cytokines IL-1 and IL-6 are not only produced by macrophages but also affect the cells in an autocrine manner. Results provide insight into IL-1 and IL-6 responsive genes in MDMs.	Co-expression
GDS3007	Kaposi's sarcoma-associated herpesvirus microRNA-K12-11 expression	Analysis of cells expressing microRNA (miR) K12-11 from Kaposi's sarcoma-associated herpesvirus. miR-K12-11 shares sequence homology with hsa-miR-155, a miRNA up-regulated in lymphomas and important in B cell development. Results provide insight into the biological activity of miR-K12-11.	Co-expression
GDS3011	Interleukin-1 effect on epidermal keratinocytes: time course	Analysis of epidermal keratinocytes at various time points up to 48 hours post-interleukin-1 (IL-1) treatment. IL-1 is a proinflammatory and immunomodulatory cytokine that plays a role in inflammatory diseases of the skin. Results provide insight into gene products that mediate the effects of IL-1.	Co-expression
GDS3012	DNA methylation inhibitor effect on melanoma cell lines	Analysis of six melanoma cell lines treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5AzadC). Results provide insight into the role of epigenetic silencing by DNA methylation in the pathogenesis of melanoma.	Co-expression
GDS3017	Cervical cancer response to chemoradiotherapy	Analysis of cervical cancer biopsy samples from patients receiving radiotherapy alone or radiotherapy plus concomitant chemotherapy with cisplatin (CRT). Results provide insight into the molecular mechanisms underlying the therapeutic response to CRT.	Co-expression
GDS3027	Early-early stage Duchenne muscular dystrophy: quadriceps	Analysis of skeletal muscles from 1.5 to 61 month old children with Duchenne muscular dystrophy (DMD). DMD is a degenerative skeletal muscle disease caused by mutations in the dystrophin gene. Results provide insight into the early phases of DMD pathogenesis and pathophysiology.	Co-expression
GDS3029	Small-cell lung carcinoma cell lines of varying sensitivity to a Bcl-2 antagonist	Analysis of small-cell lung carcinoma cell (SCLC) lines. Expression profiles compared to the cell lines' sensitivity to the Bcl-2 antagonist ABT-737 and chromosomal gains that include changes in Bcl-2 gene copy number. ABT-737 induces the regression of a fraction of SCLC solid tumors.	Co-expression
GDS3032	Quercetin effect on intestinal cell differentiation in vitro: time course	Analysis of post-confluent Caco-2 colon cancer cells up to 10 days after treatment with ascorbate-stabilized quercetin, a polyphenol antioxidant compound. Caco-2 cells differentiate after reaching confluency. Results provide insight into quercetin's role in cell-proliferation and -differentiation.	Co-expression
GDS3034	Candida albicans effect on endothelial cell line	Analysis of HUVEC umbilical vein endothelial cells (EC) exposed to Candida albicans blastopsores. ECs actively participate in the innate defense against microbial pathogens. Results provide insight into molecular mechanisms underlying the endothelial stress response to Candida infection.	Co-expression
GDS3041	Encapsulated Streptococcus pneumoniae strains effect on pharyngeal epithelial cell line	Analysis of pharyngeal epithelial cells exposed to various encapsulated strains of Streptococcus pneumoniae. Nasopharynx colonization by S. pneumoniae is mediated by adherence to the respiratory epithelium. Results provide insight into the capsule-dependent host response to pneumococcal adherence.	Co-expression
GDS3042	Imatinib effect on K562 leukemia cell line (I)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3043	Imatinib effect on K562 leukemia cell line (II)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3044	Imatinib effect on K562 leukemia cell line (III)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3045	Imatinib effect on K562 leukemia cell line (IV)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3046	Imatinib effect on K562 leukemia cell line (V)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3047	Imatinib effect on K562 leukemia cell line (VI)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3048	Imatinib effect on K562 leukemia cell line (VII)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3049	Imatinib effect on K562 leukemia cell line (VIII)	Analysis of K562 leukemia cells treated with 1 uM imatinib for 24 hours. Imatinib is a highly selective and potent growth-inhibitor of BCR/ABL1 expressing cells such as K562. Results provide insight into molecular mechanisms underlying BCR/ABL1-mediated leukemogenesis.	Co-expression
GDS3051	Fibroblast cell line response to two and three dimensional collagen-glycosaminoglycan culture environments	Analysis of IMR-90 fibroblasts cultured in a two- or a three-dimensional collagen-glycosaminoglycan (GAG) environment. The 3-D presentation of collagen-GAG stimulates increased fibroblast remodeling activity. Results provide insight into molecular changes elicited by the 3-D collagen-GAG interface.	Co-expression
GDS3054	Cigarette smoking effect on the buccal epithelium	Analysis of buccal epithelia from cigarette smokers. Cigarette smoke creates a field of injury in epithelial cells lining the respiratory tract. Results extend the concept of a smoking-induced field of injury beyond intrathoracic (bronchial) epithelia to extrathoracic epithelia that line the mouth.	Co-expression
GDS3057	Acute myeloid leukemia	Comparison of leukemic blasts from 26 acute myeloid leukemia (AML) patients with normal hematopoietic cells at a variety of different stages of maturation from 38 healthy donors. Results provide insight into the possible clinical significance of those genes with AML-specific expression changes.	Co-expression
GDS3060	Endometriosis: endometrial endothelial cells	Analysis of cultured endometrial endothelial cells derived from the eutopic endometria of patients with endometriosis. Results provide insight into the role of aberrant angiogenesis in the pathogenesis of endometriosis.	Co-expression
GDS3062	Multipotent stromal cell expansion in vitro	Temporal analysis of cultures of multipotent stromal cells (MSCs) from bone marrow aspirates from 3 donors. On day 2, the MSCs are in transition from lag phase to log phase; on day 7, they are in stationary phase. Results provide insight into the molecular changes in MSCs during in vitro expansion.	Co-expression
GDS3068	Primary hepatocytes and HepG2 liver cells response to various fluoroquinolones	Analysis of primary hepatocytes (PHs) and HepG2 liver cells treated with various fluoroquinolones. PHs are used in drug metabolism research, and HepG2 cells are surrogates for PHs. Results provide insight into the differences in the response of PHs and HepG2 cells to xenobiotics.	Co-expression
GDS3069	Various brain tumors	Analysis of 12 primary brain tumor biopsies with some variation in their histological diagnoses. These results, together with those obtained from miRNA profiling by real-time PCR, provide insight into the relationship between endogenous fluctuations in miRNA and mRNA expression levels.	Co-expression
GDS3071	Keloid fibroblast response to hydrocortisone in vitro	Analysis of keloid fibroblasts (FBs) treated with 1.5uM hydrocortisone (HC). Keloids are benign dermal tumors that form during protracted wound healing. HC at 1.5uM inhibits collagen and elastin synthesis in normal scar FBs but not in keloid FBs. Results provide insight into keloid pathogenesis.	Co-expression
GDS3073	Neutrophil response to aerobic exercise	Analysis of neutrophils from healthy males before and after 30 minutes of aerobic exercise. The number of circulating neutrophils increases after exercise. Results provide insight into the molecular response of these immune cells to exercise.	Co-expression
GDS3082	Allergic nasal epithelium response to house dust mite allergen in vitro	Analysis of cultured nasal epithelia prepared from healthy and allergic individuals following exposure to house dust mite (HDM) extract in vitro. Results provide insight into the molecular mechanisms underlying the allergic response of the nasal epithelia to allergens.	Co-expression
GDS3085	Gram-positive and gram-negative sepsis: leukocytes	Analysis of leukocytes from patients with gram-positive or gram negative sepsis. Results provide insight into the specificity of the host response to gram-positive and gram negative sepsis.	Co-expression
GDS3088	Leukotriene B4 effect on monocytes: time course	Analysis of primary monocytes treated for up 16 hours with leukotriene B4 (LTB4) in vitro. LTB4 is a mediator of inflammation. Monocytes express the cell surface receptors BLT1 and BLT2 that mediate the action of LTB4. Results provide insight into the transcriptional response of monocytes to LTB4.	Co-expression
GDS3089	Tretinoin effect on promyelocytic leukemia cell line	Analysis of promyelocytic leukemia HL60 cells treated with tretinoin (all-trans retinoic acid; ATRA) or vehicle. ATRA induces terminal differentiation or growth arrest in HL60 cells. Results suggest a 90-gene expression signature for this cell culture model of hematopoietic differentiation.	Co-expression
GDS3091	Noncancerous hepatic tissues from hepatocellular carcinoma patients with and without venous metastasis	Analysis of noncancerous hepatic tissues surrounding tumors from hepatocellular carcinoma (HCC) patients with and without venous metastasis. Results provide insight into the role of the hepatic microenvironment in HCC metastasis.	Co-expression
GDS3092	Endometriosis	Analysis of ectopic endometrial tissues implanted in the peritoneal cavity of 11 subjects. The growth of endometrial tissue outside of the uterus is called endometriosis. Results provide insight into the molecular pathology of endometriosis.	Co-expression
GDS3095	Zinc effect on malignant and non-malignant prostate cell lines: time course	Analysis of malignant PC-3 and non-malignant HPR-1 prostate cells treated for up to 6 hours with zinc. Zinc exposure induces apoptosis in PC-3 cells, but not in HPR-1 cells. Results provide insight into the molecular mechanisms underlying zinc-induced prostatic cell apoptosis.	Co-expression
GDS3096	Inflammatory breast cancer: stroma	Analysis of stromata surrounding tumors from patients with inflammatory breast cancer (IBC) and invasive non-IBC. This is part of a study that also examines the expression profiles of tumors. Results provide insight into the contribution of the tumor stroma component to the pathogenesis of IBC.	Co-expression
GDS3097	Inflammatory breast cancer: tumor	Analysis of tumor epithelia from patients with inflammatory breast cancer (IBC) and invasive non-IBC. This is part of a study that also examines the expression profiles of stromata surrounding tumors. Results provide insight into the contribution of the tumor component to the pathogenesis of IBC.	Co-expression
GDS3100	Skeletal muscles of postmenopausal women with and without hormone replacement	Analysis of skeletal muscles of postmenopausal women treated with hormone replacement therapy (HRT) or with a placebo. Menopause is accompanied by age-associated changes in muscle structure and function. Results provide insight into the effect of HRT and estrogen deprivation on skeletal muscles.	Co-expression
GDS3101	Non-small cell lung carcinoma cell line response to cisplatin	Analysis of cisplatin-resistant A549 lung adenocarcinoma cell line treated with cisplatin, a chemotherapy drug. Its cytotoxic effects are likely due to the DNA damage it induces in cells. Results provide insight into molecular mechanisms underlying the response of A549 to cisplatin insult.	Co-expression
GDS3104	Insulin-resistant polycystic ovary syndrome: muscle	Analysis of vastus lateralis muscles from women with insulin-resistant polycystic ovary syndrome (PCOS). Insulin resistance in skeletal muscles is a risk factor for the development of type 2 diabetes in women with PCOS. Results provide insight into the pathogenesis of insulin resistance in PCOS.	Co-expression
GDS3105	Cimicifuga racemosa extract effect on breast cancer cell line MCF-7	Analysis of MCF-7 breast cancer cells treated with a Cimicifuga racemosa extract. Extracts from the C. racemosa rhizome are used as an herbal alternative to hormone replacement therapy for alleviation of postmenopausal disorders. Results provide insight into the extract's molecular mode of action.	Co-expression
GDS3110	Hypothalamic hamartoma and central precocious puberty	Analysis of hypothalamic hamartomas (HHs) from patients with or without central precious puberty (CPP). HHs are congenital lesions composed of neurons and astroglia often associated with CPP. Results provide insight into the mechanisms that initiate normal puberty.	Co-expression
GDS3111	Prostate cancer cell line response to dihydrotestosterone: time course	Analysis of LNCaP prostate cancer cells treated with the androgen dihydrotestosterone (DHT). DHT binds to androgen receptor (AR), a ligand dependent transcription factor that plays a key role in prostate cancer. Results provide insight into mechanisms underlying AR-dependent prostate cancer growth.	Co-expression
GDS3112	Hypoxia effect on cultured aortic smooth muscle cells	Analysis of aortic smooth muscle cells incubated for 16 hrs or 48 hrs under hypoxic conditions (1% or 3%O2). Smooth muscle cell proliferation and survival are modulated by hypoxia. Results provide insight into molecular mechanisms underlying oxygen regulation of arterial smooth muscle cells.	Co-expression
GDS3113	Various normal tissues	Analysis of various normal tissues. Results provide insight into housekeeping and tissue-specific genes.	Co-expression
GDS3115	Heart failure: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells from chronic heart failure (CHF) patients with ischemic or non-ischemic cardiomyopathy (ICM or NICM). Results provide insight into diagnostic/prognostic markers and CHF gene expression profiles.	Co-expression
GDS3116	Letrozole effect on breast cancer tumors	Analysis of breast cancer tumors following treatment with letrozole for 14 days. The aromatase inhibitor letrozole is an anti-estrogen drug used to treat postmenopausal women with breast cancer. Results provide insight into the molecular mechanism of action of letrozole in breast cancer.	Co-expression
GDS3119	Ulcerative colitis	Analysis of colonic mucosa samples with or without signs of inflammation from patients with ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). Results provide insight into the molecular mechanisms contributing to the development of inflammation in UC.	Co-expression
GDS3124	Radioresistant tumor response to ionizing radiation	Analysis of nu61 radioresistant tumors following exposure to ionizing radiation. Nu61 tumors derived from the radiosensitive squamous cell carcinoma cell line SCC61. Results provide insight into the molecular basis of acquired tumor radioresistance.	Co-expression
GDS3125	Radioresistant tumor response to ionizing radiation: time course	Analysis of nu61 radioresistant tumors 5 and 24 hours following exposure to ionizing radiation. Nu61 tumors derived from the radiosensitive squamous cell carcinoma cell line SCC61. Results provide insight into the molecular basis of acquired tumor radioresistance.	Co-expression
GDS3126	Radioresistant tumor response to interferons	Analysis of nu61 radioresistant tumors following treatment with a mixture of interferons (IFNs) alpha, beta, and gamma. Nu61 tumors derived from the radiosensitive squamous cell carcinoma cell line SCC61. Results provide insight into the role of the IFN signaling pathway in tumor radioresistance.	Co-expression
GDS3127	Diesel exhaust inhalation effect on peripheral blood mononuclear cells: time course	Analysis of peripheral blood mononuclear cells from individuals exposed to diesel exhaust (DE), a major source of urban fine particulate matter (FPM). Exposure to ambient FPM is associated with cardiovascular disease. Results provide insight into molecular mechanisms underlying such health effects.	Co-expression
GDS3128	Parkinson's disease: substantia nigra (HG-U133A)	Analysis of medial and lateral substantia nigras (SNs) from post-mortem brain samples obtained from individuals with sporadic Parkinson's disease (PD). The SN exhibits extensive tissue damage in PD. Results provide insight into the pathogenesis of PD.	Co-expression
GDS3129	Parkinson's disease: substantia nigra (HG-U133B)	Analysis of medial and lateral substantia nigras (SNs) from post-mortem brain samples obtained from individuals with sporadic Parkinson's disease (PD). The SN exhibits extensive tissue damage in PD. Results provide insight into the pathogenesis of PD.	Co-expression
GDS3138	Metastatic breast cancer cell line response to restored miR-335 expression	Analysis of breast cancer LM2 cells transfected with a vector expressing microRNA miR-335. LM2 is metastatic to lung. miR-335 expression is lost as breast cancer cells develop metastatic potential. Restoring miR-335 expression inhibits metastatic cell invasion of lung cancer cells.	Co-expression
GDS3139	Breast cancer: histologically normal breast epithelium	Analysis of histologically normal breast epithelia of breast cancer patients. Results provide insight into the molecular abnormalities in normal appearing breast epithelium in breast cancer and the roles these abnormalities play in carcinogenesis.	Co-expression
GDS3141	Colorectal mucosae from various regions of the large intestine	Analysis of colorectal mucosae from various regions of the normal large intestine. Results provide insight into the range of variation of gene expression in normal tissues.	Co-expression
GDS3144	Comparative transcriptomic profiling of unstimulated and inflamed HUVEC exposed to apple procyanidin oligomers	We used microarrays to investigate changes in gene expression of human vascular endothelial cells (HUVEC) exposed to an apple extract enriched in procyanidins of low-medium molecular weight (dp3.9) to determine possible protective effects induced by these plant derived compounds on the endothelial cells. Keywords: Comparative gene expression, Control vs Treated cells (response to exposure with xenobiotics plant polyphenols)	Co-expression
GDS3147	GL7 determinant in various B-cell lines	Analysis of B-cell lines representing myeloma and Burkitt's lymphoma and exhibiting varied GL7 epitope expression. GL7high B-cells have higher functional activity for producing antibodies and presenting antigens. Results identify a candidate gene responsible for the biosynthesis of the GL7 epitope.	Co-expression
GDS3155	Dasatinib resistant and sensitive prostatic cancer cell lines	Analysis of 16 prostatic cancer cell lines treated with anti-tumor agent dasatinib. The cell lines display sensitivity or resistance to dasatinib.  Results used to define a gene expression profile associated with sensitivity to dasatinib.	Co-expression
GDS3158	Rheumatoid arthritis-related cartilage destruction model: chondrocytes	Analysis of chondrocytes treated with a supernatant from SV40 T-antigen immortalized human synovial fibroblasts derived from a patient with rheumatoid arthritis (RA). Results provide insight into the molecular mechanism underlying RA-related cartilage destruction.	Co-expression
GDS3160	Methotrexate resistant colon cancer cell line	Analysis of HT29 derived colon cancer cells resistant to the anticancer drug methotrexate (MTX). Results provide insight into the molecular mechanisms contributing to MTX resistance.	Co-expression
GDS3175	NF-kappaB and phosphotidylinositol 3-kinase inhibitor treated monocytes infected with the human cytomegalovirus	Analysis of monocytes treated with an NF-kappaB or a phosphatidylinositol 3-kinase (PI3K) inhibitor and then infected with the human cytomegalovirus (HCMV). Results provide insight into the role of NF-kappaB and PI3K in the activation of monocytes to a proinflammatory state after an HCMV infection.	Co-expression
GDS3177	Confluent and sub-confluent umbilical vein endothelial cell cultures	Analysis of umbilical vein endothelial cells grown to sub-confluency or confluency. Results provide insight into the molecular mechanisms underlying endothelial barrier formation.	Co-expression
GDS3179	Lung metastatic breast cancer cell line response to metadherin depletion	Analysis of LM2 breast cancer cells depleted for metadherin (MTDH), a cell surface protein in breast tumors that mediates lung metastasis. LM2 cells were grown alone or on a monolayer of lung microvascular endothelial cells. Results provide insight into molecular mechanisms underlying MTDH action.	Co-expression
GDS3181	Acute physiologic hyperinsulinemia effect on the skeletal muscle: time course	Analysis of skeletal muscles from normal, healthy glucose-tolerant individuals exposed to acute physiological hyperinsulinemia for up to 4 hours. Results suggest a low-grade inflammatory response which may provide insight into the etiology of insulin resistance in type 2 diabetes and obesity.	Co-expression
GDS3182	Young and aged skeletal muscles response to long-term vigorous endurance exercise	Analysis of skeletal muscles from young and aged individuals undergoing vigorous endurance exercise training for over 4 years. Results provide insight into the effects of endurance exercise on age-related insulin resistance and mitochondrial dysfunction.	Co-expression
GDS3191	Natural killer cell response to interleukin-2 treatment: time course	Analysis of resting natural killer (NK) cells and NK cells activated with interleukin-2 (IL-2) for up to 24 hours.  The effector function of NK cells is enhanced by cytokines such as IL-2. Results provide insight into the molecular events in NK cell activation.	Co-expression
GDS3192	Rheumatoid arthritis: synovial macrophages	Analysis of synovial fluid macrophages from 5 patients with rheumatoid arthritis (RA). The chronic inflammation and progressive joint destruction observed in RA are mediated in part by macrophages. Results provide insight into the molecular mechanisms underlying RA pathogenesis.	Co-expression
GDS3193	Monocyte-derived dendritic cell response to VAF347	Analysis of immature monocyte-derived dendritic cells following activation with anti-CD40 antibodies for 8 hours in the presence of VAF347. VAF347 is a low molecular weight compound that inhibits allergic lung inflammation in vivo. Results provide insight into the mechanism of action of VAF347.	Co-expression
GDS3196	Non-thermal low intensity pulsed ultrasound effect on leukemia cell line	Analysis of leukemia U937 cells exposed to non-thermal low intensity pulsed ultrasound (LIPUS) for 6 hours to induce apoptosis. Results provide insight into the molecular mechanisms underlying the apoptotic response to nonthermal LIPUS.	Co-expression
GDS3203	Monocyte to macrophage differentiation	Analysis of monocytes following up to 168 hours of adherence-induced differentiation. Monocytes differentiate into macrophages, which are critical in the pathogenesis of many diseases. Results provide insight into the molecular mechanisms underlying monocyte to macrophage differentiation.	Co-expression
GDS3207	Chronic loneliness effect on peripheral blood leukocytes	Analysis of leukocytes from individuals experiencing chronically high levels of subjective social isolation (loneliness). Social environment is known to influence human health. Results provide insight into transcriptional alterations in the immune system induced by chronic social isolation.	Co-expression
GDS3211	Gingival epithelial cell line response to oral pathogen infections	Analysis of gingival epithelial HIGK cells infected with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis. A. actinomycetemcomitans and P. gingivalis cause periodontal infections. Results provide insight into differences in epithelial cell responses to these pathogens.	Co-expression
GDS3215	13-cis retinoic acid effect on SEB-1 sebocyte cell line	Analysis of cultured sebaceous gland cells (SEB-1 sebocytes) treated with 13-cis retinoic acid (13-cis RA, isotretinoin), a potent acne treatment agent that reduces the size and secretion of sebaceous glands. Results provide insight into the molecular basis for 13-cis RA's acne-clearing effect.	Co-expression
GDS3217	Estradiol effect on breast cancer cell line expressing estrogen receptor: time course	Analysis of estrogen receptor (ER)-positive MCF7 breast cancer cells up to 48 hours following treatment with estradiol (E2). ERs facilitate the transcriptional effects of hormones. These results, together with ChIP-PET results, suggest potential correlations between ER binding and gene regulation.	Co-expression
GDS3218	13-cis retinoic acid effect on skin	Analysis of upper back skin biopsies of acne patients treated with 13-cis retinoic acid (13-cis RA, isotretinoin), a potent acne treatment agent that reduces the size and secretion of sebaceous glands. Results provide insight into the molecular basis for 13-cis RA's acne-clearing effect.	Co-expression
GDS3220	YAP overexpression effect on MCF10A mammary epithelial cell line	Analysis of MCF10A mammary epithelial cells overexpressing the transcriptional coactivator YAP.  The Hippo pathway impinges on YAP in mammals to coordinate cell proliferation and apoptosis. Results provide insight into molecular components of the Hippo pathway in mammalian cells.	Co-expression
GDS3223	IL-13 involvement in eosinophilic esophagitis: transcriptome analysis	3 eosinophilic esophagitis biopsies, cultured and stimulated with IL-13 : each of them was either left unstimulated or stimulated (100ng for 48h) We used microarray to uncover the IL-13-induced genes in esophageal epithelial cells of the esophagus Keywords: treated vs non treated	Co-expression
GDS3233	Cervical cancer tumorigenesis	Analysis of cervical cancer (CC) primary tumors and cell lines. Chromosomal amplification is a common cellular mechanism of gene activation in tumorigenesis; chromosome 20 is a commonly gained chromosome in CC. Results provide insight into the potential role of chromosome 20 gain in CC progression.	Co-expression
GDS3256	Metaphase II stage oocytes matured in vivo	Analysis of young, untreated metaphase II (MII) oocytes. Results provide insight into the baseline of genes expressed in in vivo matured oocytes and into the molecular mechanisms underlying biological processes such as oogenesis, folliculogenesis, fertilization, and embryonic development.	Co-expression
GDS3257	Cigarette smoking effect on lung adenocarcinoma	Analysis of different tumor stage adenocarcinoma and paired normal lung tissues of current, former and never smokers. To date, tobacco smoking is responsible for over 90% of lung cancers. Results provide insight into the molecular basis of lung carcinogenesis induced by smoking.	Co-expression
GDS3258	Monocyte-derived macrophage response to decoy receptor 3	Analysis of monocyte-derived macrophages (MDMs) treated with decoy receptor 3 (DcR3) recombinant fusion protein. DcR3, a TNF receptor superfamily member, is up-regulated in tumors from diverse lineages. Results provide insight into the role of DcR3 in tumor-associated macrophage (TAM) development.	Co-expression
GDS3260	Intestinal tissue xenograft response to pathogen Shigella flexneri infection in vivo	Analysis of human intestinal xenotransplants infected with Shigella flexneri (virulent wild-type M90T, virulent mxiE mutant, and avirulent BS176 strains). Virulent S. flexneri are highly contagious enteric pathogens. Results provide insight into the intestinal innate immune response to infection.	Co-expression
GDS3262	Pediatric malignant germ cell tumors: yolk sac tumors and seminomas	Analysis of yolk sac tumors (YSTs) and seminomas, the two principal histological variants of pediatric malignant germ cell tumors (MGCTs). Seminomas and YSTs are presumed to arise from the same progenitor cell. Results provide insight into the molecular basis for the divergence of pediatric MGCTs.	Co-expression
GDS3268	Colon epithelial biopsies of ulcerative colitis patients	Analysis of inflamed and un-inflamed colon epithelial biopsies of 67 ulcerative colitis (UC) patients from different anatomical locations of the gastrointestinal (GI) tract. Results provide insight into the regional variation of gene expression in UC patients and the pathogenesis of UC.	Co-expression
GDS3274	Chromophobe renal cell carcinoma and oncocytoma	Comparison of chromophobe renal cell carcinoma (RCC) and benign oncocytoma tumor samples. Malignant chromophobe RCC and benign oncocytoma share  morphologic features. Results provide insight into the molecular differences between the two types of tumors.	Co-expression
GDS3281	Tuberous sclerosis complex hamartomas	Analysis of tuberous sclerosis complex (TSC) skin hamartomas (angiofibromas and periungual fibromas) with normal-appearing skin from the same patients. Hamartomas overgrow epithelial and mesenchymal cells in TSC skin. Results provide insight into the pathogenesis of TSC hamartomas.	Co-expression
GDS3282	Liver transplantation tolerance: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells from operationally tolerant liver transplant patients. Operationally tolerant patients are fully immunocompetent but accept grafts without chronic immunosuppression. Results identify a molecular signature for operational tolerance.	Co-expression
GDS3283	Estradiol effect on breast cancer cell line: time course	Analysis of MCF-7 breast cancer cells treated with estradiol for 3 or 6 hours. Results combined with ChIP experiments to identify estrogen receptor alpha binding sites and estradiol target genes in breast cancer cells.	Co-expression
GDS3285	Estrogen effect on breast cancer cell line: time course	Analysis of MCF-7 breast cancer cells treated with estrogen for up to 12 hours. Results used in conjunction with estrogen receptor and RNA polymerase II binding data to provide insight into the mechanisms underlying estrogen-regulated gene expression in breast cancer.	Co-expression
GDS3289	Prostate cancer progression at the cellular level	Analysis of LCM-captured epithelial cell populations representing prostate cancer progression from benign epithelium to metastatic disease. Stromal cell populations also examined. Results provide insight into molecular mechanisms underlying the different aspects of prostate cancer progression.	Co-expression
GDS3290	Interleukin-6 effect on skeletal muscle tissue: time course	Analysis of interleukin-6 (IL-6) infused skeletal muscle (SKM) biopsies at time points up to 6hr. IL-6, a cytokine secreted from skeletal muscle during exercise, works in both an autocrine and paracrine manner. Results provide insight into IL-6-induced expression of other secreted factors in SKM.	Co-expression
GDS3291	Myelomonocytic lymphoma U937 cell line response to mild hyperthermia	Analysis of myelomonocytic lymphoma U937 cells subjected to mild hyperthermia. Mild hyperthermia alone does not induce apoptosis but it does show a synergism with radiotherapy and anti-cancer drugs. Results provide insight into molecular mechanisms underlying cellular responses to mild hyperthermia.	Co-expression
GDS3292	Preinvasive and invasive cervical squamous cell carcinomas	Analysis of LCM-harvested high-grade squamous intraepithelial lesions (HSIL) and invasive squamous cell carcinomas (SCC) from cervices. If left untreated, a subset of the HSILs will progress to SCCs. Results provide insight into the molecular mechanisms underlying cervical cancer progression.	Co-expression
GDS3297	Stage III serous ovarian adenocarcinomas	Analysis of stage III ovarian serous papillary adenocarcinomas from 5-year survivors and deceased patients. Ovarian carcinoma is often not detected until an advanced stage.  Results provide insight into gene expression patterns associated with survival that could have prognostic relevance.	Co-expression
GDS3298	Peripheral blood monocyte response to Francisella tularensis infections	Analysis of blood monocytes infected with Francisella tularensis tularensis Schu S4 (virulent) or subsp. novicida (less virulent). F. tularensis causes the disease tularemia. Results provide insight into the molecular mechanisms that enable Francisella to dampen or subvert the host immune response.	Co-expression
GDS3299	Nucleus- and cell-specific gene expression in monkey thalamus	Nuclei of the mammalian thalamus are aggregations of neurons with unique architectures and input-output connections, yet the molecular determinants of their organizational specificity remain unknown. By comparing expression profiles of thalamus and cerebral cortex in adult rhesus monkeys we identified transcripts that are unique to dorsal thalamus or to individual nuclei within it. Real-time quantitative polymerase chain reaction and in situ hybridization analyses confirmed the findings. Expression profiling of individual nuclei microdissected from the dorsal thalamus revealed additional subsets of nucleus-specific genes. Functional annotation using Gene Ontology (GO) vocabulary and Ingenuity Pathway analysis revealed over-representation of GO categories related to development, morphogenesis, cell-cell interactions, and extracellular matrix within the thalamus- and nucleus-specific genes-many involved in the Wnt signaling pathway. Examples included the transcription factor TCF7L2, localized exclusively to excitatory neurons, a calmodulin-binding protein PCP4, the bone extracellular matrix molecules SPP1 and SPARC, and other genes involved in axon outgrowth and cell matrix interactions. Other nucleus-specific genes such as CBLN1 are involved in synaptogenesis. The genes identified likely underlie nuclear specification, cell phenotype and connectivity during development and their maintenance in the adult thalamus. Keywords: brain region comparative analysis	Co-expression
GDS3300	SOX transcription factor overexpression in embryonic stem cells	Analysis of CA1 and CA2 embryonic stem cell (ESC) lines over-expressing transcription factor SOX7 or SOX17, producing extraembryonic endoderm and definitive endoderm progenitors, respectively. Results provide insight into the roles of SOX7 and SOX17 as regulators of endoderm differentiation in ESCs.	Co-expression
GDS3305	Long-Term Storage of Human Cells at Ambient Temperature	This series represents the complete series of the human 293h media depleted storage on agarose / rehydration condition course analysis. Samples include Control, monolayer; Control, monolayer/full recovery, antibiotics; Spheroid, no storage; two week storage/0hr recovery; two week storage/full recovery;  four week storage/0hr recovery; six week storage/0hr recovery. Keywords = 293h cells Keywords = desiccation Keywords = rehydration Keywords = spheroid Keywords = stabilization Keywords = ambient temperature Keywords: other	Co-expression
GDS3306	Two week Storage and Rehydration of HEK 293 Cells at Ambient Temperature	This series represents the rehydration series of the human 293h media depleted storage on agarose / rehydration condition course analysis. Samples include Control Monolayer,  0 hr desiccation, 0 hr rehydration, 6 hr rehydration, 24 hr rehydration, and 72 hr rehydration. Keywords = 293h cells Keywords = desiccation Keywords = rehydration Keywords = spheroid Keywords = stabilization Keywords = ambient temperature Keywords: other	Co-expression
GDS3308	Cytogenetically normal acute myeloid leukemia_training set (HG-U133B)	Analysis of mononuclear cells from bone marrow or peripheral blood from a training set of 163 adult patients with cytogenetically normal acute myeloid leukemia (CN-AML). Patients with CN-AML show heterogeneous treatment outcomes. Results provide insight into a prognostic gene signature for CN-AML.	Co-expression
GDS3309	Cigarette smoking effect on the nasal epithelium	Analysis of nasal epithelia from cigarette smokers. Cigarette smoke creates a field of injury in epithelial cells lining the respiratory tract. Results extend the concept of a smoking-induced field of injury beyond intrathoracic (bronchial) epithelia to extrathoracic epithelia that line the nose.	Co-expression
GDS3310	Human Herpesvirus-8 infection of pulmonary microvascular entdothelial cells	Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi’s sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD).  We have previously described evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH).  We speculated that viral infection of the pulmonary microvascular endothelial cells could cause the angioproliferative phenotype characteristic of severe pulmonary arterial hypertension (PAH).  We now demonstrate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells (HPMVECs) in vitro, confirming both latent and lytic infection.  HHV-8 infection of HPMVECs resulted in significant changes of gene expression including alterations of pathways integral to both cellular apoptosis and angiogenesis.  This infection also results in alterations of genes integral to the bone morphogenic protein (BMP) pathway, including down regulation of bone morphogenic protein receptor 1a (BMPR1a) and bone morphogenic protein 4 (BMP4).  Other genes previously implicated in the development of PAH are also altered in expression by HHV-8 infection.  These include increased expression of Interleukin-6 (IL-6) and the matrix metalloproteinases (MMP)-1, MMP-2 and MMP-10.  Lastly, cells infected with HHV-8 apoptosis resistant.   Infection of pulmonary microvascular endothelial cells with human herepesvirus-8 results in alteration of the BMP pathway as well as an anti-apoptotic phenotype, consistent with the development of plexiform lesions characteristic of pulmonary arterial hypertension. Keywords: Viral infection of endothelial cells in culture	Co-expression
GDS3312	Cytogenetically normal acute myeloid leukemia_training set (HG-U133A)	Analysis of mononuclear cells from bone marrow or peripheral blood from a training set of 163 adult patients with cytogenetically normal acute myeloid leukemia (CN-AML). Patients with CN-AML show heterogeneous treatment outcomes. Results provide insight into a prognostic gene signature for CN-AML.	Co-expression
GDS3313	Tibolone hormone effect on postmenopausal endometrium	Comparison of endometria after short-term treatment with tibolone, estradiol (E2), or E2 + medroxyprogesterone acetate (E2 + MPA) in healthy postmenopausal women undergoing hysterectomy. A synthetic steroid, Tibolone is used as an alternative for estrogen or estrogen/progesterone hormone therapy.	Co-expression
GDS3315	Estradiol effect on breast cancer cell line in the absence of protein synthesis	Analysis of MCF-7 breast cancer cells treated with estradiol (E2) and cycloheximide, an inhibitor of protein synthesis (PS). Primary E2 targets are regulated by E2 in the absence of de novo PS. Results provide insight into mechanisms underlying primary and secondary E2 target gene regulation.	Co-expression
GDS3318	Sickle cell disease: platelets	Analysis of platelets from patients with sickle cell disease. Sickle cell disease patients exhibit increased activation of platelets. Results provide insight into the molecular basis of platelet dysfunction in sickle cell disease.	Co-expression
GDS3324	Stromal cells and invasive breast cancer development	Analysis of epithelium and stroma cells in normal and invasive breast cancer tissues. Information on the role that stroma tissues have on the growth and progression of cancer is limited.Results provide insights into the molecular basis of cancer invasion and metastasis.	Co-expression
GDS3325	Differential gene expression between individuals exposed to different levels of air pollution	Comparison of genome-wide gene expression between humans living in areas of high levels of air pollution and less polluted areas. Keywords: Comparison of genome-wide gene expression between different conditions	Co-expression
GDS3326	Expression profiles of peripheral blood monocytes in periodontal therapy	Periodontal infections have been associated with systemic inflammation and risk for atherosclerosis and vascular disease. We investigated the effects of comprehensive periodontal therapy on gene expression of peripheral blood monocytes. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis, and cell signaling. We concluded that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. Keywords: time course,disease state analysis	Co-expression
GDS3329	Cytogenetically normal acute myeloid leukemia_test set	Analysis of mononuclear cells from bone marrow or peripheral blood from a test set of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML). CN-AML patients show heterogeneous treatment outcomes. Results provide insight into the prognostic value of a gene signature for CN-AML.	Co-expression
GDS3330	Methotrexate-resistant HT29 colon adenocarcinoma cell line	Analysis of HT29 colon cancer cells sensitive or resistant to methotrexate (MTX). MTX is used in the treatment of cancer. Chemotherapy effectiveness in cancer cells is compromised by development of drug resistance. Results provide insight into molecular mechanisms associated with drug resistance.	Co-expression
GDS3333	Porphyromonas gingivalis SerB mutant infection effect on immortalized gingival epithelial cells	Analysis of immortalized gingival keratinocytes (HIGKs) infected with a Porphyromonas gingivalis SerB mutant strain. SerB mutants are deficient in internalization and survival in HIGKs. Results provide insight into the role of SerB in the interaction between P. gingivalis and HIGKs.	Co-expression
GDS3341	mRNA expression profiling of nasopharyngeal carcinoma	Nasopharyngeal carcinoma is an Epstein-Barr virus-associated epithelial cancer with high prevalence in Southeast Asia. mRNA expression levels were measured for essentially all human genes and all latent Epstein-Barr virus (EBV) genes in nasopharyngeal carcinoma tissue samples and normal nasopharyngeal tissues. Data were analyzed for differential gene expression between tumor and normal tissue and  for correlations with levels of viral gene expression. Primary publications: Sengupta et al, 2006, Cancer Research 66(16): 7999-8006. Dodd et al, 2006, Cancer Epidemiology, Biomarkers & Prevention 15(11): 2216-2225. In subsequent studies using the same set of tissue samples, microRNA levels were measured in tumors and normal tissues and analyzed for correlations with differential target gene expression (Sengupta et al, 2008, Proc. Nat. Acad. Sci. USA 105: 5874-5878.)  Keywords: mRNA expression profiling	Co-expression
GDS3342	Curcumin effect on oxidatively stressed monocyte cell line: time course	Analysis of U937 monoctyes exposed to oxidative stress then treated for 4 or 18 hrs with curcumin, a dietary polyphenol. Curcumin restores oxidative stress impaired histone deacetylase-2 activity and corticosteroid efficacy in vitro. Results provide insight into the molecular basis of these effects.	Co-expression
GDS3345	Various mental disorders: postmortem brains	Analysis of postmortem prefrontal cortices from subjects with bipolar disorder, depression, and schizophrenia. Results provide insight into the molecular pathophysiology of these mental disorders.	Co-expression
GDS3353	Gene Expression of Circulating B Lymphocytes for Osteoporosis	B cells produce important cytokines regulate bone metabolism. We comparison gene expression patterns of circulating B cells in blood from 20 postmenopausal females with low or high bone mineral density (BMD): 10 low BMD vs. 10 high BMD. In total 29 differentially expressed genes were identified including some novel genes to be relevant to bone metabolism. These results provide insight into the role of B cells in pathologic osteoporosis. Keywords: disease state analysis	Co-expression
GDS3354	Transcriptome analyses in normal prostate epithelial cells following exposure to low-dose cadmium	BACKGROUND: Cadmium is implicated in prostate carcinogenesis, but its oncogenic action remains unclear. OBJECTIVES: In this study we aimed to decipher changes in cell growth and the transcriptome in an immortalized human normal prostate epithelial cell line (NPrEC) following exposure to low-dose Cd. METHODS: Synchronized NPrEC cells were exposed to different doses of Cd and assayed for cell viability and cell-cycle progression. We investigated changes in transcriptome by global profiling and used Ingenuity Pathways Analysis software to develop propositions about functional connections among differentially expressed genes. A neutralizing antibody was used to negate the effect of Cd-induced up-regulation of tumor necrosis factor (TNF) in NPrEC cells. RESULTS: Exposure of NPrEC to 2.5 μM Cd enhanced cell viability and accelerated cell-cycle progression. Global expression profiling identified 48 genes that exhibited ≥ 1.5-fold changes in expression after 4, 8, 16, and 32 hr of Cd treatment. Pathway analyses inferred a functional connection among 35 of these genes in one major network, with TNF as the most prominent node. Fourteen of the 35 genes are related to TNF, and 11 exhibited an average of > 2-fold changes in gene expression. Real-time reverse transcriptase-polymerase chain reaction confirmed the up-regulation of 7 of the 11 genes (ADAM8, EDN1, IL8, IL24, IL13RA2, COX2/PTGS2, and SERPINB2) and uncovered a 28-fold transient increase in TNF expression in Cd-treated NPrEC cells. A TNF-neutralizing antibody effectively blocked Cd-induced elevations in the expression of these genes. CONCLUSIONS: Noncytotoxic, low-dose Cd has growth-promoting effects on NPrEC cells and induces transient overexpression of TNF, leading to up-regulation of genes with oncogenic and immunomodulation functions. KEY WORDS: carcinogenesis, cytokine, global expression profiling, heavy metals, immune response, inflammation, Ingenuity Pathway Analysis, knowledge-based analysis, prostate cancer.	Co-expression
GDS3355	Gene expression profile in HUVECs before and after Angiopoietin stimulation	Angiopoietin-Tie2 sytem has been inplicated in both vascular quiescence and angiogenesis. It is unclear how these two opposing signals are regulated from the same receptor-mediated intracellular signal transduction. We have noticed that Tie2 localization upon Angiopoietin stimulation depends upon the presence or absence of cell-cell contacts. Therefore, to identify the downstream signaling of Tie2 upon Angiopoietin stimulation, we performed DNA microarray analyais using RNAs obtained from confluent human umbirical vein endothelial cells (HUVECs) or sparse HUVECs stimulated with after Angiopoietin-1. There is striking difference on gene expression profile between confluent and sparse HUVECs.  Keywords: endothelial cell, angiopoietin	Co-expression
GDS3356	Bronchopulmonary dysplasia: premature newborn umbilical cords	Analysis of umbilical cord tissues from extremely low gestational age newborns, between 23 to 27 weeks gestational age, some of who subsequently developed the chronic lung disorder bronchopulmonary dysplasia (BPD).  Results provide insight into the molecular mechanisms underlying BPD pathogenesis.	Co-expression
GDS3358	Longitudinal Analysis of Progression to Androgen Independence	Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Keywords: Time Course	Co-expression
GDS3360	Chlamydia pneumoniae infection effect on HL epithelial cells: time course	Analysis of the HL epithelial cell line at various time points up to 72 hours following Chlamydia pneumoniae infection. C. pneumonia is a common cause of respiratory infections such as pneumonia. Results provide insight into host-cell phenomena that are affected at the different stages of infection.	Co-expression
GDS3362	Monocyte gene expression profiling in familial combined hyperlipidemia and its modification by atorvastatin treatment	Introduction: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search  novel genes and pathways involved in FCH. Methods: Fasting plasma for determination of lipid profiles, inflammatory molecules, and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene expression profile was analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. Results: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared to controls. Atorvastatin treatment modified the expression of 87 genes. Changes in the expression of some genes, confirmed by real time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen tumor necrosis factor receptor superfamily, member 25 and CD96) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. Conclusions: Our results demonstrate clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment. Keywords: comparative study differential gene expression	Co-expression
GDS3363	HOCL induced airway epithelial gene expression	In inflammatory diseases of the airway, a high level (estimated to be as high as 8 mM) of HOCl can be generated through a reaction catalyzed by the leukocyte granule enzyme myeloperoxidase (MPO). HOCl, a potent oxidative agent, causes extensive tissue injury through its reaction with various cellular substances, including thiols, nucleotides, and amines. In addition to its physiological source, HOCl can also be generated by chlorine gas inhalation from an accident or a potential terrorist attack. Despite the important role of HOCl-induced airway epithelial injury, the underlying molecular mechanism is largely unknown. In the present study, we found that HOCl induced dose-dependent toxicity in airway epithelial cells. By transcription profiling using GeneChip, we identified a battery of HOCl-inducible antioxidant genes, all of which have been reported previously to be regulated by nuclear factor erythroid-related factor 2 (Nrf2), a transcription factor that is critical to the lung antioxidant response. Consistent with this finding, Nrf2 was found to be activated time and dose dependently by HOCl. Although the epidermal growth factor receptor-MAPK pathway was also highly activated by HOCl, it was not involved in Nrf2 activation and Nrf2-dependent gene expression. Instead, HOCl-induced cellular oxidative stress appeared to lead directly to Nrf2 activation. To further understand the functional significance of Nrf2 activation, small interference RNA was used to knock down Nrf2 level by targeting Nrf2 or enhance nuclear accumulation of Nrf2 by targeting its endogenous inhibitor Keap1. By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity. 	Co-expression
GDS3364	Gene expression profilie during cell cycle in T98G cells	The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence. Keywords: Gene expression analysis during cell cycle	Co-expression
GDS3367	Argyrin A effect on MCF7 breast cancer cells: time course	Temporal analysis of MCF7 breast adenocarcinoma cells treated with argyrin A, a proteasome inhibitor that induces apoptosis by stabilizing cyclin kinase inhibitor p27kip1. Results provide insight into the molecular mechanisms that make argyrin A-induced cell death dependent upon p27kip1 expression.	Co-expression
GDS337	Telomerase overexpression	Effect of overexpression of the telomerase catalytic subunit (TERT) in mammary epithelial cells (HMEC).  Findings imply that ectopic telomerase expression modulates growth-controlling genes and enhances cell proliferation.	Co-expression
GDS3370	Staufen1 regulates a variety of mammalian transcripts	It is currently unknown how extensively the double-stranded RNA binding protein Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression.  To date, Stau1 binding to the 3’ untranslated region (3’UTR) of ARF1 mRNA has been shown to target ARF1 mRNA for Stau1-mediated mRNA decay (SMD).  ARF1 SMD depends on translation and recruitment of the nonsense-mediated mRNA decay factor Upf1 to the ARF1 3’UTR by Stau1.  Here, we use microarray analyses to examine changes in the abundance of cellular mRNAs that occur when Stau1 is depleted.  Results indicate that 1.1% and 1.0% of the 11,569 HeLa-cell transcripts that were analyzed are, respectively, upregulated and downregulated at least two-fold in three independently performed experiments.  Additionally, we localize the Stau1 binding site to the 3’UTR of four mRNAs that we define as natural SMD targets.  Together, these and substantiating results suggest that Stau1 influences the expression of a wide variety of physiologic transcripts and metabolic pathways.  Keywords: Staufen1-mediated mRNA decay; Stau1 downregulation by siRNA.	Co-expression
GDS3383	Chronic stress effect on peripheral blood monocytes	Analysis of peripheral blood monocytes from individuals experiencing chronic stress due to being caregivers of family members with malignant brain cancer. Chronic stressors increase vulnerability to medical illness. Results provide insight into molecular mechanisms underlying this phenomenon.	Co-expression
GDS3388	Bisphenol A effect on nonmalignant breast epithelial cell aspirates from breast cancer patients	Analysis of random periareolar fine-needle aspirates collected from unafflicted, contralateral breast tissue of breast cancer patients and treated with bisphenol A (BPA). BPA is a prevalent xenoestrogen. Results provide insight into early molecular events induced by BPA in susceptible breast tissue.	Co-expression
GDS3393	Bronchial epithelial cells response to interleukin-22 and interleukin-17	Analysis of bronchial epithelial cells treated with interleukin (IL)-22, IL-17, or both.  IL-17 receptor mutant lungs are susceptible to Klebsiella pneumonia infections. IL-22 induces antimicrobial peptide expression. Results provide insight into the extent of IL-22 and IL-17's role in host defense.	Co-expression
GDS3401	Two distinct isogenic mesenchymal stem/stromal cell populations from umbilical cord blood (HG-U133A)	Comparison of UCB1 and UCB2 cells, two distinct isogenic mesenchymal stem/stromal cell (MSC) populations isolated from umbilical cord blood. UCB1 and UCB2 display phenotypic differences. Results provide insight into the molecular basis of the phenotypic heterogeneity among MSC populations.	Co-expression
GDS3402	Two distinct isogenic mesenchymal stem/stromal cell populations from umbilical cord blood (HG-U133B)	Comparison of UCB1 and UCB2 cells, two distinct isogenic mesenchymal stem/stromal cell (MSC) populations isolated from umbilical cord blood. UCB1 and UCB2 display phenotypic differences. Results provide insight into the molecular basis of the phenotypic heterogeneity among MSC populations.	Co-expression
GDS3413	Homocysteine effect on aortic smooth muscle cells in vitro	Analysis of cultured aortic smooth muscle cells grown for 14 days in the presence of 10 or 100 umol/L DL-homocysteine (Hcy). Elevated plasma levels of Hcy are a risk factor for atherosclerotic vascular disease. Results provide insight into the role of Hcy in atherosclerosis.	Co-expression
GDS3416	Relaxation response practice effect on blood	Analysis of whole blood from long-term practitioners of daily relaxation response (RR) practice and those with short-term (8 wks) RR training. RR is a mind-body intervention that offsets the physiological effects caused by stress. Results provide insight into molecular mechanisms underlying the RR.	Co-expression
GDS3417	Untreated juvenile dermatomyositis muscle biopsies	Analysis of skeletal muscle biopsies from untreated girls with active symptoms of juvenile dermatomyositis (JDM) less than 2 months or greater than 2 months. Results provide insight into the impact of the duration of chronic inflammation on gene expression in muscle of untreated children with JDM.	Co-expression
GDS3423	Obese liver response to a short-term low-fat hypocaloric diet	Analysis of livers from middle-aged obese women on a low-fat hypocaloric diet for 8 weeks. The diet resulted in a mean weight loss of 5% of body weight. Results provide insight into the effect of a hypocaloric diet on the liver at the molecular level.	Co-expression
GDS3424	Conjugated linoleic acid isomers effect on intestinal cell line	Analysis of intestinal Caco-2 cells treated with conjugated linoleic acid (CLA) isomer trans-10, cis-12 CLA or cis-9, trans-11 CLA. CLA exerts isomer-specific effects on transepithelial calcium transport and cell growth in Caco-2 cells. Results provide insight into molecular mechanisms of action.	Co-expression
GDS3428	Immature dendritic cell response to butanol fraction of Echinacea purpurea: time course	Analysis of immature dendritic cell lines (iDCs) treated with the butanol-fraction of stems and leaves of E. purpurea [BF/S+L/Ep] containing defined bioactive phytocompounds. Results provide insight into molecular mechanisms underlying the immune-modulatory activities induced by the phytocompounds.	Co-expression
GDS3429	Azaspiracid-1 effect on T lymphocyte cell line: time course and dose response	Analysis of T lymphocyte Jurkat cells treated with 1 or 10 nM azaspiracid-1 (AZA-1) for up to 24 hours. AZA-1 is a marine biotoxin reported to accumulate in shellfish and is associated with severe gastrointestinal intoxication. Results provide insight into the mechanism of action of AZA-1.	Co-expression
GDS3432	Osteosarcoma cell line response to activation of specific glucocorticoid receptor alpha isoforms: time course	Analysis of glucocorticoid receptor alpha (hGRalpha) isoform -A, -B, -C, or -D expressing osteosarcoma cells for up to 24 h after hGRalpha activation with dexomethasone. Cell apoptosis occurred in a GR isoform-selective manner. Results provide insight into the function of each isoform.	Co-expression
GDS3433	Azaspiracid-1 effect on T lymphocyte cell line: time course	Analysis of T lymphocyte Jurkat cells treated with 10 nM azaspiracid-1 (AZA-1) for up to 24 hours. AZA-1 is a marine biotoxin reported to accumulate in shellfish and is associated with severe gastrointestinal human intoxication. Results provide insight into the mechanism of action of AZA-1.	Co-expression
GDS3434	Macaca mulatta model of Helicobacter pylori infection: time course	Analysis of gastric mucosa from H. pylori specific pathogen free (SPF) rhesus monkeys infected with wildtype H. pylori strain J166 or its isogenic cag pathogenicity island (cag PAI) knockout mutant. Results provide insight into the role of cag PAI in the H. pylori host-pathogen interaction.	Co-expression
GDS3439	Intralobular and interlobular mammary fibroblasts	Comparison of intralobular and interlobular fibroblasts isolated from breast tissues. Intralobular fibroblasts surround mammary gland epithelial cells, and interlobular fibroblasts surround intralobular fibroblasts. Results provide insight into the differences between the two fibroblast subtypes.	Co-expression
GDS3459	Frontotemporal lobar degeneration with ubiquitinated inclusions and progranulin mutations: various brain regions	Analysis of various brain regions of patients who suffered from frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). Presence of progranulin (GRN) mutations determined. GRN mutations are associated with FTLD-U. Results identify expression signatures for GRN subtypes of FTLD-U.	Co-expression
GDS3463	Sepsis effect on the skeletal muscle	Analysis of muscle biopsies from septic patients treated in the intensive care unit. Septic patients often develop multiple organ failure including persistent skeletal muscle dysfunction. Results provide insight into the molecular defects driving loss of muscle function and metabolic homeostasis.	Co-expression
GDS3467	Preeclampsia: first trimester placentas of pre-symptomatic women	Analysis of first trimester placenta tissues obtained by chorionic villus sampling from women destined to develop preeclampsia. Preeclampsia is a cause of maternal, fetal, and neonatal morbidity and mortality. Results provide insight into the molecular pathogenesis of preeclampsia.	Co-expression
GDS3469	Leukotriene D4 effect on monocytes	Analysis of monocytes following stimulation with leukotriene D4 (LTD4), a cysteinyl leukotriene (CysLT). CysLTs are mediators of innate immune responsiveness and chronic inflammatory diseases. Results provide insight into the signaling pathways involved in monocyte activation by cysLTs.	Co-expression
GDS3470	miR-122 overexpression effect on embryonic stem cells	Analysis of embryonic stem cells (ESCs) overexpressing wild-type miR-122. miR-122 is an endoderm specific microRNA. Results provide insight into the role of miR-122 in the differentiation of ESCs.	Co-expression
GDS3472	Barrett's esophagus	Analysis of Barrett's esophagus (BE), normal esophageal, and small intestinal biopsies. In BE, normal esophageal squamous epithelium transdifferentiates into  simple columnar epithelium resembling that of small intestine. Results provide insight into the molecular basis of this transdifferentiation.	Co-expression
GDS3474	Limb girdle muscular dystrophy 2A (HG-U133A)	Analysis of skeletal muscles from patients with limb girdle muscular dystrophy 2A (LGMD2A). LGMD2A is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Results provide insight into the molecular pathogenesis of LGMD2A.	Co-expression
GDS3475	Limb girdle muscular dystrophy 2A (HG-U133B)	Analysis of skeletal muscles from patients with limb girdle muscular dystrophy 2A (LGMD2A). LGMD2A is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Results provide insight into the molecular pathogenesis of LGMD2A.	Co-expression
GDS3481	NOR1 gene and EWS/NOR1 fusion gene overexpression	Analysis of cells overexpressing NOR1 or the EWS/NOR1 fusion gene. NOR1 encodes an orphan nuclear receptor.  The EWS gene is involved in various malignancies by way of chromosomal translocations, and the EWS/NOR1 gene fusion is implicated in the pathogenesis of extraskeletal myxoid chondrosarcomas.	Co-expression
GDS3482	X-linked inhibitor of apoptosis XIAP depletion effect on a colorectal cancer cell line	Analysis of early and late passage HCT116 colon cancer cells depleted for X-linked inhibitor of apoptosis (XIAP). XIAP is overexpressed in the majority of NCI 60 cell lines compared to normal cells suggesting a potential role as a therapeutic target in a wide spectrum of malignancies.	Co-expression
GDS3484	Insulin-like growth factor-I effect on breast cancer cell line: time course	Analysis of breast cancer MCF-7 cells stimulated with insulin-like growth factor-I (IGF-I) for 3 or 24 hours. High serum IGF-I levels are associated with an elevated risk of breast cancer. Results provide insight into the role of IGF-1 in the development and progression of breast cancer.	Co-expression
GDS3487	Transcription factor CREB depletion effect on myeloid leukemic cell line	Analysis of myeloid leukemia K562 cells depleted for cAMP Response Element Binding Protein (CREB), a transcription factor. CREB is overexpressed in bone marrow samples of patients with acute leukemia. Results provides insight into the molecular mechanisms by which CREB contributes to acute leukemia.	Co-expression
GDS3489	CD133 depletion effect on metastatic melanoma cell line	Analysis of metastatic melanoma FEMX-I cells depleted for CD133. CD133 is a cancer stem cell-associated antigen expressed in many malignancies such as melanoma. Results provide insight into the role of CD133 in cancer progression.	Co-expression
GDS3492	Senescent activated hepatic stellate cells	Analysis of activated hepatic stellate cells (HSCs) induced to senesce by treatment with a DNA-damaging agent. Upon activation in response to liver damage, HSCs proliferate and produce the extracellular matrix deposited in the fibrotic scar. Senescence of activated HSCs limits liver fibrosis.	Co-expression
GDS3493	Cigarette smoke of full flavor brand effect on bronchial epithelial cells in vitro: time course	Analysis of normal bronchial epithelial cells exposed to cigarette smoke from a typical full flavor brand for up to 24 hours. Results provide insight into the impact of cigarette smoke exposure at the molecular level.	Co-expression
GDS3494	Cigarette smoke of light flavor brand effect on bronchial epithelial cells in vitro: time course	Analysis of normal bronchial epithelial cells exposed to cigarette smoke from a typical light flavor brand for up to 24 hours. Results provide insight into the impact of cigarette smoke exposure at the molecular level.	Co-expression
GDS3495	Progerin expression in a hTERT-immortalized skin fibroblast cell line: time course	Analysis of skin fibroblasts induced to express GFP-progerin for up to 10 days. Progerin is a mutant form of lamin A and the causal agent of premature-ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS). Results provide insight into molecular mechanisms underlying this pathological effect.	Co-expression
GDS3496	Alveolar macrophages of cigarette smokers	Analysis of alveolar macrophages from cigarette smokers. Cigarette smoking is associated with increased lung cell turnover. Mononuclear phagocytes, such as macrophages, play an important role in the removal of apoptotic cells.	Co-expression
GDS3497	Interleukin-12 effect on peripheral blood mononuclear cells (HG-U133A)	Analysis of cultured peripheral blood mononuclear cells (PBMCs) stimulated with interleukin-12 (IL-12). PBMCs obtained from 7 donors. IL-12 plays a central role in adaptive and innate immunity. Results provide further insight into the effects of IL-12 on the immune response.	Co-expression
GDS3498	Interleukin-12 effect on peripheral blood mononuclear cells (HG-U133B)	Analysis of cultured peripheral blood mononuclear cells (PBMCs) stimulated with interleukin-12 (IL-12). PBMCs obtained from 7 donors. IL-12 plays a central role in adaptive and innate immunity. Results provide further insight into the effects of IL-12 on the immune response.	Co-expression
GDS3499	TREM-1 activation effect on monocytes in vitro	Analysis of cultured monocytes following TREM-1 activation by treatment with an antibody against TREM-1. TREM-1 is an immunoreceptor expressed on monocytes, macrophages, and neutrophils. Results provide insight into the cellular consequences of TREM-1 activation.	Co-expression
GDS3500	Cryptosporidium infection effect on intestinal epithelial cells in vitro	Analysis of cultured intestinal epithelial cells infected with Cryptosporidium hominis or parvum. Cryptosporidium parasites are pathogens of human intestinal epithelial cells. Results provide insight into the early pathogenesis of Cryptosporidium infection.	Co-expression
GDS3501	Synchronous and metachronous liver metastases from colorectal cancer	Analysis of synchronous and metachronous liver metastatic lesions from colorectal cancer (CC). The liver is a common site of metastases from CC. Synchronous metastatic lesions arise less than 6 months after the resection of the primary tumor, metachronous lesions arise 6 months after resection.	Co-expression
GDS3502	Laser capture microdissection of endothelial and neuronal cells from human dorsolateral prefrontal cortex	We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from patients with schizophrenia and bipolar disorder and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using Affymetrix HG133plus2.0 GeneChips. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology.  Keywords: cell type comparison, laser capture microdissection	Co-expression
GDS3503	Characterization of a Colony Assay Used to Investigate Endothelial Progenitor Cells 	Subjects underwent endothelial testing and blood sampling at baseline and after 3 months of exercise training.  Microarray and flow cytometry-based characterization of cells from an endothelial progeniator colony assay was consistent with T lymphocytes, but not endothelial cells.  Keywords: expression analysis	Co-expression
GDS3510	Claudin-1 overexpression effect on lung adenocarcinoma cell line	Analysis of lung adenocarcinoma CL1-5 cells overexpressing Claudin-1 (CLDN1), a component of tight junction complexes. Low CLDN1 expression in lung adenocarcinomas is associated with shorter overall survival. Results provide insight into the role of CLDN1 in the progression of lung adenocarcinoma.	Co-expression
GDS3511	HIV-1 infection effect on macrophages in vitro: time course	Analysis of cultured macrophages for up to 7 days after HIV-1 infection. Macrophages are targets of HIV-1 infection and constitute a viral reservoir that facilitates the spread of HIV-1 to other cells. Results provide insight into the signaling networks affected by HIV-1 infection in macrophages.	Co-expression
GDS3513	Embryonic stem cell-derived cardiomyocytes	Analysis of cardiomyocytes (CMs) derived from embryonic stem cells (ESCs). Under the appropriate conditions, ex vivo ESCs can differentiate into beating cardiomyocytes via an embryoid body (EB) intermediate. Results provide insight into the mechanisms underlying the differentiation of ESC into CMs.	Co-expression
GDS3514	Liposarcoma response to doxorubicin in vitro	Analysis of various types of liposarcomas treated with doxorubicin in vitro. While doxorubicin is an established chemotherapeutic for treating liposarcomas, the response to this drug is low. Results provide insight into the molecular basis of the resistance of liposarcomas to doxorubicin.	Co-expression
GDS3516	Nodular lymphocyte-predominant Hodgkin lymphoma: lymphocytic and histiocytic cells	Analysis of neoplastic lymphocytic and histiocytic cells (L&H) dissected from nodular lymphocyte-predominant Hodgkin lymphoma tumors (NLPHL). L&H cells represent less than 1 percent of cells in NLPHL tumors. Results provide insight into the pathogenesis of NLPHL.	Co-expression
GDS3517	Oncogenic NRAS depletion effect on melanoma cell lines: time course	Analysis of melanoma 224 and BL cells for up to 3 days after suppression of the mutant NRAS Q61R gene with siRNA siMut10 or siMut12. Activating mutations in NRAS gene is a common genetic event in malignant melanoma. Results provide insight into the role of NRAS in the pathogenesis of melanoma.	Co-expression
GDS3518	Chronic myelogenous leukemia response to imatinib: Philadelphia chromosome positive CD34+ cells	Analysis of Philadelphia chromosome-positive CD34+ cells of chronic myelogenous leukemia patients treated with imatinib. The anti-cancer drug imatinib is a selective bcr-abl tyrosine kinase inhibitor. Results provide insight into the molecular events affected by bcr-abl inhibition through imatinib.	Co-expression
GDS3523	Non-migratory villous cytotrophoblasts and invasive extra-villous trophoblasts	Comparison of non-migratory villous cytotrophoblasts (CTBs) and invasive extra-villous trophoblasts.  Invasion of CTBs into uterine tissues is essential for placental development. Results provide insight into the molecular mechanisms regulating trophoblast invasion.	Co-expression
GDS3524	Hypoxia effect on a renal proximal tubule epithelial cell line	Analysis of cultured renal proximal tubule epithelial RPTEC cells subjected to hypoxia at 1% oxygen for 24 hours. Results identify hypoxia-controlled genes in epithelial cells.	Co-expression
GDS3525	Ovarian cancer and depression	Analysis of primary ovarian tumors from patients with high depressive symptoms. Results provide insight into the contribution of biobehavioral factors such as such as stress, depression, and social support to the molecular progression of cancer.	Co-expression
GDS3531	PGC-1-related coactivator partial depletion	Analysis of U2OS cells partially depleted for the PGC-1-related coactivator PRC. Loss of PRC results in a severe reduction in respiratory energy production, the proliferation of structurally defective mitochondria, and a defect in cell cycle progression.	Co-expression
GDS3532	PGC-1-related coactivator depletion	Analysis of U2OS cells nearly completely depleted for the PGC-1-related coactivator PRC. Loss of PRC results in a severe reduction in respiratory energy production, the proliferation of structurally defective mitochondria, and a defect in cell cycle progression.	Co-expression
GDS3534	Lymphatic endothelial cell response to Prox1 and NR2F2 depletion	Analysis of lymphatic endothelial cells (LECs) depleted for Prox1, NR2F2, or both regulators. LECs are derived from venous endothelial cells (VECs). Prox1 and NR2F2 regulate LEC and VEC development, respectively. Results provide insight into the role of NR2F2 and Prox1 in maintaining LEC phenotypes.	Co-expression
GDS3537	Polybrominated diphenyl ethers effect on adrenocortical carcinoma cell line	Analysis of H295R adrenocortical carcinoma cells treated with the hydroxylated polybrominated biphenyl ether (PBDE) 2-OH-BDE47 or 2-OH-BDE85. PBDEs are used as flame retardants in various products. The two PBDEs are cytotoxic. Results provide insight into the molecular basis of PBDE cytotoxicity.	Co-expression
GDS3539	Psoriasis	Analysis of lesional and non-lesional skins from patients with psoriasis. Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. Results provide insight into the molecular pathogenesis of psoriasis.	Co-expression
GDS3540	Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles	Although host genetics influences susceptibility to tuberculosis, few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of tuberculosis infection would have distinct gene expression profiles, and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb- stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary and meningeal tuberculosis (n=4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR.  We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1608 and 199 genes that were differentially expressed by >2 and >5-fold, respectively. Using cluster analysis, we identified gene expression patterns that distinguished the different clinical forms of tuberculosis.  In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups.  Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls.  To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility.  These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to tuberculosis.   Keywords: tuberculosis, tuberculous meningitis, macrophage, gene expression, microarray	Co-expression
GDS3553	Monocytes and macrophages (RNG/MRC)	Comparison of monocytes and macrophages. Samples obtained from 86 patients with acute coronary syndrome. Results used as a reference to compare the performance of Affymetrix (GDS3554) and Illumina (GDS3555) arrays.	Co-expression
GDS3554	Monocytes and macrophages (Affymetrix)	Comparison of monocytes and macrophages. Samples obtained from patients with acute coronary syndrome. Results compared to the performance of Illumina arrays (GDS3555).  The result from two-color arrays (GDS3553) was used as a reference for the Illumina and Affymetrix arrays.	Co-expression
GDS3555	Monocytes and macrophages (Illumina)	Comparison of monocytes and macrophages. Samples obtained from patients with acute coronary syndrome. Results compared to the performance of Affymetrix arrays (GDS3554).  The result from two-color arrays (GDS3553) was used as a reference for the Illumina and Affymetrix arrays.	Co-expression
GDS3556	Torcetrapib effect on adrenal carcinoma cell line	Analysis of H295 adrenal carcinoma cells treated with torcetrapib, an anti-cholesterol drug. Adverse side effects of torcetrapib treatment include changes in blood pressure, potassium, sodium, and aldosterone. Results provide insight into the molecular basis of the off-target side effects.	Co-expression
GDS3557	ERG transcription factor depletion effect on endothelial cell	Analysis of endothelial HUVEC cells depleted for the ETS-related gene (ERG) product.  ERG is a member of the ETS family of transcription factors. Results provide insight into the role of ERG in the regulation of normal endothelial cell function.	Co-expression
GDS3558	Deferasirox effect on leukemia cell line: dose response	Analysis of leukemia K562 cells treated with 10 or 50 uM deferasirox. Deferasirox is an iron chelator taken orally to treat iron toxicity. Iron depletion by deferasirox inhibits cancer cell proliferation in vitro. Results provide insight into the molecular basis of this anti-proliferative effect.	Co-expression
GDS3559	Occupational benzene exposure: peripheral blood mononuclear cells (HG-U133A)	Analysis of peripheral blood mononuclear cells from shoe factory workers exposed to benzene. Benzene is a leukemogen. Results provide insight into molecular mechanisms of benzene carcinogenicity.	Co-expression
GDS3560	Occupational benzene exposure: peripheral blood mononuclear cells (HG-U133B)	Analysis of peripheral blood mononuclear cells from shoe factory workers exposed to benzene. Benzene is a leukemogen. Results provide insight into molecular mechanisms of benzene carcinogenicity.	Co-expression
GDS3561	Occupational benzene exposure: peripheral blood mononuclear cells (HumanRef-8)	Analysis of peripheral blood mononuclear cells from shoe factory workers exposed to benzene. Benzene is a leukemogen. Results provide insight into molecular mechanisms of benzene carcinogenicity.	Co-expression
GDS3567	VEGF-A effect on endothelial cell line: time course (HG-U133 Plus 2.0)	Analysis of umbilical vein endothelial cells (HUVEC) treated with VEGF-A for up to 150 minutes in vitro.  VEGF-A is a major trigger of vasculogenesis and physiologic angiogenesis. Results provide insight into the molecular mechanisms underlying the vasculogenic and angiogenic activity of VEGF-A.	Co-expression
GDS3568	VEGF-A effect on endothelial cell line: time course (HG-U133A)	Analysis of umbilical vein endothelial cells (HUVEC) treated with VEGF-A or EGF for up to 6 hours. VEGF-A is a major trigger of vasculogenesis and angiogenesis. EGF is a general growth factor. Results provide insight into the mechanisms underlying the vasculogenic and angiogenic activity of VEGF-A.	Co-expression
GDS3570	VEGF-A effect on endothelial cell line: time course (HG-U133B)	Analysis of umbilical vein endothelial cells (HUVEC) treated with VEGF-A for up to 6 hours in vitro.  VEGF-A is a major trigger of vasculogenesis and physiologic angiogenesis. Results provide insight into the molecular mechanisms underlying the vasculogenic and angiogenic activity of VEGF-A.	Co-expression
GDS3571	Jag1 expression effect on endometrial stromal cells	Analysis of endometrial stromal cells engineered to have an increased expression of Jag1. Jag1 is a Notch ligand. Results provide insight into the role of Notch signaling in endometrial cells.	Co-expression
GDS3573	Chlamydia pneumonia infection effect on dendritic cells	Analysis of monocyte-derived dendritic cells infected with Chlamydia pneumonia. C. pneumonia is a human respiratory pathogen associated with various chronic diseases such as asthma and atherosclerosis. Results provide insight into the host defense response to C. pneumonia infections.	Co-expression
GDS3576	Diamond-Blackfan anaemia: fibroblasts	Analysis of fibroblasts from patients with Diamond-Blackfan anaemia (DBA). DBA is a rare inherited red cell hypoplasia characterized by a defect in the maturation of erythroid progenitors. Results provide insight into the involvement of non-hematopoietic tissues in DBA pathogenesis.	Co-expression
GDS3578	Beta-catenin depletion effect on multiple myeloma cell line	Analysis of multiple myeloma MM1.S cells depleted for beta-catenin. Beta-catenin is an effector of the Wnt signaling pathway. Results provide insight into the role of Wnt/beta-catenin signaling in the progression of multiple myeloma.	Co-expression
GDS358	Leprosy lesions	Molecular characterization of lepromatous leprosy (LL) and borderline tuberculoid (BT) leprosy skin lesions.	Co-expression
GDS3580	Pulmonary sarcoidosis	Analysis of lungs from patients with pulmonary sarcoidosis (PS). PS is characterized by the granulomatous inflammation of the lung. Results provide insight into the molecular pathogenesis of PS.	Co-expression
GDS3581	Anti-mitotic compound MT7 effect on immortalized cell line: time course	Analysis of HeLa cells treated for up to 12 hrs with MT7, an anti-mitotic compound from a combinatorial library. MT7 inhibits cell proliferation by arresting mitosis specifically and reversibly in various tumor cell lines of human origin. Results provide insight into the mechanism of action of MT7.	Co-expression
GDS359	Glaucoma and aqueous humor outflow	Glaucoma study investigating molecular basis of increase in aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with prostaglandin analogs latanoprost free acid or prostaglandin F2alpha.	Co-expression
GDS3592	Ovarian normal surface epithelia and ovarian cancer epithelial cells	Comparison of normal ovarian surface epithelia (OSE) and ovarian cancer epithelial cells (CEPIs). CEPIs were isolated by laser capture microdissection from serous papillary ovarian adenocarcinomas. Results provide insight into the role of OSE in the development of ovarian adenocarcinoma.	Co-expression
GDS3595	Macrophage response to H1N1 and H5N1 influenza viral infections	Analysis of macrophages at 1, 3, and 6 hours post-infection with H1N1 or H5N1 viruses in vitro. The avian H5N1 virus is highly pathogenic, while the swine H1N1 virus is less so. Alveolar macrophages are targets of H5N1. Results provide insight into the host response to H1N1 and H5N1 infections.	Co-expression
GDS360	Breast cancer and docetaxel treatment	Breast cancer core biopsies taken from patients found to be resistant (greater than 25% residual tumor volume) or sensitive (less than 25% residual tumor volume) to docetaxel treatment.	Co-expression
GDS3600	Endothelial cell response to estradiol in vitro	Analysis of cultured umbilical vein endothelial cells treated with 1 nmol/L estradiol for 24 hours. The incidence of coronary heart disease in women increases after menopause. Results provide insight into the response of the cardiovascular system to estrogens at the molecular level.	Co-expression
GDS3601	Obesity: adipocyte expression profile (HG-U95A)	Analysis of cultured abdominal subcutaneous mature adipocytes from 4 male and 5 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS3602	Obesity: adipocyte expression profile (HG-U95Av2)	Analysis of cultured abdominal subcutaneous mature adipocytes from 5 male and 5 female non-diabetic obese Pima Indians. The prevalence of obesity in Pima Indians is among the highest of any population. Results provide insight into the role of adipocytes in obesity and obesity-related inflammation.	Co-expression
GDS3603	Renal cancer response to rapamycin analog CCI-779 treatment: time course	Expression profiling of peripheral blood mononuclear cells (PBMC) from patients with advanced renal cancer following treatment with the rapamycin analog CCI-779. Gene expression examined 8 and 16 weeks after treatment. Results identify potential gene markers of CCI-779 exposure.	Co-expression
GDS3604	Tamoxifen effect on endometrioid carcinomas	Analysis of endometrial epithelial cells from stage I or II endometrioid carcinomas after treatment with oestrogen or tamoxifen (TMX). Results provide insight into the molecular basis of the association of TMX treatment of breast cancer with an increased incidence of endometrial cancer.	Co-expression
GDS3606	Myeloid leukemia cell response to thrombopoietin receptor agonist SB-559457 in vitro	Analysis of primary cultured myeloid leukemia cells treated with recombinant human thrombopoietin or the thrombopoietin receptor agonist SB-559457 (SB). SB is toxic to leukemia cells. Results provide insight into the mechanism of action of SB.	Co-expression
GDS3609	Syk depletion effect on breast epithelial cell line	Analysis of MCF10A breast epithelial cells depleted for Syk. Progressive loss of Syk mRNA occurs during breast tumor development. Results provide insight into Syk’s tumor suppressor function and role in normal breast development.	Co-expression
GDS3610	Nasopharyngeal carcinoma	Analysis of biopsies from patients with Epstein-Barr virus (EBV)-positive undifferentiated nasopharyngeal carcinoma (NPC). NPC is a common cancer in China and Southeast Asia. Results provide insight into the molecular pathogenesis of NPC.	Co-expression
GDS3615	Asthma exacerbation and convalescent phases: peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells of children with acute asthma during exacerbation and at subsequent convalescence. Severe asthma exacerbations in children are associated with viral infection and occur among atopics. Results provide insight into the significance of these comorbidities.	Co-expression
GDS3626	Macrophage migration inhibitory factor depletion effect on kidney cell line	Analysis of HEK293 kidney cells depleted for the macrophage migration inhibitory factor (MIF). MIF depletion in HEK293 cells result in G(0)/G(1) cell cycle arrest. Results provide insight into the molecular mechanisms underlying this cell cycle arrest.	Co-expression
GDS3627	Non-small lung cancer subtypes: adenocarcinoma and squamous cell carcinoma	Comparison of two non-small cell lung cancer histological subtypes: adenocarcinomas (AC) and squamous cell carcinomas (SCC). Results provide insight into the molecular differences between AC and SCC.	Co-expression
GDS3628	Rheumatoid arthritis and response to anti-TNF alpha therapy: blood	Analysis of whole blood from rheumatoid arthritis patients at baseline of infliximab therapy. Infliximab is an anti-TNF alpha antibody. Clinical response to infliximab determined at week 14 of therapy. Results identify a gene expression signature for predicting the response to infliximab.	Co-expression
GDS3630	Monozygotic and dizygotic twin pairs: intestinal mucosa	Analysis of healthy intestinal mucosa biopsies from 10 monozygotic and 10 dizygotic twin pairs. Barrier organs such as the gut are exposed to continual environmental challenge. Results provide insight into genetic and non-genetic determinants of gene expression.	Co-expression
GDS3631	Asthma and socioeconomic status: peripheral blood CD2+ leukocyte	Analysis of peripheral blood CD2+ leukocytes from asthmatic children of low and high socioeconomic families. Low socioeconomic status is a social factor associated with disease morbidity, including more severe asthma in childhood. Results provide insight into the molecular basis of this link.	Co-expression
GDS3634	miR-205 expression effect on prostate cancer cell line	Analysis of DU145 prostate cancer cells with restored miR-205 expression. miR-205 expression is lower in prostate cancer cell lines than in normal cell lines, as well as in prostate tumors than in matched normal prostate tissues. Results provide insight into the role of miR-205 in prostate cancer.	Co-expression
GDS3635	Vitamin C effect on skin fibroblast cell line	Analysis of GM5659 skin fibroblasts treated with ascorbic acid  or the stable vitamin C derivative, ascorbic acid 2-phosphate. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts.	Co-expression
GDS3638	Actein effect on breast cancer cell line: dose response and time course	Analysis of MDB-MB-453 breast cancer cells treated with 20 or 40 ug/ml actein for 6 or 24 hours. Actein is a triterpene glycoside from the herb black cohosh and inhibits the growth of cancer cells in vitro. Results provide insight into the molecular basis of this inhibitory effect.	Co-expression
GDS3640	Copper effect on liver cell line: dose response and time course	Analysis of HepG2 liver cells treated with up to 600 uM copper sulfate for up to 24 hours. Copper is an essential trace element but can be extremely toxic at supraphysiological levels. Results provide insight into the molecular basis of copper toxicity.	Co-expression
GDS3644	Cerebral palsy: wrist muscles	Analysis of wrist muscle extensors and flexors of cerebral palsy (CP) patients. CP is an upper motor neuron disease that results in a progressive movement disorder. Muscles of CP patients often become spastic. Results provide insight into the molecular alterations in spastic muscles of CP patients.	Co-expression
GDS3646	Celiac disease: primary leukocytes	Expression analysis of untouched primary leukocytes from unrelated celiac disease individuals. Results used in conjunction with genome-wide association genotype data provide insight into genetic variation effects on gene expression in primary leukocytes from an immune-mediated disease.	Co-expression
GDS3649	Proinsulin C-peptide and TGF-beta 1 effect on proximal tubular cell line: time course	Analysis of HK2 proximal tubular cells (PTCs) treated with C-peptide, TBF-beta 1, or both agents for 18 or 48 hours. C-peptide alleviates TGF-beta 1-mediated phenotypic and morphological changes in PTCs associated with epithelial-mesenchymal transformation (EMT). EMT contributes to renal fibrosis.	Co-expression
GDS3656	Folic acid effect on endothelial progenitor cells of type 1 diabetes patients	Analysis of endothelial progenitor cells (EPCs) from patients with type 1 diabetes (T1D) before and 4 weeks of dietary folic acid (FA) supplementation. EPCs are involved in vascular wall repair. T1D results in reduced circulating EPCs. Results provide insight into the effect of FA on EPC function.	Co-expression
GDS3658	Coronary collateral artery growth: monocytes	Analysis of monocytes from patients with chronic coronary occlusions who were dichotomized as sufficient or insufficient collateral responders following coronary intervention. Results of in vitro stimulation of monocytes with LPS provide insight into the role of IFN-beta in collateral artery growth.	Co-expression
GDS3665	Visceral adipose tissues of obese diabetic women	Analysis of visceral adipose omentum tissues of obese women with type 2 diabetes mellitus. Age and BMI-matched glucose-tolerant women used as controls.	Co-expression
GDS3668	Familial hypercholesterolemia and atherosclerosis: monocytes	Analysis of monocytes (MO) from familial hypercholesterolemia (FH) patients. FH patients have a defective or missing LDLR resulting in atherosclerosis. Atherosclerotic lesions often contain MO-derived, lipid-laden macrophages. Results provide insight into the role of MO in onset of atherosclerosis.	Co-expression
GDS3669	Familial hypercholesterolemia and atherosclerosis: T lymphocytes	Analysis of T cells from familial hypercholesterolemia (FH) patients. FH patients have a defective or missing LDLR resulting in atherosclerosis. In response to initial events of atherosclerosis, T cells interact with vessel wall. Results provide insight into the role of T cells in atherosclerosis.	Co-expression
GDS367	Skeletal repair in non-union fractures (HG-U95A)	Identification of mechanisms leading to lack of skeletal repair in non-union fractures. Non-union fractures do not heal six months after injury and may cause advanced arthritis or loss of limb function. Normal and non-union callous bone samples examined.	Co-expression
GDS3676	Quercetin effect on CD14+ monocyte	Analysis of CD14+ monocytes from individuals on a diet supplemented with quercetin for 2 weeks. Quercetin is a flavonoid from plant extracts used as a nutritional supplement, and has reported benefits ranging from anti-carcinogenic properties to reduced risk of cardiovascular disease.	Co-expression
GDS3678	Saturated fatty acid rich diet effect on risk of metabolic syndrome: adipose tissue	Analysis of adipose tissue from moderately overweight subjects who consumed a saturated fat (SFA)-rich diet for 2 weeks, followed by SFA or monounsaturated (MUFA)-rich intervention diets for 8 weeks. Results provide insight into role of dietary fat on the risk of developing metabolic syndrome.	Co-expression
GDS3679	Morbid obesity: subcutaneous and omental adipose tissues	Analysis of SC and OM adipose tissue collected from morbidly obese patients.  Patients grouped as Low or High Acylation Stimulating protein (ASP) and Triglyceride (TG). ASP is associated with various metabolic disorders. Results provide insight into molecular basis of the two ASP-TG lipemic indices.	Co-expression
GDS368	Skeletal repair in non-union fractures (HG-U95B)	Identification of mechanisms leading to lack of skeletal repair in non-union fractures. Non-union fractures do not heal six months after injury and may cause advanced arthritis or loss of limb function. Normal and non-union callous bone samples examined.	Co-expression
GDS3681	Type 2 diabetes: myotube	Analysis of myotube cell lines established from type 2 diabetes (T2D) subjects. Insulin resistance and reduced mitochondrial biogenesis coexist early in T2D pathogenesis independent of hyperglycemia and obesity. Results provide insight into the effect of T2D on developing skeletal muscle cells.	Co-expression
GDS3686	Colony stimulating factor 1 effect on monocyte derived macrophage	Analysis of mature monocyte derived macrophages treated with colony stimulating factor 1 (CSF-1) in vitro for 6 hours. CSF-1 supports the proliferation and differentiation of monocytes and macrophages. Results provide insight into the effect of CSF-1 stimulation on mature monocytes.	Co-expression
GDS369	Skeletal repair in non-union fractures (HG-U95C)	Identification of mechanisms leading to lack of skeletal repair in non-union fractures. Non-union fractures do not heal six months after injury and may cause advanced arthritis or loss of limb function. Normal and non-union callous bone samples examined.	Co-expression
GDS3690	Atherosclerotic Coronary Artery Disease: circulating mononuclear cell types	Analysis of various mononuclear cells from patients with severe triple-vessel coronary artery disease (CAD). CD34+ stem cells, CD4+ T-helper cells, CD14+ resting monocytes, LPS-stimulated monocytes, and macrophages were examined. Results provide insight into the pathophysiology of atherosclerosis.	Co-expression
GDS3691	Sustained olive oil consumption effect on peripheral blood mononuclear cells	Analysis of PBMCs from healthy males after 3 weeks of virgin olive oil (VOO) consumption at doses common in the Mediterranean diet.  The Mediterranean diet protects against cardiovascular diseases. Results provide insight into the molecular mechanisms underlying the beneficial action of VOO.	Co-expression
GDS3694	Skeletal muscles of diet sensitive and resistant individuals after completion of a weight loss program	Analysis of skeletal muscle from obese diet sensitive and resistant women after completion of a weight loss program. Subjects are in the highest and lowest quintiles for weight loss rate. Results provide insight into the molecular basis of the variability in weight loss during caloric restriction.	Co-expression
GDS3696	Atherosclerotic left anterior descendent coronary artery: low scan	Analysis of 8 atherosclerotic LAD coronaries presenting at least 75% stenosis and calcified plaques. Atherosclerosis affects aorta, coronary, carotid, and iliac arteries more frequently than any other vessel. Results provide insight into molecular networks underlying the atherosclerotic condition.	Co-expression
GDS3697	Atherosclerotic left anterior descendent coronary artery: medium scan	Analysis of 8 atherosclerotic LAD coronaries presenting at least 75% stenosis and calcified plaques. Atherosclerosis affects aorta, coronary, carotid, and iliac arteries more frequently than any other vessel. Results provide insight into molecular networks underlying the atherosclerotic condition.	Co-expression
GDS3698	Atherosclerotic left anterior descendent coronary artery: high scan	Analysis of 8 atherosclerotic LAD coronaries presenting at least 75% stenosis and calcified plaques. Atherosclerosis affects aorta, coronary, carotid, and iliac arteries more frequently than any other vessel. Results provide insight into molecular networks underlying the atherosclerotic condition.	Co-expression
GDS3704	Dietary polyunsaturated and saturated fatty acids effect on peripheral blood mononuclear cells	Analysis of peripheral blood mononuclear cells of individuals before and 6 hours after the consumption of shakes containing either mainly polyunsanturated (PUFA) or saturated fatty acids (SFA). Results provide insight into the molecular basis of the beneficial effect of PUFA on health.	Co-expression
GDS3705	Progressive pulmonary sarcoidosis	Comparison of lungs from patients with nodular self-limiting pulmonary sarcoidosis (PS) to those with progressive fibrotic PS. About 60-70% of patients with PS have disease that resolves spontaneously, the rest follow a chronic course. Results provide insight into the pathogenesis of progressive PS.	Co-expression
GDS3706	Benzo[a]pyrene diol epoxide effect on lung WI-38 fibroblasts: dose-response	Analysis of normal lung WI-38 fibroblasts exposed to various concentrations of the carcinogen benzo[a]pyrene diol epoxide (BPDE). BPDE is a metabolite of benzo[a]pyrene, a component of cigarette smoke. Results provide insight into the molecular response of normal lung fibroblasts to BPDE.	Co-expression
GDS3709	Cigarette smoke effect on the oral mucosa	Analysis of oral mucosae from 40 cigarette smokers and 40 age and gender matched never-smokers. Results provide insight into the carcinogenic effects of cigarette smoke.	Co-expression
GDS3710	TGF-beta-induced epithelial-mesenchymal transition model	Analysis of A549 epithelial cells treated for up to 72 hours with TGF-beta to induce epithelial-mesenchymal transition (EMT). EMT is a developmental process that facilitates the dispersion of cells. A similar process is reactivated in cancer cells as an early event during tumor metastasis.	Co-expression
GDS3711	Asthmatic atopic epithelium	Analysis of airway epithelial cells (AEC) from children with asthma and healthy non-atopic controls. Epithelial cells from asthmatic children fail to heal a wound in vitro. Results provide insight into the molecular mechanisms underlying dysregulated AEC repair.	Co-expression
GDS3712	Human Nephrosclerosis Triggers a Hypoxia-Related Glomerulopathy	Expression data from microdissected glomeruli to examine the role of hypoxia in glomerulosclerosis of human Nephrosclerosis (NSC).	Co-expression
GDS3713	Gene Expression Circulating B Lymphocytes for Smoking Females	B cells were found to be directly associated with the onset and development of many smoking-induced diseases. However, the in vivo molecular response of B cells underlying the female cigarette smoking remains unknown. Using the genome-wide Affymetrix HG-133A GeneChip® microarray, we compared the gene expression profiles of peripheral circulating B cells between 39 smoking and 40 non-smoking healthy US white females.	Co-expression
GDS3715	Insulin effect on skeletal muscle	Analysis of vastus lateralis muscle biopsies from insulin-sensitive subjects, insulin-resistant subjects, and  diabetic patients, following insulin treatment. Results provide insight into the molecular basis of insulin action in skeletal muscle and the underlying defects causing insulin resistance.	Co-expression
GDS3716	Breast cancer: histologically normal breast epithelium	Analysis of histological normal breast epithelia from both ER- and ER+ breast cancer patients and prophylactic mastectomy patients, and normal breast epithelia from reduction mammoplasty patients. Results provide insight into the mechanisms underlying breast cancer initiation and progression.	Co-expression
GDS3717	NOTCH antagonist SAHM1 effect on T-ALL cell lines	Analysis of HPB-ALL and KOPT-K1 cells treated with SAHM1, an antagonist of the NOTCH transcription factor. SAHM1 is an alpha-helical hydrocarbon stapled peptide derived from MAML1. Results provide insight into the specificity of the antagonistic effect of SAHM1 on gene expression driven by NOTCH.	Co-expression
GDS3721	Markers of Taxane Sensitivity in Breast Cancer	The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies.  Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR).  Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery.  We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane–based therapy.	Co-expression
GDS3722	Gene expression data from AP-2γ silenced MCF-7 cells	Overexpression of the AP-2γ  transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy, even in ER positive, ErbB2 negative tumours; markers of a more favourable prognosis. To understand further the role of AP-2γ in breast carcinoma, we have used an RNA interference and gene expression profiling strategy using the MCF-7 cell line as a model for ER positive, ErbB2 negative tumours with AP-2γ overexpression. Gene expression changes between control and silenced cells implicate AP-2γ  in the control of cell cycle progression and developmental signalling.  Keywords: RNA interference	Co-expression
GDS3727	Identification and analysis of miRNA target genes in a cell system	MicroRNAs are instructions used by the genetic programs of a cell to fine-regulate protein expression levels. In order to gain insight into the full spectrum of miRNA regulation in a particular cellular context, we have exploited the idea that doubling the quantity of the endogenous miRNAs by transfection would enhance downregulation of the normally targeted transcripts. To this end, we isolated the small RNA fraction from cells in culture and transfected it into an identical culture in an amount corresponding to that of the endogenous miRNAs. A comparative gene expression analysis between transfected and mock-transfected cells revealed a large number of modestly downregulated genes. In silico analysis using TargetScan 5 revealed that a very high number of the expressed genes are predicted targets of the endogenous miRNAs, which we identified by deep-sequencing the small RNA fraction. Network analysis of the downregulated genes showed that miRNAs are involved in the simultaneous regulation of many pathways by targeting key molecules that interact with multiple pathways, suggesting a role of miRNAs in the synchronization of the activities of different pathways. Interestingly, we found a very high percentage of the genes regulated by miRNAs to be related to genetic disorders. This suggests that miRNAs might play a key role in maintaining homeostasis in processes that result in disease states when disregulated. Such a crucial role for miRNA regulation further underlines its importance for cell and organism survival. These results also confirm the important experimental value of our methodology as a high-throughput tool for the identification of genes endogenously regulated by miRNAs.	Co-expression
GDS3730	Knockdown of transactive response DNA-binding protein TDP-43 downregulates histone deacetylase 6	TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and  mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias  and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear  localization is observed in disease. To identify relevant targets of TDP-43, we performed  an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation  was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic  kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation  of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither  RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression.  Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional  interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster  also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate  formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate  formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43  silenced cells. This was completely restored by co-transfection with HDAC6. In  conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby  contribute to pathogenesis.	Co-expression
GDS3750	Parkinson's disease-associated DJ-1 is required for the expression of GDNF receptor Ret in human neuroblastoma cells	DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinson’s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.	Co-expression
GDS3756	New specific molecular targets for radiochemotherapy in colorectal cancer	A promising treatment for patients with advanced colorectal cancer is preoperative radiochemotherapy. The early side effects of this treatment have been considered to be acceptable. The aim of this study was to identify the effects of preoperative radiochemotherapy (PRT) on gene expression in tumour and normal colon rectal tissue form the same patients, before and after PRT.  For that purpose, tissue samples from ten patients with operable rectal adenocarcinomas were collected for use in whole genome–microarray based gene expression analysis. A factorial experimental design allowed us to look solely at the radiation effect on tumours. This resulted in 4496 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radiochemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration (TEM).  We conclude that radiochemotherapy has a greater effect in tumour tissue gene expression than normal tissue.  Not only is the effect on normal tissue limited compared to tumour, but significantly different gene sets are enriched. The profound change of cell adhesion molecule expression in tumour tissue could either increase the risk of metastasis, or decrease the tumours invasive potential. Further characterization of genes involved in cell adhesion and leukocyte TEM may give new insights into the molecular responses to radiochemotherapy in colorectal cancer.	Co-expression
GDS3758	Chondrogenic differentiation potential of OA chondrocytes and their use in autologous chondrocyte transplantation	Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA. Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score >3, Ahlbäck Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using quantitative RT-PCR.   Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (COL2A1, COMP, aggrecan, CRTL1, SOX9) and genes involved in matrix synthesis (biglycan, COL9A2, COL11A1, TIMP4, CILP2) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (COL10A1, RUNX2, periostin, ALP, PTHR1, MMP13, COL1A1, COL3A1) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, were differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated.   Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA and OA chondrocytes fulfill the requirements for matrix-associated ACT.  Keywords: time course, cell type comparison, tissue engineered cartilage; osteoarthritis; Hyaff-11 scaffold; human chondrocytes; gene expression profiling; regenerative medicine; differentiation potential	Co-expression
GDS3759	Onconase Responsive Genes in Human Mesothelioma Cells: Implications for an RNA Damaging Therapeutic Agent	Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis.  However, there may be additional or alternative mechanism(s) of action. Microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 ug/ml Onconase for 24 h.	Co-expression
GDS3761	Time course of 1,25(OH)2D treated RWPE1 cells.	Background:  Prostate cancer is the second leading cause of cancer mortality among US men.  Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1α,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.  Results: We examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n=4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60 % up), 48 h, 3566 (38 % up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements.  Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling.  Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways).  There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h.   Conclusions: Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention.  In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.	Co-expression
GDS3762	Effects of 48h Lower Limb Unloading in Human Skeletal Muscle	Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age ± S.D = 22.1 ± 3.7 yr) following 48h unloading (UL) via unilateral lower limb suspension and 24h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48h UL, and 24h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with qRT-PCR, and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the mostly highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for UPP-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX,  which showed a trend towards increases in protein products at 48h UL) as well as extracellular matrix (ECM) component COL4. The gene expression patterns were not readily reversed upon RL suggesting that molecular responses to short-term periods of skeletal muscle inactivity may persist after activity resumes.	Co-expression
GDS3774	Persistence of seed-based activity following microRNA segmentation	microRNAs are ∼22 nucleotide regulatory RNAs that are processed into duplexes from hairpin structures and incorporated into Argonaute proteins. We find that a nick in the middle of the guide strand of an miRNA sequence allows for seed-based targeting characteristic of miRNA activity. Insertion of an inverted abasic, a dye, or a small gap between the two segments still permits target knockdown. While activity from the seed region of the segmented miRNA is apparent, activity from the 3' half of the guide strand is impaired, suggesting that an intact guide backbone is required for contribution from the 3' half. miRNA activity was also observed following nicking of a miRNA precursor. These results illustrate a structural flexibility in miRNA duplexes and may have applications in the design of miRNA mimetics.	Co-expression
GDS3781	Expression data from human adipose tissue using an expanded patient cohort	Obesity is a risk factor for numerous metabolic disorders; however, not all obese individuals are prone to insulin resistance.  The central aim of this study was to identify molecular pathways directly related to insulin resistance independent of BMI in obesity. We sought to determine the gene expression signature of adipose tissue in a body mass index (BMI)-matched obese cohort of patients that are either insulin sensitive or insulin resistant.	Co-expression
GDS3782	Gene expression profiles of beta-cell enriched tissue obtained by Laser Capture Microdissection from subjects with type 2 diabetes	Changes in gene expression in pancreatic beta-cells from type 2 diabetes could provide insights into their abnormal insulin secretion and beta-cell turnover. The laser capture microdissection technique was used to acquire beta-cells from pancreatic tissue sections obtained from type 2 diabetic (T2D) and non-diabetic controls. We found that 4% of analyzed transcripts were differentially expressed between the two groups at the lower confidence bound cutoff of 1.2, and, among the differentially expressed transcripts, 62% were up-regulated and 38% down-regulated in samples of T2D subjects compared to non-diabetic controls. We observed: 1) changes in expression of genes linked to glucotoxicity, in particular, up-regulation of LDHA and PCK1, and down-regulation of GPD2, ME1 and ACLY; 2) evidence of oxidative stress, documented by up-regulation of metallothionein genes; 3) few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress; 4) differential expression of genes associated with pancreatic regeneration, most notably up-regulation of members of the regenerating islet gene (REG) family and metalloproteinase 7; and 5) differential expression of some genes found in genome wide association studies to be related to T2D (IGF2BP2, TSPAN8, and HNF1B were up-regulated, while JAZF1 and SLC30A8 were down-regulated). In conclusion, this study has identified many novel changes in pancreatic beta-cell gene expression that enhance the understanding of the pathogenesis of T2D.	Co-expression
GDS3783	mRNA and microRNA microarray analysis on human Jurkat T cells exposed to silver nanoparticles and silver ions	To identify genes and pathways involved in AgNPs and Ag ion toxicity, mRNA microarray analysis was conducted on human Jurkat T cells. The results indicate that more DEGs were induced by AgNPs than by Ag ion and AgNPs induced gene expression were not clustered with control and Ag ion induced ones. DEG analysis indicated that metallothionein (MT) 2A, 1H, 1F, and 1A and endonucleases G like 1 (ENDOGL1) were upregulated by AgNPs exposure more than 2 folds compared to control.	Co-expression
GDS3784	Gene expression response to implanted drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries	[original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries.  Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes.	Co-expression
GDS3785	Expression difference between osteoarthritic chondrocytes and mesenchymal stem cells during chondrogenic differentiation	The recruitment of mesenchymal stem cells in order to reconstruct damaged cartilage of osteoarthritis joints is a challenging tissue engineering task. Vision towards this goal is blurred by a lack of knowledge about the underlying differences between chondrocytes and MSC during the chondrogenic cultivation process. The aim of this study was to shed light on the differences between chondrocytes and MSC occurring during chondral differentiation through tissue engineering. As a model we used the pellet culture system under chondrogenic conditions for the comparison of chondrocyte and MSC differentiation. Immunohistology was followed by microarray analysis, which was filtered through already published datasets describing different developmental processes. Validation was performed with quantitative RT-PCR. Results describe inferior chondrogenic ECM-production by MSCs and underline their closer link to the osteogenic lineage. Chondrocytes have an upregulated fatty acid/cholesterol metabolism which might give hints for future modifications of culture conditions.	Co-expression
GDS3787	CXCL4 induces a unique transcriptome in monocyte-derived macrophages	Human blood monocytes were differentiated over six days with either 100 ng/ml M-CSF or 1 umol/l CXCL4 In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors like macrophage colony-stimulation factor (MCSF) and chemokines like platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with MCSF-induced macrophages or macrophages polarized with IFN-γ/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for six days. mRNA expression was measured by Affymetrix gene chips and differences were analyzed by Local Pooled Error test, Profile of Complex Functionality and Gene Set Enrichment Analysis. 375 genes were differentially expressed between MCSF- and CXCL4-induced macrophages, 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, antigen processing/presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level, however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently up- or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters higher expression in CXCL4- than MCSF-induced macrophages, resulting in lower LDL content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4.	Co-expression
GDS3788	Genome-wide analysis of YY2 versus YY1 target genes	Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation, development and DNA damage responses. Although two homologous Drosophila YY family members (pleiohomeotic (pho)) and pleiohomeotic-like (phol)) are redundant, the functional significance of a recently described mammalian YY1-like gene (YY2) is unknown. Using microarray and gene set enrichment analysis (GSEA), we found that lentiviral constructs containing short hairpin loop YY1- and YY2-specific inhibitory RNAs (shYY1 and shYY2) caused significant changes in both redundant and distinguishable expression patterns. Ribosomal protein genes were the most significant gene set up-regulated by both shYY1 and shYY2, although combined shYY1/shYY2 knockdowns were not additive. In contrast, shYY2 reversed anti-proliferative effects of shYY1 on E2F target genes, and shYY2 particularly altered UV damage response, platelet-specific genes and mitochondrial function genes. The most YY2-specific gene was the platelet glycoprotein CD36 whose ligand is thrombospondin - a key UV response gene. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Taken together, our studies show that YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously thought to uniquely respond to YY1. Functions of thrombospondin and CD36 in inflammation, atherogenesis, innate immunity and malaria pathogenesis reveal new potential regulatory roles for YY1 and YY2.	Co-expression
GDS3789	Transcriptional Profiling of CD133+ Cells in Coronary Artery Disease and Effects of Exercise on Gene Expression	Bone marrow-derived progenitor cells are under investigation for cardiovascular repair, but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients.	Co-expression
GDS3790	MEK5D-transfected HUVEC	We expressed a constitutively active mutant of MEK5 (MEK5D) in human primary endothelial cells (EC) to study the transcriptional and functional responses to Erk5 activation under static conditions.	Co-expression
GDS3791	BRCA1 depletion effect on HeLa cells	Analysis of HeLa cells following depletion of BRCA1 tumor supressor using RNAi against BRCA1. Results provide insight into the molecular mechanisms underlying loss of the BRCA1 function.	Co-expression
GDS3792	Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer	We performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization.  Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level.  Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints. Time-course and pathway analyses identified 317 genes and 40 pathways (designated time-course and pathway signatures) deregulated following carboplatin exposure.  Both types of signatures were validated in two separate platinum-treated ovarian and NSCLC cell lines using published microarray data.  Expression of time-course and pathway signature genes distinguished between patients with unfavorable and favorable survival in two independent ovarian cancer datasets. Among the pathways most highly induced by carboplatin in vitro, the NRF2, NF-kB, and cytokine and inflammatory response pathways were also found to be upregulated prior to chemotherapy exposure in poor prognosis tumors.	Co-expression
GDS3793	Effect of maternal tobacco smoke exposure on the placental transcriptome	Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious health problems during the newborn period, chronic lifelong disabilities (such as cerebral palsy, mental retardation and learning problems), and even death.  Further, smoking women have placental problems such as placenta previa (a low-lying placenta that covers part or all of the opening of the uterus), placental abruption (in which the placenta peels away, partially or almost completely before delivery) often resulting in bleeding during delivery. Gene expression profiles in placentas from women exposed to tobacco smoke in pregnancy and from those without the exposure were determined by Illumina HumRef8 Beadchips with 20,589 gene probes. Comparative analysis, smokers versus non-smokers, revealed differential expression of 241 genes at p<0.05. In smokers we identified deregulated genes that represent general biomarkers of exposure as well as candidate genes likely involved in placental abnormalities found in smoking women. Functional annotation determined deregulated processes that were mainly related to development, metabolism, ion transport, and adhesion.	Co-expression
GDS3794	Immunity and Defense Genes in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis patients	Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study is to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells from 18 RA patients and 15 Controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR<5%). Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO) in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated) between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in peripheral blood mononuclear cells of RA patients compared to Controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarrays data were validated by real time PCR in a set of nine genes showing a high degree of correlation. Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic intervention. Further studies on larger scale groups of patients should be performed with the same technology to replicate these results and to allow clinical stratification.	Co-expression
GDS3795	Expression data from bone marrow CD34+ cells of MDS patients and healthy controls	In order to gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathway. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or –7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with –7/del(7q) by pathways involved in cell survival, whilst patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder thereby providing new targets for therapeutic intervention.	Co-expression
GDS3796	Influence of alkyl-phospholipids on the gene expression profile of immortalized keratinocytes HaCaT	New alkyl-phospholipids (APLs) that are structurally derived from the platelet-activating factor are promising candidates for anticancer treatment. After the incorporation into cell membranes, APLs are able to interfere with a wide variety of key enzymes implicated in cell growth, motility, invasion and apoptosis. Besides the prototype edelfosine, we presented a novel group of APLs, glycosidated phospholipids that efficiently inhibit cell proliferation. Two members of this group, Ino-C2-PAF and Glc-PAF, display high efficacy and low cytotoxicity in immortalized non-tumorigenic skin keratinocyte cell line HaCaT. However, the influence of APLs on the transcription of the whole genome is still unknown. Here, using Agilent cDNA microarray technology, we compared global gene expression profiles of HaCaT cells treated with edelfosine, Ino-C2-PAF or Glc-PAF with the profile of control cells.	Co-expression
GDS3797	Expression profile after β-TrCP inhibition and androgen ablation in prostate cancer cells	We examined gene expression of LAPC4 cells after knocking down β-TrCP, androgen ablation, or the combined treatments compared to non treated cells.	Co-expression
GDS3806	Expression data for human epithelium from subjects with atopic dermatitis, psoriasis and nonatopic controls	The expression and function of tight junction genes, in particular claudin-1, was studied in order to further understanding of the biology underlying atopic dermatitis.	Co-expression
GDS3814	The human reticulocyte transcriptome (HG-U133_Plus2.0)	RNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133Plus 2.0 arrays were hybridized with probe from total RNA isolated from blood sampled from 6 umbilical cords and 6 healthy adult humans.	Co-expression
GDS3819	Patients affected with autosomal dominant monocytopenia with increased susceptibility to mycobacterial infection	We identified 18 patients with the distinct clinical phenotype of disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis and molds. This syndrome typically had its onset in adulthood and was characterized by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels.  This novel clinical syndrome links mycobacterial, viral, and fungal susceptibility with malignancy and is transmitted in an autosomal dominant pattern. In order to elucidate the possible genetic defect that results in this novel clinical syndrome, we performed microarray expression analysis on polymorphonuclear leukocytes (PMNs) isolated from affected patients and healthy controls.  Keywords: healthy donor vs affected patient	Co-expression
GDS3820	Patients affected with autosomal dominant monocytopenia with increased susceptibility to mycobacterial infection	We identified 18 patients with the distinct clinical phenotype of disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis and molds. This syndrome typically had its onset in adulthood and was characterized by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels.  This novel clinical syndrome links mycobacterial, viral, and fungal susceptibility with malignancy and is transmitted in an autosomal dominant pattern. In order to elucidate the possible genetic defect that results in this novel clinical syndrome, we performed microarray expression analysis on polymorphonuclear leukocytes (PMNs) isolated from affected patients and healthy controls.  Keywords: healthy donor vs affected patient	Co-expression
GDS3829	Sequential gene expression profiling in CLL during treatment	Purpose: Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs.  Patients and Methods:  Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy.  Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments.   Conclusion  Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL.	Co-expression
GDS3830	Expression profiling in Williams-Beuren Syndrome patient fibroblast cell lines	Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals  Keywords: disease state analysis, gene expression profiling	Co-expression
GDS3834	Definition, conservation and epigenetics of housekeeping and tissue-enriched genes	Background Housekeeping genes (HKG) are constitutively expressed in all tissues while tissue-enriched genes (TEG) are expressed at a much higher level in a single tissue type than in others.  HKGs serve as valuable experimental controls in gene and protein expression experiments, while TEGs tend to represent distinct physiological processes and are frequently candidates for biomarkers or drug targets.  The genomic features of these two groups of genes expressed in opposing patterns may shed light on the mechanisms by which cells maintain basic and tissue-specific functions. Results Here, we generate gene expression profiles of 42 normal human tissues on custom high-density microarrays to systematically identify 1,522 HKGs and 975 TEGs and compile a small subset of 20 housekeeping genes that can be used as experimental reference and are superior to many commonly used HKGs.  Cross-species comparison shows that both the functions and expression patterns of HKGs are conserved. TEGs are enriched with respect to both segmental duplication and copy number variation, while no such enrichment is observed for HKGs, suggesting the high expression of HKGs are not due to high copy numbers. Analysis of genomic and epigenetic features of HKGs and TEGs reveals that the high expression of HKGs across different tissues is associated with decreased nucleosome occupancy at the transcription start site as indicated by enhanced DNase hypersensitivity.  Additionally, we systematically and quantitatively demonstrated that the CpG islands' enrichment in HKGs transcription start sites (TSS) and their depletion in TEGs TSS.  Histone methylation patterns differ significantly between HKGs and TEGs, suggesting that methylation contributes to the differential expression patterns as well. Conclusions We have compiled a set of high quality HKGs that should provide higher and more consistent expression when used as references in laboratory experiments than currently used HKGs. The comparison of genomic features between HKGs and TEGs shows that HKGs are more conserved than TEGs in terms of functions, expression pattern and polymorphisms.  In addition, our results identify chromatin structure and epigenetic features of HKGs and TEGs that are likely to play an important role in regulating their strikingly different expression patterns. 	Co-expression
GDS3836	Expression data from epithelial cells during the process of multistep pancreatic carcinogenesis	The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis, we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages.	Co-expression
GDS3837	Genome-wide screening of transcriptional modulation in non-smoking female lung cancer in Taiwan	Although smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of cigarette smoking, extremely lower than those in Caucasian females.  This report is a comprehensive analysis of the molecular signature of non-smoking female lung cancer in Taiwan.	Co-expression
GDS3838	Analysis of gene expression in esophageal squamous cell carcinoma (ESCC)	To characterize gene expression in esophageal squamous cell carcinoma, we examined gene expression in tumor and matched normal adjacent tissue from 17 ESCC patients from a high-risk region of China.	Co-expression
GDS3841	Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients	Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis.  Design: Prospective case - control study. Setting: University Hospital. Patients:  25 patients undergoing IVF-ICSI treatment.  Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean).  Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients.   Conclusions:  Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS. We used microarrays to study the gene expression of human cultured cumulus cells. We  compared the genes expression of lean PCOS,  Obese PCOS, lean controls and obese controls. Different molecular pathways are associated with PCOS in Lean and Obese patients. Keywords: disease state analysis	Co-expression
GDS3842	Gene expression signatures for human iPS cell lines	The reprogramming of human fibroblasts to generate induced pluripotent stem cells (hiPSCs) has been achieved through the expression of only a few exotic factors1-8, which is morphologically and molecularly verified in outer cellular states by characteristic markers, due to the remodeling of the somatic cell transcription programs in inner cellular states to the ES-like condition. Transcription factor-induced reprogramming to self-renewal and pluripotency raises the question as to how the exotic factors act to bring about these changes in the two cellular states9-11. Here, we applied RNA profiling to uncover gene expression changes and glycan profiling12 to survey structural changes in glycans, to compare hiPSCs and parental somatic cells, in total 51 cells, which were originally cultured and established, and the changes were analyzed by the combination of standard statistical techniques and a network approach13. We fist found a gene expression signature of 2502 genes with significant difference between iPSCs and SCs, and by the following network analysis by considering the expression signature, we found a network signature of 28 regulatory networks of 76 genes, which were related to the glycan biosynthetic pathways including 3 glycosyltransferase, in addition to well known signal pathways and cell-cell interaction pathways. Concomitantly, we found a glycan signature of six glycan structures characterized 16 lectins on lectin microarray by the correspondence with 12 glycosyltransferases in expression signature. In particular, the correspondence detected between the three expression signatures revealed 14 candidate glycosyltransferase, which are responsible for glycan transfer related to known epitopes for the differentiation such as SSEA epitope family in glycan biosynthesis pathway, based on characteristic changes in the cellular surface states of the hiPSCs. This sheds new light on a possible linkage between the inner and outer cellular states for reprogramming to self-renewal and pluripotency in hiPSC.	Co-expression
GDS3848	Multiomics study to identify virulence factors of Rickettsia prowazekii revealed its adaptive mutation capabilities	We identified four virulence phenotypes of Rickettsia prowazekii (the deadly agent of epidemic typhus) that are associated with the upregulation of antiapoptotic genes (virulent strain) or the Interferon I pathway (avirulent). Transcriptional and proteomic analyses of R. prowazekii linked surface protein expression and methylation with virulence. By sequencing a virulent strain and using comparative genomics, we found hotspots of mutations in homopolymeric tracts of poly(A) and poly(T)  that lead to gene split and inactivation and explain the loss of virulence in the vaccine strain. These areas of instability explains adaptive mutations leading to virulence recovery in the vaccine strain.	Co-expression
GDS3851	Gene expression during SMC cord morphogenesis	SMCs must undergo specialzed patterning during blood vessel stabilization. We used microarray analysis to identify differentially expressed genes as smooth muscle cells were induced to assemble into a network of elongated cords.	Co-expression
GDS3852	Gene expression during SMC cord morphogenesis	SMCs must undergo specialzed patterning during blood vessel stabilization. We used microarray analysis to identify differentially expressed genes as smooth muscle cells were induced to assemble into a network of elongated cords.	Co-expression
GDS3853	Expression profiling of human DCIS and invasive ductal breast carcinoma	Human healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas. Using this approach, we were able to identify a set of genes which might allow a better detection of DCIS and invasive carcinomas in the future.	Co-expression
GDS3855	Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy	Analysis of gene expression profiles in skeletal muscle tissue after long-term use of HRT. Networks of enriched processes in skeletal muscle responding to long-term use of estrogen-based HRT in comparison with women without any HRT in a genetically controlled setting were contructed. The association between the expression of specific biological processes and muscle composition or performance was tested. The hypothesis was that the differences in gene expression profiles reflect the known differences in muscle composition and performance.	Co-expression
GDS3856	Gene expression in human oral mucosal fibroblasts and patient-matched skin fibroblasts	Wound healing within the oral mucosa results in minimal scar formation compared to wounds within the skin. We have recently demonstrated distinct differences in the ageing profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesize that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles with a number of genes linked to wound healing/tissue repair. We analyzed the gene expression profiles of oral mucosal and patient-matched skin fibroblasts for multiple patients both prior to (0h) and (6h) following a wounding stimulus.	Co-expression
GDS3858	Mature dendritic cells under hypoxic condition	Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs and maturation into mature DCs. Mature DCs were differentiated in vitro from human monocytes under normoxic or hypoxic  conditions and the gene expression profile was determined. 	Co-expression
GDS386	Arthritis synoviocyte response to TNF alpha	Temporal analysis of arthritic synovial biopsies treated with TNF alpha at 0, 4 and 24 hours.	Co-expression
GDS3860	Transcriptome of the maturing erythroblast	Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation.	Co-expression
GDS3861	Identification of an SRF- and androgen-dependent gene signature in prostate cancer	The androgen receptor (AR) is the principal target for treatment of non-organ confined prostate cancer (PCa).  Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes and point towards a role for secondary transcription factors (TFs) therein. We identified a novel indirect mechanism of androgen action in which effects of androgens on PCa cells are mediated by Serum Response Factor (SRF).    To identify and characterize genes and cellular processes that are androgen-regulated in an SRF-dependent manner in PCa, Affymetrix HG-U133 Plus 2.0 GeneChip Array analysis was performed starting from RNA obtained from LNCaP cells in which androgen stimulation was combined with siRNA-mediated SRF silencing.  To this end, LNCaP cells were seeded in 60 mm dishes at a density of 550,000 cells per dish in antibiotic-free medium.  The next day, cells were transfected with siGenome SmartPool siRNA targeting SRF (Dharmacon, Lafayette, CO) or a custom-made control SmartPool targeting luciferase (LUC condition) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions.  Forty-two hours after transfection, cells were treated with 5nM R1881 or ethanol vehicle.  3 biological triplicates were included per treatment group.  Forty-eight hours later, cells were harvested in Trizol reagent (Invitrogen). RNA was isolated, purified on RNeasy columns (Qiagen, Germantown, MD) and checked for integrity by Agilent testing (Affymetrix, Santa Clara, CA).  cDNA was generated and hybridized to Human Genome U133 Plus 2.0 arrays (Affymetrix) according to the manufacturer’s instructions at the Mayo Clinic Advanced Genomics Technology Microarray Shared Resource core facility.	Co-expression
GDS3864	Gene expression data of non-leukemic individuals before and during in-vivo glucocorticoid treatment	Article title: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells.  Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as a GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC.	Co-expression
GDS3867	Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells	Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a transcriptional memory of the original cells. The persistent expression of somatic genes can be partially explained by incomplete promoter DNA methylation. This epigenetic mechanism underlies a robust form of memory that can be found in iPS cells generated by multiple laboratories using different methods, including RNA transfection. Incompletely silenced genes tend to be isolated from other genes that are repressed during reprogramming, indicating that recruitment of the silencing machinery may be inefficient at isolated genes. Knockdown of the incompletely reprogrammed gene C9orf64 (chromosome 9 open reading frame 64) reduces the efficiency of human iPS cell generation, indicating that somatic memory genes may be functionally relevant during reprogramming.	Co-expression
GDS3868	HUVECs cultured under normal or high laminar shear stress	Many studies have characterised the effect of normal laminar shear stress (LSS) on endothelial responses, however elevated shear stress, as would be experienced overlying a stenotic plaque, has not been studied in depth. Therefore we used transcriptomics and related functional analyses to compare cells exposed to laminar shear stress at 15 or 75 dynes/cm2 for 24 hours (LSS15-normal or LSS75-high shear stress).	Co-expression
GDS3869	Definition and characterization of the systemic T cell dysregulation in untreated indolent B cell lymphoma and very early CLL	Epidemiological data show that the immune system may control or promote emergence and growth of a neoplastic lymphomatous clone. Conversely, systemic lymphomas, especially myeloma and CLL, are associated with clinical immunodeficiency. This prospective controlled study demonstrates substantially reduced circulating T helper cells, predominantly naive CD4+ cells, in patients with non-leukemic follicular and extranodal marginal zone lymphomas, but not in monoclonal gammopathy and early CLL. These numerical changes were correlated with a preactivated phenotype, hyperreactivity in vitro, presenescence, and a Th2 shift of peripheral T helper cells. No prominent alterations were found in the regulatory T cell compartment. Gene expression profiling of in vitro-stimulated CD4+ cells revealed an independent second alteration of T helper cell physiology which was most pronounced in early CLL but also detectable in FL/eMZL. This pattern consisted of downregulation of proximal and intermediate T-cell receptor signaling cascades and globally reduced cytokine secretion. Both types of T cell dysfunction may contribute to significant immunodeficiency in non-leukemic indolent B-cell lymphomas as demonstrated by refractoriness to hepatitis B vaccination. The precise definition of systemic T cell dysfunction serves as the basis to study its prognostic impact, its relationship to the established influence of the lymphoma microenvironment, and its therapeutic manipulation	Co-expression
GDS3872	Integrated Genomics of Ovarian Xenograft Tumor Progression and Chemotherapy Response	Xenograft ovarian tumors are useful model to test therapeutic candidates in vivo. We used microarrays to gain insight into the expression changes during tumor growth and induced by the vitamin D analog, MT19C at multiple time points.	Co-expression
GDS3874	Gene expression in PBMCs from children with diabetes	Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients. Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D. Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy. Keywords: Diabetes, microarray analysis, peripheral blood mononuclear cells	Co-expression
GDS3875	Gene expression in PBMCs from children with diabetes	Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients. Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D. Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy. Keywords: Diabetes, microarray analysis, peripheral blood mononuclear cells	Co-expression
GDS3876	Expression data from liver of obese (with or without type 2 diabetes) and lean human subjects.	Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays.	Co-expression
GDS3880	Skeletal muscle mitochondrial dysfunction is secondary to T2DM	Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training  Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However, a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects.  Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased.  Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration.	Co-expression
GDS3881	Resolution of Type 2 Diabetes Following Bariatric Surgery is Associated with Changes in Whole Blood Gene Expression	To investigate the effects of bariatric surgery on gene expression profile changes in whole blood in obese subjects with type 2 diabetes in a pilot study setting.  Whole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6-12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays.  Clinical and expression data were analyzed using a paired t-test, and correlations between changes in clinical trait and transcript levels were calculated.  Pathways were identified using Ingenuity Pathway Analysis and DAVID gene ontology software.  Bariatric surgery resulted in significant reduction of BMI, fasting plasma glucose and normalization of HbA1c levels.  The expression levels of 204 transcripts, representing 200 unique genes, were significantly altered after bariatric surgery.  Among the significantly regulated genes were GGT1, CAMP, DEFA1, LCN2, TP53, ZNF684, GPR50, PDSS1, OLR1, CNTNAP5, DHCR24, HHAT and SARDH, which have been previously implicated in lipid metabolism, obesity and/or type 2 diabetes.  The changes in expression of seven transcripts, WDR35, FLF45244, DHCR24, TIGD7, TOPBP1, TSHZ1, and FAM8A1 were strongly correlated with the changes in body weight, fasting plasma glucose and HbA1c content.   These preliminary data suggest that whole blood expression levels of specific transcripts may identify biomarkers associated with susceptibility for type 2 diabetes and/or therapeutic response.  	Co-expression
GDS3882	Expression data from type 2 diabetic and non-diabetic isolated human islets	We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples.	Co-expression
GDS3884	Increased SRF Transcriptional Activity is a Novel Signature of Insulin Resistance in Humans and Mice	Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) and is even present in offspring of diabetic parents. However, molecular mediators of insulin resistance remain unclear. We find that the top-ranking gene set in expression analysis of muscle from humans with T2D and normoglycemic insulin resistant subjects with parental family history (FH+) of T2D is increased expression of actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator MKL1. Furthermore, the SRF activator STARS is upregulated in FH+ and T2D and inversely correlated with insulin sensitivity. These patterns are recapitulated in insulin resistant mice, and linked to alterations in two other regulators of this pathway: reduced G-actin and increased nuclear localization of MKL1. Both genetic and pharmacologic manipulation of STARS/MKL1/SRF pathway significantly alter insulin action: 1) Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation; 2) reduced STARS expression increased insulin signalling and glucose uptake, and 3) SRF inhibition by CCG-1423 reduced nuclear MKL1, improved glucose uptake, and improved glucose tolerance in insulin resistant mice in vivo. Thus, SRF pathway alterations are a signature of insulin resistance which may also contribute to T2D pathogenesis and be a novel therapeutic target.	Co-expression
GDS3885	Expression data of glioblastoma stem-like (GS) cell lines, conventional glioma cell lines and primary tumors	We compared a large panel of human glioblastoma stem-like (GS) cell lines,  corresponding primary tumors and conventional glioma cell lines to identify cell lines that preserve the transcriptome of human glioblastomas most closely, thereby allowing identification of shared therapeutic targets. We used Affymetrix HG-U133 Plus 2.0 microarrays to compare human glioblastoma stem-like (GS) cell lines,  corresponding primary tumors and conventional glioma cell lines.	Co-expression
GDS3886	Expression profiles of PBMC from multiple sclerosis patients	Affymetrix GeneChip Human Gene 1.0 ST Array was applied to compare the expression profiles in peripheral blood mononuclear cells(PBMC) between  healthy controls and  multiple sclerosis patients(MS pt). It suggested that certain genes involved in apoptosis pathway have been changed regulated in PBMC from MS pt.	Co-expression
GDS3889	Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects	2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic disease, diabetes, infertility and cancer. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 253 differentially modulated probe sets, identifying 217 well-characterized genes. A large part of these were associated with cell adhesion and/or angiogenesis and with transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway, were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems.	Co-expression
GDS3892	Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome  	Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging.	Co-expression
GDS3897	Transcription levels in human colon biopsies in IBS and IBD patients before and after participating in a high red-meat dietary intervention	Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk  Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans.  Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon  Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans.	Co-expression
GDS3898	Differential gene expression in circulating leukocytes from chronically lonely individuals	Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 93 older adults participating in the Chicago Health Aging and Social Relations Study (CHASRS).  The primary research question is whether gene expression differs in participants who are chronically lonely.  Keywords: Risk prediction	Co-expression
GDS390	Idiopathic thrombocytopenic purpura	Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematologic disorder. CD3+ cells were studied in duplicate from healthy controls, patients with active ITP and patients with ITP in remission.	Co-expression
GDS3901	Expression data from Burkitt lymphoma cases	Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in  Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma). We used microarrays to detail the global programme of gene expression in different subtypes of Burkitt lymphoma.	Co-expression
GDS3902	Gene expression analysis of 12  B-cell Chronic Lymphocytic Leukemia samples and 5 CD19+ control samples	Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of MIR155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription. We have studied differentially expressed genes in the whole genome and also in the preselected groups of  MYB target genes and miR-155 microRNA predicted targets.	Co-expression
GDS3903	Transcriptome-wide characterization of gene expression associated with unruptured intracranial aneurysms	The biological mechanisms by which cerebral aneurysms emerge, enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays.	Co-expression
GDS3910	Real-time Monitoring of Cisplatin Toxicity on Cancer Cells	Treatment of MCF7 breast cancer cells by cisplatin leads to a very specific metabolic response and an onset of cell death about 10-11 h after beginning of treatment. For more detailed understanding of the molecular processes underlying the specific metabolic response, mRNA was isolated from MCF7 cells when the specific changes, (i) induction of glycolysis and (ii) onset of cell death, were detected during online measurement in the cell biosensor system.	Co-expression
GDS3911	Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells	Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. LGC006, a less potent SR1 analog, was also examined.  KEYWORDS: two compounds, multiple doses, one time point	Co-expression
GDS3912	Characterization of differential gene expression in adrenocortical tumors harbouring β-catenin  (CTNNB1) mutations.	Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However, the target genes of CTNNB1 have not yet been identified in adrenocortical tumors. Our objective was to identify genes de-regulated in adrenocortical tumors harbouring CTNNB1 genetic alterations.	Co-expression
GDS3916	Gene Expression in the Human Mammary Epithelium during Lactation: the Milk Fat Globule Transcriptome through 4 Days	The 4 day gene expression profile in the lactating mammary gland was demonstrated using the Human Ref-8 BeadChip array (Illumina, Inc). Of the 22,184 gene transcripts on the array, 14,070 genes were consistently expressed and represented the milk fat globule transcriptome. Milk protein genes were among the most highly expressed along with genes involved in the milk syntesis processes.	Co-expression
GDS3919	Expression profiling of critically ill influenza and bacterial pneumonia patients, also influenza vaccination recipients	Longitudinal Gene expression profiling of whole blood from critically ill influenza and bacterial pneumonia patients.  In addition before vs 7 days post influenza vaccination volunteer samples are assayed.	Co-expression
GDS3920	Expression data from peripheral blood mononuclear cells in multiple sclerosis patients and controls	Multiple sclerosis (MS) is a neurodegenerative disease with a presumed autoimmune component. Expression profiling in immune cells can therefore be used in order to identify genes and pathways involved in MS pathogenesis. We conducted a genome-wide expression study in peripheral blood mononuclear cells (PBMC) from 12 MS patients and 15 controls in order to identify differentially expressed genes and pathways in MS.	Co-expression
GDS3926	Human embryonic stem cells as a tool to study hepatocyte differentiation	The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocyte–like fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate.	Co-expression
GDS3929	Comprehensive Study of Tobacco Smoke-Related Transcriptome Alterations in Maternal and Fetal Cells	Maternal smoking has a severe negative effect on all stages of pregnancy that in consequence impairs fetal growth and development. Tobacco smoke-related defects are well established at the clinical level; however, little is known about molecular mechanisms underlying these pathological conditions. We thus employed a genomic approach to determine transcriptome alterations induced by maternal smoking  in pregnancy. We assayed gene expression profiles in peripheral blood (M) leukocytes and placentas (PL) of pregnant smokers and those without significant exposure, and in cord blood (D) leukocytes of their babies. Comparative analyses defined significant deregulation of 193 genes in M cells, 329 genes in placentas, and 49 genes in D cells of smokers. These genes were mainly involved in xenobiotic metabolism, oxidative stress, inflammation, immunity, hematopoiesis, trophoblast differentiation, and vascularization. Functional annotation of the deregulated genes outlined processes and pathways affected by tobacco smoke. In smoker newborns, we identified several deregulated pathways associated with autoimmune diseases. The study demonstrates a limited ability of placenta to modulate toxic effects of maternal tobacco use at the gene expression level.	Co-expression
GDS3936	Effects of EPO and EST on erythroid maturation	Transcriptional profiles of human CD34+ cells cultured in EPO and EST conditions.	Co-expression
GDS3938	Comparing Control and Schizophrenic hiPSC-derived Neurons	Schizophrenia is a debilitating neurological disorder for which no cure exists. Few defining characteristics of schizophrenic neurons have been identified and the molecular mechanisms responsible for schizophrenia are not well understood, in part due to the lack of patient material for study. Human induced pluripotent stem cells (hiPSCs) offer a new strategy for studying schizophrenia. We have created the first cell-based human model of a complex genetic psychiatric disease by generating hiPSCs from schizophrenic patients and subsequently differentiating these cells to hiPSC-derived neurons in vitro. Schizophrenic hiPSC-derived neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of schizophrenic hiPSC-derived neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the schizophrenic phenotype were ameliorated following treatment of schizophrenic hiPSC-derived neurons with the antipsychotic loxapine.	Co-expression
GDS3940	Gene expression in minor salivary gland of patients with Sjogren's syndrome (SS) and control	To study the gene expression profile of salivary glands with varying degrees of inflammation in Sjogren's and non Sjogren's patients	Co-expression
GDS3941	Vaginal epithelial gene expression in postmenopausal women suffering from vaginal dryness	The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.	Co-expression
GDS3942	Expression data from human bone marrow hematopoietic stem cells	In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.	Co-expression
GDS3945	Mutant thyroid hormone receptors (TRs) isolated from distinct cancer types display distinct target gene specificities: a unique regulatory repertoire associated with renal clear cell  carcinomas.	Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that regulate a diverse array of biological activities, including metabolism, homeostasis, and development.  TRs also serve as tumor suppressors, and aberrant TR function (via mutation, deletion, or altered expression) is associated with a spectrum of both neoplastic and endocrine diseases.  A particularly high frequency of TR mutations has been reported in renal clear cell carcinoma (RCCC) and in hepatocellular carcinoma (HCC). We have shown that HCC-TR mutants regulate only a fraction of the genes targeted by wild-type TRs, but have gained the ability to regulate other, unique, targets.  We have suggested that this altered gene recognition may contribute to the neoplastic phenotype.  Here, to determine the generality of this phenomenon, we examined a distinct set of TR mutants associated with RCCCs. We report that two different TR mutants, isolated from independent RCCC tumors, possess greatly expanded target gene specificities that extensively overlap one another, but only minimally overlap that of the WT-TRs, or those of two HCC-TR mutants.  Many of the genes targeted by either or both RCCC-TR mutants have been previously implicated in RCCC, and include a series of metallothioneins, solute carriers, and genes involved in glycolysis and energy metabolism.  We propose that TR mutations from RCCC and HCC are likely to play tissue-specific roles in carcinogenesis, and that the divergent target gene recognition patterns of TR mutants isolated from the two different types of tumors arises from different selective pressures during development of RCCC versus HCC.	Co-expression
GDS3946	Airway smooth muscle reponse to dexamathasone at 4 and 24 hours	Glucocorticoids, which activate glucocorticoid receptor signaling and thus modulate gene expression, are widely used to treat asthma. Glucocorticoids exert their therapeutic effects in part through modulating airway smooth muscle structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. Here, we used transcription profiling to characterize the effects of a potent glucocorticoid, dexamethasone, on cultured human airway smooth muscle gene expression at 4 and 24 hours.	Co-expression
GDS395	Biomaterial engineering	Temporal gene expression analysis of fetal lung fibroblast cell line IMR-90 seeded onto collagen/chondroitin sulfate tissue engineering scaffold mesh material. Integration of genomic information with biomaterial engineering.	Co-expression
GDS3951	Systems biology of interstitial lung diseases	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3952	Integrating Factor Analysis and a Transgenic Mouse Model to Reveal a Peripheral Blood Predictor of Breast Tumors	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3954	Expression data from human liver cells	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3955	Expression data from human liver cells	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3959	Time course expression data from early Bovine embryo, Human embryo, and Mouse embryo	The process of early development of mammals is subtly and accurately controlled by the regulation networks of embryo cells. Time course expression data measured at different stages during early embryo development process can give us valuable information by revealing the dynamic expression patterns of genes in genome wide scale. In this study, bovine embryo expression data were generated  at oocyte, one cell stage, two cell stage, four cell stage, eight cell stage, sixteen cell stage, morula, and blastocyst; Human embryo expression data were generated at one cell stage, two cell stage, four cell stage, eight cell stage, morula, and blastocyst; Mouse embryo expression data were generated at one cell stage, two cell stage, four cell stage, eight cell stage, morula, and blastocyst.   Keywords: time course	Co-expression
GDS3961	Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3962	Expression data from human adipose tissue	Obesity is a risk factor for numerous metabolic disorders; however, not all obese individuals are prone to insulin resistance. The central aim of this study was to identify molecular pathways directly related to insulin resistance independent of BMI in obesity. We sought to determine the gene expression signature of adipose tissue in a body mass index (BMI)-matched obese cohort of patients that are either insulin sensitive or insulin resistant.	Co-expression
GDS3963	Type 2 Diabetes mellitus: mRNA and miRNA profiling	This SuperSeries is composed of the SubSeries listed below.	Co-expression
GDS3964	Gene Signature for Aggression of Melanoma Metastases - Melanoma Metastasis (LeiATCC)	Metastasis is the deadliest phase of cancer progression.  Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis.  We report here the identification of a “metastasis aggressiveness gene expression signature” derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model.  Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients.  Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis.   Keywords: disease state	Co-expression
GDS3965	Gene Signature for Aggression of Melanoma Metastases - Melanoma Metastasis (LeiFidler)	Metastasis is the deadliest phase of cancer progression.  Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis.  We report here the identification of a “metastasis aggressiveness gene expression signature” derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model.  Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients.  Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis.  Keywords: disease state analysis	Co-expression
GDS3966	Gene Signature for Aggression of Melanoma Metastases - Melanoma Metastasis 	Metastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a “metastasis aggressiveness gene expression signature” derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis. Keywords: disease state	Co-expression
GDS3973	Expression data from docetaxel-resistant prostate cancer cell lines	Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment. The aim of the study was to identify key molecular genes and networks associated with docetaxel resistance in 2 models of docetaxel-resistant castration-resistant prostate cancer cell lines.	Co-expression
GDS3975	Gene expression profiles of endometriosis	Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we carried out transcriptome:microRNAome analysis of endometriomas and eutopic endometrium, using gene expression arrays and next generation small RNA sequencing technology. Keywords: two group comparison	Co-expression
GDS3977	Xenograft model systems of adenoid cystic carcinoma	Adenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands, with an incidence of 4.5 per 1,000,000. It can also arise in glandular tissue closely related to salivary glands in the lacrimal gland, nasal passages and tracheobronchial tree, as well as in glands of the breast and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform or tubular patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis and/or spread along peripheral nerves. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACC, and recently it has been discovered that in a majority of ACC the MYB gene on chromosome 6 is fused to the 3’ terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation.    Recently it has been determined that most cell lines with attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB-NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and pre-clinical models systems of ACC, we have for several years been establishing xenograft tumor lines from clinical samples of ACC. We describe our experience with these models and their characterization here.	Co-expression
GDS3980	Gene expression profiling in arterial tissue from type 2 diabetic patients	Gene expression profiling in arterial tissue from type 2 diabetic patients	Co-expression
GDS3981	Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans	Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol supplementation significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces profound metabolic changes in obese subjects, mimicking the effects of calorie restriction.	Co-expression
GDS3983	Genome-wide mRNA profiling of adult human pancreatic beta and duct cells in comparison to other human tissues	Aims: establishment of reference samples to investigate gene expression selective for endocrine or ductal-exocrine cells within the adult human pancreas. To this end, human islet endocrine cells, FACS-enriched in insulin+ cells, (n=3) and human exocrine ductal cells (n=2) are compared on Affymetrix HG133A platform with duplicate hybridizations of a panel of other primary human tissues.	Co-expression
GDS3984	Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro	Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, while evidence supports the replicative capacity of adult beta cells in vivo, attempts at expanding human islet cells in tissue culture resulted in loss of beta-cell phenotype. Using a genetic lineage-tracing approach we have provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain a partially open chromatin structure in expanded BCD cells, although they are not transcribed. Here we report that BCD cells can be induced to redifferentiate by a combination of soluble factors. The redifferentiated cells express beta-cell genes, store insulin in typical secretory vesicles, and release it in response to glucose. The redifferentiation process involves mesenchymal-epithelial transition, as judged from changes in gene expression. Moreover, inhibition of the EMT effector SLUG using shRNA results in stimulation of redifferentiation. BCD cells also give rise at a low rate to cells expressing other islet hormones, suggesting  transition through an islet progenitor-like stage during redifferentiation. These findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening.	Co-expression
GDS3998	Gene expression changes in human hepatocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)	Organophosphorus compounds induce hepatotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human hepatocytes after exposure to VX, and identified pathways underlying these changes.	Co-expression
GDS400	DNA damage and UV radiation	Temporal analysis of differences in WS1 human skin fibroblast gene expression response to low (10 J/m2; induces transient cellular replicative arrest) or high (50 J/m2; induces apoptosis) doses of short wavelength UV radiation (UVC; 254 nm).	Co-expression
GDS4006	HDACI and DAC induce specific epigenetic profile in DLBCL	Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid neoplasm in the world representing 30-40% of all lymphomas. Standard immunochemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) ensures cure in 60 to 65% of patients, while the rest progress or relapse. While advances have been made in the treatment of DLBCL, especially with the addition of rituximab, it is now apparent that there may be significant differences in prognosis that are related to the cell of origin, and that this disease is heterogeneous and novel treatment options are needed. It has been hypothesized that the combination of HDACI and hypomethylating agents might be a new approach to the treatment of relapsed or refractory DLBCL. This combination is thought to disrupt the transcription repressor complex consisting of methyl binding domain proteins (MBDP) and histone deacetylases (HDACs). We have explored the effect of different HDACI and decitabine combinations in in vitro and in vivo models of DLBCL. These data suggest a class effect, with all four HDACI (panobinostat, belinostat, vorinostat, depsipeptide) synergizing with decitabine in cytotoxicity assay across the spectrum of DLBCL cells. Synergy was validated in a number of other assays including a caspase 3 activation and apoptosis. Furthermore, the combination of panobinostat and decitabine induced markedly increased histone acetylation. The in vitro observations were confirmed in an in vivo murine xenograft experiment with the Ly1 DLBCL line. Genome wide methylation analysis and gene expression profiling demonstrated that the combination of these two epigenetic therapies produced a unique gene expression profile  compared to the samples treated with single drugs.  These data strongly support the potential therapeutic role of a combinatorial epigenetic platform for the treatment of B-cell lymphomas, in particular in patients with DLBCL. Clearly, future studies will need to focus on integrating the appropriate correlative studies, with an effort to identify and or validate biomarkers of activity with these combinations. The likelihood moving forward is that the mechanism of action of these combinations may vary from disease context to disease context.  Genome-wide array findings from these kinds of studies could be expanded to samples from patients on clinical trials to identify novel biomarkers of response, leading to the rational treatment of individual diseases based upon the underlying pathogenesis.	Co-expression
GDS4007	Niche modulated versus niche modulating genes in multiple myeloma	Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown.  Design and Methods. BM aspiration samples were obtained from MM-patients with a high tumor load. Gene expression profile (GEP) was recorded immediately following aspiration and at subsequent time points. Identification of niche-regulated genes relied on spontaneous gene modulation following loss of niche regulation.  Results. Compared to the reference samples fixed immediately following aspiration, the BM samples fixed after longer delay acquired numerous changes in GEP. The top modulated genes included a common subset of ~ 60 genes displaying prompt and sustained “switch” in expression consistently, among which were oncogenes (FOS, JUN) and genes regulating homing (CD69, RGS1), expansion and angiogenesis (AREG, PTGS2, RGS2, NR4A2). Interestingly, the “switch” in GEP was reversible and turned “off” and “on” in culture conditions resuming cell-cell-matrix contact versus re-spread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of the tumor cells out-of-niche and the regression of the “contactless switch” was followed by induction of a new set of genes this time mostly encoding extracellular proteins, including angiogenic factors (IL8, CXCL5), extracellular-matrix proteins (SPP1, FN1), chemokines (CXCL5, CCL2, CCL20) and growth factors (CCL2, IL6).   Conclusions. Our dataset, being unique in authentic expression design, uncovered contact-regulated genes capable of controlling homing, expansion and tumorigenesis. The adaptive response of the tumor cells to culture conditions deficient of integral niche components (e.g., vascular vessels) uncovered inducible niche-regulating tumor genes.	Co-expression
GDS4008	Niche modulated versus niche modulating genes in multiple myeloma	Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown.  Design and Methods. BM aspiration samples were obtained from MM-patients with a high tumor load. Gene expression profile (GEP) was recorded immediately following aspiration and at subsequent time points. Identification of niche-regulated genes relied on spontaneous gene modulation following loss of niche regulation.  Results. Compared to the reference samples fixed immediately following aspiration, the BM samples fixed after longer delay acquired numerous changes in GEP. The top modulated genes included a common subset of ~ 60 genes displaying prompt and sustained “switch” in expression consistently, among which were oncogenes (FOS, JUN) and genes regulating homing (CD69, RGS1), expansion and angiogenesis (AREG, PTGS2, RGS2, NR4A2). Interestingly, the “switch” in GEP was reversible and turned “off” and “on” in culture conditions resuming cell-cell-matrix contact versus re-spread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of the tumor cells out-of-niche and the regression of the “contactless switch” was followed by induction of a new set of genes this time mostly encoding extracellular proteins, including angiogenic factors (IL8, CXCL5), extracellular-matrix proteins (SPP1, FN1), chemokines (CXCL5, CCL2, CCL20) and growth factors (CCL2, IL6).   Conclusions. Our dataset, being unique in authentic expression design, uncovered contact-regulated genes capable of controlling homing, expansion and tumorigenesis. The adaptive response of the tumor cells to culture conditions deficient of integral niche components (e.g., vascular vessels) uncovered inducible niche-regulating tumor genes.	Co-expression
GDS4011	microRNA and mRNA expression profiles of human pancreatic islet-like cell clusters	Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, and it is important to find new alternative source of the islet beta cells to replace the damaged cells. Human embryonic stem (hES) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into embryoid bodies and then induced to generate the pancreatic islet-like cell clusters, which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the pancreatic islet-like cell clusters were further analyzed and compared with those of undifferentiated hES-T3 cells and differentiated embryoid bodies. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The pancreatic islet-like cell clusters were found to exhibit very high expression of microRNAs miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs are very likely to play important regulatory roles in the differentiation of pancreatic islet cells and early embryonic development.	Co-expression
GDS4012	Sural nerve of progressive and non-progressive diabetic neuropathy patients	Diabetic neuropathy (DN) is a common complication of diabetes.  While multiple pathways are implicated in the pathophysiology of DN, there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. To examine gene expression signatures related to DN, microarray experiments were performed on a subset of human sural nerves collected during a 52-week clinical trial of acetyl-L-carnitine. A series of bioinformatics analyses analyzed differential gene expression and identified gene networks and pathways potentially responsible for the progression of DN. We identified 532 differentially expressed genes (DEGs) between patient samples with progressing or non-progressing DN, which were functionally enriched in pathways involving defense and inflammatory responses and lipid metabolism. A literature-derived co-citation network of the DEGs revealed gene sub-networks centered on apolipoprotein E (APOE), jun oncogene (JUN), leptin (LEP), serpin peptidase inhibitor E Type 1 (SERPINE1) and peroxisome proliferator-activated receptor gamma (PPARG). DEGs were used to predict DN progression in a test set of patients. Ridge-regression classification models with 14 DEGs achieved an overall accuracy of 92%, correctly classifying the progression status of 11 out of 12 patients. To our knowledge, this is the first study to identify transcriptional changes associated with DN progression in human sural nerves biopsies and describe their potential utility for molecular prediction of DN. Our results identifying the unique gene signature of patients with progressive DN will facilitate the development of new mechanism-based diagnostics and therapies.	Co-expression
GDS4027	Meta analysis of gene expression in human islets after in vitro expansion.	Pancreatic islet transplantation as a cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols, and their potential for differentiation into functional beta cells, remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and attempted re-differentiation. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at re-differentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increases our understanding of the active pathways in expanded and re-differentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta cell mass in T1D patients.	Co-expression
GDS4030	Gene expression of innate immune response in endothelial cells	Gene expression in human umbilical vein endothelial cells (HUVEC) was investigated by microarray analysis after 4 h infection with S. aureus isolated from healthy nasal carriers (n=5) and from blood (n=5) of septic patients. All bacterial isolates were spa-typed and characterized with a DNA microarray to determine the presence of virulence genes.  Keywords: infection studies, pathogen, S. aureus	Co-expression
GDS4037	Profiling Gene Expression in Human Placentae of Different Gestational Ages: an OPRU Network and UW SCOR Study	We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days), and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport.  Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age.  CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those in women experiencing gestational diabetes, pre-eclampsia and teratogenic sequelae. Keywords: time series	Co-expression
GDS4041	Global transcriptional response of macrophage-like THP-1 cells 	Shiga toxins (Stxs) are bacterial cytotoxins produced by the enteric pathogens Shigella dysenteriae serotype 1 and some serotypes of Escherichia coli that cause bacillary dysentery and hemorrhagic colitis, respectively. To date, approaches to studying the capacity of Stxs to alter gene expression in intoxicated cells have been limited to individual genes. However, it is known that many of the signaling pathways activated by Stxs regulate the expression of multiple genes in mammalian cells. To expand the scope of analysis of gene expression and to better understand the underlying mechanisms for the various effects of Stxs on cell functions, we carried out comparative microarray analyses to characterize the global transcriptional response of human macrophage-like THP-1 cells to Shiga toxin type 1 (Stx1) and LPS. Data were analyzed using a rigorous combinatorial approach with three separate statistical algorithms. Thirty-six genes met the criteria of up-regulated expression in response to Stx1 treatment with 14 genes uniquely up-regulated by Stx1. Microarray data were validated by real time RT-PCR for genes encoding Egr-1 (transcriptional regulator), COX-2 (inflammation), and DUSP1, 5 and 10 (regulation of MAPK signaling). Stx1-mediated signaling through ERK1/2 and Egr-1 appears to be involved in the increased expression of the proinflammatory mediator TNF-α. Activation of COX-2 expression is associated with the increased production of proinflammatory and vasoactive eicosanoids. However, the capacity of Stx1 to increase the expression of genes encoding phosphatases suggests that mechanisms to dampen the macrophage proinflammatory response may be built into host response to the toxins.	Co-expression
GDS4043	GSK-3 inhibitor treatment effect on MLL leukemia cell	Human leukemia cell line RS4.11 was treated with GSK-3 inhibitor SB216763 for 20 hours.  Gene expression profiling was performed to analyze genes affected by GSK-3 inhibition. 	Co-expression
GDS4045	Expression analysis of Reh cells after transfection with shRNA targeting CBFA2T3 and/or constitutively active IKKβ(EE)	Genome-wide gene expression analysis of Reh cells following transfection with shRNA targeting CBFA2T3, constitutively active IKKβ(EE), or both in combination.	Co-expression
GDS4046	ZMYM2/FGFR1, BCR/FGFR1 or BCR/ABL1 in human cord blood CD34+ cells reveals similar but distinct gene expression profiles	The 8p11 myeloproliferative syndrome (EMS), also referred to as the stem cell leukemia/lymphoma syndrome, is a chronic myeloproliferative disorder that rapidly progresses into an acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinase activity within FGFR1. The two most common fusion genes in human EMS are ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) and BCR/FGFR1. To study the transcriptional programs becoming deregulated by the FGFR1 fusion genes, global gene expression analysis on human CD34+ cord blood cells expressing either of the fusion oncogenes ZMYM2/FGFR1 and BCR/FGFR1 was performed. As a reference gene we also included the more studied BCR/ABL1 fusion oncogene associated with chronic myeloid leukemia. We found that the 3 different fusion oncogenes had in common the upregulation of several genes involved in the JAK/STAT signalling pathway and also other sets of genes. However, the gene expression profiles were not identical, suggesting that both the tyrosine kinase containing gene and the partner gene would affect the transcription of downstream target genes.	Co-expression
GDS4047	Effective Targeting of Quiescent Chronic Myelogenous Leukemia Stem Cells by Histone Deacetylase Inhibitors in Combination with Imatinib Mesylate	We investigated the ability of HDAC inhibitors (HDACi) to target CML stem cells. Treatment with HDACi combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACi with IM markedly diminished LSC in a transgenic mouse model of CML. The interaction of IM and HDACi inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents a novel and effective strategy to target LSC in CML patients receiving tyrosine kinase inhibitors.	Co-expression
GDS4051	High-throughput ectopic expression screen for tamoxifen resistance	Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.	Co-expression
GDS4052	Genomic Collaboration of Estrogen Receptor-α and ERK2 in Regulating Gene and Proliferation Programs	The nuclear hormone receptor, estrogen receptor-alpha (ERα), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ERα activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ERα colocalization at chromatin binding sites across the genome of breast cancer cells. KEYWORDS: siRNA knock-down, ligand treatment	Co-expression
GDS4053	Gene expression data in estrogen receptor alpha positive breast tumors with and without PIK3CA mutations.	PI3K/AKT pathway plays one of pivotal roles in breast cancer development and maintenance. PIK3CA, coding PIK3 catalytic subunit, is the oncogene which shows the high frequency of gain-of-function mutations leading to the PI3K/AKT pathway activation in breast cancer. In particular in the ERα-positive breast tumors PIK3CA mutations have been observed in 30% to 40%. However, genes expressed in connection to the pathway activation in breast tumorigenesis remain largely unknown. To identify downstream relevant target genes (and signaling pathways) turned on by the aberrant PI3K/AKT signal in breast tumors, we analyzed gene expression by pangenomic oligonucleotide microarray in a series of 43 ERα-positive tumors with and without PIK3CA mutations.	Co-expression
GDS4054	Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells	Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment.	Co-expression
GDS4055	Fibroblast triggered gene expression in tumor	Personalized biological insights into heterogeneous tumors, such as breast cancer could improve clinical management. While genomic analysis has contributed significantly towards dissecting breast cancer heterogeneity, limitations in clinical application are partly rooted in the inter-tumor variability arising from a largely uncharacterized interactive exchange between diverse cell types in the tumor microenvironment. Here we first identified a common response signature to stromal coculture across breast cancer of varying clinicopathologic phenotypes. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probe sets, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). Prominent features of tumor cell response included transcript repression related to biofunctions encompassing inflammatory signaling, cell movement, cell death, and cell growth and proliferation. In an evaluation of intertumor heterogeneity, the FTExT classifier stratified moderate and high histopathologic grade breast cancer according to clinical outcome (dataset 1, n=401, p=0.031; dataset 2, n=200, p=0.013), delineating a novel phenotype of stromal crosstalk underlying the prognostic potential of tumor grade. Extending correlative data through functional analysis of stromal-epithelial cocultures of both malignant and nonmalignant derivation, significant differences in cell cycle regulation, rate of proliferation, resistance to therapy-induced apoptosis, and growth arrest were observed in FTExT-based subgroups. Instead of a stromal impact that is uniformly cancer promoting, our data demonstrate striking variability in tumor cell response that directly contributes to contrasting functional aggressiveness of malignant breast tissue. Our findings uniquely reveal dynamically interacting paracrine components underlying the molecular and functional heterogeneity of breast cancer, thus presenting novel opportunities for tumor targeting.	Co-expression
GDS4056	Expression data from breast cancer FNA biopsies from patients (US samples)	This is Phase II Trial of 4courses of 5-fluorouracil, doxorubicin and cyclophosphamide follwed by 4 additional courses of weekly docetaxel and capecitabine administered as Preoperative Therapy for Patients with Locally Advanced Breast Cancer, Stages II and III by US oncology (PROTOCOL 02-103) We performed gene set analysis (GSA) using functionally annotated gene sets corresponding to almost all known biological processes in ER-positive/HER2negative and ER-negative/HER2-negative breast cancer, respectively.	Co-expression
GDS4057	Expression data from breast cancer FNA biopsies from patients	We assess if distinct biological processes might be associated with chemotherapy sensitivity in the different clinical subsets of breast cancers. We performed gene set analysis (GSA) using functionally annotated gene sets corresponding to almost all known biological processes in ER-positive/HER2negative and ER-negative/HER2-negative breast cancer, respectively.	Co-expression
GDS4059	Expression data of MCF-7 cells treated with gamma tocotrienol (g-T3)	Gamma tocotrienol induces apoptosis in breast cancer cells however, the molecular mechanisms are not completely understood. We used microarrays to detail the global programme of gene expression underlying the effects of gamma tocotrienols on MCF-7 cells and identified distinct classes of up-regulated genes during this process.	Co-expression
GDS4061	Expression data from MCF7 cell line after silencing of Estrogen receptor	We propose the hypothesis that loss of estrogen receptor function which leads to endocrine resistance in breast cancer, also results in de-differentiation from an epithelial to a mesenchymal phenotype that is responsible for increased aggressiveness and metastatic propensity. siRNA mediated silencing of the estrogen receptor in MCF7 breast cancer cells resulted in estrogen/tamoxifen resistant cells (pII) with altered morphology, increased motility with rearrangement and switch from an actin to a vimentin based cytoskeleton, and ability to invade simulated components of the extracellular matrix. Phenotypic profiling using an Affymetrix Human Genome U133 plus 2.0 GeneChip indicated fold changes ≥ 3 in approximately 2500 identifiable unique sequences, with about 1270 of these being up-regulated in pII cells. Changes were associated with genes whose products are involved in cell motility, loss of cellular adhesion and interaction with the extracellular matrix. Selective analysis of the data also showed a shift from luminal to basal cell markers and increased expression of a wide spectrum of genes normally associated with mesenchymal characteristics, with consequent loss of epithelial specific markers. Over-expression of several peptide growth factors and their receptors are indicative of an increased contribution to the higher proliferative rates of pII cells as well as aiding their potential for metastatic activity. Signalling molecules that have been identified as key transcriptional drivers of epithelial to mesenchymal transition were also found to be elevated in pII cells. We suggest that these data support our hypothesis that induced loss of estrogen receptor in previously antiestrogen sensitive cells is a trigger for the concomitant loss of endocrine dependence and onset of a series of possibly parallel events that changes the cell from an epithelial to a mesenchymal type. Inhibition of this transition through targeting of specific mediators may be a useful supplementary strategy to circumvent the effects of loss of endocrine sensitivity. We used microarrays to detail the global programme of gene expression underlying Epithelial to mesenchymal transition and identified distinct classes of regulated genes during this process.	Co-expression
GDS4063	Expression data from MCF-7 cells stimulated by Estrogen or IGF-I	Although estrogen receptor (ER) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of gene transcription, remains poorly understood.  We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr.  IGF-I regulated mRNA of 5-10-fold more genes than estradiol, and many genes were co-regulated by both ligands.  Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer.  Closer examination revealed enrichment of repressed transcripts.  Interestingly, a number of potential tumor suppressors were down-regulated by IGF-I and estradiol.  In fact, BLNK, one of the top repressed genes, is a potential growth suppressor in breast cancer cells.  Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ER.  However, repression by IGF-I or estradiol required common downstream kinases.  In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome.  There is enrichment of repressed transcripts, and the down-regulation is independent at the receptor level.  This may be important clinically, as tumors with active ER and IGF-IR signaling may require co-targeting of both pathways. KEYWORDS: multiple group comparison	Co-expression
GDS4065	Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor α1 apoprotein	Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor α1 apoprotein. Basal proliferation persisted in estrogen-sensitive breast cancer cells grown in hormone depleted conditioned media without or with 4-hydroxytamoxifen (OH-Tam). Downregulating ER using siRNA  inhibited basal proliferation by promoting cell cycle arrest. The basal expression of RARα1, the only RARα isoform that was expressed in breast cancer cell lines and in most breast tumors, was supported by apo-ER but was unaffected by OH-Tam. The overlapping tamoxifen-insensitive gene regulation by apo-ER and apo-RARα1 comprised activation of mainly genes promoting cell cycle and mitosis and suppression of genes involved in growth inhibition.	Co-expression
GDS4066	Tissue Specific Pathways for Estrogen Regulation of Ovarian Cancer Growth and Metastasis	Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER- and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM.	Co-expression
GDS4067	Isolation and characterization of a metastatic hybrid cell line generated by ER negative and ER positive breast cancer cells in mouse bone marrow	The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other’s metastatic behavior.	Co-expression
GDS4069	FZD7 Plays a Critical Role in Triple Negative Breast Cancer Proliferation	Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of beta-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer.	Co-expression
GDS4070	Pin1/mutant-p53 jointly controlled genes	To investigate the specific gene expression program by which mutant-p53 and Pin1 control invasion and metastasis in breast cancer cells, we compared the transcriptomic profile of control,  mutant-p53 depleted or Pin1 depleted MDA-MB-231 cells.	Co-expression
GDS4071	Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells	TGFβ is known to be a potent inducer of EMT, a process involved in tumor invasion. TIF1γ has been reported to participate to TGFβ signaling. In order to understand the role of TIF1γ in TGFβ signaling and its requirement for EMT, we analyzed the TGFβ1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGFβ1 treatment, whereas Smad4 inactivation completely blocked this process. In support of these observations, microarray data show that the functions of several TIF1γ target genes can be linked to EMT. As a negative regulator of Smad4, TIF1γ could be critical for the regulation of TGFβ signaling. This work highlights the molecular relationship between TIF1γ and Smad4 in TGFβ1 signaling and EMT.	Co-expression
GDS4074	Expression data from zinc-finger-transcription-factor-induced Fulvestrant-Resistant MCF7 Cell Lines	Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance.  Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype.  Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent.  We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype.  Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients.	Co-expression
GDS4078	Paclitaxel resistant MDA-MB-231 Cells and resensitization with bexarotene treatment	Acquired drug resistance represents a major challenge in chemo-therapy treatment for various types of cancers.  We have found that the retinoid X receptor–selective agonist bexarotene (LGD1069, Targretin) was efficacious in treating chemo-resistant cancer cells. The goal of this microarray study was to understand the mechanism of bexarotene’s role in overcoming acquired drug resistance using human breast cancer cells MDA-MB-231 as a model system and paclitaxel as model compound.  After MDA-MB-231 cells were repeatedly treated with paclitaxel for 8 cycles with each cycle including a 3-day treatment with 30 nM paclitaxel and followed by a 7-day exposure to control medium, MDA cells resistant to paclitaxel were developed and their growth was no longer inhibited by paclitaxel treatment.  Those MDA cells with acquired drug resistance, when treated with paclitaxel and bexarotene in combination, could regain their sensitivity and their growth were again inhibited.  Therefore, RNA samples from parental MDA-MB-231 cells, paclitaxel-resistant MDA cells treated with vehicle, paclitaxel alone or in combination with bexarotene, were used for perform global gene expression profiling with Affymetrix HG-U133A gene chips.  Keywords: Drug Treatment	Co-expression
GDS4079	Comparison of WAT CD34+ vs LAF CD34+	A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects.	Co-expression
GDS4080	GATA3 Reprograms Basal Breast Cancer Cells towards a Luminal Subtype and Inhibits Metastases through Suppression of Lysyl Oxidase	The transcription factor GATA3 is essential for luminal cell differentiation during mammary gland development and critical for formation of the luminal subtypes of breast cancer. Ectopic expression of GATA3 promoted global alterations of the transcriptome of basal triple-negative breast cancer cells resulting in molecular and cellular changes associated with a more differentiated, luminal tumor subtype and a concomitant reduction in primary tumor growth, lung metastasis, and macrophage recruitment at the metastatic site.  Importantly, we demonstrate that the inhibition of metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix protein that affects cell proliferation, cross-linking of extracellular collagen types, and establishment of the metastatic niche.	Co-expression
GDS4082	Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer	Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer.  NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer.  However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy.  A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer.  The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006).  In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated.	Co-expression
GDS4083	BT474 and BT474-J4 microarray data	These data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line.	Co-expression
GDS4084	Prolonged Drug Selection of Breast Cancer Cells and Enrichment of Cancer Stem Cell Characteristics.	Background: Cancer stem cells are presumed to have virtually unlimited proliferative and self-renewal abilities and to be highly resistant to chemotherapy, a feature that is associated with overexpression of ATP-binding cassette transporters. We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem-like cells. Methods: Cancer stem cells were defined as CD44+/CD24– cells that could self-renew (ie, generate cells with the tumorigenic CD44+/CD24– phenotype), differentiate, invade, and form tumors in vivo. We used doxorubicin-selected MCF-7/ADR cells, weakly tumorigenic parental MCF-7 cells, and MCF-7/MDR, an MCF-7 subline with forced expression of ABCB1 protein. Cells were examined for cell surface markers and side-population fractions by microarray and flow cytometry, with in vitro invasion assays, and for ability to form mammospheres. Xenograft tumors were generated in mice to examine tumorigenicity (n = 52). The mRNA expression of multidrug resistance genes was examined in putative cancer stem cells and pathway analysis of statistically significantly differentially expressed genes was performed. All statistical tests were two-sided. Results: Pathway analysis showed that MCF-7/ADR cells express mRNAs from ABCB1 and other genes also found in breast cancer stem cells (eg, CD44, TGFB1, and SNAI1). MCF-7/ADR cells were highly invasive, formed mammospheres, and were tumorigenic in mice. In contrast to parental MCF-7 cells, more than 30% of MCF-7/ADR cells had a CD44+/CD24– phenotype, could self-renew, and differentiate (ie, produce CD44+/CD24– and CD44+/CD24+ cells), and overexpressed various multidrug resistance-linked genes (including ABCB1, CCNE1, and MMP9). MCF-7/ADR cells were statistically significantly more invasive in Matrigel than parental MCF-7 cells (MCF-7 cells = 0.82 cell per field and MCF-7/ADR = 7.51 cells per field, difference = 6.69 cells per field, 95% confidence interval = 4.82 to 8.55 cells per field, P<.001). No enrichment in the CD44+/CD24– or CD133+ population was detected in MCF-7/MDR. Conclusion: The cell population with cancer stem cell characteristics increased after prolonged continuous selection for doxorubicin resistance.	Co-expression
GDS4085	Two types of estrogen receptor-positive (ER+) and -negative (ER-) breast cancer will be compared with glycan structure analyses	ER+ve and ER-ve breast cancers tend to show different patterns of metastasis, with ER+ve tumours having a propensity to metastasize to the bone while ER-ve tumours tend to induce visceral metastasis. Glycans can play an important role in metastasis through their interactions with glycan binding proteins. Moreover we, and others have also shown that expression of particular tumor-associated glycoforms of the mucin MUC1, allows it to interact with lectins of the immune system. We now have data showing differences in the level of expression of some glycosyltransferases in ER+ve and ER-ve of breast cancer suggesting the expression of different O-linked glycoforms.	Co-expression
GDS4088	Study for evaluating the effect of cold ischemic time and RNA stabilization method on RNA integrity and gene expression measurements	Time series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision. A different 2x2 factorial within this study evaluated the effect of stabilization method (RNAlater vs snap freezing) and stablization delay (0 and 40 min) at room temperature.	Co-expression
GDS4089	Proteasome inhibition blocks estrogen-dependent gene transcription by decreasing histone H2B monoubiquitination in human breast cancer cells	The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription.	Co-expression
GDS4090	Estrogen-dependent gene expression in human breast cancer cells relies upon proteosome-dependent monoubiquitination of histone H2B	The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription.	Co-expression
GDS4091	Expression profiles of CD24-/CD44+/ESA+ population in MDA-MB-231 and its highly metastatic variants.	Breast cancer is a curable disease if it is diagnosed at an early stage.  However, only little options are left once the tumor is metastasized to distant organs, and more than 90% of breast cancer death is attributed to metastatic disease.  The process of metastasis is highly complex and involves many steps for successful colonization of tumor cells at a target organ.  According to the cancer stem cell (CSC) theory, which still remains a hypothesis, these metastatic cells must have stem cell-like capability for their self-renewal in addition to their invasive ability. Therefore, it has been predicted that a “metastatic stem cell”, which is distinct from a cancer stem cell, must exist in the primary tumor mass. To identify genes that are involved in metastasis of CSCs, we isolated CSC populations from a well-established model cell line of breast cancer, MDA-MB231, and that of highly metastatic variants, 231BoM-1833 and 231BrM-2a, using CD24, CD44 and EpCAM (ESA), which have been identified as surface markers for CSCs in breast cancers. Overall yield of CSCs from these cells ranged from 2% to 4%. We then performed global expression profile analysis for these CSCs using the Affymetrix Human Gene 1.0ST array.	Co-expression
GDS4092	CHAC1 mRNA expression is a strong prognostic biomarker in breast and ovarian cancer	Extracellular, cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology.	Co-expression
GDS4093	A phase II neoadjuvant trial of anastrozole (A), fulvestrant (F) and gefitinib (I - iressa) in patients with newly diagnosed estrogen receptor positive breast cancer	Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks.  After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.	Co-expression
GDS4095	SRC1 gene regulation in endocrine resistant breast cancer cells	The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid independent tumour.  The p160 steroid coactivator protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors drives this tumour adaptability.  Here, using discovery studies we identify ADAM22, a non-protease member of the ADAMs family, as a direct target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression.  ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer.	Co-expression
GDS4096	Mutant p53 Disrupts Mammary Acinar Morphogenesis via the Mevalonate Pathway	p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis.  To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures.  We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53.  Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors.  Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53.	Co-expression
GDS4100	Multiple Salivary Biomarkers for Early Detection of Pancreatic Cancer	Pancreatic cancer is the fourth leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. Oral fluid (saliva) meets the demand for non-invasive, accessible, and highly efficient diagnostic medium. The level of salivary analytes, such as mRNA and microflora, vary upon disease onset; thus possess valuable signatures for early detection and screening. In this study, we evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for non-invasive detection of early pancreatic cancer. Two biomarker discovery technologies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 early pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. Importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This study comprehensively compared the salivary transcriptome and microflora between pancreatic cancer and control subjects. We have discovered and validated eleven mRNA biomarkers and two microbial biomarkers for early detection of pancreatic cancer in saliva. The logistic regression model with four salivary biomarkers can detect pancreatic cancer specifically without the complication of chronic pancreatitis. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer.  Keywords: Salivary biomarker, pancreatic cancer, early detection, salivary transcriptome, salivary microflora	Co-expression
GDS4101	Targetting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or siRNA	CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer.	Co-expression
GDS4102	Expression data from Mayo Clinic Pancreatic Tumor and Normal samples	We used microarrays to identify the expression differences of FKBP5 gene between the pancreatic tumor and normal samples.On average normal samples had more FKBP5 expression compared to tumor samples	Co-expression
GDS4103	Whole-Tissue Gene Expression Study of Pancreatic Ductal Adenocarcinoma	Expression analysis of 36 pancreatic ductal adenocarcinoma tumors and matching normal pancreatic tissue samples from pancreatic cancer patients of the Clinical Institute Fundeni (ICF) using Affymetrix U133 Plus 2.0 whole-genome chips.	Co-expression
GDS4104	Microarray analysis of skeletal muscle hypertrophy induced by heat-stress in healthy humans	This study was aimed at examining the effects of long-term of heat-stress on the gene expression of skeletal muscle hypertrophy. Heat- and stream-generating (HSG) sheets were placed on thigh laterally. The HSG sheets (heat-stress) were applied 8-hrs/day, once a day, 4 days/weeks, for 10 weeks. A muscle biopsy was taken from the vastus lateralis muscle (2 cm depth) of the treated leg before and after the experiment. Oligonucleotide microarray revealed that genes related to ATP-synthesis, protein synthesis and the molecular chaperonic activity were increased by heat stress. These results suggest that heat-stress might be a useful countermeasure for muscular atrophy during aging. 	Co-expression
GDS4105	Novel treatment of human pancreatic cancer using masitinib combined with standard gemcitabine chemotherapy	Masitinib is a tyrosine kinase inhibitor of c-Kit, PDGFRα and β, and to some extent Lyn of the Src kinase family. We evaluated the therapeutic potential of masitinib in vitro on human pancreatic tumour cell lines and in vivo in a mouse model of human pancreatic cancer.	Co-expression
GDS4106	Expression data from TGF-beta treated Panc-1 pancreatic adenocarcinoma cell line	TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques.	Co-expression
GDS4107	Identification of EP4 as a Potential Target for the Treatment of Castration-Resistant Prostate Cancer Using a Novel Xenograft Model	More effective therapeutic approaches for castration-resistant prostate cancer (CRPC) are urgently needed, thus reinforcing the need to understand how prostate tumors progress to castration resistance. We have established a novel mouse xenograft model of prostate cancer, KUCaP-2, which expresses the wild-type androgen receptor (AR) and which produces the prostate-specific antigen (PSA). In this model, tumors regress soon after castration, but then reproducibly restore their ability to proliferate after 1 to 2 months without AR mutation, mimicking the clinical behavior of CRPC. In the present study, we used this model to identify novel therapeutic targets for CRPC. Evaluating tumor tissues at various stages by gene expression profiling, we discovered that the prostaglandin E receptor EP4 subtype (EP4) was significantly upregulated during progression to castration resistance. Immunohistochemical results of human prostate cancer tissues confirmed that EP4 expression was higher in CRPC compared with hormone-naïve prostate cancer. Ectopic overexpression of EP4 in LNCaP cells (LNCaP-EP4 cells) drove proliferation and PSA production in the absence of androgen supplementation in vitro and in vivo. Androgen-independent proliferation of LNCaP-EP4 cells was suppressed when AR expression was attenuated by RNA interference. Treatment of LNCaP-EP4 cells with a specific EP4 antagonist, ONO-AE3-208, decreased intracellular cyclic AMP levels, suppressed PSA production in vitro, and inhibited castration-resistant growth of LNCaP-EP4 or KUCaP-2 tumors in vivo. Our findings reveal that EP4 overexpression, via AR activation, supports an important mechanism for castration-resistant progression of prostate cancer. Furthermore, they prompt further evaluation of EP4 antagonists as a novel therapeutic modality to treat CRPC.	Co-expression
GDS4109	Optimizing molecular signatures for prostate cancer recurrence	The derivation of molecular signatures indicative of disease status and predictive of subsequent behavior could facilitate the optimal choice of treatment for prostate cancer patients. In this study, we conducted a computational analysis of gene expression profile data obtained from 79 cases, 39 of which were classified as having disease recurrence, to investigate whether advanced computational algorithms can derive more accurate prognostic signatures for prostate cancer.  At the 90% sensitivity level, a newly derived prognostic genetic signature achieved 85% specificity. This is the first reported genetic signature to outperform a clinically used postoperative nomogram. Furthermore, a hybrid prognostic signature derived by combination of the nomogram and gene expression data significantly outperformed both genetic and clinical signatures, and achieved a specificity of 95%.  Our study demonstrates the feasibility of utilizing gene expression information for highly accurate prostate cancer prognosis beyond the current clinical systems, and shows that more advanced computational modeling of tissue-derived microarray data is warranted before clinical application of molecular signatures is considered.	Co-expression
GDS4110	Normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed	Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as  MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family  transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play  key roles  in inducing malignancy via20q amplification.	Co-expression
GDS4113	Hormone-Independence of Prostate Cancer Cells is Supported by the Androgen Receptor without Binding to Classical Response Elements	Treatment of late passage (LP50) LNCaP cells with R1881 (androgen) and AR shRNA identified a gene program controlled by androgen receptor in the absence of androgen.	Co-expression
GDS4114	Stromal molecular signatures of breast and prostate cancer	Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.	Co-expression
GDS412	Amyotrophic lateral sclerosis (Lou Gehrig's Disease)	Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Attempt to identify mechanisms by which ALS destroys motor neurons.	Co-expression
GDS4120	The effect of androgen deprivation on human prostate xenograft tumor LuCaP35	Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration.	Co-expression
GDS4121	Expression data of HGF/cMET pathway in prostate cancer DU145 cell line	DU145 prostate cancer cells were treated with 25 ng/ml hepatocyte growth factor (HGF) or vehicle for 2, 8, or 24 hours. HGF stimulates the cMET protein, a tyrosine kinase transmembrane protein. The aim of this study is to determine the role of the HGF/cMET pathway in immature cells of established prostate cancer. HGF stimulation of DU145 prostate cancer cell line led to cell migration in culture, formation of sprouts in Matrigel and inhibition of growth. These biological effects went together with induction of a stem-like phenotype as defined by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 on gene-expression arrays and quantitative PCR. The shift towards a stem-like phenotype was reflected by protein modifications on FACS, Western blot, and enhanced rapid adhesion to collagen I. Small molecules SU11274 and PHA665752 were able to inhibit both morphologic and molecular HGF effects.	Co-expression
GDS4123	Genome-wide analysis of gene expression in isoflavone and 3,3’-diindolylmethane treated C4-2B prostate cancer cells	Expression profiling of isoflavone and 3,3’-diindolylmethane treated C4-2B prostate cancer cells was conducted using Affymetrix Human Genome U133 Plus 2.0. Array	Co-expression
GDS4124	Reprogramming of prostate cancer-associated stromal cells	CD90+ prostate cancer-associated (CP) stromal cells represent a disease cell type found only in tumor tissue. Genetic reprogramming by induced pluripotent stem (iPS) cell technology might be used to “normal gene expression of diseased cells thereby providing a cure. The resultant iPS cells would no longer express the disease program, and, like stem cells, might respond to normal differentiative signaling. Thus, CP stromal cells, isolated from tumor tissue and cultured in vitro, were transfected with POU5F1/LIN28/NANOG/SOX2 lentiviral vectors. iPS cells were obtained at a frequency of 10^4. Transcriptome analysis showed an almost complete match in gene expression between the iPS cells and human embryonic stem cells. Genes of CP stromal cells were fully inactivated.	Co-expression
GDS4128	Gene expression data from temporal cortex of young adult, old and AD-like Microcebus murinus	Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented b-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group.  Functional categorization showed that most of the genes that were up-regulated in healthy old and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates.	Co-expression
GDS4129	Expression levels in immortalized B cells from unrelated individuals and twins undergoing ER stress	The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in the condition called “ER stress” which induces the unfolded protein response (UPR) which is a complex cellular process that includes changes in expression of many genes. Failure to restore homeostasis in the ER is associated with human diseases. To identify the underlying changes in gene expression in response to ER stress, we induced ER stress in human B-cells and then measured gene expression at 10 time-points. We followed up those results by studying cells from 60 unrelated people. We rediscovered genes that were known to play a role in ER stress response and uncovered several thousand genes that are not known to be involved. Two of these are VLDLR and INHBE which showed significant increase in expression following ER stress in B-cells and in primary fibroblasts. To study the links between unfolded protein response and disease susceptibility, we identified ER stress responsive genes that are associated with human diseases and assessed individual differences in ER stress response. Many of the UPR genes are associated with Mendelian disorders such as Wolfram syndrome and complex human diseases including amyotrophic lateral sclerosis and diabetes. Data from two independent samples showed extensive individual variability in ER stress response. Additional analyses with monozygotic twins revealed significant correlations within twin pairs in their responses to ER stress thus showing evidence for heritable variation among individuals. These results have implications for basic understanding of ER function and its role in disease susceptibility.   Keywords: array-based gene expression	Co-expression
GDS4130	Expression levels in immortalized B cells from unrelated individuals and twins undergoing ER stress	The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in the condition called “ER stress” which induces the unfolded protein response (UPR) which is a complex cellular process that includes changes in expression of many genes. Failure to restore homeostasis in the ER is associated with human diseases. To identify the underlying changes in gene expression in response to ER stress, we induced ER stress in human B-cells and then measured gene expression at 10 time-points. We followed up those results by studying cells from 60 unrelated people. We rediscovered genes that were known to play a role in ER stress response and uncovered several thousand genes that are not known to be involved. Two of these are VLDLR and INHBE which showed significant increase in expression following ER stress in B-cells and in primary fibroblasts. To study the links between unfolded protein response and disease susceptibility, we identified ER stress responsive genes that are associated with human diseases and assessed individual differences in ER stress response. Many of the UPR genes are associated with Mendelian disorders such as Wolfram syndrome and complex human diseases including amyotrophic lateral sclerosis and diabetes. Data from two independent samples showed extensive individual variability in ER stress response. Additional analyses with monozygotic twins revealed significant correlations within twin pairs in their responses to ER stress thus showing evidence for heritable variation among individuals. These results have implications for basic understanding of ER function and its role in disease susceptibility.   Keywords: array-based gene expression	Co-expression
GDS4132	Gene expression profiling in skeletal muscle of PCOS after pioglitazone therapy	Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity.  Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp. Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy control women. Treatment with pioglitazone improved insulin-stimulated total, oxidative and non-oxidative glucose metabolism, and reduced fasting serum insulin (all p < 0.05). Global pathway analysis using Gene Map Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome complexes in PCOS patients after pioglitazone therapy. Quantitative real-time PCR suggested that upregulation of OXPHOS genes was mediated by an increase in PGC-1α expression (p < 0.05). Expression of genes involved in ribosomal proteins and OXPHOS was down-regulated in PCOS patients before treatment compared to matched healthy women using GenMAPP 2.1 and GSEA 2.1. These data indicate that pioglitazone therapy restores insulin sensitivity in part by a coordinated upregulation of genes involved in mitochondrial oxidative metabolism and protein biosynthesis in skeletal muscle of PCOS. These transcriptional effects of pioglitazone therapy may contribute to prevent the onset of type 2 diabetes in these women. Keywords: PCOS, microarray, global pathway analysis, insulin resistance, pioglitazone, protein metabolism, mitochondrial oxidative metabolism	Co-expression
GDS4133	Gene expression profiling in skeletal muscle of PCOS after pioglitazone therapy	Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity.  Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp. Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy control women. Treatment with pioglitazone improved insulin-stimulated total, oxidative and non-oxidative glucose metabolism, and reduced fasting serum insulin (all p < 0.05). Global pathway analysis using Gene Map Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome complexes in PCOS patients after pioglitazone therapy. Quantitative real-time PCR suggested that upregulation of OXPHOS genes was mediated by an increase in PGC-1α expression (p < 0.05). Expression of genes involved in ribosomal proteins and OXPHOS was down-regulated in PCOS patients before treatment compared to matched healthy women using GenMAPP 2.1 and GSEA 2.1. These data indicate that pioglitazone therapy restores insulin sensitivity in part by a coordinated upregulation of genes involved in mitochondrial oxidative metabolism and protein biosynthesis in skeletal muscle of PCOS. These transcriptional effects of pioglitazone therapy may contribute to prevent the onset of type 2 diabetes in these women. Keywords: PCOS, microarray, global pathway analysis, insulin resistance, pioglitazone, protein metabolism, mitochondrial oxidative metabolism	Co-expression
GDS4135	Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype	Astrocyte dysfunction impacts their normal function, including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology. The aim of the present study was to combine immuno-LCM and microarray analysis to characterise the astrocyte transcriptome at different Braak stages, and with respect to ApoE genotype, in post-mortem human temporal cortex sampled dervied from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS).	Co-expression
GDS4136	Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer’s disease	Alzheimer's disease (AD) is a devastating neurodegenerative disorder that threatens to reach epidemic proportions as our population ages. Although much research has examined molecular pathways associated with AD, relatively few studies have focused on critical early stages. Our prior microarray study correlated gene expression in human hippocampus with AD markers. Results suggested a new model of early-stage AD in which pathology spreads along myelinated axons, orchestrated by upregulated transcription and epigenetic factors related to growth and tumor suppression (Blalock et al., 2004). However, the microarray analyses were performed on RNA from fresh frozen hippocampal tissue blocks containing both gray and white matter, potentially obscuring region-specific changes. In the present study, we used laser capture microdissection to exclude major white matter tracts and selectively collect CA1 hippocampal gray matter from formalin-fixed, paraffin-embedded (FFPE) hippoc ampal sections of the same subjects assessed in our prior study. Microarray analyses of this gray matter-enriched tissue revealed many correlations similar to those seen in our prior study, particularly for neuron-related genes. Nonetheless, in the laser-captured tissue, we found a striking paucity of the AD-associated epigenetic and transcription factor genes that had been strongly overrepresented in the prior tissue block study. In addition, we identified novel pathway alterations that may have considerable mechanistic implications, including downregulation of genes stabilizing ryanodine receptor Ca2+ release and upregulation of vascular development genes. We conclude that FFPE tissue can be a reliable resource for microarray studies, that upregulation of growth-related epigenetic/ transcription factors with incipient AD is predominantly localized to white matter, further supporting our prior findings and model, and that alterations in vascular and ryanodine receptor-relat ed pathways in gray matter are closely associated with incipient AD.	Co-expression
GDS4137	Gene expression profile of DAP12 knockdown THP-1 cells following exposure to phorbol 12-myristate 13-acetate 	Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA (siRNA) targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD. We found that both DAP12 knockdown and control clones were capable of equally responding to phorbol 12-myristate 13-acetate (PMA), a known inducer of morphological differentiation of THP-1 cells, by exhibiting almost similar gene expression profiles between both, following a 24-hour exposure to 50 nM PMA.	Co-expression
GDS4141	Gene expression profiles of familial Alzheimer's disease with presenilin 2 mutation patient-specific induced pluripotent stem cells	We established two clones of induced pluripotent stem cells (iPSC) with the presenilin 2 mutation, N141 (PS2-1 iPSC and PS2-2 iPSC) by retroviral transduction of primary human fibroblasts. To show the similarity among  201B7 iPSC, PD01-25 iPSC(Sporadic Parkinson's disease patient derived iPSC), PS2-1 iPSC, PS2-2 iPSC, this experiment was designed.	Co-expression
GDS4142	Microarray expression analysis of PRF1 (perforin 1) haplotypes in patients with primary progressive multiple sclerosis	A genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes.	Co-expression
GDS4145	Expression data of multiple sclerosis patients receiving subcutaneous Interferon-beta-1b therapy [U133 A and B]	The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 µg every other day) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 25 MS patients within the first two years of IFN-beta administration.	Co-expression
GDS4146	Expression data of multiple sclerosis patients receiving subcutaneous Interferon-beta-1b therapy [U133 A and B]	The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 µg every other day) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 25 MS patients within the first two years of IFN-beta administration.	Co-expression
GDS4147	Search for specific biomarkers of IFN-beta bioactivity in patients with MS	We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.	Co-expression
GDS4150	Gene expression profile in CD4+ and CD8+ T cells from identical twins discordant for Multiple sclerosis	To gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS. We studied 4 monozygotic twin pairs discordant for disease, with the affected co-twin free of disease modifying therapies (F/M = 3/1, mean age 36.25±3.9). Following leukapheresis, CD4+ and CD8+ T cells were separated and studied by Affymetrix GeneChip®	Co-expression
GDS4151	Non-phosphorylated FTY720 induces apoptosis of human microglia by activating SREBP2	A synthetic analog of sphingosine named FTY720 (Fingolimod), phosphorylated by sphingosine kinase-2, interacts with sphingosine-1-phosphate (S1P) receptors expressed on various cells. FTY720 suppresses the disease activity of multiple sclerosis (MS) chiefly by inhibiting S1P-dependent egress of autoreactive T lymphocytes from secondary lymphoid organs, and possibly by exerting anti-inflammmatory and neuroprotective effects directly on brain cells. However, at present, biological effects of FTY720 on human microglia are largely unknown. We studied FTY720-mediated apoptosis of a human microglia cell line HMO6. The exposure of HMO6 cells to non-phosphorylated FTY720 (FTY720-non-P) induced apoptosis in a dose-dependent manner with IC50 of 10.6±2.0 microM, accompanied by the cleavage of caspase-7 and caspase-3 but not of caspase-9. The apoptosis was inhibited by Z-DQMD-FMK, a caspase-3 inhibitor, but not by Pertussis toxin, a Gi protein inhibitor, suramin, a S1P3/S1P5 inhibitor, or W123, a S1P1 competitive antagonist, although HMO6 expressed S1P1, S1P2, and S1P3. Furthermore, both phosphorylated FTY720 (FTY720-P) and SEW2871, a S1P1 selective agonist did not induce apoptosis of HMO6. Genome-wide gene expression profiling and molecular network analysis indicated activation of transcriptional regulation by sterol regulatory element-binding protein (SREBP) in FTY720-non-P-treated HMO6 cells. Western blot verified activation of SREBP2 in these cells, and apoptosis was enhanced by pretreatment with simvastatin, an activator of SREBP2, and by overexpression of the N-terminal fragment of SREBP2. These observations suggest that FTY720-non-P-induced apoptosis of HMO6 human microglia is independent of S1P receptor binding, and positively regulated by the SREBP2-dependent proapoptotic signaling pathway.	Co-expression
GDS4152	Sema4A, a novel serum marker of multiple sclerosis, implicates Th17 pathology and efficacy of interferon-β.	Background: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system and the leading cause of lasting neurological disabilities in young adults. Increasing evidence suggests that early treatment prevents the development of disability. However, there have been no reliable serum markers to assist the early diagnosis. In addition, interferon (IFN)-β, which is the major treatment for MS, is not always effective. Therefore, the development of simple serological test to help the early diagnosis and predict responsiveness to IFN-β is of clinical importance. On the other hand, a transmembrane-type semaphorin, Sema4A, has been implicated in experimental autoimmune encephalomyelitis (EAE) by regulating helper T (Th) cell differentiation. Thus, we aimed to identify the implications of Sema4A in diagnosis and pathogenesis of MS. Methods: We assayed serum Sema4A in 59 patients with relapsing-remitting MS (RRMS), 22 patients with clinically isolated syndrome (CIS) and 126 patients with other neurological diseases (OND) by developing a sandwich ELISA. To identify a source of soluble Sema4A and characteristics of MS patients with high levels of Sema4A, we analyzed peripheral blood mononuclear cells (PBMCs) from MS patients and healthy controls by flow cytometry (FACS) and gene chip analysis. The effect of Sema4A was examined in vitro and in vivo using an EAE model. Findings: Sema4A was significantly increased in sera of patients with MS and CIS compared to controls. Sema4A expression was increased on the surface of DCs in MS patients and shed from these cells in a metalloproteinase-dependent manner, affecting the Th17skewing. In addition, patients with high Sema4A levels exhibited more severe disabilities, and IFN-β treatment was not beneficial to those patients. Interpretation: Measuring Sema4A is a practical laboratory test to help diagnose MS and to predict responsiveness to IFN-β therapy.  Microarray analysis showed that metalloproteinases such as ADAM 10 and MMPs 1, 3, 9, 12 and 25, which are reported to be involved in the pathogenesis of MS, were increased in PBMCs from MS patients with high Sema4A levels compared to those with low Sema4A and healthy controls. However, ADAM 17 and MMP 2 and 7 did not correlate with Sema4A levels. Taken together, these findings strongly suggest that Sema4A, abundantly expressed on monocytes and DCs in MS patients, is enzymatically cleaved and shed in a portion of the patients, which contributes to the high soluble Sema4A detected by the ELISA.	Co-expression
GDS4154	Imaging-guided microarray: Identifies molecular markers in the pathogenesis of Parkinson’s disease	The full complement of molecular pathways contributing to Parkinson’s disease (PD) pathogenesis remains unknown.  Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1).  Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport.   Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing α-synuclein.  DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology.  Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified.  Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis. 	Co-expression
GDS4156	Expression data from Parkinson's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative	A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent.	Co-expression
GDS4158	Expression data from LNCap cell line treated with COP1 (RFWD2), ETV1, and JUN siRNAs	The proto-oncogenes ETV1, ETV4, and ETV5 encode members of the E26 transformation-specific (ETS) transcription factor family, which includes the most frequently rearranged and overexpressed genes in prostate cancer.  Despite being critical regulators of development, little is known about their post-translational regulation.  Here we identify the ubiquitin ligase COnstitutive Photomorphogenic-1 (COP1, also called RFWD2) as a tumor suppressor that negatively regulates ETV1, ETV4, and ETV5.  ETV1, which is the member mutated more frequently in prostate cancer, was degraded after being ubiquitinated by COP1.  Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs (degrons) and was 50-fold more stable than wild-type ETV1.  Almost all patient translocations eliminate these ETV1 degrons, implying that translocations rendering ETV1 insensitive to COP1 confer a significant selective advantage to prostate epithelial cells.  Indeed, COP1 deficiency in mouse prostate elevated ETV1 levels and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia.  The combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas.  Finally, relatively rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein expression, and abnormally elevated ETV1 protein while lacking a translocation event.  These findings identify COP1 as a bona fide tumor suppressor whose down-regulation promotes prostatic epithelial cell proliferation and tumorigenesis.	Co-expression
GDS4159	Expression data from LNCap cell line treated with COP1 (RFWD2), ETV1, and JUN siRNAs	The proto-oncogenes ETV1, ETV4, and ETV5 encode members of the E26 transformation-specific (ETS) transcription factor family, which includes the most frequently rearranged and overexpressed genes in prostate cancer.  Despite being critical regulators of development, little is known about their post-translational regulation.  Here we identify the ubiquitin ligase COnstitutive Photomorphogenic-1 (COP1, also called RFWD2) as a tumor suppressor that negatively regulates ETV1, ETV4, and ETV5.  ETV1, which is the member mutated more frequently in prostate cancer, was degraded after being ubiquitinated by COP1.  Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs (degrons) and was 50-fold more stable than wild-type ETV1.  Almost all patient translocations eliminate these ETV1 degrons, implying that translocations rendering ETV1 insensitive to COP1 confer a significant selective advantage to prostate epithelial cells.  Indeed, COP1 deficiency in mouse prostate elevated ETV1 levels and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia.  The combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas.  Finally, relatively rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein expression, and abnormally elevated ETV1 protein while lacking a translocation event.  These findings identify COP1 as a bona fide tumor suppressor whose down-regulation promotes prostatic epithelial cell proliferation and tumorigenesis.	Co-expression
GDS4160	The Effect of Hepatitis C Virus Infection on Host Gene Expression	Hepatitis C Virus is a leading cause of chronic liver disease. The identification and characterisation of key host cellular factors that play a role in the HCV replication cycle is important for the understanding of disease pathogenesis and the identification of novel anti-viral therapeutic targets. Gene expression profiling of HCV infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defence mechanisms (apoptosis, proliferation and anti-oxidant responses), cellular metabolism (lipid and protein metabolism) and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV associated pathogenesis. These include an increase in pro-inflammatory and pro-apoptotic signalling and a decrease in the anti-oxidant response pathways of the infected cell.	Co-expression
GDS4161	Gene expression associated with liver metabolism during viral hemorrhagic fever	Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man.  Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly.  Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections.  In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased.  We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus.  Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus.  During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion.  For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated.  In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.	Co-expression
GDS4163	IFN alpha-induced gene expression in human NK cells	NK cells are believed to contribute to the control of hepatitis C virus infection and pathogenesis of liver disease. Standard treatment of both acute and chronic hepatitis C is based on the administration of interferon alpha, however, the effects of type I interferons on human NK cells have not been studied in the context of hepatitis C. We therefore first performed a microarray screen for genes differentially regulated in human NK cells after stimulation of PBMC with recombinant interferon alpha-2b. One of the genes upregulated was TRAIL which was confirmed in vitro on the protein level.  Keywords: Interferon alpha; human NK cells; stimulation for 6 hours; cells sorted after stimulation of whole PBMC	Co-expression
GDS4165	Differential expression associated with GB virus C in HCV/HIV co-infection	The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection.	Co-expression
GDS4167	Gene expression profiles in CLL	Evaluation of differential expression between CLL patients in a chemoimmunotherapy trial with age-matched controls	Co-expression
GDS4168	Gene expression profiles in CLL	Evaluation of differential expression between CLL patients in a chemoimmunotherapy trial with age-matched controls	Co-expression
GDS4172	Effect of Protease-resistant PML-RARα on the leukemogenic potential in a mouse model of Acute Promyelocytic Leukemia	Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001).  Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.  Keywords: Time course	Co-expression
GDS4175	Effect of imatinib on philadelphia chromosome positive acute lymphoblastic leukemia	The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. In this study, the tyrosine kinase inhibitor imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of Ph+ ALL cell lines were analyzed in response to imatinib treatment.	Co-expression
GDS4176	The lymph node microenvironment promotes B-cell receptor signaling, NF-κB activation, and tumor proliferation in chronic lymphocytic leukemia (CLL)	To elucidate effects of tumor host interactions in vivo in CLL, purified tumor cells were obtained concurrently from blood, bone marrow and/or lymph node and analyzed by gene expression profiling.  Keywords: RNA	Co-expression
GDS4177	Effect of Imatinib on chronic myelogenous leukemia	The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which is present in almost every patient with chronic myeloid leukemia. In this study, the tyrosine kinase inhibitor Imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of CML cell lines were analyzed in response to Imatinib treatment.	Co-expression
GDS4179	Gene expression analysis of Hodgkin and non-Hodgkin lymphoma cell lines	Genomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin	Co-expression
GDS4180	Gene expression profiling of ATRA-differentiated wild-type and TG2 knockout NB4 cells	Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNAi-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions and their silencing lead to reduced adhesive, migratory and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, 3, 22, 24 and cytokines IL1B and IL8 involved in the development of differentiation syndrome (DS) are expressed at significantly lower levels in TG2-KD NB4  cells than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of DS.	Co-expression
GDS4181	Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance	Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as “AML not otherwise specified” or “AML with myelodysplasia-related changes”  The WHO classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetic information, data on patients’ history, and multilineage dysplasia (MLD). The category “AML with MDS-related changes” (AML-MRC) is separated from AML not otherwise specified (AML-NOS) by the presence of either MLD, MDS-related cytogenetics or MDS history. To clarify whether MLD alone is clinically relevant, we analyzed 408 adult patients categorized as AML-MRC or AML-NOS. EFS (Median 13.8 months vs. 16.0 months) and 3-year-OS (45.8% vs. 53.9%) did not differ significantly between patients with MLD and without. However, MLD correlated with pre-existing MDS (p<0.001) and MDS-related cytogenetics (p=0.035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n=90) had less frequently FLT3-ITD (p=0.032), and a lower median age than AML-NOS (n=232), but EFS, OS, and WBC did not differ significantly. Contrarily, patients with AML-NOS plus AML-MLD-sole (n=323) versus patients with MDS history or MDS-related cytogenetics (n=85) had better EFS (16.9 vs. 10.7 months; p=0.005) and 3-year-OS (55.8% vs. 32.5%; p=0.001). Gene expression profiles were measured for a subset of 96 patients. Analysis of the expression data showed distinct clusters for AML-MLD-sole and AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD demonstrated no independent clinical impact, while cytogenetics and MDS history were of prognostic relevance. This data suggest modifications in a revised WHO proposal.	Co-expression
GDS4182	Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance	Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as “AML not otherwise specified” or “AML with myelodysplasia-related changes”  The WHO classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetic information, data on patients’ history, and multilineage dysplasia (MLD). The category “AML with MDS-related changes” (AML-MRC) is separated from AML not otherwise specified (AML-NOS) by the presence of either MLD, MDS-related cytogenetics or MDS history. To clarify whether MLD alone is clinically relevant, we analyzed 408 adult patients categorized as AML-MRC or AML-NOS. EFS (Median 13.8 months vs. 16.0 months) and 3-year-OS (45.8% vs. 53.9%) did not differ significantly between patients with MLD and without. However, MLD correlated with pre-existing MDS (p<0.001) and MDS-related cytogenetics (p=0.035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n=90) had less frequently FLT3-ITD (p=0.032), and a lower median age than AML-NOS (n=232), but EFS, OS, and WBC did not differ significantly. Contrarily, patients with AML-NOS plus AML-MLD-sole (n=323) versus patients with MDS history or MDS-related cytogenetics (n=85) had better EFS (16.9 vs. 10.7 months; p=0.005) and 3-year-OS (55.8% vs. 32.5%; p=0.001). Gene expression profiles were measured for a subset of 96 patients. Analysis of the expression data showed distinct clusters for AML-MLD-sole and AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD demonstrated no independent clinical impact, while cytogenetics and MDS history were of prognostic relevance. This data suggest modifications in a revised WHO proposal.	Co-expression
GDS4185	Expression data from human peripheral blood subsets	Gene expression profile studies have identified an interferon signature in whole blood or mononuclear cell samples from patients with systemic lupus erythematosus. This study was designed to determine whether specific lymphocyte and myeloid subsets freshly isolated from the blood of systemic lupus erythematosus patients demonstrated unique gene expression profiles compared to subsets isolated from healthy controls. Keywords: patient compared to control	Co-expression
GDS4188	Activation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation	CD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE.  All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease.  Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCRζ protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.	Co-expression
GDS4193	B cell signature during inactive systemic lupus	Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes.	Co-expression
GDS4196	A Transcriptomic Analysis of NET1 (a RhoA GEF Exchange Factor) in AGS Gastric Cancer Cells	Stable knockdown of NET1, a RhoGEF, was achieved in AGS Gastric Cancer cells.  This gene is known to be overexpressed in the disease. Knockdown was achieved using lentiviral shRNA particles.  Gene expression was compared between knockdown and scrambled shRNA treated control cells. Cells were treated with and without LPA, a known activator of RhoA.	Co-expression
GDS4198	Gastric Cancer Subtyping (Australian Patient Cohort)	Genome-wide mRNA expression profiles of 70 primary gastric tumors from the Australian patient cohort. Like many cancers, gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities. Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-xpression-based clustering of a large collection of gastric adenocarcinomas from Singaporean patients [GSE34942 and GSE15459]. We developed and validated a classifier for the three subtypes in Australian patient cohort.	Co-expression
GDS420	Severe combined immunodeficiency (HG-U133A)	Investigation of molecular basis for immunodeficiency in severe combined immunodeficiency (SCID) patient. Thymocytes isolated from SCID patient compared with control subject.	Co-expression
GDS4202	LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells	[original title] LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells and minimal toxicity for normal hematopoietic cells.  LMP-420 induces cytotoxicity and apoptosis to CLL cells in vitro without any negative effects to normal immune cells. This gene expression experiment compares CLL cells treated with LMP-420 versus media alone to investigate the mechanism of action of LMP-420.	Co-expression
GDS4203	Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines	Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases  (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells  Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC. Generation of the GC sensitive and resistant clones is described in Parson et al. FASEB J 2005 (Pubmed id 15637111). In brief GC sensitive clones were generated by limiting dilution subcloning from the GC sensitive T-ALL cell line CCRF-CEM-C7H2. To generate GC resistant clones the CCRF-CEM-C7H2 cell line was clutured in the presence of 10E-7 M dexametasone.	Co-expression
GDS4206	Early Relapse in ALL is identified by Time To Leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways	Gene expression analysis identified a specific signature of differentially expressed genes discriminating TTLshort and TTLlong phenotypes. Gene expression signatures of xenografted leukemia samples with different TTL phenotypes were analyzed on  cohorts of pediatric BCP-ALL patients.	Co-expression
GDS4209	Expression profiling MOLT-4 treated with MABL	Analysis of MOLT-4 cells at various time points up to 6 hours following treatment with mouse anti-CD47 antibody (MABL) and goat anti-mouse IgG (GAM) as the crosslinker of MABL. MABL induces apoptosis in CD47-positive MOLT-4 cells. Cell death signals via CD47 ligation were analyzed by using Affymetrix Human Genome U133A microarray.	Co-expression
GDS421	Severe combined immunodeficiency (HG-U95A)	Investigation of molecular basis for immunodeficiency in severe combined immunodeficiency (SCID) patient. Thymocytes isolated from SCID patient compared with control subject.	Co-expression
GDS4210	MLL partner genes confer distinct biological and clinical signatures of pediatric AML, an AIEOP study	We retrospectively analyzed AML patients enrolled in the AIEOP since 2000, 42 patients with 11q23 rearrangement were analyzed by gene expression profile Gene expression analyses were performed to compare AML MLL partner genes (AF9, AF10, AF6, ENL, ELL, Septin 6, and AF1q)  Keywords: Expression data	Co-expression
GDS4212	A Pathobiological Role of the Insulin Receptor in CLL.	Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Results:  We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q.  High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels.	Co-expression
GDS4213	The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia	The NF-κB pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-κB response is regulated by the activation state of the IκB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-κB is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-κB activation and the potential importance of NF-κB in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-κB activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo. Transcriptional consequences of NF-kB inactivation in human T-ALL1 cell line	Co-expression
GDS4218	Janus-Like Opposing Roles of CD47 in Autoimmune Brain Inflammation in Human and Mice	Gene transcripts and proteins expressed during disease pathogenesis identify targets for therapy. We performed microarray analysis of histologically characterized multiple sclerosis (MS) brain lesions in comparison with control brain samples to identify differentially expressed molecules. We identified CD47 as a target of interest and studied its biology in MS and EAE.	Co-expression
GDS4219	Transcriptional profiling of CD16+ and CD16- peripheral blood monocytes from healthy individuals	Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCGRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including HIV infection. To gain insight into the developmental relationship and functions of CD16+ and CD16- Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16+ compared to CD16- Mo. CD16+ Mo were distinguished by upregulation of dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (MF) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16- Mo were distinguished by upregulation of myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential gene expression in CD16+ and CD16- Mo was confirmed by quantitative real time RT-PCR (i.e., CD16, C3AR1, C1QR1, ICAM-2, CSF1R, CSF3R, CDKN1C, TNFRSF1, and LTB) and flow cytometry (i.e., CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1). Furthermore, increased expression of RARA and KLF2 transcripts in CD16+ Mo coincided with absence of cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing. These results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MF- and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MF in vivo.	Co-expression
GDS422	Normal human tissue expression profiling (HG-U95A)	Analysis of gene expression in a variety of normal tissues. Samples typically composed of a pool of 10-25 individuals. Included as part of the GeneNote project.	Co-expression
GDS4221	Molecular Classification of AIDS-Related Lymphomas	Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype.	Co-expression
GDS4222	Expression data of diagnostic biopsy samples from Hodgkin lymphoma patients	Despite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.	Co-expression
GDS4224	Microarray Analysis of West Nile Virus infected Human Retinal Pigment Epithelium	Low-level infection is believed to play a role in the degradation of the outer blood retinal barrier, which is composed of retinal pigment epithelial (RPE) cells. By investigating immunopathogenic West nile virus (WNV) infected RPE via microarray, we sought to find key genes involved in a low-level viral infection, which are vital for normal immune responses.	Co-expression
GDS4225	A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells	Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine.	Co-expression
GDS4226	Phenotype, Function and Gene Expression Profiles of PD-1 high CD8 T cells in Healthy Human Adults	T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that PD-1 regulates T cell dysfunction during chronic LCMV infection in mice and PD-1 high cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, HCV and HBV. However, it is not known if PD-1 high cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function and gene expression profiles of PD-1 high versus PD-1 low CD8 T cells in the peripheral blood of healthy human adults as following: 1) The percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans and PD-1 was expressed by the memory CD8 T cells. 2) PD-1 high CD8 T cells in healthy humans did not significantly correlated with the PD-1 high exhausted gene signature of HIV specific human CD8 T cells or chronic LCMV specific CD8 T cells from mice. 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults. 4) PD-1 was expressed by the effector memory (TEM) compared to ‘terminally differentiated effector’ (TEMRA) CD8 T cells. 5) Finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed.	Co-expression
GDS4227	Expression data from HAART interruption in HIV patients	We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4  T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients.	Co-expression
GDS4228	HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue	Exploratory microarray analysis identified significant changes in gene expression in adipose tissue.  These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART).  Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls.	Co-expression
GDS423	Normal human tissue expression profiling (HG-U95B)	Analysis of gene expression in a variety of normal tissues. Samples typically composed of a pool of 10-25 individuals. Included as part of the GeneNote project.	Co-expression
GDS4231	Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders	Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART.	Co-expression
GDS4232	Expression data from IFN alpha 2-treated macrophages infected with HIV	Temporal changes of the expression levels of the complete human transcriptome during the first 24 hours following infection of IFN-pre-treated macrophages. This approach has allowed us to identify genes involved in the IFN signaling that have an impact on HIV-1 infection of macrophages KEYWORDS: time course	Co-expression
GDS4233	Systems approach identifies HIPK2 as a critical regulator of kidney tubulointerstitial fibrosis	We used an integrated computational/experimental systems biology approach to identify upstream protein kinases that regulate gene expression changes in kidneys of HIV-1 transgenic mice (Tg26), which have significant tubulo-interstitial fibrosis (TIF) and glomerulosclerosis (GS). We identified the homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of TIF and GS. HIPK2 was upregulated in kidneys of Tg26 and patients with various kidney diseases. HIV infection increased the protein level of HIPK2 by promoting oxidative stress, which inhibited Siah1-mediated proteasomal degradation of HIPK2. The data contain two sets: kidney corticies from WT and Tg26 mice and HEK293 transfected with HIPK2, HIPK2-DN and wild type.	Co-expression
GDS4236	Targeting the MTOR-AKT pathway in DLBCL	The mTOR (mammalian Target of Rapamycin) pathway is constitutively activated in Diffuse Large B-Cell Lymphoma (DLBCL).  mTOR inhibition has been shown to have clinical activity in patients with DLBCL, although overall response rates remain low. We therefore evaluated differences in the transcriptome between DLBCL cell lines with differential sensitivity to the mTOR inhibitor Rapamycin, to (A) identify gene-expression patterns(GEP) capable of identifying sensitivity to Rapamycin, (B) understand the underlying mechanisms of resistance to Rapamycin in DLBCL and (C) identify bioactive molecules likely to synergize with mTOR inhibitors.  Using Affymetrix HuGene ST 1.0 microarrays, we were able to identify a gene expression signature capable of accurately predicting sensitivity and resistance to Rapamycin in DLBCL cell lines.  Pathway analysis identified the serine/threonine kinase Akt as central to the differentially-expressed gene network.  Connectivity mapping of our datasets identified compounds targeting the AKT pathway with a high likelihood of reversing the GEP associated with resistance to Rapamycin.  Specifically, we evaluated the HIV protease inhibitor (PI) Nelfinavir, which is known to have anti-cancer and Akt-inhibitory properties, as well as the small molecule Akt inhibitor MK-2206, for their potential to synergize with to Rapamycin in DLBCL.  Nelfinavir and MK-2206 caused profound inhibition of cell viability in combination with Rapamycin in DLBCL cell lines. Low nanomolar concentrations of Rapamycin inhibited phosphorylation of Akt and also downstream targets of activated mTOR when used in combination with these Akt inhibitors.  These findings have the potential to significantly improve patient selection for mTOR inhibitor therapy, and to improve rates and depths of response.  More broadly, they support the use of global RNA expression and connectivity mapping to improve patient selection and identify synergistic drug combinations for cancer therapy.	Co-expression
GDS4238	Dynamic responses of primary human bronchial epithelial cells to influenza virus, viral RNA and interferon-beta	We  defined the major transcriptional responses in primary human bronchial epithelial cells (HBECs) after either infection with influenza or treatment with relevant ligands. We used four different strategies, each highlighting distinct aspects of the response. (1) cells were infected with the wild-type PR8 influenza virus that can mount a complete replicative cycle. (2) cells were transfected with viral RNA (‘vRNA’) isolated from influenza particles. This does not result in the production of viral proteins or particles and identifies the effect of RNA-sensing pathways (e.g., RIG-I.). (3) Cells were treated with interferon beta (IFNb), to distinguish the portion of the response which is mediated through Type I IFNs. (4) Cells were infected with a PR8 virus lacking the NS1 gene (‘DNS1’). The NS1 protein normally inhibits vRNA- or IFNb-induced pathways, and its deletion can reveal an expanded response to infection.	Co-expression
GDS4239	Expression data of influenza A-infected human type I-like alveolar epithelial cells	Pandemic influenza H1N1 (pdmH1N1) virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses, suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However, a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus.	Co-expression
GDS424	Normal human tissue expression profiling (HG-U95C)	Analysis of gene expression in a variety of normal tissues. Samples typically composed of a pool of 10-25 individuals. Included as part of the GeneNote project.	Co-expression
GDS4240	Peripheral blood cells expression data form 7 patients with severe pdm(H1N1) influensa and 7 gender and age matched healthy controls	Using PAXgene tubes, peripheral blood samples were collected  from seven patients >18 years with documented pdm(H1N1) influenza, bilateral chest infiltrates, and in need of ventilation support. Significant co-morbidity was exclusion criterion. Expression profiles were compared with 7 age matched controls. Using  a false discovery rate < 5% and  an absolute fold change > 2, 370 genes  were differentially expressed in case and controls. A second sample was collected after ca 6 days in the 7 patients and temporal changes in expression profiles investigated. Over expressed putative mediators of inflammatory lung dammage were measured on the protein level.	Co-expression
GDS425	Normal human tissue expression profiling (HG-U95D)	Analysis of gene expression in a variety of normal tissues. Samples typically composed of a pool of 10-25 individuals. Included as part of the GeneNote project.	Co-expression
GDS4252	Exposure of cystic fibrosis bronchial epithelial cells (CFBE 41 o-) to Pseudomonas aeruginosa (PA01) biofilms	In the clinical setting, mutations in the CFTR gene enhance the inflammatory response to P. aeruginosa (PA01) infection, but measurements of the inflammatory response to pathogen stimulation by isolated airway epithelia can yield variable results. In this series, we exposed CFBE41o- cells over-expressing ∆F508/∆F508 CFTR and CFBE41o- cells rescued with wt-CFTR to P. aeruginosa  biofilms. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL2,  CXCL3, CXCR4 and TNF-α) in CFBE-wt-CFTR cells compared to CFBE-∆F508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o- ∆F508/∆F508-CFTR cells.	Co-expression
GDS4255	A microRNA network regulates expression and biosynthesis of CFTR and CFTR-ΔF508.	Production of functional proteins requires multiple steps including gene transcription and post-translational processing.  MicroRNAs (miRNA) can regulate individual stages of these processes.  Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain.  We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A.  Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels.  A miR-138 anti-miR had the opposite effects.  Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis.  The most common CFTR mutation, ΔF508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-ΔF508 and restored Cl- transport to cystic fibrosis airway epithelia.  This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized.  This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.	Co-expression
GDS4256	Gene expression profiles of caseous human pulmonary TB granulomas derived from TB patients	Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci.  However, when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway.  Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology.  Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues.	Co-expression
GDS4258	The time-course transcriptomic responses of THP-1 human macrophage-like cells  to W-Beijing Mycobacterium tuberculosis strains of different sublineages	The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.	Co-expression
GDS4259	Paired whole blood human transcription profiles from children with severe malaria and mild malaria	Whole blood transcriptomes from a longitudinal study of  5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria We used microarrays to identify transcripts that were associated with each clinical presentation.	Co-expression
GDS426	Normal human tissue expression profiling (HG-U95E)	Analysis of gene expression in a variety of normal tissues. Samples typically composed of a pool of 10-25 individuals. Included as part of the GeneNote project.	Co-expression
GDS4262	LOX-1-dependent transcriptional regulation after oxidized LDL (OxLDL) treatment of human aortic endothelial cells.	LOX-1 is the primary endothelial receptor for oxidized LDL in endothelial cells and plays a role in the development of atherosclerosis.  Expression profiling was carried out on samples from HAECT cells over-expressing either LOX-1 or GFP control and treated with or without OxLDL over a time course of  2, 6, 12 and 24 Hours.  The goal of the study was to identify genes expression changes activated by OxLDL binding to LOX-1 at several different time points.	Co-expression
GDS4263	Age-related expression data from composite bone marrow from healthy humans	Human bone marrow is a complex, diversified and well-organized hematopoietic network changing composition with age. The purpose of this study was to analyze variations in relative precursor B cell abundance in bone marrow with age by means of global gene expression profiling. RNA was isolated from composite bone marrow from 25 healthy children, adolescents and adults age 2 months to 28 years. As reference transcript for precursor B cells we used recombination activating gene RAG1 exploring the data for other transcripts showing the same profile as RAG1 with age. We identified 54 genes with correlated expression profiles to RAG1 (r ≥ 0.9, p = 0), characterized by high expression at 3 - 20 months followed by a fast decline to lower signal levels maintained until early adulthood. Immunophenotyping from a similar healthy age-matched cohort (n = 37) showed a comparable decrease of precursor B cells. Of the 54 genes 15 were characteristically B cell associated representing cell surface molecules (CD19, CD72, CD79A, CD79B, CD180, IGL@, IGLL1, VPREB1, VPREB3), a signal transduction molecule (BLNK) and transcription factors (DNTT, EBF1, PAX5, POU2AF1, RAG2). Of the remaining transcripts some may represent novel B cell transcripts or genes involved in control of B cells. Bone marrow was obtained from healthy children eligible for elective minor surgery and voluntary health care workers. The bone marrow samples (2.5ml) were immediately after aspiration transferred to PAXgene tubes for mRNA stabilization before RNA extraction and hybridization on Affymetrix microarrays. To that end, the study presents a picture of the total marrow activity with minimal manipulation that would otherwise influence gene expression results.	Co-expression
GDS4264	The Effect of Translocation-Induced Nuclear Re-organization on Gene Expression	To study the effect of balanced chromosomal rearrangements on gene expression, we compared the transcriptomes of cell lines from control and t(11;22)(q23;q11) individuals. This translocation between chromosomes 11 and 22 is the only recurrent constitutional non-Robertsonian translocation in humans. The number of differentially expressed transcripts between the translocated and control cohort is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Altered expression is not limited to genes close to the translocation breakpoint suggesting that a long-range effect is operating. Indeed we show that the nuclear position of the derivative chromosome is altered compared to the normal chromosomes. Our results are consistent with recent studies that indicate a functional role for nuclear position in regulating the expression of some genes in mammalian cells. They may also have implications on reproductive separation, as we show that reciprocal translocations not only provide partial isolation for speciation but also significant changes in transcriptional regulation through alteration of nuclear chromosomes territories.  Keywords: Genetic modification	Co-expression
GDS4265	Induced Sputum Genes Associated With Spirometroc and Radiological Disease Severity in COPD Ex-smokers	Induced sputum is used to sample inflammatory cells, predominantly neutrophils and macrophages, from the airways of COPD patients. Our aim was to identify candidate genes associated with the degree of airflow obstruction and the extent of emphysema by expression profiling, and then to confirm these findings for selected candidates using specific PCR and protein analysis.	Co-expression
GDS4266	Identification of a B cell signature associated with renal transplant Tolerance in humans	In this study, investigators recruited the largest reported cohort of tolerant kidney transplant recipients who maintained their graft after ceasing to take their immunosuppression drug, and compared this cohort to subjects with stable  allograft function while on immunosuppression and healthy non transplated, controls.  Using gene expression studies, they identified genetic markers that are strong candidates for predicting kidney transplant candidates who may benefit from minimization or withdrawl of immunosuppression. Microarrays were used to detect expressed gene profiles of whole-blood total RNA from subjects in the tolerant, standard immunotherapy and healthy control participants	Co-expression
GDS4267	Immature cell populations and an erythropoiesis gene expression signature in systemic juvenile idiopathic arthritis: Implications for pathogenesis	Objective. Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared to related conditions.  125 patients with JIA (18 sJIA and 107 non-sJIA) and 29 controls were studied. PBMC were isolated and analyzed for multiple surface antigens by flow cytometry and for gene expression profiles. The proportions of different PBMC subpopulations were compared among sJIA, non-sJIA patients and controls and subsequently correlated with the strength of the erythropoiesis signature. Additional gene expression data from patients with familial hemophagocytic lymphohistiocytosis (FHLH) and from a published sJIA cohort were analyzed to determine if the erythropoiesis signature was present.  Keywords: Patient Vs Control, reassassment of phenotype	Co-expression
GDS4268	Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension	Rationale:  Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms.  Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension.  The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial. Objective:  To identify genes that are differentially expressed in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension which could be used as biomarkers of disease for early diagnosis and provide insight into pathogenesis of pulmonary hypertension in at-risk populations. Methods and Results:  Gene expression analysis was performed on a carefully characterized Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension.  Differentially expressed genes were confirmed in the Microarray Cohort and validated in a separate Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR.  We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 (CCR7) as differentially expressed in patients with scleroderma-associated pulmonary hypertension.  Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T cells from scleroderma patients with pulmonary hypertension. Conclusions:  Differences exist in the expression of inflammatory and immune-related genes  in peripheral blood cells derived from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures.  These findings may have implications as biomarkers to screen at-risk populations to facilitate early diagnosis and provide insight into inflammatory and autoimmune mechanisms of scleroderma-related pulmonary hypertension.	Co-expression
GDS4269	Integrative Transcriptome Analysis Reveals Common Molecular Subtypes of Human Hepatocellular Carcinoma (HT-HG_U133A)	Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation but rather was the result of transforming growth factor-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease.	Co-expression
GDS4270	Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis	Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy. We aimed to determine whether genes expressed in whole blood early following initiation of intravenous corticosteroid treatment can be associated with response.	Co-expression
GDS4272	Expression data from SPARKS CHARMS JIA cohort	Gene expression on peripheral blood mononuclear cells (PBMC) from SPARKS CHARMS juvenile idiopathic arthritis (JIA) cohort pre and post methotrexate therapy. This is the first study to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyze genetic variation in differentially expressed genes. We have identified a gene, which may contribute to genetic variability in MTX response in JIA.	Co-expression
GDS4273	Expression data from validation cohort of children with septic shock	Background:  Septic shock heterogeneity has important implications for the conduct of clinical trials and individual patient management. We previously addressed this heterogeneity by indentifying 3 putative subclasses of children with septic shock based on a 100-gene expression signature corresponding to adaptive immunity and glucocorticoid receptor signaling. Herein we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Methods:  Gene expression mosaics were generated from the 100 class-defining genes for 82 individual patients in the validation cohort. Patients were classified into 1 of 3 subclasses (“A”, “B”, or “C”) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. Separate classifications were conducted by 21 individual clinicians and a computer-based algorithm. After subclassification the clinical database was mined for clinical phenotyping. Results:  In the final consensus subclassification generated by clinicians, subclass A patients had a higher illness severity, as measured by illness severity scores and maximal organ failure, relative to subclasses B and C. The k coefficient across all possible inter-evaluator comparisons was 0.633. Similar observations were made based on the computer-generated subclassification. Patients in subclass A were also characterized by repression of a large number of genes having functional annotations related to zinc biology. Conclusions:  We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses can be indentified by clinicians without formal bioinformatics training, at a clinically relevant time point, and have clinically relevant phenotypic differences.	Co-expression
GDS4274	Expression data for derivation of septic shock subgroups	Background:  Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods:  Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results:  Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the 3 putative subclasses (ANOVA, Bonferonni correction, p < 0.05) identified 6,934 differentially regulated genes. K means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the 3 subclasses. Leave one out cross validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C. Conclusions:  Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.	Co-expression
GDS4275	Identification of Growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a Novel Tumor Suppressor in Pituitary Gonadotrope Tumors	Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options.   To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples.  Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1.  PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β  in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression.	Co-expression
GDS4276	An early inflammatory gene profile in visceral adipose tissue in children	The aim of this study was to characterize expression profiles of visceral and subcutaneous adipose tissue in children. Adipose tissue samples were collected from children having elective surgery (n=71, [54 boys], 6.0 +- 4.3 years). Affymetrix microarrays (n=20) were performed to characterize the functional profile and identify genes of interest in adipose tissue. Visceral adipose tissue had an overrepresentation of Gene Ontology themes related to immune and inflammatory responses and subcutaneous adipose tissue had an overrepresentation of themes related to adipocyte growth and development. Likewise, qPCR performed in the whole cohort showed a 30-fold increase in haptoglobin (P < 0.005), 7-fold increase in IL-10 (P < 0.001), 8-fold decrease in VEGF (P < 0.01) and a 28-fold decrease in TBOX15 (P < 0.001) in visceral compared to subcutaneous adipose tissue.The inflammatory pattern in visceral adipose tissue may represent an early stage of the adverse effects of this depot, and combined with chronic obesity, may contribute to increased metabolic and cardiovascular risk.	Co-expression
GDS4277	Expression of HOXB genes is significantly different in acute myeloid leukemia with a partial tandem duplication of MLL vs. a MLL translocation: a cross-laboratory study	In acute myeloid leukemia (AML), the mixed lineage leukemia (MLL) gene may be rearranged to generate a partial tandem duplication (PTD), or fused to partner genes through a chromosomal translocation (tMLL). In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other studies enriches samples for analysis and yields more conclusive results.	Co-expression
GDS4278	Gene expression profiling of CEBPA double-, single-mutant and CEBPA wild type AML	A previously predictive CEBPA double mutant (CEBPAdm) signature was hampered by the recently reported CEBPA silenced AML cases that carry a similar gene expression profile (GEP). Two independent AML cohorts were used to train and evaluate the predictive value of the CEBPAdm signature in terms of sensitivity and specificity. A predictive signature was created, containing 25-probe sets by using a logistic regression model with Lasso regularization, which selects discriminative probe sets between the classes, CEBPAdm and all other AML cases, CEBPA wild type (CEBPAwt) and CEBPA single mutant (CEBPAsm). Subsequently, a classifier was trained on the entire HOVON-SAKK cohort based on a two-class approach; CEBPAdm versus all other cases (CEBPAwt and CEBPAsm). This trained classifier subsequently classified 16 candidate CEBPAdm cases in the AMLSG-cohort out of 154 AML cases. This approach showed perfect sensitivity and specificity (both 100%). In addition, we have performed a classification between CEBPAdm ,CEBPAsm, and CEBPAwt to infer if we were able to accurately classify CEBPAsm cases. We observed that all CEBPAsm cases were classified as CEBPAwt, thus CEBPAsm cases do not have a consistent gene expression pattern and are different from the CEBPAdm group.	Co-expression
GDS4279	Validated Gene Expression Signatures of Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets.	Co-expression
GDS4280	Whole-exome sequencing identifies mutations of BCOR in acute myeloid leukemia with normal karyotype	Among acute myeloid leukemias (AML) with normal karyotype (CN-AML), NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES. BCOR somatic mutations were: i) disruptive events similar to germline BCOR mutations causing the oculo-cranio-facial-dental (OCFD) genetic syndrome; ii) associated with markedly decreased BCOR mRNA levels, absence of full-length BCOR and absent or low expression of a truncated BCOR protein; iii) almost mutually exclusive with NPM1 mutations and frequently associated with DNMT3A and RUNX1 mutations, pointing to a cooperation between these events. Finally, BCOR mutations correlated with poor outcome among a cohort of 160 CN-AML patients (28% versus 66% overall survival at 2 yrs, P=0.024). Our results implicate for the first time BCOR in the pathogenesis of CN-AML without NPM1 mutations.	Co-expression
GDS4281	Syntenin-1 is expressed in uveal melanoma and correlates with metastatic progression 	Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover,  we found that high expression of SDCBP gene was related to metastatic progression in two  additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound–healing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target. 	Co-expression
GDS4282	Molecular Genetic Classification of clear-cell Renal Cell Carcinoma (ccRCC) based on the Gene Expression Profiling of Tumors and Tumorgrafts deficient for BAP1 or PBRM1	Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.	Co-expression
GDS4283	The Effect of Lifestyle on Gene Expression in Moroccan Amazighs	The human transitions from nomadic to agrarian to urban lifestyles are likely to impact physiology and disease susceptibility.  In order to estimate the magnitude of the impact of lifestyle on genome function, we profiled gene expression in total leukocytes of Moroccan Amazigh from three distinct localities.  Despite great expression heterogeneity in humans, as much as one third of the PBMC transcriptome was found to differ between the localities. Keywords: Population genomic comparison	Co-expression
GDS4284	The novel antisense Bcl-2 inhibitor SPC2996 causes rapid leukemic cell clearance and immune activation in chronic lymphocytic leukemia	SPC2996 is a novel locked nucleic acid (LNA) phosphorothioate antisense molecule targeting the mRNA of the Bcl-2 oncoprotein. We investigated the mechanism of action of SPC2996 and the basis for its clinically observed immunostimulatory effects in chronic lymphocytic leukemia (CLL). Patients with relapsed CLL were treated with a maximum of six doses of SPC2996 (0.2-6mg/ kg) in a multicenter phase I trial. Microarray-based transcriptional profiling of circulating CLL cells was carried out before and after the first infusion of SPC2996 in eighteen patients. We used microarrays to characterize global  gene expression changes  of circulating CLL cells in response to SPC2996 infusion in 18 patients Key word : Response to therapeutic agent	Co-expression
GDS4285	Deregulated apoptosis signaling in core binding factor leukemia differentiates clinically relevant, molecular marker independent subgroups	Core binding factor (CBF) leukemias, characterized by translocations t(8;21) or inv(16)/t(16;16) targeting the core binding factor, constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, about 40% of patients relapse, and the current classification system does not fully reflect this clinical heterogeneity. Previously, gene expression profiling (GEP) revealed two distinct CBF leukemia subgroups displaying significant outcome differences and identified apoptotic signaling, MAPKinase signaling and chemotherapy-resistance mechanisms among the most significant differentially regulated pathways. We now tested different inhibitors of the respective pathways in a cell line model (six cell lines reflecting the CBF subgroup specific gene expression alterations), and found apoptotic signaling to be differentiating between the CBF subgroup models. In accordance, primary samples from newly diagnosed CBF AML patients (n=23) also showed differential sensitivity to in vitro treatment with a Smac mimetic such as BV6, an antagonist of inhibitor of apoptosis (IAP) proteins , and ABT-737, a BCL2 inhibitor. Furthermore, GEP revealed the BV6 resistant cases to resemble the previously identified unfavorable CBF subgroup. Thus, our current findings show deregulated IAP expression and apoptotic signaling to differentiate clinically relevant CBF subgroups, which were independent of known molecular markers, thereby providing a starting point for novel therapeutic approaches.	Co-expression
GDS4288	Determinants of sensitivity to DZNep induced apoptosis in multiple myeloma cells	The 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM.	Co-expression
GDS4289	Expression profiling of human T-LL cell line CUTLL1	Notch is normally activated by cleavage and nuclear translocation of its intracellular domain (ICN1), which turns on downstream target genes. Human T cell acute lymphoblastic leukemia (T-ALL), an aggressive immature T cell malignancy, is associated with Notch 1 gain-of-function mutations in more than 50% of the cases. Efforts to date to identify direct Notch1 targets have been confounded by the lack of a method to turn Notch1 on in a controlled fashion in T-ALL cells that are poised to respond to Notch signals. Of note, because Notch signaling activates transcriptional repressors that feedback to dampen the expression of many target genes (a process referred to as incoherent logic), it is likely that many direct targets are missed in Notch off analyses, which are further complicated by an inability to identify direct targets in a clear-cut fashion. We have overcome this limitation by developing a GSI washout method that results in the rapid translocation of activated Notch1 to the nucleus. We intend to use this method to study the assembly and loading of transcriptional complexes onto downstream targets, the kinetics of target activation. To date, our efforts have been devoted to comparing the gene expression signature of Notch-on and Notch-off in the human T-ALL cell line CUTLL. In addition to previously identified Notch1 target genes, we have also identified a series of novel genes upregulated by GSI washout in the presence of cycloheximide, suggesting that they are likely to be direct targets. Additional controls included transduction of cells with dominant negative MAML1, a specific antagonist of canonical Notch1 signaling, prior to Notch1 reactivation, and a mock GSI  washout to control for cycloheximide effects.	Co-expression
GDS4290	Expression Profiling of Mixed Lineage Leukemia Cells Treated with a Potent Small-Molecule DOT1L Inhibitor	Cell lines bearing MLL translocations (MV4-11 and MOLM-13) were treated with a potent, selective inhibitor of the DOT1L histone methyl transferase.  Treatment of MLL-rearranged cell lines with the DOT1L inhibitor selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes.  Here we provide expression profiling data of cells treated with DOT1L inhibitor or vehicle control.	Co-expression
GDS4291	Human T-ALL cell line response to inhibition of Notch signaling	Analysis of five Notch signaling-dependent human T-ALL cell lines (ALLSIL, DND41, HPBALL, KOPTK1, TALL-1) treated with gamma-secretase inhibitor (GSI) to block Notch signaling. Samples include parental cells, cells rescued by retroviral transduction with ICN (a GSI-independent form of activated Notch1), and cells retrovirally transduced with c-Myc (an important downstream target of Notch1). Results allow segregation of bona fide Notch targets from other genes affected by gamma-secretase inhibition as well as from targets downstream of c-Myc.	Co-expression
GDS4296	Comparison between cell lines from 9 different cancer tissue (NCI-60) (Affymetrix U133 Plus 2.0)	Comparison between cell lines from 9 different cancer tissue of origin types (Breast, Central Nervous System, Colon, Leukemia, Melanoma, Non-Small Cell Lung, Ovarian, Prostate, Renal) from NCI-60 panel.	Co-expression
GDS4297	In vitro prednisolone resistance signature in MLL-rearranged infant ALL	Acute Lymphoblastic Leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence of MLL translocations which is associated with a poor prognosis. Contributing to this poor prognosis is cellular drug resistance, especially to glucocorticoids like prednisolone. Although in vitro prednisolone resistance mechanisms have been proposed in pediatric ALL, it has never been studied in MLL-rearranged infant ALL, which are highly resistant to glucocorticoids in vitro and in vivo.	Co-expression
GDS4298	The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression	Background: ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation, whereas its role in leukemia propagation and maintenance remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. Findings: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-DOWN set was significantly enriched for genes included in the cell activation, immune response, apoptosis, signal transduction and development and differentiation categories, whereas in the E/R KD-UP set only the PI3K/AKT/mTOR signaling and hematopoietic stem cells categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories stem cell properties, B-cell differentiation, immune response, cell adhesion and DNA damage with RT-qPCR. Conclusion: The results of our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with regular B-cell development by repressing key functions that are necessary under physiological circumstances. E/R may thus constitute also the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.	Co-expression
GDS4299	Discovery of novel recurrent mutations and rearrangements in early T-cell precursor acute lymphoblastic leukemia by whole genome sequencing	Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole genome sequencing of tumour and normal DNA from 12 children with ETP ALL and assessed the frequency of somatic alterations in 52 ETP and 42 non-ETP T-ALL samples by sequencing and DNA copy number analysis. ETP ALL was characterised by a high frequency of activating mutations in genes regulating cytokine receptor and Ras signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF); alterations disrupting haemopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1, EP300); and inactivating mutations in histone modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of mutation including DNM2, ECT2L and RELN. Ten of 12 ETP ALL cases harboured chromosomal rearrangements, several of which complex and resulted in the expression of novel chimeric in-frame fusion genes disrupting haemopoietic regulators. Thus, similar to myeloid malignancies, mutations that drive proliferation, impair differentiation and disrupt histone modification are hallmarks of ETP ALL. Moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haemopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.	Co-expression
GDS4300	EZH2 mutations can be detected in 23% of PICALM-MLLT10 (CALM-AF10) positive acute leukemias	Interest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 6–53 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients). In contrast, no EZH2mut was found in an independent cohort of 12 PICALM-MLLT10-negative T-ALL. Gene expression profiling revealed increased expression of genes with a role for transcription or intracellular transport processes in the PICALM-MLLT10-positive cases. The frequent occurrence of EZH2mut in PICALM-MLLT10-positive malignancies emphasizes a cooperative effect in acute leukemias.	Co-expression
GDS4301	Gene expression profiles of AML derived stem cells: similarity to hematopoietic stem cells	Tumors contain a fraction of cancer stem cells that maintain the  propagation of the disease. The CD34‏CD38_ cells, isolated  from acute myeloid leukemia (AML), were shown to be enriched  leukemic stem cells (LSC). We isolated the CD34‏CD38_ cell  fraction from AML and compared their gene expression profiles  to the CD34‏CD38‏ cell fraction, using microarrays. We  found 409 genes that were at least twofold over- or underexpressed  between the two cell populations. These include  underexpression of DNA repair, signal transduction and cell  cycle genes, consistent with the relative quiescence of stem  cells, and chromosomal aberrations and mutations of leukemic  cells. Comparison of the LSC expression data to that of normal  hematopoietic stem cells (HSC) revealed that 34% of the  modulated genes are shared by both LSC and HSC, supporting  the suggestion that the LSC originated within the HSC progenitors.  We focused on the Notch pathway since Jagged-2, a  Notch ligand was found to be overexpressed in the LSC  samples. We show that DAPT, an inhibitor of gamma-secretase,  a protease that is involved in Jagged and Notch signaling,  inhibits LSC growth in colony formation assays. Identification  of additional genes that regulate LSC self-renewal may provide  new targets for therapy.	Co-expression
GDS4304	Expression data from untreated and ATP treated AML blasts	In the present study, we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization. GEP analysis demonstrated that ATP induced the expression of cell cycle inhibitors and negative modulators of cell motility, such as inhibitors of GTPase activity. On the contrary, ATP inhibits the expression cell-cycle related genes (cyclins and CDKs), activators of cell motility (Rho GTPases regulators, matrix degradation enzyme and cytoskeleton proteins) and adhesion molecules involved in homing and engraftment.	Co-expression
GDS4305	GSK-3A and GSK-3B knockdown in AML cell lines	Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6). Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3A–specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML.	Co-expression
GDS4308	Gene expression changes in the human diaphragm following cardiothoracic surgery	It is unknown how soon the diaphragm begins to start the process of atrophy following the start of MV. We hypothesized that genes responsible for maintaining diaphragmatic contractile function, stress response, energy transduction would be altered over the course of a 5 hour cardiothoracic surgery.	Co-expression
GDS4312	Expression data from patient iPSC and iPSC-derived cardiomyocytes	Dilated cardiomyopathy (DCM) is the leading cause of heart failure and transplantation worldwide. We used iPSCs to model this disease and compared gene expression change before and after gene therapy of cardiomyocytes derived from DCM-specific iPSCs. We used microarrays to detail the global gene expression of patient specific iPSCs, iPSC-derived cardiomyocytes and its response to gene therapy.	Co-expression
GDS4314	Transcriptome analysis of diabetic and non diabetic patients affected by post-ischemic heart failure	Increased morbidity and mortality associated with post-ischemic heart failure (HF) in diabetic patients underscore the need for a better understanding of the underlying molecular events. Indeed, effective HF therapy in diabetic patients requires a complex strategy encompassing the development of improved diagnostic and prognostic markers and innovative pharmacological approaches. Whole mRNAs expression was measured in the heart of patients with heart failure (HF) with or without concomitant Type 2 diabetes mellitus (T2DM)  and compared it to control non-failing hearts.  We identified distinct genes modulated in HF patients compared to controls, as well as to T2DM HF  patients compared to  not diabetic HF patients.	Co-expression
GDS4318	Gene expression and genotype in normal heart	Genome-wide association studies have identified a small region at chromosome 9p21.3 strongly associated with coronary heart disease risk. The region contains no protein-coding genes and the mechanism underlying its association with heart disease is unknown. We investigated associations between rs1333049, a single nucleotide polymorphism representing the 9p21.3 locus, and levels of cardiac gene expression in myocardial tissue from donors with no documented history of heart disease.	Co-expression
GDS4322	Expression data from human iPS cells treated by a small molecule KY02111	Human pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs. To reveal how KY02111 function on promoting cardiac differentiation of hPSCs, we analyzed the gene expression profiles in KY02111-treated IMR90-1 hiPSCs using the microarray technique.	Co-expression
GDS4327	Expression data of hepatocytes isolated from chimeric mouse livers repopulated with human hepatocytes and from normal human livers	We generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed. Additionally, we performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with hepatocytes. A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) were examined.	Co-expression
GDS4329	Pancreatic cancer circulating tumor cells express a cell motility gene signature that predicts survival after surgery	Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC). A negative depletion fluorescence activated cell sorting (FACS) procedure was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumor (T), and non-tumoral pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. The ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we finally retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were over-expressed in CTC. High co-expression of TGF-1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 4 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 – 1.861)). Pancreatic CTC isolated from blood samples using a FACS-based negative depletion method,express a cell motility gene signature. The expression of this newly defined cell motility gene signature in the primary tumor is able to predict survival of patients who undergo surgical resection for pancreatic cancer.	Co-expression
GDS4330	Gene expression profiling of neuroendocrine primary tumors: effect of Octreotide treatment	The management of neuroendocrine tumors (NETs) is very variable, depending on many specific aspects, such as the type of tumor, spread and patient general health. Several advances have been made with the newly developed somatostatin analogues to cure this type of malignancies. Somatostain analogues such as octreotide have been used in clinic to treat patients with neuroendocrine tumors (NETs). However, the molecular mechanism leading either to successful therapy or acquired resistance to the analogues is still to large extent unclear. Patients develop drugs resistance during a long term treatment. Therefore, to identify the pivotal regulatory genes involved in the development of drug resistance is an actual challenge. We studied five human neuroendocrine tumor cell lines, CNDT2.5, KRJ1, QGP-1, NCI H720 and NCI H727. We also investigated a long-term treated CNDT2.5 by using octreotide. We performed gene expression profiling in all the human neuroendocrine cell lines.   Keywords: Gene Expression profiling, treatment comparison	Co-expression
GDS4336	Microarray gene-expression profiles of 45 matching pairs of pancreatic tumor and adjacent non-tumor tissues from 45 patients with pancreatic ductal adenocarcinoma	In order to identify biologically relevant tumor markers with prognostic significance, we set out to analyze gene expression profiling of tumor and adjacent non-tumor tissues from PDAC cases. We compared the microarray gene-expression profiles of 45 matching pairs of pancreatic tumor and adjacent non-tumor tissues. This data set were used to obtained genes that were differentially expressed and associated with survival. 51 genes were selected for further validation.	Co-expression
GDS4337	Expression data from human pancreatic islets	Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors.	Co-expression
GDS4342	The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models	Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome.  Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective γ-secretase inhibitor, in preclinical PDAC models.  We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity.  In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity.  Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice.  In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts.  Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFκB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. 	Co-expression
GDS4345	Gene expression in skeletal muscle of cancer patients before and after potentially curative surgery	The mechanisms underlying muscle wasting in cancer patients remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies.	Co-expression
GDS4346	Gene expression analysis in Panc-1 cells in response to treatment with Gli3T, a dominant-negative repressor of Gli	Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive human malignancies. In our studies, we find that the Gli transcription factors are required for Kras initiation of pancreatic tumorigenesis. In order to identify the downstream transcriptional targets of Gli in PDAC, we conducted gene expression analysis using Gli3T, a transcriptional repressor of Gli. In this data set we include the expression data from 6 samples with three of them expressing a control vector and another three expressing Gli3T	Co-expression
GDS4349	Identification of novel tissue-specific transcription arising from E-cadherin/CDH1 intron2: a novel protein isoform increases gastric cancer cell invasion and angiogenesis.	E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach. Results: In this sense we have searched for additional CDH1 transcripts arising from intron 2. From the four found, one (CDH1a) was demonstrated to be tissue specific and to be translated in vivo. When overexpressed in an E-cadherin negative context CDH1a replaced the canonic protein functions Conclusions: We have demonstrated, for the first time, transcripts arising from CDH1 intron 2. One of these, CDH1a, was found to modulate E-cadherin function representing a novel mechanism underlying invasion and angiogenesis in epithelial cancers and opening the way for novel therapeutic approaches.	Co-expression
GDS4350	Gene expression profile in Barrett's esopahgus	Microarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)	Co-expression
GDS4353	Transcriptional Alterations of Hamstring Muscle Contractures in Children with Cerebral Palsy	Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders.  Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function.  With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood.  This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures.  Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery.  Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray.  Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately.  Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398).  Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks.  These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity.  The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability.  These data lay a framework for further studies and novel therapies.	Co-expression
GDS4354	Gene expression analysis of bone biospies from nine patients with endogenous Cushings syndrome before and after  treatment	Glucose intolerance and diabetes mellitus are classical parts of endogenous Cushing’s syndrome (CS), and insulin resistance is a feature of cortisol excess. CS patients display characteristics including hyperglycemia, abdominal obesity, reduced high-density lipoprotein cholesterol levels and elevated triglycerides, and arterial hypertension. Hypercortisolism is a well known cause of bone loss, and patients with CS frequently display low bone mass and fragility fractures. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut, and affects the secretion of several hormones, cytokines, and growth factors with potential influence on bone metabolism. Bone biopsies from nine CS patients, before and mean 3 months after surgery, were screened for expressional candidate genes using Affymetrix human Gene Plus 2.0 Arrays. Analyses were performed to identify genes in glucocorticoid-induced osteoporosis and genes in glucose metabolism and energy homeostasis.	Co-expression
GDS4356	ZEBOV-induced changes in macrophage gene expression	Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response.	Co-expression
GDS4358	The National NeuroAIDS Tissue Consortium Brain Gene Array: Two types of HIV-associated neurocognitive impairment	Finding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients. 	Co-expression
GDS4359	MCF10A cells expressing HER2 and HER3 and grown in three-dimensional cultures	The tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.	Co-expression
GDS4360	Effect of EGF and/or HER2 on the growth of MCF10A cells on extracellular matrix: time course	Mammary epithelial cells MCF10A  and HER2 overexpressing MCF10A  cells were grown on matrigel in the absence or presence of epidermal growth factor. Cells were lysed and RNA was collected  at 1.5,3,5,7,9 days.	Co-expression
GDS4361	Controlled ErbB receptor dimerization	In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers.	Co-expression
GDS4362	Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals	Normal cells require continuous exposure to growth factors, in order to cross a restriction point and commit to cell cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse, and enables restriction point crossing. Through integration of comprehensive proteomic and transcriptomic analyses of each pulse, we identified three processes that regulate restriction point crossing: (i) The first pulse induces essential metabolic enzymes and activates p53-dependent restraining processes. (ii) The second pulse eliminates, via the PI3K/AKT pathway, the suppressive action of p53, as well as (iii) sets an ERK-EGR1 threshold mechanism, which digitizes graded external signals into an all-or-none decision obligatory for S-phase entry. Together, our findings uncover novel gating mechanisms, which ensure that cells ignore fortuitous growth factors, and undergo proliferation only in response to consistent mitogenic signals.	Co-expression
GDS4365	Expression data from intestinal mucosa of patients with UC	Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC, as well as non-inflammatory controls.	Co-expression
GDS4374	Role of REG 1 in Entamoeba histolytica colitis	Differential expression was used to access gene differences after Entamoeba histolytica infection. Entamoeba histolytica is an important diarrheal pathogen worldwide, and induces apoptosis of the intestinal epithelium as part of its disease process.  Regenerating (REG) 1 protein is anti-apoptotic.  We investigated the involvement of REG 1 in E. histolytica colitis.  Colonic biopsy samples were obtained from 8 subjects with acute E. histolytica colitis, and again 60 day later during convalescence. Gene expression in the human colon during acute and convalescent E. histolytica disease was evaluated using microarray and confirmed by polymerase chain reaction (PCR).  REG 1 protein expression was evaluated with immunohistochemistry.  The mechanism of REG 1 involvement in E. histolytica disease was subsequently investigated with a mouse model.  REG 1A and REG 1B were the most upregulated genes in the human intestine in acute versus convalescent E. histolytica disease (p=0.003 and p=0.006 respectively).  PCR confirmed the microarray results (p=<0.001 and p=0.001 respectively).  Increased REG 1A and REG 1B protein expression was similarly observed by immunohistochemistry. REG 1 -/-mice were found to be significantly more susceptible to E. histolytica infection than wild type mice.	Co-expression
GDS4377	Expression data from trisomy 21 and euploid induced pluripotent stem cell hematopoietic progenitors	We modeled human Trisomy 21 primitive hematopoiesis using induced pluripotent stem cells (iPSCs).  Primitive multipotent progenitor populations generated from Trisomy 21 iPSCs showed normal proliferative capacity and megakaryocyte production, enhanced erythropoiesis and reduced myeloid development compared to euploid iPSCs.	Co-expression
GDS4379	Gene expression data from 62 colorectal cancers	We stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.	Co-expression
GDS4380	A new classification of chromosome instability (CIN) phenotype, CIN-high and CIN-low	Samples were taken from colorectal cancers in surgically resected specimens in 35 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for CIN phynotype.	Co-expression
GDS4381	Molecular Evaluation of Patient-Derived Colorectal Cancer Explants as a Pre-clinical Mouse Model of Colorectal Cancer	Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies.  While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use.  However, it remains unclear if drug efficacy data obtained from xenograft models translate into clinically-relevant treatment modalities.  In this study, we have generated a panel of 28 patient-derived colorectal cancer explants (PDCCEs), an extension of our previous work, by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice.  A comprehensive histological and molecular evaluation of PDCCEs and their corresponding patient tumor demonstrates that PDCCEs maintain histological features and global biology through multiple passages.  Furthermore, we demonstrate that in vivo sensitivity of PDCCEs to oxaliplatin can predict patient outcomes. Our findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and can serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with CRC.	Co-expression
GDS4382	Screening for Epigenetically Masked Genes in Colorectal Cancer using 5-aza-2’-deoxycytidine treatment, Microarray and Gene Expression Profile	Unearthing of silenced genes in colorectal cancer (CRC) is of great importance. We employed oligonucleotide microarray to find changes in global gene expression of five CRC cell lines. These were analyzed before and after treatment with the 5-aza-2'-Deoxycitidine. Expression of the responding genes was integrated with gene expression profiling generated by microarray analysis of matched colorectal tissue samples. Selected candidates were subjected to methylation-specific PCR (MSP) and real-time quantitative reverse transcription-PCR using CRC cell lines and paired tumor and normal samples from CRC patients. Sixty eight genes were re-expressed after 5-aza-2'-Deoxycitidine treatment and over-expressed in normal colorectal mucosa, including genes that were known to be methylated in CRC. After applying study selection criteria, we identified 16 potential genes. Two candidates were selected (ASPP1 and SCARA5). Among 15 CRC cell lines, methylation was identified in SCARA5 (20%). The methylation status of SCARA5 was subsequently investigated in 23 paired colorectal tissue samples; methylation was detected in 17%, respectively. Observed promoter methylation showed a tendency towards methylation in tumor-derived samples, in SCARA5 gene. Significant down expression of SCARA5 mRNA was observed in CRC cell lines and tumor tissues compared to adjacent normal tissues (P < 0.001 and P = 0.001, respectively). The use of genome-wide screening led to the identification of a group of candidate genes. Among them, SCARA5 was methylated and markedly down-regulated in CRC. SCARA5 gene may have a role in CRC tumorigenesis.	Co-expression
GDS4383	Common PIK3CA mutants and a novel 3’UTR mutation are associated with increased sensitivity to saracatinib	Sensitive versus Resistant patient-derived colorectal cancer tumor xenografts with PIK3CA mutant against saracatinib (AZD0530)	Co-expression
GDS4384	Prognostic Significance and Gene Expression Profiles of p53 Mutations in Microsatellite Stable Stage III Colorectal Adenocarcinoma	Clinical Significance: Understanding the differences in colorectal cancer (CRC) aggressiveness and clinical outcomes in relation to tumor stage and different molecular subsets is at most important for designing treatment regimens. However, molecular signatures for specific phenotypic subsets that predict the aggressiveness and clinical outcomes of CRC, specifically in advanced disease stage are lacking. Therefore, for the first time, the current study has identified a set of molecular markers that are associated with aggressive Stage III CRCs that exhibited microsatellite stable and mutant p53 phenotypic features. These findings might aid in designing aggressive treatment regimens and help to provide insights into the development of novel therapeutic targets. Results: Increased incidence of p53 mutations in MSS CRCs (58%) was associated with higher CRC-specific mortality than MSS-p53 wild-type phenotypes (log-rank, P=0.025; and hazard ratio, 2.52; 95% confidence interval, 1.25-5.08). Of 49 down-regulated genes, LPAR6, PDLIM3 and PLAT and of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8, were confirmed by qNPA, qRT-PCR, and IHC platforms.  Conclusions: p53 mutations are associated with poor prognosis of Stage III microsatellite stable CRCs.	Co-expression
GDS4385	CD133+ colon cancer cells are more interactive with the tumor microenvironment than CD133- cells	CD133-positive colorectal cancer cells exhibit enhanced tumorigenicity over CD133-negative cells. The CD133+ cells are more interactive with and responsive to their stromal microenvironment because they also express the cognate receptors, such as CXCR4, for ligands produced by their neighboring carcinoma-associated fibroblasts, such as SDF-1 (stromal-derived growth factor).	Co-expression
GDS4386	Deciphering the Wnt-dependent gene signature in colorectal cancer cells	Microarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against β-catenin.	Co-expression
GDS4387	Liver Regeneration Gene Signature in Hepatitis B virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling	The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology.  Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion:  Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer.	Co-expression
GDS4388	SIN3A-regulated LIF-responsive genes in MCF7 cells	Tyrosine phosphorylation is a hallmark for activation of Signal Transducer and Activator of Transcription (STAT) proteins, but their transcriptional activity also depends on other secondary modifications. Type I interferons (IFNs) can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the Sin3a complex as an important mediator of this STAT3 transcriptional repression. Sin3a directly interacts with the DNA-binding domain of STAT3 and alters its acetylation status. SIN3A silencing enhances recruitment of STAT3 and enhanceosome components to the SOCS3 promoter, resulting in histone hyperacetylation and enhanced transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against Influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent STAT1/3 transcriptional switch.	Co-expression
GDS4389	Transcriptome Analysis Identifies Fn14, a TNF Superfamily Receptor Member, as a Therapeutic Target in Alcoholic Hepatitis	Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease and occurs in patients with excessive alcohol intake It is characterized by marked hepatocellular damage, steatosis and pericellular fibrosis. Patients with severe AH have a poor short-term prognosis. Unfortunately, current therapies (i.e. corticosteroids and pentoxyphylline) are not effective in many patients and novel targeted therapies are urgently needed. The development of such therapies is hampered by a poor knowledge of the underlying molecular mechanisms. Based on studies from animal models, TNF alfa was proposed to play a pivotal role in the mechanisms of AH.   Consequently, drugs interfering TNF alfa were tested in these patients. The results were disappointing due to an increased incidence of severe infections. Unluckily, there are not experimental models that mimic the main findings of AH in humans. To overcome this limitation, translational studies with human samples are required. We previously analyzed samples from patients with biopsy-proven AH. In these previous studies, we identified CXC chemokines as a potential therapeutic target for these patients. We expanded these previous observations by performing a high-throughout transcriptome analysis.	Co-expression
GDS4390	A Robust Induction of  Type III Interferons and Chemokines Defines a Unique Pattern of Hepatic Innate Immunity in Response to Hepatitis C Virus Infection	Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood.  Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression.  In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways.  Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs.    Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders.	Co-expression
GDS4391	Ribavirin Treated Huh7.5.1 Cells	The combination of peginterferon and ribavirin is the standard treatment for chronic hepatitis C.  Our recent clinical study suggests that ribavirin augments the induction of interferon stimulated genes (ISGs) in patients treated for HCV infection [1].  In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture. In addition, the effect of ribavirin on infectious HCV cell culture systems was also studied. Similar to interferon-alpha, ribavirin potently inhibits JFH-1 infection of Huh7.5.1 cells in a dose-dependent manner, which spans the physiological concentration of ribavirin in vivo. Microarray analysis and subsequent quantitative PCR assays demonstrated that ribavirin treatment resulted in the induction of a distinct set of ISGs. These ISGs, including IRF7 and IRF9 are known to play an important role in anti-HCV responses. When ribavirin is used in conjunction with interferon, induction of specific ISGs is synergistic when compared to either drug applied separately. Direct up-regulation of these antiviral genes by ribavirin is mediated by a novel mechanism different from those associated with interferon signaling and intracellular double stranded RNA sensing pathways such as RIG-I and MDA5. RNA interference studies excluded the activation of the Toll-like receptor and NF-KappaB pathways in the action of ribavirin. In conclusion, our study suggests that ribavirin, acting via a novel innate mechanism, potentiates the anti-HCV effect of interferon. Understanding the mechanism of action of ribavirin would be valuable in identifying novel antivirals.	Co-expression
GDS4392	Host Factors with Reduced Expression in Two HCV Permissive Cell Lines as Compared to the Non-Permissive Parent Cell Line Huh7	Drugs directly targeting Hepatitis C (HCV) are often rendered useless by the high mutation rate of the virus. Thus, we deduce that targeting of host factor that affect HCV replication may provide enhanced therapy fort HCV infection. Hepatocyte cell line Huh7 is known to be non-permissive for Hepatits C (HCV) replication.  Through a method developed by the Rice laboratory (Blight, K.J.,  et al., J Virol, 2002), selection of a small subset of permissive hepatocytes is possible. The Rice laboratory generated the first permissive cell line, Huh7.5, using this method. We generated another permissive cell line, HRP1, using the same method. With microarray, we compared the expression of host mRNAs in non-permissive Huh7 to both Huh7.5 and HRP1 searching for host factors lost in the cell lines permisive for HCV replication.	Co-expression
GDS4393	CRC samples for FOLFOX therapy prediction	The aim of this study is to identify responders to FOLFOX therapy by applying the Random Forests (RF) algorithm to gene expression data. Eighty-three unresectable colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets.	Co-expression
GDS4395	Molecular-genetic correlates of fatigue in cancer patients receiving localized external beam radiation therapy	The etiology behind cancer-related fatigue (CRF) is currently unknown. The physiological mechanisms of CRF are based on limited evidence that genetic factors, energy expenditure, metabolism, aerobic capacity, and the individual's immune response to inflammation are responsible for the experience of CRF. Gene expression profiling using microarray analysis from white blood cells of men with non-metastatic prostate cancer shows significant, differential expression of 463 probesets during localized external beam radiation therapy (EBRT). Pathway analysis shows a central role of SNCA (alpha-synuclein gene) among these differentially expressed probesets. Significant expression of SNCA was confirmed by qPCR (p<.001) and ELISA (p<.001) over time during EBRT. A significant correlation was noted between averaged fatigue scores and delta CT values of SNCA expression using confirmatory qPCR over time during EBRT (R=-.90, p=.006). Development of fatigue experienced by these men during EBRT may be mediated by SNCA expression. Pathways related to alpha-synuclein may serve as useful biomarkers to understand the mechanisms behind the development of fatigue.	Co-expression
GDS4396	CRC samples for FOLFOX therapy prediction	The aim of this study is to identify responders to FOLFOX therapy by applying the Random Forests (RF) algorithm to gene expression data. Eighty-three unresectable colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets.	Co-expression
GDS4397	Screening for Epigenetically Masked Genes in Colorectal Cancer using 5-aza-2’-deoxycytidine treatment, Microarray and Gene Expression Profile	Unearthing of silenced genes in colorectal cancer (CRC) is of great importance. We employed oligonucleotide microarray to find changes in global gene expression of five CRC cell lines. These were analyzed before and after treatment with the 5-aza-2'-Deoxycitidine. Expression of the responding genes was integrated with gene expression profiling generated by microarray analysis of matched colorectal tissue samples. Selected candidates were subjected to methylation-specific PCR (MSP) and real-time quantitative reverse transcription-PCR using CRC cell lines and paired tumor and normal samples from CRC patients. Sixty eight genes were re-expressed after 5-aza-2'-Deoxycitidine treatment and over-expressed in normal colorectal mucosa, including genes that were known to be methylated in CRC. After applying study selection criteria, we identified 16 potential genes. Two candidates were selected (ASPP1 and SCARA5). Among 15 CRC cell lines, methylation was identified in SCARA5 (20%). The methylation status of SCARA5 was subsequently investigated in 23 paired colorectal tissue samples; methylation was detected in 17%, respectively. Observed promoter methylation showed a tendency towards methylation in tumor-derived samples, in SCARA5 gene. Significant down expression of SCARA5 mRNA was observed in CRC cell lines and tumor tissues compared to adjacent normal tissues (P < 0.001 and P = 0.001, respectively). The use of genome-wide screening led to the identification of a group of candidate genes. Among them, SCARA5 was methylated and markedly down-regulated in CRC. SCARA5 gene may have a role in CRC tumorigenesis.	Co-expression
GDS4399	Differential Gene Expression in Granulosa Cells from Polycystic Ovary Syndrome Patients with and without Insulin Resistance:  Identification of Susceptibility Gene Sets through Network Analysis	Polycystic ovary Syndrome (PCOS) is a heterogeneous endocrine disorder that shows evidence of genetic predidposition among affected individuals. We have utilized the Microarray data from  granulosa cells of normal and PCOS women for network construction.	Co-expression
GDS4400	Gene expression analysis of human iPSC generated from pathogenic LRRK2 (G2019S) mutation bearing patients	Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study, we generated human induced pluripotent stem cell (iPSC) lines from LRRK2 (G2019S) bearing patient fibroblasts by cell reprogramming. We performed global gene expression profiling of LRRK2 (G2019S) heterozygous and homozygous patient iPSC lines, and the corresponding fibroblast lines they originated from. An age-matched wildtype human fibroblast line and H1 human embryonic stem cell (ESC) line were used as controls.	Co-expression
GDS4401	Gene expression analysis of H9 hESC derived neuron stem cells (NSC) harboring pathogenic LRRK2 (G2019S) mutation	Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study, we generated H9 hESC harboring LRRK2 (G2019S) mutation by gene knockin. Wildtype and LRRK2 mutant hESC were differentiated into NSC using a chemically defined protocol.	Co-expression
GDS4403	Genetic module and miRNome trait analyses reflect the distinct biological features of endothelial progenitor cells from different anatomic locations	Background: Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair, yet EPCs from different anatomic locations possess unique biological properties. The underlying mechanisms are unclear.     Method: We performed transcriptome analysis for EPCs isolated from 2 different sources: cord blood (CB) or adult peripheral blood (PB). Both gene expression microarray and small RNA sequencing (smRNA-seq) technologies were applied. Results: EPCs from CB expressed abundant genes involved in cell cycle, hypoxia signalling and blood vessel development, correlating with the phenotypes that CB-EPCs proliferated more rapidly, migrated faster, and formed tubule structure more efficiently. smRNA-seq further deciphered miRNome patterns in EPCs isolated from CB or PB: 54 miRNAs were enriched in CB-EPCs, while another 50 in PB-EPCs. Specifically, CB-EPCs expressed more angiogenic miRNAs such as miR-31, while PB-EPCs possessed more tumor suppressive miRNAs including miR-10a. Knocking down miR-31 levels in CB-EPCs suppressed cell migration and microtubule formation, while overexpressing miR-31 in PB-EPCs helped to recapitulate some of CB-EPC functions. Conclusion: Our results show the foundation for a more detailed understanding of EPCs from different anatomic sources. Stimulating the expression of angiogenic microRNAs or genes in EPCs of low activity (such as those from patients with cardiovascular diseases) might allow the development of novel therapeutic strategies.	Co-expression
GDS4404	Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers	Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives.	Co-expression
GDS4407	Multilineage dysplasia does not influence prognosis in patients with CEBPA mutated AML supporting the WHO proposal to classify these patients as a unique entity	By WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; ≥50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for  biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was  irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.	Co-expression
GDS4409	GAA deficiency (Pompe Disease) in infantile-onset patients	Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.	Co-expression
GDS4410	GAA deficiency (Pompe Disease) in infantile-onset patients	Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.	Co-expression
GDS4412	Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity	Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance.  Keywords: expression profiling by array	Co-expression
GDS4416	NOD2 and desease associated variant NOD2-L1007fsinsC dependent genomewide transcriptional regulation in stable Flp-In HEK cells	NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined.  To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-κB, e.g. TNFAIP3 (A20) and IER3.	Co-expression
GDS4417	Comparison of two sets of microarray experiments to define allergic asthma expression pattern	Allergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers.	Co-expression
GDS4418	Comparison of two sets of microarray experiments to define allergic asthma expression pattern	Allergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers.	Co-expression
GDS4419	Data expression in alveolar macrophages induced by lipopolysaccharide in humans	Rationale: Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases, including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens.   Objectives: To obtain insight into which innate immune pathways become activated within human alveolar macrophages upon exposure to LPS in vivo.	Co-expression
GDS4424	Virus-induced inflammatory gene networks underlying asthma exacerbations in vivo	Global patterns of gene expression was profiled in nasal lavage samples obtained from asthmatic children during an acute Picornavirus-induced exacerbation and 7-14 days later. Gene coexpression network analysis and prior knowledge was employed to reconstruct the wiring diagram of the underlying gene networks.	Co-expression
GDS4425	Comparison of mRNA expression in circulating T-cells from patients with severe asthma	Comparison of mRNA expression showed widespread changes in the circulating CD8+ but not CD4+ T-cells from patients with severe asthma. No changes were observed in the CD4+ and CD8+ T-cells in non-severe asthmatics versus healthy controls. Bioinformatics analysis showed that the changes in CD8+ T-cell mRNA expression were associated with multiple pathways involved in T-cell activation. As with mRNAs, we also observed widespread changes in expression of non-coding RNA species including natural antisense, pseudogenes, intronic long ncRNAs and long intergenic long ncRNAs in CD8+ T-cells from severe asthmatics. Measurement of the miRNA expression profile showed selective down-regulation of miR-28-5p in CD8+ T-cells and reduction of miR-146a and miR-146b in both CD4+ and CD8+ T-cells.	Co-expression
GDS4426	Gene expression pattern of skin biopsies of epidermolysis bullosa simplex patients in comparison with control subjects	Tha altered biological pathways in Epidermolysis bulloda simplex, a rare monogenetic skin disease, have not been well characterized. Thus, the goal of this study is to characterize the expression profile of EBS patients compared with normal subjects using genomic expression analyses. Microarray analyses were performed with RNA isolated from skin biopsies. Robust multiarray analysis (RMA) normalization and Smyth’s moderated t test were used to select differentially expressed genes. Expression profiling comparisons show that 28 genes are differentially expressed in EBS patients compared to control subjects and 41 genes in EBS-DM compared to their matched controls. Nine genes involved in fatty acid metabolism and 2 genes in epidermal keratinisation are common altered expressed genes between the two subgroups. These two biological pathways contribute both to the formation of the cell envelope barrier and seem to be defective in the severe EBS phenotype. This study demonstrates, for the first time, the relevance of metabolic cluster, specifically fatty acid metabolism in EBS biology. Difference of expression for three (AWAT2, ELOVL , and SPRR4 ) of the five selected genes were validated using real-time reverse transcription–polymerase chain reaction. To our knowledge, the distinctive pattern of gene expression that characterizes EBS versus healthy skin tissue has never been reported.	Co-expression
GDS4431	Autism and increased paternal age related changes in global levels of gene expression regulation	A causal role of mutations in genes encoding for multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations at the global level of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for global changes in the overall distribution of gene expression levels. For instance, in mice, we recently showed that variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in the variance in gene expression levels might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on purified RNA from peripheral blood lymphocytes of children with autism (n=82) and controls (n=64). The variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance in the overall distribution of gene expression levels. A decrease in the variance in the distribution of gene expression levels in peripheral blood lymphocytes (PBL) was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.	Co-expression
GDS4435	Expression data from patient iPSC and iPSC-derived cardiomyocytes	Dilated cardiomyopathy (DCM) is the leading cause of heart failure and transplantation worldwide. We used iPSCs to model this disease and compared gene expression change before and after gene therapy of cardiomyocytes derived from DCM-specific iPSCs. We used microarrays to detail the global gene expression of patient specific iPSCs, iPSC-derived cardiomyocytes and its response to gene therapy.	Co-expression
GDS4444	Reversal of Atopic Dermatitis with Narrow-Band UVB Phototherapy and Biomarkers for Therapeutic Response	Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response.  Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies.  Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“T22”-associated cytokines and chemokines, and normalized expression of barrier proteins.  Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD.  By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the “inside-out” hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus.	Co-expression
GDS4448	Expression data from HeLa cells transiently transfected with control siRNA or SON siRNA	SON is a large Ser/Arg (SR)-related protein localized in nuclear speckles. SON siRNA causes defects in mitotic progression and genome instability. We used microarrays to detail the pattern of gene expression after SON knockdown.	Co-expression
GDS4451	Gene expression profiles of fibroblasts and fibroblast-reprogrammed induced pluripotent stem cells (iPSCs) from childhood cerebral adrenoleukodystrophy patients and healthy controls	Although not an affected cell type, skin fibroblasts from individuals with CC-ALD, an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. Skin fibroblasts from CC-ALD patients can be reprogrammed into iPS cells with all the hallmark properties of pluripotency. The iPS cell phenotypes may reflect the tissue-specificity of the lipid metabolic defects found in CC-ALD patients. We report the gene expression profiles of fibroblasts and fibroblast-reprogrammed iPSCs from childhood cerebral adrenoleukodystrophy patients and healthy controls	Co-expression
GDS4454	FGFR3-shRNA induced transcriptional changes in RT112 bladder cancer cells	Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood.  In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development.	Co-expression
GDS4455	Discovery of genes regulated by the metastasis suppressor gene, RhoGDI2	A number of studies find that metastasis suppressor proteins, including RhoGDI2, may function in part though controlling expression of genes regulating metastasis (reviewed in Smith and Theodorescu, Nature Reviews Cancer, 2009, PMID: 19242414). To uncover systematically gene expression patterns dependent on RhoGDI2 expression, we profiled gene expression in stably transfected control (GFP empty vector) UM-UC-3 bladder carcinoma cells (which have lost endogenous expression of RhoGDI2, as occurs commonly in the progression of bladder cancer PMID: 15173088), as well as stably transfected GFP-tagged RhoGDI2 expressing UM-UC-3 cells.  References:  Moissoglu K, McRoberts KS, Meier JA, Theodorescu D et al. Rho GDP dissociation inhibitor 2 suppresses metastasis via unconventional regulation of RhoGTPases. Cancer Res 2009 Apr 1;69(7):2838-44. PMID: 19276387  Wu Y, Moissoglu K, Wang H, Wang X et al. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proc Natl Acad Sci U S A 2009 Apr 7;106(14):5807-12. PMID: 19321744  Smith SC, Theodorescu D. Learning therapeutic lessons from metastasis suppressor proteins. Nat Rev Cancer 2009 Apr;9(4):253-64. PMID: 19242414  Theodorescu D, Sapinoso LM, Conaway MR, Oxford G et al. Reduced expression of metastasis suppressor RhoGDI2 is associated with decreased survival for patients with bladder cancer. Clin Cancer Res 2004 Jun 1;10(11):3800-6. PMID: 15173088	Co-expression
GDS4456	Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer  	Urothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer.	Co-expression
GDS4458	IL-17A is an essential cytokine to sustain pathogenic cell activation and inflammatory gene circuits in psoriasis vulgaris	In psoriasis, inflammation and epidermal hyperplasia are thought to be controlled by T cell-derived cytokines. Evidence now suggests that Th17 and Th22 cells infiltrate psoriasis lesions and by secreting IL-17 and IL-22, respectively, may drive disease-specific gene or cell responses. While studies in model systems indicate that IL-22 has a dominant pathogenic role, there is evolving evidence that IL-17 contributes to features of psoriasis. To more fully understand the role of IL-17 in human disease pathogenesis, we examined psoriatic skin lesions obtained from patients treated with an anti-IL-17 (IL-17 A) monoclonal antibody, LY2439821. In a phase 1, randomized, double-blind, placebo-controlled dose escalation trial, patients with chronic psoriasis were randomized to receive 3 doses of subcutaneous LY2439821 at 5 mg (n=8), 15 mg (n=8), 50 mg (n=8), 150 mg (n=8) or placebo (n=8) at weeks 0, 2 and 4. Repeat biopsies were taken from the same lesional area at baseline, week 2 and 6. At week 6, a PASI75 was observed in 0/8, 2/8, 5/7 and 8/8 patients receiving 5 mg, 15 mg, 50 mg or 150 mg LY2439821 respectively and 0/8 patients receiving placebo. The antibody was well-tolerated. In patients receiving the two highest doses, histological and immunohistochemical analyses of biopsies revealed significant reductions from baseline in keratinocyte proliferation, hyperplasia and epidermal thickness after 2 weeks, as well as reduced infiltration into the dermis and epidermis by T-cells (CD3+) and dendritic cells (CD11c and DC-LAMP). Keratinocyte expression of innate defense proteins, S100A7, S100A8, beta-defensin2 and LL37/cathelicidin was also reduced. By week 6, the skin appeared normal with a reversal of disease defining pathological features. Quantitative RT-PCR revealed decreased expression of interferon gamma (IFN-gamma), IL-22 and IL-17, key cytokines from T cell subsets Th1, Th22 and Th17, respectively. In order to explore the extent to which IL-17 blockade influences an even broader set of inflammatory or psoriatic disease related genes, mRNA levels from skin biopsy samples were evaluated using whole genome microarrays. At week 2, the highest dose of LY2439821 modulated over 1500 genes significantly (>1.5 fold change [FC], p<0.05). Of these, 51 genes were strongly suppressed (>7-fold) including IL-19, lipocalin, amphiregulin, granzyme B, and several chemokines. In a separate analysis, those genes known to be synergistically regulated by both IL-17 and TNF-alpha showed the greatest normalization in expression compared to genes known to be regulated by TNF-alpha alone, IFN-gamma or Interferon alpha. Our data suggest that Th17 cells, through the expression of IL-17, mediate psoriasis pathogenesis, and that neutralization of IL-17 with LY2439821 suppresses signaling through multiple inflammatory circuits by inhibiting expression of cytokines from multiple T cell subsets, as well as chemokines, and antimicrobial proteins from keratinocytes.	Co-expression
GDS4459	Prevention of acute liver failure	Aim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined. The primary study objective  was to determine on a genome-wide basis whether intraoperative and intraportal treatment of the allograft with tacrolimus reduces inflammatory signature in the liver. The secondary objective was the causally test, whether suppression of genes belongong to the ontologies of inflammation and immune response by tacrolimus will lead to a better initial function of the liver.	Co-expression
GDS4460	Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.	Topical corticosteroids and calcineurin inhibitors are well known treatments of atopic dermatitis (AD), but differ in their efficacy and side effects. A study in AD patients has demonstrated that betamethasone valerate (BM) though clinically more efficient impaired skin barrier repair in contrast to pimecrolimus. Objective: The present study elucidates the mode of action of topical BM and pimecrolimus cream in AD. Methods: These two components were subjected to gene expression profile analysis in lesional AD skin after topical treatment. Results: BM resulted in a significant reduction of mRNA levels of genes encoding for markers for dendritic cells, T cells, cytokines, chemokines and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. Conclusion: The gene expression profiles are consistent with previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Hence, this study confirms the hypothesis at the molecular level that corticosteroids are a suitable treatment for acutely exacerbated AD, but that pimecrolimus is preferable for long-term treatment and stabilization.	Co-expression
GDS4464	Expression data from primary central nervous system lymphoma (PCNSL) patients	This study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed.	Co-expression
GDS4465	Expression data from high grade astrocytoma surgical samples	Survival in the majority of high grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGA would aid development of more effective therapy and prognostication. We used microarray gene expression profiling of 26 patient surgical samples with known clinical outcomes to discover novel prognostic markers.	Co-expression
GDS4466	Bone morphogenetic protein-7 is a MYC target with pro-survival functions in childhood medulloblastoma	Medulloblastoma (MB) is the most common malignant brain tumor in children, among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB.	Co-expression
GDS4467	Gene expression profiling of human gliomas and human glioblastoma cell lines	To identify signaling pathways that are differentially regulated in human gliomas, a microarray analysis on 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and on  5 glioblastoma cell lines (LN018, LN215, LN229, LN319 and BS149) was performed. Normal brain tissue (NB) and normal human astrocytes (NHA) were used as a control. Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control.  Keywords: Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control.	Co-expression
GDS4468	Gene expression profiling of human gliomas and human glioblastoma cell lines	To identify signaling pathways that are differentially regulated in human gliomas, a microarray analysis on 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and on  5 glioblastoma cell lines (LN018, LN215, LN229, LN319 and BS149) was performed. Normal brain tissue (NB) and normal human astrocytes (NHA) were used as a control. Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control.  Keywords: Kinase expression in each tumor was compared to expression in normal brain and expression values from normal human astrocytes were used as an additional control.	Co-expression
GDS4469	Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway	Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes. miRNA profiling of medulloblastomas was carried out using Taqman Low Density Density Aarray v 1.0 having 365 human microRNAs. In parallel, genome--wide expression profiling of protein coding genes was carried out using Affymetrix gene 1.0 ST arrays. Both the profiling studies identified four molecular subtypes of medulloblastomas. Expression levels of select protein-coding genes and miRNAs could classify an independent set of medulloblastomas. Twelve of 31 medulloblastomas were found to overexpress genes belonging to the canonical WNT signaling pathway and carry a mutation in CTNNB1 gene. A number of miRNAs like miR-193a, miR-224/miR-452 cluster, miR-182/miR-183/miR-96 cluster, and miR-148a having potential tumor/metastasis suppressive activity were found to be overexpressed in the WNT signaling associated medulloblastomas. Exogenous expression of miR-193a and miR-224, two miRNAs that have the highest WNT pathway specific upregulation, was found to inhibit proliferation, increase radiation sensitivity and reduce anchorage-independent growth of medulloblastoma cells. Expression level of tumor/metastasis suppressive miRNAs in the WNT signaling associated medulloblastomas is likely to determine their response to treatment, and thus, these miRNAs would be important biomarkers for risk stratification within the WNT signaling associated medulloblastomas.	Co-expression
GDS4470	Gene expression data from glioblastoma tumor samples	Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins. To further dissect the biological differences between epigenetic glioblastoma subgroups, we looked at the transcriptomic profiles of glioblastoma samples.	Co-expression
GDS4471	Novel mutations target distinct subgroups of medulloblastoma.	Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify  mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched  normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were  sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet  implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different  disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A  and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g.,  SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate  WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated  genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new  insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic  development.	Co-expression
GDS4472	OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation	The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling	Co-expression
GDS4473	Stem-like glioma-propagating cells contribute to molecular heterogeneity and survival outcome in oligodendroglial tumors	Brain tumors are among the most malignant cancers and can arise from neural stem cells or oligodendrocyte progenitor cells (OPCs). Glioma-propagating cells (GPCs) that have stem-like properties have been derived from tumor variants such as glioblastoma multiforme (GBM) and oligodendroglial tumors, the latter being more chemosensitive with better prognosis. It has been suggested that such differences in chemosensitivity arise from the different profiles of OPCs versus neural stem cells. We thus explored if GPCs derived from these glioma variants can serve as reliable in vitro culture systems for studies. We utilized gene expression analyses, since GBM and oligodendrogliomas can be molecularly classified. Accordingly, we derived a gene signature distinguishing oligodendroglial GPCs from GBM GPCs collated from different studies, which was enriched for the Wnt, Notch and TGF-beta pathways. Using a novel method in glioma biology, the Connectivity Map, we mapped the strength of gene signature association with patient gene expression profiles in 2 independent glioma databases [GSE16011, http://caintegrator-info.nci.nih.gov/rembrandt]. Our gene signature consistently stratified survival in glioma patients. This data would suggest that in vitro low passage GPCs are similarly driven by transcriptomic changes that characterize the favorable outcome of oligodendrogliomas over GBM. Additionally, the gene signature was associated with the 1p/19q co-deletion status, the current clinical indicator of chemosensitivity. Our gene signature detects molecular heterogeneity in oligodendroglioma patients that cannot be accounted for by histology or the 1p/19q status alone, and highlights the limitation of morphology-based histological analyses in tumor classification, consequently impacting on treatment decisions.	Co-expression
GDS4474	Gene expression profile of U373MG exposed to novel anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids	Background: Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2’-N-4”-pyridinecarbonyl derivative of ET-770 (ET-770-DR; the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG. Methods: We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. Results: All of these compounds dissolved in dimethyl sulfoxide (DMSO) as a vehicle induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B. Conclusion: Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets.	Co-expression
GDS4475	Tetracycline-Inducible Cyr61 effect on LN229 glioma cells	Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting, but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy. We used microarray to detail the global program of gene expression underlying Cyr61 mediated oncolytic HSV-1 inhibition and identified distinct classes of up-regulated genes during this process.	Co-expression
GDS4476	Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival	Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.	Co-expression
GDS4477	Frequent driver mutations in histone H3.3 and chromatin remodeling genes in paediatric glioblastoma	Whole exome sequencing identified frequent driver mutations in a series of paediatric glioblastomas We used microarray-based profiling to investigate differences in gene expression according to mutational status of driver genes	Co-expression
GDS4482	Engineering endochondral ossification using Sonic Hedgehog for bone regeneration	Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration.	Co-expression
GDS4487	Suppression of IFN-induced transcription underlies IFN defects generated by activated Ras/MEK in human cancer cells	Certain oncolytic viruses exploit activated Ras signalling in order to replicate in cancer cells. Constitutive activation of the Ras/MEK pathway is known to suppress the effectiveness of the interferon (IFN) antiviral response, which may contribute to Ras-dependent viral oncolysis. Here, we identified 10 human cancer cell lines (out of 16) with increased sensitivity to the anti-viral effects of IFN-α after treatment with the MEK inhibitor U0126, suggesting that the Ras/MEK pathway underlies their reduced sensitivity to IFN. To determine how Ras/MEK suppresses the IFN response in these cells, we used DNA microarrays to compare IFN-induced transcription in IFN-sensitive SKOV3 cells, moderately resistant HT1080 cells, and HT1080 cells treated with U0126. We found that 267 genes were induced by IFN in SKOV3 cells, while only 98 genes were induced in HT1080 cells at the same time point. Furthermore, the expression of a distinct subset of IFN inducible genes, that included RIGI, GBP2, IFIT2, BTN3A3, MAP2, MMP7 and STAT2, was restored or increased in HT1080 cells when the cells were co-treated with U0126 and IFN. Bioinformatic analysis of the biological processes represented by these genes revealed increased representation of genes involved in the anti-viral response, regulation of apoptosis, cell differentiation and metabolism. Furthermore, introduction of constitutively active Ras into IFN sensitive SKOV3 cells reduced their IFN sensitivity and ability to activate IFN-induced transcription. This work demonstrates for the first time that activated Ras/MEK in human cancer cells induces downregulation of a specific subset of IFN-inducible genes.	Co-expression
GDS4489	DNA microarrays of Turner Syndrome induced pluripotent stem cells	We have generated iPSCs from monosomy X (Turner Syndrome), trisomy 8 (Warkany Syndrome 2), trisomy 13 (Patau Syndrome) and partial trisomy 11;22 (Emanuel Syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells (ESCs) in all tested assays. Turner Syndrome iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body (EB) formation. These data support that abnormal organogenesis and early lethality in Turner Syndrome are not caused by a tissue-specific differentiation blockade but rather involves other abnormalities including impaired placentation.	Co-expression
GDS449	Cell cycle and Tat transactivation	Analysis of effect of Tat transactivation during cell cycle. HeLa CD4+ cells transfected with epitope-tagged Tat plasmid or parental vector pCEP4. Cells synchronized with cell cycle blocker hydroxyurea or nocodazole and sampled at 0, 3, 6 and 9 hours.	Co-expression
GDS4491	Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities	Atopic dermatitis (AD) is a common inflammatory skin disease with a T(H)2 and T22 immune polarity. Despite recent data showing a genetic predisposition to epidermal barrier defects in some patients, a fundamental debate still exists regarding the role of barrier abnormalities versus immune responses in initiating the disease. An extensive study of nonlesional AD (ANL) skin is necessary to explore whether there is an intrinsic predisposition to barrier abnormalities, background immune activation, or both in patients with AD. We sought to characterize ANL skin by determining whether epidermal differentiation and immune abnormalities that characterize lesional AD (AL) skin are also reflected in ANL skin.  We performed genomic and histologic profiling of both ANL and AL skin lesions (n = 12 each) compared with normal human skin (n = 10). We found that ANL skin is clearly distinct from normal skin with respect to terminal differentiation and some immune abnormalities and that it has a cutaneous expansion of T cells. We also showed that ANL skin has a variable immune phenotype, which is largely determined by disease extent and severity. Whereas broad terminal differentiation abnormalities were largely similar between involved and uninvolved AD skin, perhaps accounting for the background skin phenotype, increased expression of immune-related genes was among the most obvious differences between AL and ANL skin, potentially reflecting the clinical disease phenotype. Our study implies that systemic immune activation might play a role in alteration of the normal epidermal phenotype, as suggested by the high correlation in expression of immune genes in ANL skin with the disease severity index.	Co-expression
GDS4497	The expression profiles of AML cell lines	EVI1 is one of the famous poor prognostic markers for a chemotherapy-resistant acute myeloid leukemia (AML). To identify molecular targets on the surface of leukemia cells with EVI1high expression, we compared the gene expression profiles of several AML cell lines by DNA microarray	Co-expression
GDS4500	Gene expression profiling in acute myeloid leukemia with mutated NPM	Approximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of Nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal.  These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor.	Co-expression
GDS4501	Gene expression profiling in acute myeloid leukemia with mutated NPM	Approximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of Nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal.  These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor.	Co-expression
GDS4509	Expression data from normal human fibroblasts expressing prelamin A or progerin, untreated or treated with farnesyltransferase inhibitor (FTI)	We compared the transcriptomes of isogenic diploid fibroblasts expressing progerin or elevated levels of wild-type prelamin A with that of wild-type fibroblasts. We subsequently used the reversion towards normal of two phenotypes, reduced cell growth and dismorphic nuclei, by treatment with farnesyltransferase inhibitor (FTI) or overexpression of ZMPSTE24, as a filtering strategy to identify genes linked to the onset of these two phenotypes.	Co-expression
GDS4511	Roles of  EMT regulator in colon cancer	Isolation and enrichment of cancer stem cells in colorectal carcinoma to study role of epithelial-mesenchymal transition regilators in tumor malignancy.	Co-expression
GDS4512	Expression data from colon fibroblasts treated with Sonic hedgehog homolog (SHH)	Canonical Hedgehog (Hh) signaling regulates the expression of genes that are critical to the patterning and development of a variety of organ systems. In adult, both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligand, activation occurs within the stromal microenvironment (Yauch et al., 2009). In situ hybridization of the pathway target gene, Ptch1, shows that signaling is located at stromal perivascular fibroblast-like cells in xenograft tumor sections derived from Hh-expressing colorectal cancer cell lines. To study the downstream genes regulated by Hh signaling, we treated a primary human colon myofibroblast, CCD-18Co, with SHH (1 ug/ml) or no treatment (control) in serum-free medium supplemented with 0.1% BSA for 72 hrs and performed microarray analysis (Affymetrix U133P) on these samples.	Co-expression
GDS4513	Correlation of molecular profiles and clinical outcome of stage UICC II colon cancer patients	Background  Published multi-gene classifiers suggested outcome prediction for patients with stage UICC II colon cancer based on different gene expression signatures. However, there is currently no translation of these classifiers for application in routine diagnostic. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable RNA and protein detection in routine diagnostic specimens.    Results  Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of five selected previously published classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). Correlation of protein expression data with clinical outcome within a 5-year post-surgery course failed to separate patients with a disease-free follow-up [Group DF] and relapse [Group R]). In addition, RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by Nearest Shrunken Centroids with cross-validation. Although gene expression profiling allowed the identification of differentially expressed genes between the groups DF and R, a stable classification and prognosis signature was not discernable in our data. Furthermore, the application of previously published gene signatures consisting of 22 and 19 genes, respectively, to our gene expression data set using ‘global tests’ and leave-one-out cross-validation was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse in multivariate analysis with established clinical and pathological parameters including microsatellite status.  Conclusions  Our protein and gene expression analyses currently do not support application of molecular classifiers for prediction of clinical outcome in routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.	Co-expression
GDS4515	Expression data from human MSI colorectal cancer and normal colonic mucosa	Microsatellite instability (MSI), caused by defective mismatch repair, is observed in a subset of colorectal cancers (CRCs). We evaluated somatic mutations in microsatellite repeats of genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat.	Co-expression
GDS4516	Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer	Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC.	Co-expression
GDS4519	Genome wide expression data from discordant twins (ulcerative colitis, primary mucosal tissue)	Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo.   Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblings’ microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings.  Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal  bacterial species.	Co-expression
GDS4521	Blood genomic expression profile for ischemic stroke (IS)	Stroke is a “brain attack” cutting off vital blood, and consequently the nutrients and oxygen vital to the brain cells that control everything we do. Stroke is a complex disease with unclear pathogenesis resulting from environmental and genetic factors. To better understand IS´s etiology, we performed genomic expression profiling of patients and controls.	Co-expression
GDS4522	Comparison of post-mortem tissue from Brodman Brain BA22 region between schizophrenic and control patients	Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development Schizophrenia is a highly debilitating psychiatric disorder which is known to have heritable genetic and environmental components. To gain some insight into the mechanisms underpinning both positive and negative symptoms of the disease, we determined the genome wide expression of mRNA transcripts in post-mortem tissue from the superior temporal cortex (Brodmann Area 22, BA22) in schizophrenic and control patients. The BA22 region is known to mediate the positive pathophysiology of schizophrenia; we compared this to the anterior prefrontal cortex (BA10) from the same subjects, which is known to mediate negative symptoms. Following adjustments for confounding clinical, sample and experimental sources of variation, we carried out gene set enrichment analysis in each region using pathway data. We identified an over-representation of genes involved in cytoskeletal remodelling, neurodevelopment, cell adhesion, cellular signalling, neurotransmission and autophagy. Collectively our analysis indicates a disruption of processes underpinning synaptic plasticity in both regions. Region-specific changes support the dysregulation of distinct pathways in the BA10 and BA22 regions. This may highlight new therapeutic opportunities to treat both negative and positive symptoms of the disease.	Co-expression
GDS4523	Comparison of post-mortem tissue from brain BA10 region between schizophrenic and control patients.	Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients.	Co-expression
GDS4532	Patterns of gene expression and evolution in the human developing cerebral cortex	The cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown.  In order to uncover genetic networks underlying the development of the human cerebral cortex, we profiled the transcriptome of human fetal cortical domains containing language areas of Broca and Wernicke, as well as associative areas. We thus identified hundreds of genes displaying differential expression between the two areas or between distinct temporal stages. A subset of these genes was further validated by qRTPCR and in situ hybridization, revealing novel patterns of area and layer-specific expression throughout the developing cortex at midgestation, a critical period of cortical patterning.  Computational genomic analyses revealed that the proportion of genes located close to evolutionarily accelerated regions was far more abundant among the genes differentially expressed between the two cortical areas examined, but not among those differentially expressed between different stages of development. In silico screening enabled to identify accelerated regions displaying increased turnover of change in transcription factor binding sites, which were enriched among those closer to genes differentially expressed between cortical areas.  Overall our work points to the identification of cortical genes that display a unique combination of patterns of evolution and expression, which may constitute an important part of the genetic framework underlying human-specific neural traits and diseases.	Co-expression
GDS4535	Microarray analysis of differentiation of human glioblastoma stem cells	Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NFκB was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NFκB signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NFκB target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NFκB pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NFκB may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation.	Co-expression
GDS4536	A Computational Profiling of Changes in Gene Expression and Transcription Factors Induced by vFLIP K13 in Primary Effusion Lymphoma	Infection of Kaposi's sarcoma associated herpes virus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), which is characterized by the loss of expression of  B cell markers and effusions in the body cavities. This unique clinical feature of PEL has been attributed to their distinctive  gene expression profile which shows overexpression of genes in various signaling pathways. KSHV-encoded latent protein vFLIP K13 has been  shown to promote the survival and proliferation of PEL cells. In this study, we have employed gene array analysis followed by bioinformatics analysis of coordinated transcriptional factors network as well as biological pathways  to characterize the effect of K13 on PEL-derived BCBL1 cells. We observed that genes associated with Cytokine signaling, Cell death, NF-kappaB and Cell adhesion pathways were differentially regulated by K13. We used computational approach complemented with microarrays to detail the global gene expression and identified distinct classes of differentially regulated genes in various cellular processes.	Co-expression
GDS4538	Impaired intrinsic immunity to HSV-1  in human iPSC-derived TLR3-deficient CNS cells	In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies	Co-expression
GDS4539	In vitro responses of PBMC and fibroblasts from patients with TRIF deficiency after TRIF dependent and independent stimuli	We report here unrelated HSE patients with autosomal recessive (AR) or autosomal dominant (AD) TRIF deficiency. The AR form of the disease is due to a homozygous nonsense mutation, resulting in a complete absence of the TRIF protein. Both the TLR3 and the TRIF-dependent TLR4 signaling pathways are abolished. The AD form of TRIF deficiency is due to a heterozygous missense mutation resulting in a dysfunctional protein. The TLR3 signaling pathway is impaired, whereas the TRIF-dependent TLR4 pathway is unaffected. Both patients however showed reduced capacity to respond to cytosolic double stranded RNA, consistent with recent reports of TRIF’s involvement in the DExD/H-box helicases pathway.	Co-expression
GDS4540	In vitro responses of PBMC and fibroblasts from patients with TRIF deficiency after TRIF dependent and independent stimuli	We report here unrelated HSE patients with autosomal recessive (AR) or autosomal dominant (AD) TRIF deficiency. The AR form of the disease is due to a homozygous nonsense mutation, resulting in a complete absence of the TRIF protein. Both the TLR3 and the TRIF-dependent TLR4 signaling pathways are abolished. The AD form of TRIF deficiency is due to a heterozygous missense mutation resulting in a dysfunctional protein. The TLR3 signaling pathway is impaired, whereas the TRIF-dependent TLR4 pathway is unaffected. Both patients however showed reduced capacity to respond to cytosolic double stranded RNA, consistent with recent reports of TRIF’s involvement in the DExD/H-box helicases pathway.	Co-expression
GDS4541	The transcriptional modulator H2AFY marks Huntington's disease activity in men and mice	To accelerate the development of disease-modifying therapeutics for Huntington’s disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed.	Co-expression
GDS4544	Microarray gene expression profiling of kinase-dependent and kinase-independent effects of GRK2	The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2, ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice.	Co-expression
GDS4547	Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma	Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. We used microarray analysis to evaulate the effect of ischemia and tissue procurement conditions on the gene expression changes in renal cell carcinoma	Co-expression
GDS4548	Modulation of gene expression in cultured human intestinal colon explants by probiotic bacteria	Background: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p ≤ 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-γ, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells.	Co-expression
GDS4549	Gene expression profiles based on Pulmonary Artery Pressures in Pulmonary Fibrosis	Pulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear. We used microarray to identifiy the gene expression profiles in PF patients with and without PH	Co-expression
GDS4550	Whole blood gene expression data from PFAPA syndrome	PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown. In order to shed more insights into pathogenesis, we performed microarray expression analysis on samples from patients with PFAPA during and between flares, healthy controls and patients with hereditary autoinflammatory diseases during flares.	Co-expression
GDS4551	Microarray analysis of IL-10 stimulated adherent peripheral blood mononuclear cells	The immune mechanisms that control resistance vs. susceptibility to mycobacterial infection in humans were investigated by studying leprosy skin lesions, the site where the battle between the host and the pathogen is joined.  Using an integrative genomics approach, we found an inverse correlation between of IFN-beta and IFN-gamma gene expression programs at the site of disease.  The Type II IFN, IFN-gamma and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in the lesions from patients with the self-healing tuberculoid form of the disease and mediated antimicrobial activity against the pathogen, Mycobacterium leprae in vitro.  In contrast, the Type I IFN, IFN-beta and its downstream genes, including IL-27 and IL-10, were induced in monocytes by M. leprae in vitro, and were preferentially expressed in the lesions of disseminated and progressive lepromatous form.  The IFN-gamma induced macrophage antimicrobial response was inhibited by IFN-beta/IL-10, by a mechanism involving blocking the generation of bioactive 1,25-dihyroxy vitamin D as well as inhibiting induction of antimicrobial peptides cathelicidin and DEFB4.  The ability of IFN-B to inhibit the IFN-gamma induced vitamin D pathway including antimicrobial activity was reversed by neutralization of IL-10, suggesting a possible target for therapeutic intervention.  Finally, a common IFN-beta and IL-10 gene signature was identified in both the skin lesions of leprosy patients and in the peripheral blood of active tuberculosis patients.  Together these data suggest that the ability of IFN-beta to downregulate protective IFN-gamma responses provides one general mechanism by which some bacterial pathogens of humans evade protective host responses and contribute to pathogenesis.	Co-expression
GDS4557	Human CD34+-derived erythoblast (polychromatophilic and orthochromatic) response to co-culture with Plasmodium falciparum 3D7	Global, genomic responses of erythrocytes to infectious agents have been difficult to measure, because these cells are e-nucleated. We have previously demonstrated that in vitro matured, nucleated erythroblast cells at the orthochromatic stage can be efficiently infected by the human malaria parasite Plasmodium falciparum. We now show that infection of orthochromatic cells induces change in 609 host genes. 592 of these transcripts are up-regulated and associated with metabolic and chaperone pathways unique to P. falciparum infection, as well as a wide range of signaling pathways that are also induced in related apicomplexan infections of mouse hepatocytes or human fibroblast cells. Our data additionally show that polychromatophilic cells, which precede the orthochromatic stage and are not infected when co-cultured with P. falciparum, up-regulate a small set of 35 genes, 9 of which are associated with pathways of hematopoiesis and/or erythroid cell development. These data unexpectedly predict that blood stage P. falciparum may induce host responses common to infections of other pathogens. Further P. falciparum may modulate gene expression in bystander erythroblasts and thus influence pathways of erythrocyte development.	Co-expression
GDS4558	Human CD34+-derived erythoblast (polychromatophilic and orthochromatic) response to co-culture with Plasmodium falciparum 3D7	Global, genomic responses of erythrocytes to infectious agents have been difficult to measure, because these cells are e-nucleated. We have previously demonstrated that in vitro matured, nucleated erythroblast cells at the orthochromatic stage can be efficiently infected by the human malaria parasite Plasmodium falciparum. We now show that infection of orthochromatic cells induces change in 609 host genes. 592 of these transcripts are up-regulated and associated with metabolic and chaperone pathways unique to P. falciparum infection, as well as a wide range of signaling pathways that are also induced in related apicomplexan infections of mouse hepatocytes or human fibroblast cells. Our data additionally show that polychromatophilic cells, which precede the orthochromatic stage and are not infected when co-cultured with P. falciparum, up-regulate a small set of 35 genes, 9 of which are associated with pathways of hematopoiesis and/or erythroid cell development. These data unexpectedly predict that blood stage P. falciparum may induce host responses common to infections of other pathogens. Further P. falciparum may modulate gene expression in bystander erythroblasts and thus influence pathways of erythrocyte development.	Co-expression
GDS4559	Gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls	Although not an affected cell type, skin fibroblasts from individuals with childhood cerebral adrenoleukodystrophy (CCALD), an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. We report the gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls	Co-expression
GDS4560	Expression data from oral squamous cell carcinoma (OSCC)-derived cell lines and normal oral keratinocytes	Oral squamous cell carcinoma (OSCC) is a lethal disease and early death usually occurs as a result of local invasion and regional lymph node metastases. We used microarrays to identify down or upregulated genes in OSCCs compared with non-malignant controls.	Co-expression
GDS4562	A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence	Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients.	Co-expression
GDS4567	Filarial nematode AsnRS interacts with interleukin 8 receptors in iDCs but causes different gene expression patterns compared to iDCs stimulated by interleukin 8.	Nematode derived  substances are known to down regulate host immune responses in order to survive in the human host. Brugia malayi is a parasitic nematode responsible for long lasting and disabling infection known as lymphatic filariasis in humans.  The therapeutic benefit of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) has been demonstrated in both animal and human models.  However the inability of individual purified nematode proteins to recreate this beneficial effect has limited the application of component immunotherapy to human disease. This experiment addresses the hypothesis that the genes regulated by IL8 and recombinant Brugia malayi AsnRS (rBmAsnRS) are different even though it is known that both molecules interact with IL-8 receptors. Furthermore, we theorize that the signal transduction pathways activated by IL-8 and rBmAsnRS are different because it is known that the extracellular G protein loops utilized by IL-8 and rBmAsnRS to activate IL8 receptors, are different.   These results obtained with a single recombinant nematode protein, rBmAsnRS, share immunological features with those observed in a whole nematode infection and include desirable features for treatment of idiopathic inflammatory diseases, such as IBD.	Co-expression
GDS4569	Host gene expression response to Toxoplasma gondii infection is not different between RH∆ku80 and RH∆ku80∆rop5 parasites	The normally virulent type-I RH parasite is rendered avirulent when lacking ROP5. The avirulent phenotype is a consequence of interaction with the host innate immune system. We sought to understand if ROP5 alters host gene expression in order to escape host defenses. We saw no gene expression differences between host cells infected with wt (RH∆ku80) or RH∆ku80∆rop5 parasites. We have included uninfected HFF samples that were harvested in parallel with the infected samples.	Co-expression
GDS4574	Expression data from human primary fibroblasts treated with Trypanosoma cruzi-conditioned medium	The intracellular pathogen Trypanosoma cruzi secretes an activity that blocks TGF-β-dependent induction of connective tissue growth factor (CTGF/CCN2).  Here, we address the mechanistic basis for T. cruzi-mediated interference of CTGF/CCN2 expression by examining host cell signaling pathways and the global inhibitory effect on TGF-β-dependent gene expression. We show that the expression of a discrete subset of TGF-β-inducible genes involved in cell proliferation, wound repair, and immune regulation are blocked by the soluble T. cruzi activity, demonstrating that this parasite-derived activity has broad, but specific effects on fibroblast gene regulation.	Co-expression
GDS4580	Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis:  A model for “active” disease	Genomic profiling of RNA from cultured human fibroblasts of donor samples in the 10-14th passage was carried out to determine expression changes in the fibroblasts of individual with different degrees of pulmonary fibrosis. Donors consisted of individuals with rapid progressing pulmonary fibrosis, slow progressing pulmonary fibrosis, or no fibrosis.	Co-expression
GDS4587	Sarcoidosis-specific markers from whole blood gene expression	We hypothesized that microarray analyses of whole blood gene expression would identify patterns of gene expression useful in the diagnosis for sacroidosis and identify inflammatory mediators relevant to the underlying pathophysiology.	Co-expression
GDS4589	Gene Expression Analysis of Stage I Endometrial Cancers	Global gene expression patterns associated with early stage endometrial cancer have been reported, but changes in molecular expression associated with tumor grade, depth of myometrial invasion, and non-endometrioid histology have not been previously elucidated.  Our group hypothesized there are unique genetic events underlying early endometrial carcinogenesis.  Ninety-two samples of pathologically reviewed stage I endometrial cancers (80 endometrioid and 12 serous) with a heterogeneous distribution of grade and depth of myometrial invasion (i.e. 9 IAG1, 14 IAG2, 7 IAG3, 14 IBG1, 12 IBG2, 13 IBG3, 7 ICG1, 10 ICG2, and 6 ICG3)  were examined in relation to 12 samples of atrophic endometrium from postmenopausal women.  Specimens were analyzed using oligonucleotide microarray analysis and a subset of the differentially expressed transcripts was validated using quantitative PCR.  Comparison of early stage cancers with normal endometrium samples by the univariate t-test with 10,000 permutations identified 900 genes that were differentially regulated by at least 4-fold at a p value of <0.001.   Unsupervised analysis revealed that when compared to normal endometrium, serous and endometrioid stage I cancers appeared to have similar expression patterns.  However, when compared in the absence of normal controls, they were distinct.   Differential expression analysis revealed a number of transcripts that were common as well as unique to both histologic types.  This data uncovers previously unrecognized, novel pathways involved in early stage endometrial cancers and identifys targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.	Co-expression
GDS4592	Transcriptomic Analysis of Placenta Affected by Antiphospholipid Antibodies: Following the TRAIL of trophoblast death	Antiphospholipid antibodies, a maternal risk factor for preeclampsia, increase shedding of necrotic trophoblast debris from the placenta, leading to endothelial dysfunction. Using Affymetrix HGU133 Plus 2 microarrays, we found changes in the transcriptome of placental explants treated with antiphospholipid antibodies including seven mRNAs encoding for genes BCL2L1, MCL1, PDCD2L, FASLG, SEMA6A, PRKCE and TRAIL that are involved in the regulation of apoptosis. Quantitative real-time RT-PCR and immunohistochemistry confirmed a reduction in TRAIL expression. These results may help to understand how antiphospholipid antibodies affect trophoblast cell death and how the antibodies could contribute to the pathogenesis of preeclampsia.	Co-expression
GDS4593	Identification of a Myometrial Molecular Profile for Dystocic Labor	This study identifies a transciptomic myometrial profile associated with dystocia in spontanous nulliparous term labour We used microarrays to compare myometrial biopsies obtained at cesarean section from women in spontaneous term labour	Co-expression
GDS4595	Expression data from human amnion mesenchymal cells treated with interleukin-1-beta for 1hr and 8hr	Premature birth continues to be a challenging pregnancy complication, and a body of literature indicates that inflammation can contribute to premature delivery by converting a receptive uterine environment to a hostile one.  Cytokines have been demonstrated to provoke up-regulation of inflammatory genes (e.g. interleukin-1, 6, and 8, tumor necrosis factor-alpha, cyclooxygenase-2, and microsomal prostaglandin E synthase-1). Using monolayer cultures of human amnion mesenchymal cells (AMCs) as a model, we aimed to detail the global programme of gene expression that occurs in response to cytokine challenge.	Co-expression
GDS4596	Roles of  EMT regulator in colon cancer	Isolation and enrichment of cancer stem cells in colorectal carcinoma to study role of epithelial-mesenchymal transition regilators in tumor malignancy.	Co-expression
GDS4597	TREM-1 is a novel therapeutic target in Psoriasis	Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.	Co-expression
GDS4598	A global transcriptome analysis of keratinocytes upon suppression of endogenous microRNA-31	MiR-31 is one of the most highly overexpressed miRNAs in psoriasis skin; however, its biological role in the disease has not been studied. Here we show that miR-31 is markedly overexpressed in psoriasis keratinocytes. To study the biological role of miR-31 in keratinocytes, we transfected miR-31 hairpin inhibitor (anti-miR-31) into primary human keratinocytes to inhibit endogenous miR-31. We performed a global transcriptome analysis of keratinocytes upon suppression of endogenous miR-31 using Affymetrix arrays.	Co-expression
GDS4599	ZNF750 in late keratinocyte differentiation	Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrheic dermatitis. We defined ZNF750 as a nuclear effector that is strongly activated in and essential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of  epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differentiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier	Co-expression
GDS4600	Expression data from skin biopsy samples from patients with moderate-to-severe psoriasis	A gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin.	Co-expression
GDS4601	Expression data from primary human keratinocytes exposed to cytokines in vitro (IL-4, IL-13, IL-17A, IFN-alpha, IFN-gamma, TNF)	The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin.	Co-expression
GDS4602	Gene expression data of skin from psoriatic patients and normal controls	Gene expression has been proposed as an intermediate phenotype that can increase power in complex trait gene-mapping studies. Psoriasis, an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints, provides an ideal model system to evaluate this paradigm, as conclusive evidence demonstrates that psoriasis has a genetic basis and the disease tissue is readily accessible. To better understand the complex nature of processes in psoriasis, we characterize gene expression profiles in uninvolved and involved skin from affected individuals as well as normal skin from control individuals.  Keywords: disease state analysis	Co-expression
GDS4606	Post-therapeutic relapse of psoriasis associated with CD11a blockade is associated with T cells and inflammatory myeloid DCs	To understand the development of new psoriasis lesions, we studied a group of moderate-to-severe psoriasis patients who experienced a relapse after ceasing efalizumab (anti-CD11a, Raptiva, Genentech). There were increased CD3+ T cells, neutrophils, CD11c+ and CD83+ myeloid DCs, but no increase in CD1c+ resident myeloid DCs. In relapsed lesions, there were many CD11c+CD1c-, inflammatory myeloid DCs identified by TNFSF10/TRAIL, TNF, and iNOS. CD11c+ cells in relapsed lesions co-expressed CD14 and CD16 in situ. Efalizumab induced an improvement in many psoriasis genes, and during relapse, the majority of these genes reversed back to a lesional state. Gene Set Enrichment Analysis (GSEA) of the transcriptome of relapsed tissue showed that many of the gene sets known to be present in psoriasis were also highly enriched in relapse. Hence, on ceasing efalizumab, T cells and myeloid cells rapidly enter the skin to cause classic psoriasis.	Co-expression
GDS4607	A single intradermal injection of IFN-γ induces a psoriasis-like state in both non-lesional psoriatic and healthy skin	Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of T cells and dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, important contributors to the inflammatory cascade in psoriasis lesions.  To determine if IFN-γ indeed induces the pathways leading to the development of psoriasis lesions, a single intradermal injection of IFN-γ was administered to an area of clinically normal, non-lesional skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-γ induced molecular and histological features characteristic of psoriasis lesions.  IFN-γ increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products TNF, iNOS, IL-23, and TRAIL were present in IFN-γ-treated skin. Thus, IFN-γ, which is significantly elevated in non-lesional skin compared to healthy skin, appears to be a key pathogenic cytokine that can induce the inflammatory cascade in psoriasis.	Co-expression
GDS4608	Human keratinocytes have a response to injury that upregulates CCL20 and other genes linking innate and adaptive immunity	In the early stages of wound healing, keratinocytes become “activated” and release inflammatory molecules such as interleukin-1 and interleukin-8 that are linked to innate immune responses and neutrophil recruitment. It is unclear, however, whether keratinocytes release molecules linked to adaptive immune responses, e.g. CCL20, in their early state of activation without signals from infiltrating T cells. This study aims to isolate the immediate alterations in protective and inflammatory gene expression that occur in epidermal keratinocytes, with a particular focus on molecules associated with cell-mediated immunity. We used dispase-separated epidermis, followed by intercellular disassociation by trypsinization, as a model for epidermal injury. We obtained a pure population of keratinocytes using flow cytometry. As a control for uninjured epidermis, we performed laser capture microdissection on normal human skin. Sorted keratinocytes had an early burst of upregulated gene expression, which included CCL20, IL-15, IL-23A, IFN-κ, and several antimicrobial peptides. Our results provide insight into the potential role of keratinocytes as contributors to cell-mediated inflammation, and expand knowledge about gene modulation that occurs during early wound healing. Our findings may be relevant to cutaneous diseases such as psoriasis, where micro-injury can trigger the formation of psoriatic plaques at the site of trauma.	Co-expression
GDS4610	Synthetic circuits for tracking human cell fate	Cells respond heterogeneously to DNA damage. We engineered genetic circuits to detect differential responses in a population that persist for many days post-stimulus. We used microarrays to compare memory and non-memory subpopulations 3 days after DNA damage or doxycycline exposure.	Co-expression
GDS4618	Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas	Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics.  Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and half of the cases are highly aggressive.  By treating NB cell lines (SKNAS, SKNBE(2)C, CHP134, SY5Y) with epigenetic modifiers for a short time followed by sphere-forming culture conditions, we have established stem cell-like NB cells that are phenotypically stable for over a year.  These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure.  We referred to these cells as induced CSC (iCSC).  SKNAS iCSC and SKNBE(2)C iCSC clones (as few as 100 cells) injected subcutaneously into SCID/Beige mice formed tumors, and in one case, SKNBE(2)C iCSC metastasized to the adrenal gland, suggesting their increased metastatic potential.  SKNAS iCSC xenografts showed the histologic appearance of totally undifferentiated “large-cell” NBs (LCNs), the most aggressive and deadly form of NB in humans.  Immunohistochemical analyses showed that SKNAS iCSC xenografts expressed high levels of the stem cell marker CXCR4, while the SKNAS monolayer cell xenografts did not.  The patterns of CXCR4 and MYC expression in SKNAS iCSC xenografts resembled those in the LCNs.  The xenografts established from the NB iCSCs shared two common features: the LCN phenotype and high-level MYC/MYCN expression.  These observations suggest that NB cells with large and vesicular nuclei, representing their open chromatin structure, are indicative of stem cell-like tumor cells, and that epigenetic changes may have contributed to the development of these most malignant NB cells.	Co-expression
GDS4620	Comparison of bone-marrow mesenchymal stromal cells from multiple myeloma patients and healthy donors	It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,…) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1β and TNF-α as compared with normal BM-MSCs.  In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs.	Co-expression
GDS4664	Involvement of the TGF-β and β-catenin pathways in pelvic lymph node metastasis in early stage cervical cancer	Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer. Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways. Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05). Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer.	Co-expression
GDS4665	Expression data from HeLa cells treated with Casiopeina Cas-II-gly	Copper-based chemotherapeutic compounds Casiopeinas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application. Microarrays were used to determine the expression profile from HeLa cells in order to propose a model for the role played by intrinsic apoptosis triggered by the oxidative stress caused by Cas-II-gly.	Co-expression
GDS4669	Impaired intrinsic immunity to HSV-1  in human iPSC-derived TLR3-deficient CNS cells	In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies	Co-expression
GDS470	Cervical cancer	Expression profiling of normal and cancerous cervix tissue samples at stages 1B, 2A, 2B and 3B.	Co-expression
GDS4700	Expression of BRAF inhibitor resistant colon cancer lines	Colon cancer cell lines with partial sensitivity to the BRAF inhibitor PLX4720 were grown in increasing concentration of the drug to develop acquired resistance.  Gene expression was performed for comparison of the resistant clones to the parental lines.	Co-expression
GDS4718	Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer	Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC.	Co-expression
GDS4719	Activation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation	CD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE.  All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease.  Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCRζ protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.	Co-expression
GDS472	Muscle function and aging - female (HG-U133A)	Comparison of gene expression in vastus lateralis skeletal muscle biopsies in healthy young (20-29 year old) and older (65-71 year old) women	Co-expression
GDS473	Muscle function and aging - female (HG-U133B)	Comparison of gene expression in vastus lateralis skeletal muscle biopsies in healthy young (20-29 year old) and older (65-71 year old) women	Co-expression
GDS4754	Gene expression profile of the human T-ALL cell line JURKAT after TYK2 and STAT1 knockdown	Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the JAK tyrosine kinase family, TYK2, and its downstream effector STAT1 in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently demonstrated TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK kinase activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of IL-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the anti-apoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway.	Co-expression
GDS4756	The effect of IM and MSC treatment on gene expression in CML CD34+ cells	Tyrosine kinase inhibitors (TKI) are highly effective in treatment of chronic myeloid leukemia (CML) but do not eliminate leukemia stem cells (LSC), which remain a potential source of relapse. TKI treatment effectively inhibits BCR-ABL kinase activity in CML LSC, suggesting that additional kinase-independent mechanisms contribute to LSC preservation. We investigated whether signals from the bone marrow (BM) microenvironment protect CML LSC from TKI treatment. Coculture with human BM mesenchymal stromal cells (MSC) significantly inhibited apoptosis and preserved CML stem/progenitor cells following TKI exposure, maintaining colony forming ability and engraftment potential in immunodeficient mice. We found that the N-Cadherin receptor plays an important role in MSC-mediated protection of CML progenitors from TKI. N-Cadherin-mediated adhesion to MSC was associated with increased cytoplasmic N-Cadherin-β-catenin complex formation, as well as enhanced β-catenin nuclear translocation and transcriptional activity. Increased exogenous Wnt-mediated β-catenin signaling played an important role in MSC-mediated protection of CML progenitors from TKI treatment. Our results reveal a close interplay between N-Cadherin and the Wnt-β-catenin pathway in protecting CML LSC during TKI treatment. Importantly, these results reveal novel mechanisms of resistance of CML LSC to TKI treatment, and suggest new targets for treatment designed to eradicate residual LSC in CML patients.	Co-expression
GDS4758	Expression data from post mortem Alzheimer's disease brains	To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and Alzheimer’s disease.	Co-expression
GDS476	HCMV infection of foreskin fibroblasts	Expression profiles of foreskin fibroblasts at 12 time points beginning 30 minutes after infection by human cytomegalovirus (HCMV) and continuing until 48 hours after infection.	Co-expression
GDS4760	Gene expression profiling in true interval breast cancer reveals overactivation of mTOR signalling pathway	Background: Interval breast cancers can occur through failure to detect an abnormality at the time of screening (missed interval cancer), or as a new event after a negative screen (true interval cancer). The development and progression of true interval tumors (TIBC) is known to be different than screen-detected tumors (SDBC). However, much work still needs to be done to understand the biological characteristics and clinical behaviour of these TIBC.  Objectives: To characterize the gene expression profile in TIBC and SDBC aimed to identify biological markers that may be associated with the emergence of symptomatic breast cancer in the screening interval.   Material and Methods: An unsupervised exploratory gene expression profile analysis was performed among 10 samples (discovery set, TIBC=5 and SDBC=5) using Affymetrix Human Gene 1.0 ST arrays and interpreted by Ingenuity Pathway Analysis. Differential expression of selected genes was confirmed in validation series of 91 patients (TIBC=12 and SDBC=79) by immunohistochemistry and 24 patients (TIBC=8 and SDBC=16) by RT-qPCR, expanding the analysis to other genes in same pathway (mTOR, 4E-BP1, eIF-4G and S6).  Results: Exploratory gene expression analysis identified 1060 transcripts with a p value <0.05 and 132 transcripts with an adjusted p value <0.01 difference between TIBC and SDBC samples. Based on biological implications in breast cancer, four genes were selected for further validation: CP (ceruloplasmin) and RPS6KB2 (ribosomal protein S6 kinase, 70kDa, polypeptide 2) both up-regulated in TIBC vs SDBC and PTEN (phosphatase and tensin homolog) and TGFBR3 (transforming growth factor beta receptor III), down-regulated in TIBC vs SDBC. Their differential expression was confirmed by RT-qPCR and immunohistochemistry, suggesting mTOR pathway overexpression in TIBC at both mRNA and protein level. Further expanded analysis by immunohistochemistry for mTOR pathway activation, including expression of phosphorylated forms of mTOR, 4E-BP1, eIF-4G, RPS6KB2 and S6, confirmed the upregulation of this pathway in TIBC.  Conclusions: TIBC and SDBC shows differential expression profile both at the gene and protein levels. The mTOR signaling is significantly upregulated in TIBC compared with SDBC, suggesting an enhanced aggressiveness of TIBC. Besides, CP may also represent novel immunohistochemical marker helpful in distinguishing between TIBC and SDBC. Further studies with larger sets of patients are guaranteed to verify these findings associated with TIBC. 	Co-expression
GDS4761	Expression data from fine-needle aspiration biopsies of breast cancer metastases from different anatomical sites	Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases  with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity	Co-expression
GDS4762	System-Wide Analysis Reveals a Complex Network of Tumor-Fibroblast Interactions Involved in Tumorigenicity	We’ve undertaken a genome-wide approach to identify and test genes in fibroblasts that are both induced upon interaction with basal breast cancer cells in culture and upregulated in stromal cells from primary human breast cancers.  Several of the upregulated genes encode secreted growth factors or cytokines.  Using RNAi and a co-injection tumorigenicity assay, we determined that the majority of secreted factors selected for functional validation played significant, yet functionally diverse, roles in promoting tumorigenicity.  Rather than a single major mediator, these results indicate multiple points of intervention to prevent fibroblasts from supporting basal breast cancer.  Additionally, we show that breast cancer subtypes differ markedly in the expression of these and other stromally secreted proteins using data from microdissected stromal samples.	Co-expression
GDS4763	A Myc transcriptional program that is independent of EMT drives a poor prognosis tumor-propagating phenotype in HER2+ breast cancer	The HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature and acquisition of a self renewing phenotype independent of an EMT programme or regulation of cancer stem cell markers. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in patients receiving adjuvant chemotherapy (but not targeted anti-HER2 therapy), MYC amplification is associated with a poor outcome in HER2+ breast cancer patients. These findings demonstrate the importance of molecular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have important diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.	Co-expression
GDS4764	Gene expression profiling of MDA231, BT549, and SUM159PT cells after selumetinib treatment or DUSP4 siRNA knockdown	MDA231, BT549, and SUM159PT basal-like breast cancer cell lines were transfected with non-targeting siRNA (siCONTROL), siRNA targeting DUSP4 (siDUSP4), or siCONTROL + 4 or 24 hr of 1uM selumetinib.  Cells were harvested at 96 hr post-siRNA transfection.  Data were Log2 RMA normalized.	Co-expression
GDS4765	27-Hydroxycholesterol links cholesterol and breast cancer pathophysiology.	The cholesterol metabolite and SERM, 27HC, is the signaling molecule that links cholesterol to breast cancer pathophysiology Hypercholesterolemia is a risk factor for breast cancer, and patients taking statins demonstrate lower breast cancer incidence and decreased breast cancer recurrence, data that highlights the potential importance of the recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, acts as a selective estrogen receptor modulator (SERM). The goal of this study was to evaluate the impact of 27HC on breast cancer pathophysiology. Elevation of 27HC in murine models increased tumor growth in an estrogen receptor dependent manner. Importantly, a high cholesterol diet decreased the time to tumor onset and increased tumor growth, and this response required presence of CYP27A1. Within human breast cancer samples, CYP27A1 expression increasesd with grade, in addition to being highly expressed in tumor associated macrophages. Finally 27HC increases metastasis to the lung. The findings herein strongly support a role for 27HC in breast cancer pathophysiology, providing support for the exploration of potential chemopreventative benefits of lower cholesterol diets, and pharmacological inhibitors of HMG-CoA reductase or CYP27A1.	Co-expression
GDS4766	Molecular Signature of Pregnancy Associated Breast Cancer (PABC)	Malignant epithelia and tumor-associated stroma of PABC and Non-PABC were isolated by laser capture microdissection and gene expression profiled. Additionally, normal breast epithelia and stroma adjacent to the two tumor types were profiled. Lastly, subsets of previously identified E- and P-regulated genes were defined in all tissues.	Co-expression
GDS477	Coxsackievirus B3 pathogenesis (I)	Temporal analaysis of an in vitro model of coxsackievirus B3 (CVB3) infection. HeLa cells infected with either CVB3 or control PBS and samples examined at 0, 0.5, 1, 3, 5, 7 and 9 hours following treatment.	Co-expression
GDS4772	Expression data from human heart	Global gene expression is altered in heart failure. This syndrome can be caused by cardiovascular diseases, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy, viral or toxic myocarditis, hypertension, and valvular diseases. We used microarrays to evaluate the impact of heart failure on human nucleocytoplasmic transport-related genes examining simultaneoulsly both dilated and ischemic human cardiomyopathies compared to normal hearts.	Co-expression
GDS4773	Acute venous hypertension induces local release of inflammatory cytokines and endothelial activation in humans	Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 35±2 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF.	Co-expression
GDS4777	UNRAVELING A NOVEL TRANSCRIPTION FACTOR CODE INDUCTIVE FOR THE HUMAN ARTERIAL-SPECIFIC ENDOTHELIAL CELL SIGNATURE	Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current ‘golden standard’ pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity	Co-expression
GDS4778	UNRAVELING A NOVEL TRANSCRIPTION FACTOR CODE INDUCTIVE FOR THE HUMAN ARTERIAL-SPECIFIC ENDOTHELIAL CELL SIGNATURE	Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current ‘golden standard’ pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity	Co-expression
GDS4779	Early Relapse in ALL is identified by Time To Leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways	Gene expression analysis identified a specific signature of differentially expressed genes discriminating TTLshort and TTLlong phenotypes. Gene expression signatures of xenografted leukemia samples with different TTL phenotypes were analyzed on  cohorts of pediatric BCP-ALL patients.	Co-expression
GDS478	Coxsackievirus B3 pathogenesis (II)	Temporal analysis of in vitro model of coxsackievirus B3 (CVB3) infection. HeLa cells infected with either CVB3, CVB3 and U0126 (blocks cytokines and metalloproteinases) or control PBS, and samples examined at 0, 0.5, 3 and 9 hours after treatment.	Co-expression
GDS4781	Vitamin D treatment of M.tb. infected macrophages	As macrophages are the primary site of Mtb infection and are sites of vitamin D signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). Microarrays were used to measure the changes in gene expression induced by 1,25D treatment of H37Rv-infected THP-1 cells	Co-expression
GDS4786	Gene expression analysis of PBMC from HIV and HIV/TB co-infected patients	Diagnosis of TB, especially in the presence of an HIV co-infection, can be challenging when using conventional diagnostic methods.  In this study, we analyzed global gene expression data from PBMC of patients that were either mono-infected with HIV or co-infected with HIV and TB in order to identify a TB-specific gene signature.	Co-expression
GDS479	Ionizing radiation effect on lymphoblastoid cells	Temporal analysis of effect of 3 Gy and 10 Gy ionizing radiation (IR) exposure on lymphoblastoid cells. Various time points up to 24 hours examined.	Co-expression
GDS4794	Gene repression with H3K27me3 modification in human small cell lung cancer	Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis due to early dissemination and rapid growth. We here analyze gene expression profile of 23 clinical SCLC samples. EZH2 was found to be highly expressed in SCLC samples compared to 42 normal tissues including the normal lung, and other PRC2 members, SUZ12 and EED, were also highly expressed in SCLC. To obtain target genes of PRC2 in SCLC, H3K27me3 mark was mapped in three SCLC cell lines, Lu130, H209 and DMS53, and compared to normal small airway epithelial cells (SAEC). Whereas H3K27me3(+) genes in SAEC were significantly overlapped with PRC-target genes in ES cells (P=1.7x10-31), genes with H3K27me3 in SCLC cell lines but not in SAEC were not significantly overlapped with PRC-target genes in ES cells (P=0.64). These genes with H3K27me3 specifically in SCLC cell lines but not in SAEC showed decreased expression, not only in SCLC cell lines but also in clinical SCLCs, and showed enrichment of GO-terms such as plasma membrane (P=8.1x10-21) and cell adhesion (P=1.7x10-8). Introduction of JUB, a gene showing specific H3K27me3 modification and the strongest repression in the three SCLC cell lines, resulted in repression of cellular growth in DMS53. In clinical SCLC cases, lower JUB level correlated to shorter survival (P=0.002), or a set of PRC target genes (JUB, EPHB4) and marker genes of classic type SCLC (GRP, ASCL1) correlated to shorter survival (P=0.0001) and classified SCLC into two groups with distinct prognosis. Growth of SCLC cell lines was repressed when treated with 3-Deazaneplanocin A, an inhibitor against PRC2. It is suggested that high expression of PRC2 in SCLC contributed to repression of genes including non-PRC-target genes in ES cells, and that the gene repression may play a role in genesis of SCLC.	Co-expression
GDS4797	Gene expression profiling of MCF10A (miR-221/222 vs control)	Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222	Co-expression
GDS4798	Expression Data from HNF4a RNAi Knockdown in HepG2 cells	HNF4a is an important liver transcription factor that regulates at least a thousand genes in the liver. Here we used expression profiling in HepG2 cells, a hepatocellular carcinoma cell line, in which HNF4a was knocked down by RNAi to identify some of those target genes. This dataset accompanies the article in Hepatology 2010 Feb;51(2):642-53. Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays by Bolotin E, Liao H, Ta TC, Yang C, Hwang-Verslues W, Evans JR, Jiang T, Sladek FM.	Co-expression
GDS4800	Expression data from knockdown of G9a in MDA-MB231 cells	G9a is an H3K9m2 methyltransferase, which is critical in controlling gene suppression and DNA methylation. We used microarray analysis to identify the target genes that are regulated by G9a in MDA-MB231 cells, in which E-cadherin is silenced.	Co-expression
GDS4801	SOX11 Gene Expression Profiling	The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL), but its functional role in malignant B-cells is unknown. To identify target genes transcriptionally regulated by SOX11 in malignant lymphoid cells, we have used Gene Expression Profiling (GEP) after SOX11 silencing in MCL cell lines.	Co-expression
GDS4802	Gene expression profiling after induction of WTX in HEK293 cells	WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53 and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell cycle arrest, apoptosis, and p53-target gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.	Co-expression
GDS4803	Expression data from human bronchial airway smooth muscle (ASM) cells	Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals.	Co-expression
GDS4807	Human keratinocytes stimulated with IL-17C	IL-17C is important for the pathogenesis of inflammatory diseases such as IBD and psoriasis. We found that IL-17C is highly induced in a murine model of psoriasis. Recent results suggest that IL-17C can target epithelial cells that express both IL-17RA and IL-17RE receptor chains. Here we identify genes induced in response to IL-17C treatment of human keratinocytes to provide the tools for dissection of the IL-17C signaling pathway.	Co-expression
GDS4808	Gene profile of glioblastoma cells treated with y15 and temozolomide	The gene expression profiles were identified in glioblastoma cells treated with FAK inhibitor Y15, temozolomide alone or with combination of Y15 and Temozolomide	Co-expression
GDS4813	Gene expression profile in A375 melanoma cells after 45 functionally important molecules were knocked down using siRNA	Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signalling molecules.	Co-expression
GDS4814	Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer	The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response. This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combination therapy in vivo highlights that there are both common and distinct downstream effects to different HER2 antibodies and that pathways may be invoked more strongly or in a different manner by a combination of agents. Some of the in vivo results for ovarian tumors differ from previous in vitro studies in breast cancer cells, emphasizing that the molecular response to anti-cancer agents involves variable and complex disease-specific interactions of signaling mechanisms.	Co-expression
GDS4818	Differential gene expression profiles between SUM149 cells transfected with control siRNA and SUM149 cells transfected with siRNA targeting tarzarotene-induced gene 1 (TIG1)	We identified tazarotene-induced gene 1 (TIG1) as a potential tumorigenic gene in IBC. To investigate the underlying mechanism by which TIG1 promotes tumor growth and invasiveness of IBC cells, we first sought to identify TIG1 functional partners by using DNA microarray analysis to compare gene expression profiles between SUM149 cells transfected with control siRNA and SUM149 cells transfected with siRNA targeting TIG1. We identified receptor tyrosine kinase Axl as a functional partner of TIG1.	Co-expression
GDS4819	Expression data of A375 melanoma cells after DMSO or MLN4924 treatment from 1 hour to 24 hour	Microarrays were used to determine the change in gene expression of genes involved in the CDT1/NAE pathway	Co-expression
GDS4820	Transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training	We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180°.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout.  Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and αB-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and αB-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and αB-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE naïve volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation.	Co-expression
GDS4824	Gene Expression Profiling of Prostate Benign and Malignant Tissue	We profiled genome-wide gene expression of human prostate benign and malignant tissue to identify potential biomarkers and immunotherapy targets. We stratified malignant specimens according to their TMPRSS2:ERG gene fusion status.	Co-expression
GDS4825	Influenza virus A infected monocytes	Gene expression profiles 6 hours post-influenza A virus infection in human monocytes at multiplicities of infection of 10 versus uninfected monocytes	Co-expression
GDS4826	Expression analysis of genes responding to ARID1A knockdown	Illumina array was employed to analyze the genes whose expression are altered when ARID1A gene is downregulated by shRNA in normal ovarian surface epithelial cells OSE4 and IOSE80pc.  This leads to discovery of p53-regulated genes such as p21 and SMAD3.	Co-expression
GDS4828	Cyclophilin B supports the survuval of glioblastoma multiforme cells	We have found that cyclophilin B (CypB) expression is important for malignant glioblastoma multiforme (GBM) cell proliferation. To identify molecular mechanisms that could explain CypB-dependent survival in human GBM cells, a microarray analysis was performed using RNA prepared from U251MG GBM cells transduced with lentiviral CypB shRNA. These data revealed that about 130 genes were more than 2-fold affected by CypB depletion. Significant alterations in the expression of genes related to cell death, cell proliferation and cell migration were found in the shCypB cells.	Co-expression
GDS4829	Genome-wide expression analysis of VprBP knockdown in DU145 cells	VprBP has been implicated in transcriptionally silent chromatin formation and cell cycle regulation, but the molecular basis underlying such effects remains unclear. To investigate the role of VprBP on gene regulation, genme-wide gene expression analysis is carried out in DU145 cells expressing either control shRNA or VprBP shRNA.	Co-expression
GDS483	DACH1-responsive genes	Analysis of effect of DACH1 in breast cancer cell line MDA-MB-231. DACH1 induced by ponasterone A treatment for 0, 18 or 36 hours.  DACH1 may regulate aberrant TGF beta signals that have role in breast cancer progression.	Co-expression
GDS4831	COP1 siRNA knockdown in human Hepatocellular carcinoma cells	Development of targeted therapeutics for hepatocellular carcinoma (HCC) remains a major challenge. We have previously demonstrated that constitutively photomorphogenic 1 (COP1), which regulates p53 activity by ubiquitination, is frequently overexpressed in human HCC. Here we examined whether molecular targeting of COP1 by small interfering (si) RNA can affect the course of HCC progression. COP1-1 was selected as the most effective target siRNAs in terms of growth inhibition and apoptotic induction in several HCC cell lines. Interestingly, the growth inhibition occurred both in HCC cells that retain wild-type p53 or express mutant p53 (Y220C or R249S). Next we have determined to investigate the molecular mechanisms underlying the phenotypic changes. Given the recent findings that COP1 functions as a negative regulator of p53, we addressed whether the phenotypic changes caused by COP1 silencing were due to alterations in p53 and/or p21 status. Indeed, in COP1-depleted HepG2 cells expressing wild type p53, induction of apoptosis was associated with restoration of p53 function as judged by a marked increase in the levels of p53 and its target p21, suggesting that cell death was p53-dependent. However, the COP1 silencing in Huh7 cells, which carry Y220C mutation, caused a strong induction of apoptosis without changing p53 levels. To further address this issue, we next looked for the global transcriptional changes underlying the antitumor effects of COP1 silencing in HCC cells [with different p53 status]. For this purpose, Huh7 and HepG2 were treated with NCsiRNA and COP1-1siRNA for 48 hours and subjected to illumina microarray analysis. We found that the number of differentially expressed genes which displayed more than a 2-fold change (P < 0.01 by Bootstrap t-test) was 462 (167 up- and 295 down-regulated genes) and 522 (179 up- and 343 down-regulated genes) in COP1siRNA-treated Huh7 and HepG2 cells, respectively. As expected, the expression levels of RFWD2 (COP1) mRNA were significantly reduced in both treated HCC cell lines. Consistent with phenotypic changes, COP1-depleted Huh7 cells also displayed changes in p53-associated group of genes functionally involved in regulation of apoptosis, growth and differentiation including CASP6, GLIPR1, FHL2, GADD45A, HMOX1 BCL6, FOXO3, GDF15, and SCNN1A genes. Finally, we generated the common COP1 knockdown gene signature which included 78 genes. The Ingenuity Pathway Analysis analysis revealed that the 5 top putative networks with high score (>19) were strongly associated with NF-κB, HNF4α, TNF, and p53 pathways, suggesting that a common subset of molecular alterations in the diverse oncogenic pathways may cooperatively result in growth inhibition of HCC cells with wild type and mutant p53. Analysis of COP1 knockdown gene expression signatures by microarray revealed that the anti-proliferative effect was driven by a common subset of molecular alterations including p53-associated functional network. Systemic delivery of a modified COP1siRNA by stable-nucleic-acid-lipid-particles (SNALP) significantly suppressed neoplastic growth in liver, without unwanted immune response in an orthotopic xenograft model. These findings provide the first proof of principle that COP1 is a promising target for systemic therapy of HCC. 	Co-expression
GDS4832	Human airway epithelial responses to rhinovirus infection and cigarette smoke extract alone and in combination	This study was performed to test the hypothesis that cigarette smoke extract would alter the responses of primary cultures of human bronchial epithelial cells to infection with purified human rhinovirus 16. The data show marked alterations in rhinovirus-induced expression profiles of a number of genes in the presence of cigarette smoke extract (CSE).	Co-expression
GDS4833	Expression data for Cediranib in Metastatic ASPS	Gene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS)	Co-expression
GDS4837	Expression data from Patients with Bipolar (BP) Disorder and Matched Control Subjects	There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated bipolar patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD. We employed microarray technology to measure global leukocyte gene expression in first-episode (n=3) and currently medicated BPD patients (n=26), and matched healthy controls (n=25). Following an initial feature selection of the microarray data, we developed a cross-validated 10-gene model that was able to correctly predict the diagnostic group of the training sample (26 medicated patients and 12 controls), with 89% sensitivity and 75% specificity (p<0.001). The 10-gene predictor was further explored via testing on an independent test cohort consisting of three pairs of monozygotic twins discordant for BPD, plus the original enrichment sample cohort (the three never-medicated BPD patients and 13 matched control subjects), and a sample of experimental replicates (n=34). 83% of the independent test sample was correctly predicted, with a sensitivity of 67% and specificity of 100% (although this result did not reach statistical significance). Additionally, 88% of sample diagnostic classes were classified correctly for both the enrichment (p=0.015) and the replicate samples (p<0.001).	Co-expression
GDS4838	Gene expression analysis of primitive neuroectodermal tumors	Central nervous system primitive neuroectodermal tumors (CNS PNET) and medulloblastomas are both embryonal tumors that predominantly occur in children. We used microarrays to analyse a cohort of CNS PNETs and medulloblastomas to identify gene expression related to tumor subgroups.	Co-expression
GDS484	Uterine fibroid and normal myometrial tissue	Comparison of normal myometrium and uterine leiomyomas obtained from fibroid afflicted patients.	Co-expression
GDS4841	Expression data from inflammatory myopathies	MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).	Co-expression
GDS4843	Gene expression profiling in tibial muscular dystrophy and control skeletal muscle	Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade of molecular events leading from the causative Titin mutations to the preterm death of muscle cells in TMD is largely unknown. To identify these components, we used gene expression profiling of muscle biopsies from TMD patients and healthy controls.	Co-expression
GDS4844	Gene expression in rectal epithelia of cystic fibrosis patients	Gene expression profiles were recorded from rectal suction specimens of Cystic Fibrosis (CF) patients, carrying the CF-specific D508 mutated CFTR-allele.  These profiles were compared with gene expression profiles from rectal suction specimens of non-CF subjects (control).	Co-expression
GDS4846	Genes up and down regulated in LNCaP cells overexpressing MED1	To identify MED1 target genes involved in prostate tumorigenesis.	Co-expression
GDS4852	Clonal Immortalized Human Glial Cell Lines Support Varying Levels of JC Virus Infection due to Differences in Cellular Gene Expression	JC virus (JCV) is a ubiquitous human polyomavirus that causes the demyelinating disease Progressive Multifocal Leukoencephalopathy (PML). JCV replicates in limited cell types in culture, predominantly in human glial cells. Thus, productive JCV infection is an indicator of the host cell transcription environment. Following introduction of a replication defective SV40 mutant that expressed large T protein into a heterogeneous culture of human fetal brain cells, multiple phenotypes became immortalized (SVG cells). A subset of SVG cells could support JCV replication. This mixed culture was called SVG cells. In the current study, clonal cell lines were selected from the original SVG cell culture. The SVG-5F4 clone showed low levels of viral growth. The SVG-10B1 clone was highly permissive for JCV DNA replication and gene expression. Microarray analysis revealed that viral infection did not significantly change gene expression in these cells. More resistant 5F4 cells expressed high levels of transcription factors known to inhibit JCV transcription. Interestingly, 5F4 cells highly expressed RNA of markers of Bergman or radial glia and 10B1 cells had high expression of markers of immature glial cells and activation of transcription regulators important for stem/progenitor cell self-renewal. These SVG-derived clonal cell lines provide a biologically relevant model to investigate cell type differences in JCV host range and pathogenesis, as well as neural development.	Co-expression
GDS4853	Stem cell factor Sox2 regulates the tumorigenic potential in human gastric cancer cells	Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells. Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation.	Co-expression
GDS4854	Gene expression analysis in children with complex seizures by influenza A (H1N1)pdm09 or rotavirus gastroenteritis	The differences of clinical characteristics in complex seizures induced by influenza A(H1N1)pdm09 and rotavirus gastroenteritis are well known, but the pathogenic mechanisms remain unclear. We analyzed the gene expression profiles in the peripheral whole blood cells isolated from pediatric patients using an Affymetrix oligonucleotide microarray. Results provide insights into the difference of the pathogenesis in the patients with complex seizures induced by influenza A(H1N1)pdm09 and rotavirus infections.	Co-expression
GDS4855	Expression data from well-differentiated human bronchial epithelial cells infected with H1N1 Influenza isolates	We used microarrays to compare the  gene expression profiles of different H1N1 isolates (seasonal and pandemic) in lung epithelial cells in vitro.	Co-expression
GDS4857	Visceral fat trancriptome in obstructive sleep apnea	Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.   	Co-expression
GDS4858	Sex and aging effect on skeletal muscle transcriptome in humans	The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex.	Co-expression
GDS4859	Human prolactinoma	Human prolactinomas (n=4, 3 males and 1 female) were obtained during trans-sphenoidal surgery as part of an ongoing accession of human pituitary tumors.  The study was approved Institutional Review Board (IRB) of Emory University, and informed consent obtained for all subjects. Tumors were microdissected and removed using the surgical microscope, rinsed in sterile saline, snap-frozen in liquid nitrogen, and stored (-80 ℃) until analysis. Each tumor fragment was confirmed independently by a neuropathologist by histology and immunohistochemistry prior to molecular analysis. Three normal pituitary glands from cadavers were obtained from the National Resource Center (NDRI, www.ndriresource.org).   Each human tissue sample was analyzed using Affymetrix Human Genome U95Av2 arrays.	Co-expression
GDS486	Rheumatoid arthritis and TNFalpha	Analysis of rheumatoid arthritis synovial fibroblasts (RASF) expressing dominant negative form of inhibitor of nuclear factor kappa B (Ik-B). Ik-B blocks TNFalpha. Cells treated with TNFalpha at 18 hours. TNFalpha known to increase progression of RA.	Co-expression
GDS4877	TOV112D cells treated with NSC319726	Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant.  Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant.  This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner.  This activity depends upon the zinc ion chelating properties of the compound as well as redox changes.  These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. We utilized gene expression microarrays to examine the transcriptional activity of p53 targets in TOV112D cells after treatment with NSC319726.	Co-expression
GDS4879	Stress-response pathways are altered in the hippocampus of chronic alcoholics.	Comparison of gene expression in post-mortem hippocampus from 20 alcoholics and 19 controls. The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis. Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differentially expressed genes that may play a role in the risk for alcoholism or whose expression is modified by chronic consumption of alcohol. We identified 639 named genes whose expression significantly differed between alcoholics and controls at a False Discovery Rate (FDR) ≤ 0.20; 52% of these genes differed by at least 1.2-fold. Differentially expressed genes included the glucocorticoid receptor and the related gene FK506 binding protein 5 (FKBP5), UDP glycosyltransferase 8 (UGT8), urea transporter (SLC14A1), zinc transporter (SLC39A10), Interleukin 1 receptor type 1 (IL1R1), thioredoxin interacting protein (TXNIP), and many metallothioneins. Pathways related to inflammation, hypoxia, and stress showed activation, and pathways that play roles in neurogenesis and myelination showed decreases. The cortisol pathway dysregulation and increased inflammation identified here are seen in other stress-related conditions such as depression and post-traumatic stress disorder and most likely play a role in addiction. Many of the detrimental effects on the hippocampus appear to be mediated through NF-κB signaling. Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF).	Co-expression
GDS4880	T lymphocytes from Chronic HCV-infected patients express unique pro-apoptotic gene signature.	Although extensive studies have demonstrated the gene expression patterns of antigen-specific CD4+ and CD8+ T-cells during chronic hepatitis C virus (HCV) infection, the transcriptional profiles of global CD4+ and CD8+ T-cells remains unclear. In this report, we recruited 10 long-term (~20 years) treatment-naïve chronic HCV (CHC) patients and 5 healthy donors (HDs) to investigate differences in global CD4+ and CD8+ T-cells gene expression profile. Global CD4+ and CD8+ T-cells showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4+ T-cells and IER3 and BCL2A1 in CD8+ T-cells from CHC patients as HCV-specific gene signatures. The unique apoptosis-related gene expression profilesin global CD4+ and CD8+ T-cells  programmed by chronic HCV infection seemed to enhance activation-induced apoptosis, which was suffered by  global CD4+ and CD8+ T-cells.	Co-expression
GDS4881	Human liver biopsy of different phases from control to NASH	Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (N=45) with all stages of NAFLD and controls (N=18) were analysed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, PLCG1) and insulin/insulin-like signalling (including IGF1, IGFBP2, PRKCE) and replicated by bisulfite pyrosequening (independent N=39). Transcription factor binding sites at NAFLD-specific CpG sites were >1000-fold enriched for ZNF274, PGC1A and SREBP2. Intra-individual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Post-bariatric and NAFLD-specific methylation signatures were clearly distinct both in gene-ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1 and ESRRA sites. Our findings provide one of the first examples of treatment-induced epigenetic organ remodelling in humans.	Co-expression
GDS4882	Expression profiling of PBMC from patients with hepatocellular carcinoma	Aberrant gene expression analysis between peripheral blood mononuclear cell (PBMC) samples from healthy individuals and patients with pancreatic carcinoma, gastric carcinoma and hepatocellular carcinoma (HCC) were identified using Affymetrix gene arrays.	Co-expression
GDS4884	Gene expression from MDA-MB-231	Gene expression from MDA-MB-231 cells shControl and shLOXL2.	Co-expression
GDS4885	Gene-expression profiling of ZNF217-overexpressing MDA-MB-231 cells	To obtain an overview of the cellular functions regulated by ZNF217 signaling in breast-cancer cell lines, we performed global gene-expression profiling on MDA-MB-231-pcDNA6 and MDA-MB-231-ZNF217 cells	Co-expression
GDS4887	Hepatic gene expression of HCV related Hepatocellular carcinoma and non-cancerous tissue with Il28B rs8099917 TT genotype and TG/GG genotype	IL28B genotype was shown to be associated with treatment outcome of antiviral thearpy for HCV infection. We tried to clarify the molecular feature that was asocciated with IL2B genotype by comparing Hepatic gene expression of HCV related Hepatocellular carcinoma and non-cancerous tissue with Il28B rs8099917 TT genotype and TG/GG genotype.	Co-expression
GDS4891	Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis	Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely because of a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome with that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data support a role for IL-17 and T helper type 17 (Th17) cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole-skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway.	Co-expression
GDS4894	Human skeletal muscle transcriptional response to exercise	The aim of this investigation was to evaluate the effect of training on the global transcriptional response of skeletal muscle to an acute bout of resistance exercise.	Co-expression
GDS4896	Expression data from severe asthmatics, mild asthmatics and healthy controls	Background: Around 5% of children with asthma suffer from chronic symptoms and/or severe exacerbations despite extensive treatment. The causes of severe therapy-resistant childhood asthma are poorly understood. Objectives: To define global patterns of gene expression in severe therapy-resistant vs. controlled asthma and healthy controls. Methods: Children with severe, therapy-resistant (SA, n=20) and controlled asthma (CA, n=20) were identified from a Swedish nation-wide study including extensive clinical and immunological characterisation. In addition, healthy controls were recruited (Ctrl, n=19). White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip. Results: 1378 genes were differentially expressed in one or several of the CA vs. Ctrl, SA vs. CA or SA vs. Ctrl contrasts. A large number could uniquely differentiate the SA group from the CA (n=351 genes) and Ctrl (n=315) groups, whereas fewer genes differentiated the CA from the Ctrl group (n=149). Several non-coding RNAs were found up-regulated in SA compared to CA or Ctrl. Three significantly enriched KEGG pathways were represented; bitter taste transduction, TAS2Rs (up-regulated mostly in SA), natural killer cell mediated cytotoxicity (up-regulated in CA) and N-Glycan biosynthesis (down-regulated in SA). An unsupervised hierarchical clustering of the 1378 genes could crudely separate the SA, CA and Ctrl individuals. Conclusion: Our data indicate a separation in gene expression patterns between children with severe, therapy-resistant asthma and controlled persistent asthma, and suggest novel pathways characterizing the severe therapy-resistant asthma phenotype.	Co-expression
GDS4897	A PGC-1alpha-dependent decrease in mitochondrial oxidative metabolism in muscle of humans with inherited insulin resistance	We used microarrays to assess gene expression profiling of 6 patients with a mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene (INSR) and 10 matched healthy controls	Co-expression
GDS4901	Analysis of Human Tendinopathy Gene Expression	Chronic tendon injuries, also known as tendinopathy, are common among professional and recreational athletes.  These injuries result in a significant amount of morbidity and health care expenditure and yet little is known about the molecular mechanism leading to tendinopathy.  We have used histological evaluation and molecular profiling to determine the gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy.  Diseased tendons have altered extracellular matrix, fiber disorientation, increased cellular content and vasculature and the absence of inflammatory cells.  Global gene expression profiling identified 1783 transcripts with significant different expression patterns in the diseased tendons.  Global pathway analysis further suggests altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response.  We have identified pathways and genes regulated in tendinopathy samples that will help contribute to the understanding of the disease towards the development of novel therapeutics.	Co-expression
GDS4903	Effects of Rituximab on global gene expression profiles in the RA synovium	Objective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug.  Methods: Paired synovial biopsies were obtained from the affected knee of anti-TNF resistant RA patients before (T0) and 12 weeks after initiation of rituximab therapy (T12). Total RNA was extracted, labeled according to standard Affymetrix procedures and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time PCR experiments were performed to confirm the differential expression of selected transcripts.  Results: According to paired Student’s t-tests, 549 out of 54,675 investigated probe sets were differentially expressed between T0 and T12. Pathway analysis revealed that genes down-regulated between T0 and T12 were significantly enriched in immunoglobulin genes, and genes involved in chemotaxis, leucocyte activation and immune responses (Gene Ontology annotations). By contrast, genes up-regulated between T0 and T12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (GSEA). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy.  Conclusion: Rituximab displays unique effects on global gene expression profiles in synovial tissue of RA patients. These observations open new perspectives in the understanding of the biological effects of the drug and in the selection of patients likely to benefit from this therapy.	Co-expression
GDS4915	Expression data from TK6 exposed to low-dose metals	We are investigating the response of human lymphoblastoid cells to low-dose exposure of environmental metals We used microarrays to detail the global programme of gene expression upon response to low-dose metals  Keywords: dose	Co-expression
GDS4916	Expression data from TK6 exposed to low-dose metals	We are investigating the response of human lymphoblastoid cells to low-dose exposure of environmental metals We used microarrays to detail the global programme of gene expression upon response to low-dose metals  Keywords: dose	Co-expression
GDS4917	Effect of 10 Cigarette Smoke Condensates on Primary Human Airway Epithelial Cells	Nine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours.	Co-expression
GDS4926	Expression data from human Ishikawa cells treated with Bisphenol A	This study provides a comprehensive evaluation of changes in gene expression during treatment with Bisphenol A in vitro. Ishikawa cells were maintained and grown (to confluency or at a desired cell density between 500,000 - 1 million cells/mL) in DMEM/F-12 Medium (supplemented with 10% Fetal Bovine Serum + 1X penicillin/streptomycin) in xenoestrogen-free Corning plasticware.  Cells were gently washed in warm PBS and transferred to phenol red-free DMEM/F-12 Medium (supplemented with 10% Charcoal-Stripped Fetal Bovine Serum + 1X penicillin/streptomycin) in Corning Cell Culture Cluster wells overnight and then challenged with 1pM (very low, vL), 100pM (low, L), 10nM (high, H), and 1uM (very high, vH) levels of BPA.  Prior to collection, cells were washed in warm PBS, resuspended & briefly incubated in TRI-Reagent, & finally collected (in quintuplicate replicates) at each specific time point: 8 hours, 24 hours, and 48 hours.  Following RNA isolation, the best RNA yields for each quadruplicate set was selected for target preparation and GeneChip processing.  Keywords: Dose Response/Time Course	Co-expression
GDS493	Cystic fibrosis pathology and 4-phenylbutyrate (HG-U133A)	Effect of 1mM 4-phenylbutyrate (PBA) at 0, 12 and 24 hours in cystic fibrosis bronchial epithelial model cell line IB3-1. PBA modulates heat shock protein and promotes trafficking of deltaF508 cystic fibrosis transmembrane conductance regulator (CFTR).	Co-expression
GDS4930	Transcriptomic analysis of human lung development	We decompose the genome-wide expression patterns in 38 embryonic human lung (53-154 days post conception/dpc) into their independent, dominant directions of transcriptomic sample variation in order togain global insight of the developing human lung transcriptome.The characteristic genes and their corresponding bio–ontologic attribute profile for the latter were identified. We noted the over–representation of lung specific attributes (e.g., surfactant proteins) traditionally associated with later developmental stages, and highly ranked attributes (e.g., chemokine–immunologic processes) not previously reported nor immediately apparent in an early lung development context. We defined the 3,223–gene union of the characteristic genes of the 3 most dominant sources of variation as the developing lung characteristic sub–transcriptome (DLCS). It may be regarded as the minimal gene set describing the essential biology of this process. The developing lung series in this transcriptomic variation perspectiveform a contiguous trajectory with critical time points that both correlate with the 2 traditional morphologic stages overlapping -154 dpc and suggest the existence of 2 novel phases within the pseudoglandular stage. To demonstrate that this characterization is robust, we showed that the model could be used to estimate the gestational age of independent human lung tissue samples with a median absolute error of 5 days, based on the DLCS of their lung profile alone. Repeating this procedure on the homologous transcriptome profiles of developing mouse lung 14–19 dpc, we were able to recover their correct developmental chronology. Whole human fetal lung gene expression profiling from estimated gestational ages 53 to 154 days post conception.  Keywords: Whole lung gene expression profiling, lung development, human fetus.	Co-expression
GDS4931	Gene expression data from S. aureus-exposed macrophages	It is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination.  Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis. In order to examine the effect of S. aureus on the macrophage transcriptome, we performed microarray expression analysis on human monocyte-derived macrophages treated with S. aureus.  Keywords: time course	Co-expression
GDS4936	Gene Expression Analysis of ARC (NSC 188491) Treated  MCF7 cells	ARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.	Co-expression
GDS494	Cystic fibrosis pathology and 4-phenylbutyrate (HG-U133B)	Effect of 1mM 4-phenylbutyrate (PBA) at 0, 12 and 24 hours in cystic fibrosis bronchial epithelial model cell line IB3-1. PBA modulates heat shock protein and promotes trafficking of deltaF508 cystic fibrosis transmembrane conductance regulator (CFTR).	Co-expression
GDS495	Angiogenesis	Temporal analysis of human umbilical cord vein endothelial cell (HUVEC) isolates treated with angiogenic factors vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) in low or high serum media.	Co-expression
GDS4950	Gene expression data from high grade serous ovarian cancer	Background: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer.   Methods: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with the same standard platinum-based chemotherapy. Twelve patient tumors demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumors from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using a Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumors from the resistant group and the sensitive group.   Results: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NFκB/ERK gene signalling networks.   Conclusions: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials.	Co-expression
GDS4956	KSHV vIRF4-mediated cellular genes alteration	Approximately, KSHV vIRF4 deregulate 284 genes by two-folds	Co-expression
GDS4957	Effect of FOXA1 overexpression in prostate cancer	FOXA1 is a transcription factor which aids AR function in prostate. There is controversary over the effect of high FOXA1 level has on prostate cancer so we forced the overexpression in the LNCaP prostate cancer cell line.	Co-expression
GDS4960	Gene expression in human healthy control and ISCU myopathy patient muscle biopsies	We performed microarray analysis on ISCU myopathy patient muscle biopsies to identify transcriptional modulation of pathways involved in the cellular response to Fe-S cluster deficiency.	Co-expression
GDS4962	A functional liaison between E2F and the aberrant ETS oncogene EWS/FLI1 in Ewing's sarcoma	Translocations of ETS transcription factors are driver mutations in diverse cancers. We investigated the genomic network of the ETS fusion EWS/FLI1 in Ewing's sarcoma (ESFT) as a model of ETS-driven tumorigenesis. ChIP-Seq and transcriptional analysis identified E2F3 as a principle co-factor of EWSFLI1 defining functionally distinct gene sets. While EWS/FLI1 binding independent of E2F3 predominantly associated with repressed differentiation genes, significant co-localization with E2F3 was discovered at proximal promoters of activated growth-related genes. Thus, EWS/FLI1 promotes oncogenesis by simultaneously perturbing differentiation state and augmenting the expression of genes co-regulated by E2F3. Integration of additional E2F3 and ERG localization data from prostate cancer containing TMPRSS2/ERG verified that the ETS-E2F module is also found in prostate cancer and may be of general relevance to ETS driven cancers.	Co-expression
GDS4964	Expression data by telomere elongation in vivo (xenograft)	Limitless reproductive potential is one of the hallmarks of cancer cells1. This ability is accomplished by maintaining telomeres, which erosion otherwise causes cellular senescence or death. Human cancer cells often maintain shorter telomeres than do cells in surrounding normal tissues2-5. While most cancer cells activate telomerase, which can elongate telomeres6, it remains elusive why cancer cells keep telomeres short. Here we show that forced elongation of telomeres in cancer cells promotes their differentiation in a tumor microenvironment in vivo. We elongated telomeres of human prostate cancer PC-3 cells, which possess short telomeres7, by enhancing their telomerase activity. The resulting cells with long telomeres retain an ability to form tumors in a mouse xenograft model. Strikingly, these tumors exhibit many duct-like structures and reduced N-cadherin expression, reminiscent of well-differentiated adenocarcinoma. These phenotypic changes are caused by telomere elongation per se but not enhanced telomerase activity. Gene expression profiling revealed that telomere elongation correlates with inhibition of cell-cycle processes. Together, our results suggest a functional contribution of short telomeres to tumor malignancy by regulating cancer cell differentiation.	Co-expression
GDS4966	Expression data from peripheral blood	C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.	Co-expression
GDS4968	Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies	To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. The analysis showed that 126 genes were differentially expressed in MGUS, SMM and MM as compared to NPC. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules (snoRNA) and zinc finger proteins. GADD45A was the most significant up-regulated gene in clonal PC compared to NPC. Several proapoptotic genes (AKT1 and AKT2) were downregulated and antiapoptotic genes (APAF1 and BCL2L1) were upregulated in MM, both symptomatic and asymptomatic, compared to MGUS. Myc mediated apoptosis signaling is one of the top canonical pathways differentiating the asymptomatic and symptomatic myeloma. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation in the transition from MGUS to SMM and to MM. In conclusion, our data show that although MGUS, SMM and MM are not clearly distinguishable groups according to their GEP, several signaling pathways and genes were significant deregulated in the different steps of transformation process.	Co-expression
GDS4969	Gene expression data from 8 pairs of CD138+/- myeloma cell lines	8 pairs of myeloma cell lines were sorted by MACS CD138-microbead, and the each cell lines were divided into two fraction CD138+ and CD138-. We used microarrays to detail the global programme of gene expression in these 8 pairs of CD138+/- myeloma cell lines	Co-expression
GDS4970	Expression data of myeloma CD138+ and CD138- populations	Comparison of gene expression profiles between CD138+ and CD138- populations from human myeloma cell lines RPMI-8226 and NCI-H929. We used Affymetrix human gene 1.0ST array and analyzed with GeneSpring GX.	Co-expression
GDS4971	Whole blood transcriptome of survivors and nonsurvivors of sepsis	There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3677 genes, biological pathway analysis identified 86 genes significantly down-regulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis including lymphocyte depletion, reduced T lymphocyte activation and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of down-regulation found in non-survivors compared to survivors. The results show that whole blood gene-expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression based assay, to assess immunosuppression and guide immunotherapy in future clinical trials.	Co-expression
GDS4972	Gene expression data from MCF-7 cells treated with Lacciac Acid A	Lacciac Acid A was indentified as an inhibitor of DMNT1. MCF-7 cells were treated with Lacciac Acid A (200 uM) for 5 days. Changes in gene expression were identified by using Affymetrix Human gene ST1.0 arrays. We used microarrays to determine global changes in gene expression upon treatment with Lacciac Acid A an inhibitor of DMNT1.	Co-expression
GDS4974	Gene expression of PBMC of chinese nickel refinery workers when compared to the gene expression profile of PBMCs from referent subjects	Up to date the studies examining the gene expression profiles in response to exposure to nickel compounds have only been conducted using in vitro tissue culture systems. Here, we have compared the gene expression profiles in peripheral blood mononuclear cells (PMCs) of eight nickel refinery workers in Jinchang, China to the expression profiles of referent subjects with only environmental exposure.	Co-expression
GDS4978	PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma	In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms.	Co-expression
GDS4979	Acquired resistance to lapatinib	These studies are aimed at understanding gene expression chnages in a Her2 positive breast cancer cell line that has developed acquired resistance to lapatinib. Samples include SKBR3 parental and resistant (SKBR3-R) under basal conditions and in response to 0.1 and 1uM lapatinib treatment after 24 hours.	Co-expression
GDS498	Inflammatory cytokine effect on primary lung endothelial cells	Examination of gene expression induced by interferon gamma (IFNg), tumor necrosis factor alpha (TNFa) and interleukin 4 (IL4) inflammatory cytokines on primary lung endothelial cells.	Co-expression
GDS4981	Gene Expression Effects of IL-13 on Primary Human Airway Epithelial Cells	Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD. Keywords: IL13, mucus, goblet cell	Co-expression
GDS4984	Mantle Cell Lymphoma	Gene expression analyis of primary MCL including IGHV mutated and unmutated cases Gene set analysis was perfomed in  MCL samples, comparing IGHV mutated cases vs. IGHV unmutated cases	Co-expression
GDS4987	Mesenchymal Stem/Progenitors and Other Endometrial Cell Types from Women with Polycystic Ovary Syndrome (PCOS) Display Inflammatory and Oncogenic Potential	Context: Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer.  Objective: We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial “disease phenotype” affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny.   Design and setting: A prospective study conducted at an academic medical center.  Patients and Main Outcome Measures: Proliferative phase endometrium was obtained from 6 overweight/obese PCOS (NIH criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting (FACS)-isolated endometrial epithelial cells (eEP), endothelial cells (eEN), stromal fibroblasts (eSF) and mesenchymal stem cells (eMSC). Gene expression data were validated using microfluidic Q-RT-PCR and immunohistochemistry (IHC).   Results: The comparison between eEPPCOS and eEPCtrl showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSFPCOS and eSFCtrl showed upregulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSCPCOS vs. eMSCCtrl the most upregulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). IHC scoring showed increased expression of CCL2 in eEPPCOS and eSFPCOS compared to eEPCtrl and eSFCtrl and IL-6 in eEPPCOS compared to eEPCtrl.    Conclusions: Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and pro-oncogenic changes, independent of BMI, especially in eEPPCOS and eMSCPCOS, compared to controls. The study reveals an endometrial  “disease phenotype” in women with PCOS with potential negative effects on endometrial function and long-term health.	Co-expression
GDS4989	Profiling A375P melanoma cells following PGC1a suppression	PGC1a is a transcriptional coactivator that regulates energy metabolism. PGC1a is highly expressed in a subset of melanoma tumors and cell lines. We generated gene-expression profile of control and PGC1alpha depleted A375P melanoma cells, a melanoma cell line that expresses very high levels of PGC1a to investigate the role of this gene in melanoma.	Co-expression
GDS499	Inflammatory cytokine effect on primary aortic endothelial cells	Examination of gene expression induced by interferon gamma (IFNg), tumor necrosis factor alpha (TNFa) and interleukin 4 (IL4) inflammatory cytokines on primary aortic endothelial cells.	Co-expression
GDS4994	IFNb-1a in-vivo treatment induces the expression and signaling of IFNAR1 and inhibits Th17 responses in PBMCs derived from CIS patients	IFNb has been used as a first line therapy for relapsing remitting multiple sclerosis (RRMS).  Since only a few studies have addressed the role of endogenous IFNb in the pathogenesis of the disease, our objective was to characterize its role in the transcriptional regulation of pathogenic Th17 cytokines in patients with RRMS.  In-vitro studies have demonstrated that IFNb inhibited IL-17A, IL-17F, IL-21, IL-22 and IFN-b secretion in CD4+ lymphocytes through the induction of suppressor of cytokine secretion (SOCS)1 and 3.  We found that patients with RRMS have increased serum and cerebrospinal fluid (CSF) Th17 (IL-17A and IL-17F) cytokine levels in comparison to the control subjects, suggesting that deficient endogenous IFNbeta secretion and/or signaling may contribute to the dysregulation of those pathogenic cytokines in CD4+ cells.  We identified that the endogenous IFNb from serum of RRMS patients induced a significantly lower IFN-inducible gene expression in comparison to healthy controls (HCs).  In addition, in-vitro studies have revealed a deficient endogenous and exogenous IFNb signaling in CD4+ cells derived from MS patients. Interestingly, upon inhibition of the endogenous IFNb signaling by silencing interferon regulatory factor (IRF)7 gene expression, the resting CD4+ T cells secreted significantly higher level of IL-17A, IL-17F, IL-21, IL-22 and IL-9, suggesting that endogenous IFNb suppresses the secretion of these pathogenic cytokines. In-vivo recombinant IFNb-1a treatment induced IFNAR1 and its downstream signaling molecules’ gene expression, suggesting that treatment may reconstitute a deficient endogenous IFNbeta regulation of the CD4+ T-cells’ pathogenic cytokine production in MS patients.	Co-expression
GDS501	Inflammatory cytokine effect on primary dermal endothelial cells	Examination of gene expression induced by interferon gamma (IFNg), tumor necrosis factor alpha (TNFa) and interleukin 4 (IL4) inflammatory cytokines on primary dermal endothelial cells.	Co-expression
GDS5015	Gene expression profiling in cumulus cells (CC) derived from a modified natural and stimulated in vitro fertilization (IVF) procedures	Cumulus cells surrounding mature oocytes that developed to moruale/blastocyst stage on day 5 of IVF cycle were collected and used for gene expression profiling using Affymetrix Human Gene 1.0 ST Arrays in order to determine differences in gene expression between the modified natural and stimulated in vitro fertilization (IVF) procedures.	Co-expression
GDS5016	The human placental sexome differs between trophoblast epithelium and villous vessel endothelium	As susceptibility to many adult disorders originates in utero, we here hypothesized that fetal sex influences gene expression in placental cells and produces functional differences in human placentas. We found that fetal sex differentially affects gene expression in a cell-phenotype dependent manner among all four placental cell-phenotypes studied: cytotrophoblasts, syncytiotrophoblasts, arterial endothelial cells and venous endothelial cells. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems, both supporting the hypothesis that there is reduced maternal-fetal compatibility for male fetuses. Our study is the first microarray study investigating sexual dimorphism in purified and characterized somatic cells from a single human tissue, the placenta, that underlines the importance of considering fetal sex as an independent variable in any work using human placenta.	Co-expression
GDS5017	Differences in gene expression and cytokines levels between newly diagnosed and chronic pediatric immune thrombocytopenia (ITP)	Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves but in some it becomes chronic. To investigate whether the two forms of the disease are similar or separate entities we performed DNA microarray analysis of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the expression files between the two forms of the disease. Furthermore, the gene expression of several cytokines differed between the two forms of the disease. This was also reflected in plasma with increased levels of IL-16 and TWEAK and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that the two forms of the disease may be separate entities.	Co-expression
GDS502	Inflammatory cytokine effect on primary colon endothelial cells	Examination of gene expression induced by interferon gamma (IFNg), tumor necrosis factor alpha (TNFa) and interleukin 4 (IL4) inflammatory cytokines on primary colon endothelial cells.	Co-expression
GDS5021	Effects of maternal choline intake on placental gene expression	To explore the influence of maternal choline intake on placental gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed in placental tissues obtained from  women consuming two different doses (480 vs. 930 mg/d) of choline throughout the third trimester of pregnancy. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d. Full thickness placental samples were collected at delivery to extract RNA and perform the arrays.	Co-expression
GDS5022	Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.	Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for cardiovascular disease. However, the utility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome.  Whole-genome microarray and targeted cytokine expression profiling on blood samples from normal cardiac function controls and first-time AMI patients within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways in AMI patients. To determine molecular signatures at the time of AMI that could prognosticate long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially expressed genes. Bioinformatic analysis of this differential gene set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of the developmental epithelial-to-mesenchymal transition, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. In conclusion, differentially regulated genes and modulated pathways were identified that predicted recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI warrants a larger study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. A validated transcriptome assay could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients.	Co-expression
GDS5023	Gene expression data from MGHU3 bladder cancer cells (FGFR3-Y375C) treated with TAK1 siRNA and/or PD173074	The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation.  A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1).  Here, we identify TAK1 as a novel interacting protein and direct target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes which regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types.  Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.	Co-expression
GDS5026	Novel Roles for ERK5 and Cofiin as Critical Mediators Linking Estrogen Receptor α-Driven Transcription, Actin Reorganization and Invasiveness in Breast cancer	Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ERα)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor-α determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ERα-gene transcription. Notably, ERK5 works with the actin remodeling protein, CFL1, and upon hormone exposure both became localized to transcription factories in the nucleus, verified by immunofluorescence and proximity ligation assays. Both factors facilitated PAF1 recruitment to the RNA Pol II complex and both ERK5 and CFL1 were required for regulation of gene transcription. By contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely to contribute to the generally poorer prognosis of ERα-negative breast cancers. Our study uncovers the dynamic interplay of nuclear receptor-mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness, and highlights new prognostic biomarkers and suggests novel approaches for developing targeted therapies to moderate cancer aggressiveness.	Co-expression
GDS5028	Differentiation of human amniotic fluid kidney progenitor cells into podocytes and comparison with human conditionally immortalized podocytes	In this work, we isolated and characterized a novel cell population derived from human amniotic fluid cells (hAKPC-P), and we differentiated them into podocytes. We used microarrays to study global changes in gene expression before and after differentiation in hAKPC-P and human immortalized podocytes (hIPod, positive control) and performed a detailed comparison between the different populations	Co-expression
GDS5029	Inhibiting tankyrases sensitizes KRAS mutant cancer cells to MEK inhibitors by FGFR2 feedback signaling	Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis and mitosis, offering attractive targets for anti-cancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors in KRAS mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and anti-tumor activity both in vitro and in vivo than effects observed by previously reported MEK inhibitor combinations. Altogether, our results show how a novel combination of TNKS and MEK inhibitors can be highly effective in targeting KRAS mutant cancers by suppressing a newly discovered resistance mechanism. This experiment is designed to detect genes differentially expressed in the combination treatment compared to others	Co-expression
GDS5030	Expression data from peripheral blood	C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.	Co-expression
GDS5037	Asthma	Bronchial Epithelial Cells were isolated processed as described (Chu et al., 2002 and Zhao et al., 2011). The objective of the study was to identify differentially expressed genes between normal control (NC), mild-moderate asthmatic (MMA) and severe asthmatic (SA) patients.	Co-expression
GDS504	Pulmonary arterial hypertension and PBMC	Analysis of peripheral blood mononuclear (PBMC) cells in patients with pulmonary arterial hypertension (PAH). Altered gene expression patterns in PAH PBMCs may allow disease subgroup identification and prediction of treatment response.	Co-expression
GDS5040	Gene expression profiling of lung cancer cells transfected with scrambled siRNA and siRNA targeting the ETS2 gene	ETS2 is a canonical transcriptional factor and member of the ETS family of genes. ETS2 binds to consensus ERE binding sites in a broad spectrum of genes thus affecting many intracellular molecular functions. However, the role of ETS2 in the biology and pathogenesis of lung cancers is still not known. We have found that ETS2 is down-regulated in lung tumors compared to normal lung tissue and the expression of the coding protein of the gene was a significant independent predictor of favorable outcome in NSCLC patients pinpointing to a potential tumor suppressor role for this gene. To better understand its molecular function in NSCLC, we compared and contrasted the transcriptome of lung cancer cells transfected with control siRNA and siRNA targeting ETS2.	Co-expression
GDS5045	Identification of chondrocyte subsets during human development	Joint injury and osteoarthritis affect millions of people worldwide, but attempts to  generate articular cartilage using adult stem/progenitor cells have been unsuccessful.  We hypothesized that recapitulation of the human developmental chondrogenic  program using pluripotent stem cells (PSCs) may represent a superior approach for  cartilage restoration. Using laser capture microdissection followed by microarray  analysis, we first defined a surface phenotype  (CD146low/negCD166low/negCD73+CD44lowBMPR1B+) distinguishing the earliest  cartilage committed cells (pre-chondrocytes) at 5-6 weeks of development; pellet  assays confirmed these cells as functional, chondrocyte-restricted progenitors. Flow  cytometry, qPCR and immunohistochemistry at 17 weeks revealed that the superficial  layer of peri-articular chondrocytes was enriched in cells with this surface phenotype.  Isolation of cells with a similar immunophenotype from differentiating human PSCs  revealed a population of CD166negBMPR1B+ putative pre-chondrocytes. Functional  characterization confirmed these cells as cartilage-committed, chondrocyte  progenitors. The identification of a specific molecular signature for primary cartilagecommitted  progenitors may provide essential knowledge for the generation of purified,  clinically relevant cartilage cells from PSCs.	Co-expression
GDS5046	Identification of chondrocyte subsets during human development	Joint injury and osteoarthritis affect millions of people worldwide, but attempts to  generate articular cartilage using adult stem/progenitor cells have been unsuccessful.  We hypothesized that recapitulation of the human developmental chondrogenic  program using pluripotent stem cells (PSCs) may represent a superior approach for  cartilage restoration. Using laser capture microdissection followed by microarray  analysis, we first defined a surface phenotype  (CD146low/negCD166low/negCD73+CD44lowBMPR1B+) distinguishing the earliest  cartilage committed cells (pre-chondrocytes) at 5-6 weeks of development; pellet  assays confirmed these cells as functional, chondrocyte-restricted progenitors. Flow  cytometry, qPCR and immunohistochemistry at 17 weeks revealed that the superficial  layer of peri-articular chondrocytes was enriched in cells with this surface phenotype.  Isolation of cells with a similar immunophenotype from differentiating human PSCs  revealed a population of CD166negBMPR1B+ putative pre-chondrocytes. Functional  characterization confirmed these cells as cartilage-committed, chondrocyte  progenitors. The identification of a specific molecular signature for primary cartilagecommitted  progenitors may provide essential knowledge for the generation of purified,  clinically relevant cartilage cells from PSCs.	Co-expression
GDS5047	A molecular profile of chronic cocaine abuse includes differential expression of genes regulating transcription, chromatin and dopamine cell phenotype	Midbrain dopamine (DA)-synthesizing neurons play a key role in the addiction process, providing a compelling rationale for determining drug-induced molecular changes arising in these cells. This microarray-based study determined the profiles of midbrain gene expression in chronic cocaine abusers (n = 10) and well-matched drug-free control subjects (n = 10). Array-related procedures were performed in triplicate for each subject. Data analysis revealed that 98 array probes (corresponding to 91 genes) exhibited robust, statistically significant expression differences between chronic cocaine abusers and matched control subjects (p ≤ 0.05, FDR = 5%; with ≥ 1.4 fold-change cut-off applied). Changes in transcript abundance identified by microarray were validated by qPCR analysis in every instance examined (n = 11), regardless of the direction or magnitude of change, supporting the validity of the larger dataset of genes differentially expressed in cocaine abusers. Many of the genes exhibiting robust differential expression were associated with the regulation of transcription, chromatin function, or dopamine cell phenotype. For approximately one-half of these genes, transcript abundance was significantly predictive for subject assignment to the cocaine-abusing versus control cohort. The findings suggest that there is a molecular signature associated with core pathophysiological changes in the DA neurons of chronic cocaine abusers that can be exploited for the development of potential biomarkers and novel therapeutic targets for addiction.	Co-expression
GDS505	Renal clear cell carcinoma (HG-U133A)	Investigation into mechanisms of renal clear cell carcinogenesis (RCC). Comparison of renal clear cell tumor tissue and adjacent normal tissue isolated from the same surgical samples.	Co-expression
GDS5056	Expression data from Adipose Stem Cells (ASC) from morbidly obese and non-obese individuals	The adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and “stemcellness” has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells. We used microarrays to analyze differences in transcriptomic profiles between the adipose stem cells from morbidly obese and non-obese individuals.	Co-expression
GDS5058	Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Reassortant ML29, a Vaccine Candidate	The virulent Lassa fever virus (LASV) and the non-pathogenic Mopeia virus (MOPV) infect rodents and incidentally people in West Africa. The mechanism of LASV damage in human beings is unclear. A live-attenuated reassortant of MOPV and LASV protects rodents and primates from Lassa fever disease. Peripheral blood mononuclear cells from healthy human subjects were expose to either LASV or ML29 in order to identify early cellular responses that could be attributed to the difference in virulence between both viruses. Differential expression of interferon-related genes as well as coagulation-related genes could lead to an explanation for Lassa fever pathogenesis and lead to protective treatments for Lassa fever disease.	Co-expression
GDS5059	In Vitro Transformation of Primary Human CD34+ Cells by AML Fusion Oncogenes: Early Gene Expression Profiling Reveals Possible Drug Target in AML	Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of major groups of AML fusion oncogenes on primary human CD34+ cells.	Co-expression
GDS5064	The effect of Neuroserpin expression upon HeLa cell gene expression	HeLa cells were stably transfected using the Tet-On® Advanced Cell Line system with Wildtype, G392E and Delta Neuroserpin with neuroserpin expression induced with doxycycline.  Gene expression was examined in the absence or presence of 2 ug/ml doxycycline.	Co-expression
GDS5067	Designed Oligooxopiperazines as Modulators of Hypoxia-Inducible Factor Signaling	We performed gene expression profiling of oligooxopiperazines (OPs) targeting the hypoxia-inducible transcription factor complex.  Treatment of cells with OPs inhibited hypoxia-inducible gene expression in A549 cells.	Co-expression
GDS507	Renal clear cell carcinoma (HG-U133B)	Investigation into mechanisms of renal clear cell carcinogenesis (RCC). Comparison of renal clear cell tumor tissue and adjacent normal tissue isolated from the same surgical samples.	Co-expression
GDS5070	Expression data from knockdown of ZXDC1/2 in PMA-treated U937	ZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA.  Likewise, knockdown of ZXDC1 restricts the induced expression of these markers.  We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls. We used microarray to identify genes regulated by ZXDC during PMA-induced differentiation of U937 monoblasts towards a monocyte/macrophage phenotype	Co-expression
GDS5071	Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate	Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88x10-2 – 5.02x10-9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 involved in DNA repair are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show that cellular defences against DNA damage may take part in the pathogenesis of NSCL/P, in accordance with the hypothesis of aetiological overlap between this malformation and cancer. These results provide more information regarding the aetiology of NSCL/P and have the potential tocan potentially assist incontribute to the development of future preventive strategies.	Co-expression
GDS5072	Expression data from High-grade prostate cancer cells	To identify molecules to serve as diagnostic markers for high-grade prostate cancer (PC) and targets for novel therapeutic drugs, we investigated the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection.	Co-expression
GDS5074	Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.	Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for cardiovascular disease. However, the utility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome.  Whole-genome microarray and targeted cytokine expression profiling on blood samples from normal cardiac function controls and first-time AMI patients within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways in AMI patients. To determine molecular signatures at the time of AMI that could prognosticate long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially expressed genes. Bioinformatic analysis of this differential gene set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of the developmental epithelial-to-mesenchymal transition, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. In conclusion, differentially regulated genes and modulated pathways were identified that predicted recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI warrants a larger study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. A validated transcriptome assay could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients.	Co-expression
GDS5076	Effect of PIAS1 on gene expression	To study the effect of PIAS1 on transcriptional regulation, we establishedstable PIAS1 shRNA knockdown cells in breast cancer cell line MDA-MB231. By comparing the expression profiles of control vs PIAS1 knockdown cells, we can identify potential PIAS1 target genes involved in breast tumorigenesis.	Co-expression
GDS5077	TMEM88 knockdown during human embryonic stem cell cardiac differentiation	TMEM88 is indispensable for heart development and acts in the pre-cardiac mesoderm to specify lineage commitment of the cardiovascular progenitor cell through inhibition of Wnt signaling.	Co-expression
GDS5080	Differentiation of human amniotic fluid kidney progenitor cells into podocytes and comparison with human conditionally immortalized podocytes	In this work, we isolated and characterized a novel cell population derived from human amniotic fluid cells (hAKPC-P), and we differentiated them into podocytes. We used microarrays to study global changes in gene expression before and after differentiation in hAKPC-P and human immortalized podocytes (hIPod, positive control) and performed a detailed comparison between the different populations	Co-expression
GDS5083	Genome-wide expression study of human carotid atheroma	The aim of this study was to identify new biomarkers and to investigate pathways involved in the progression of human carotid atheroma.	Co-expression
GDS5085	Expression data from BRAFV600E A375 melanoma cells treated with vehicle or vemurafenib	Vemurafenib is a BRAF inhibitor with specificity for the most common BRAF mutant encountered in melanomas (BRAFV600E). Vemurafenib suppresses the proliferation of BRAF mutant human melanoma cells by suppressing downstream activation of the MEK/ERK mitogen activated protein kinases. We used microarrays to examine the transcriptional response of a vemurafenib-sensitive BRAFV600E human melanoma cell line (A375) to vemurafenib in order to further delineate the mechanisms by which BRAFV600E drives cell proliferation and energy metabolism in human melanoma.	Co-expression
GDS5086	Expression data from Leishmania major infected human dendritic cells	Leishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity.  In this study, we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs.  Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA.  Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections. In the current study, we further investigate the L. major infected DC transcriptional during early time points after infection via microarray analysis.	Co-expression
GDS5088	Microarray Data of cell-free RNA across pregnancy time course	Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs.  We employed high throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects.  By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA, and to monitor changes in tissue development and health. As one such application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the presence of messenger RNA, we observed and characterized non-coding species such as long non-coding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma.  We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus, and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer’s disease, and showed that disease specific neural transcripts are present at increased levels in the blood of affected patients.  Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.	Co-expression
GDS5093	Systems biological analysis of immunity to dengue	Dengue virus (DENV) infects hundreds of millions of people annually, yet there is only a limited knowledge of the host immune response to dengue. Here, we used a systems biological approach to perform a detailed analysis of the innate immune response to DENV infection in the whole blood samples of acutely infected humans in Bangkok, Thailand. Transcriptomic analysis revealed that genes encoding pro-inflammatory mediators and type I IFN related proteins, were associated with high levels of virus during the first few days of infection. Individuals with low or negative viremia at the late stage of fever were enriched with genes associated with pathways involved in cell cycle, proliferation, cell metabolism and translational control. Meta-analysis showed significant enrichment in genes specific for innate cells (monocytes, macrophages and DCs) in the specimens with high VL and enrichment in genes specific for NK cells, CD4+ and CD8+ T cells as well as B cells in specimens with low VL. Furthermore, flow cytometric analysis revealed an expansion in the numbers of CD14+CD16+ monocytes and depletion of CD14dimCD16++ cells and BDCA-1+ myeloid DC in blood. Consistent with this, in a non-human primate model, infection with DENV boosted the numbers of CD14+CD16+ monocytes in the blood and in secondary lymphoid organs. In vitro, freshly isolated blood monocytes infected with DENV up regulated CD16 and mediated robust differentiation of resting B cells to CD27++CD38++ plasmablasts and IgG and IgM secretion. Taken together, these data provide a detailed picture of the innate response to dengue infection in humans, and highlight an unappreciated role for CD14+CD16+ monocytes in promoting the differentiation of plasmablasts and mediating antibody response to DENV.	Co-expression
GDS511	Postmortem skeletal muscle	Transcriptional profile of normal skeletal muscle collected at autopsy compared to surgical specimens.	Co-expression
GDS513	Familial combined hyperlipidemia and USF1 haplotype	Comparison of subcutaneous adipose tissue from individuals with familial combined hyperlipidemia (FCHL) exhibiting either upstream transcription factor 1 (USF1) susceptibility or protective haplotype. USF1 regulates glucose and lipid metabolism genes.	Co-expression
GDS525	Extraocular and limb muscle comparison	Molecular definition of extraocular muscle (EOM). Autopsy superior rectus EOM compared with biopsy limb quadriceps femoris muscle.	Co-expression
GDS527	Colorectal tumor cell response to X radiation (19K 3 Part A)	Evaluation of colorectal tumor cell line (HCT116) response to X radiation (XR). XR sensitive HCT116-CloneK cells treated at 4 Gy for 10 minutes, 6 hours, and 24 hours.	Co-expression
GDS528	Colorectal tumor cell response to X radiation (19K 3 Part B)	Evaluation of colorectal tumor cell line (HCT116) response to X radiation (XR). XR sensitive HCT116-CloneK cells treated at 4 Gy for 10 minutes, 6 hours, and 24 hours.	Co-expression
GDS53	CD34+ cell analysis	Comparison of gene expression in CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood to investigate why the latter are optimal for allogeneic transplant recipients.	Co-expression
GDS531	Multiple myeloma and bone lesions	Comparison of gene expression in bone marrow plasma cells of multiple myeloma patients with and without bone lesions. Osteolytic lesions increase in multiple myeloma patients.	Co-expression
GDS532	Hydrostatic pressure-responsive genes in optic nerve head astrocytes	Temporal analysis of how astrocytes in the optic nerve head (ONH) respond to changes in intraocular pressure (IOP). ONH astrocytes exposed to 60 mm Hg hydrostatic pressure for 6, 24, and 48 hours. Lends understanding to pathogenesis of glaucoma.	Co-expression
GDS533	Uterine smooth muscle tumor characterization	Comparison of gene expression in uterine smooth muscle tumors. Normal myometrium, benign uterine leiomyoma, malignant uterine and extra-uterine leiomyosarcoma examined.	Co-expression
GDS534	Smoking-induced changes in airway transcriptome	Analysis of cigarette smoking-induced changes in  bronchial epithelia, and reversibility of effects when smoking is discontinued. May provide insight to molecular events leading to chronic obstructive pulmonary disease (COPD) and lung cancer.	Co-expression
GDS535	Prostate cancer antiandrogen resistance	Analysis of mechanisms of prostate cancer resistance to antiandrogen therapy. Isogenic hormone-sensitive and drug-resistant hormone-refractory xenograft pairs examined.	Co-expression
GDS536	Androgen receptor antagonist to agonist conversion	Examination of antagonist to agonist conversion in androgen receptor-expressing hormone-sensitive LNCaP prostate cancer cells. Cells challenged with increasing doses of R1881, or bicalutamide.	Co-expression
GDS552	Essential thrombocythemia megakaryocytes	Malignant bone marrow CD34+ thrombopoietin-treated megakaryocytes from essential thrombocythemia (ET) patients compared with normal megakaryocytes.	Co-expression
GDS556	Extraocular muscle layer profiles (HG-U133A)	Analysis of adult monkey whole medial and lateral rectus extraocular muscle (EOM), and microdissected medial rectus global and orbital EOM layers.	Co-expression
GDS557	Extraocular muscle layer profiles (HG-U133B)	Analysis of adult monkey whole medial and lateral rectus extraocular muscle (EOM), and microdissected medial rectus global and orbital EOM layers.	Co-expression
GDS559	Inflammatory bowel disease (HG-U133A)	Investigation into inflammatory bowel disease gene expression. Terminal ileum and colon transversum biopsies from Crohn´s disease, ulcerative colitis and control patients examined.	Co-expression
GDS560	Inflammatory bowel disease (HG-U133B)	Investigation into inflammatory bowel disease gene expression. Terminal ileum and colon transversum biopsies from Crohn´s disease, ulcerative colitis and control patients examined.	Co-expression
GDS561	Osteopontin overexpression	Investigation into effect of constitutive overexpression of osteopontin (OPN) in breast carcinoma cell line 21NT.	Co-expression
GDS562	Bone cell tissue culture on amino acid conjugated surfaces	Evaluation of osteosarcoma TE85 cell tissue culture on a variety of amino acid conjugated surfaces at 6 and 32 hours. Study holds potential applications for bone tissue engineering.	Co-expression
GDS563	Duchenne muscular dystrophy (II) (HG-U95A)	Search for modifying factors and pathogenic pathways involved in Duchenne muscular dystrophy (DMD). Quadricep skeletal muscle biopsies from 12 DMD patients and 11 unaffected control patients examined.	Co-expression
GDS564	Sex specific transcription in hypothalamus	Examination of sex specific transcription in hypothalamus using postmortem samples from individuals averaging 70 years of age.	Co-expression
GDS596	Large-scale analysis of the human transcriptome (HG-U133A)	Gene atlas of human protein-encoding transcriptome. Examined gene expression profiles from 79 physiologically normal tissues obtained from various sources.	Co-expression
GDS609	Duchenne muscular dystrophy (II) (HG-U95B)	Search for modifying factors and pathogenic pathways involved in Duchenne muscular dystrophy (DMD). Quadricep skeletal muscle biopsies from DMD patients and unaffected control patients examined.	Co-expression
GDS610	Duchenne muscular dystrophy (II) (HG-U95C)	Search for modifying factors and pathogenic pathways involved in Duchenne muscular dystrophy (DMD). Quadricep skeletal muscle biopsies from DMD patients and unaffected control patients examined.	Co-expression
GDS611	Duchenne muscular dystrophy (II) (HG-U95D)	Search for modifying factors and pathogenic pathways involved in Duchenne muscular dystrophy (DMD). Quadricep skeletal muscle biopsies from DMD patients and unaffected control patients examined.	Co-expression
GDS612	Duchenne muscular dystrophy (II) (HG-U95E)	Search for modifying factors and pathogenic pathways involved in Duchenne muscular dystrophy (DMD). Quadricep skeletal muscle biopsies from DMD patients and unaffected control patients examined.	Co-expression
GDS622	Endothelial cell microenvironment effect  (1.2I)	Comparison of high endothelial venules endothelial cells (HEVEC) freshly isolated from tonsils with dedifferentiated HEVEC cultured ex vivo for 48 hours identifies gene expression controlled by tissue microenvironment.	Co-expression
GDS623	Endothelial cell microenvironment effect (1.2II)	Comparison of high endothelial venules endothelial cells (HEVEC) freshly isolated from tonsils with dedifferentiated HEVEC cultured ex vivo for 48 hours identifies gene expression controlled by tissue microenvironment.	Co-expression
GDS624	Endothelial cell microenvironment effect (cardiovascular array)	Comparison of high endothelial venules endothelial cells (HEVEC) freshly isolated from tonsils with dedifferentiated HEVEC cultured ex vivo for 48 hours identifies gene expression controlled by tissue microenvironment.	Co-expression
GDS625	Gastric mucosa immune response to Helicobacter pylori	Examination of gastric mucosa inflammatory response to Helicobacter pylori infection. Gastric biopsies from healthy and H. pylori-infected patients compared. Infection can lead to cellular hyperproliferation and malignant transformation.	Co-expression
GDS647	Aging of cultured myotubes and glucose metabolism	Examination of aging myotubes from a muscle biopsy incubated in glucose.  Myotubes in 25 mM glucose at 2, 3, 4, 5, and 7 weeks, and in 10 mM glucose at 4 weeks examined in reference to 0 mM glucose control at 1 week.	Co-expression
GDS649	Inflammatory response of interleukin-1-stimulated endothelial cells	Temporal analysis of human umbilical vein endothelial cell (HUVEC) inflammatory response to interleukin-1 (IL-1) stimulation for 0, 0.5, 1, 2.5, and 6 hours. Immediate-early to early gene expression program characterized.	Co-expression
GDS651	Heart  failure arising from different etiologies	Examination of left ventricle in idiopathic dilated and ischemic cardiomyopathy.  Diseased ventricles examined in reference to normal.	Co-expression
GDS670	Emphysema lung tissue expression profiling	Expression profiling of lung tissue from normal individuals, and patients with either 'usual' emphysema or alpha-1 antitrypsin (AAT) deficiency-related emphysema. Global reduction in gene expression observed in emphysemic lungs.	Co-expression
GDS686	Store-operated calcium entry in HEK-293 cells	Comparison of HEK-293-derived monoclonal cell lines with high or low levels of store-operated Ca2+ entry (SOCE). Levels of SOCE confirmed by monitoring thapsigargin-stimulated Ba2+ entry.	Co-expression
GDS687	Dermal papilla-induced epithelial stem cell differentiation	Analysis of dermal papilla (DP) induced epithelial stem cell differentiation. Keratinocyte stem cells from bulge area of telogen hair follicle co-cultured with DP over a 5 day period.	Co-expression
GDS690	Intestinal epithelial cell immune response	Analysis of intestinal epithelial cell immune response. 14 day old colon adenocarcinoma cell lines Caco-2 and T84 stimulated 4 hours with flagellin, or lymphotoxin beta or TNF alpha cytokines.	Co-expression
GDS705	RENT1 nonsense-mediated mRNA decay component knockdown	Analysis of mRNA abundance changes in Hela cells following knockdown of nonsense-mediated mRNA decay component RENT1 using RNAi.   Results identify transcripts potentially regulated by RENT1.	Co-expression
GDS707	Aging brain: frontal cortex expression profiles at various ages	Analysis of gene expression profiles obtained from the postmortem frontal cortex of 18 normal males and 12 normal females at 26 to 106 years of age.  Results provide insight into molecular events underlying the onset of brain aging.	Co-expression
GDS708	HIV integration sites and gene transcription activity	Correlation of HIV integration sites to gene activity in SupT1 (T cell), PBMC (peripheral blood mononuclear cell), and IMR90 (lung fibroblast) cell lines infected with an HIV-based vector.  Results provide insight into sites preferred in HIV integration.	Co-expression
GDS709	Enterocyte differentiation time course	Enterocyte differentiation analyzed using colonic adenocarcinoma cell line Caco-2 BBe as a model.  Cells examined at 2, 8, and 15 days in culture: these are in the proliferating, postproliferative nondifferentiated, and differentiated stages respectively.	Co-expression
GDS719	Prostate adenocarcinoma response to radiation (HG-U95A)	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following ionizing radiation (IR) to a dose of 10 Sv. Cells harvested 6 or 24 hours after IR. Dose applied in 1 or 4 fractions.	Co-expression
GDS720	Prostate adenocarcinoma response to radiation (HG-U95B)	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following ionizing radiation (IR) to a dose of 10 Sv. Cells harvested 6 or 24 hours after IR. Dose applied in 1 or 4 fractions.	Co-expression
GDS721	Prostate adenocarcinoma response to radiation (HG-U95C)	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following ionizing radiation (IR) to a dose of 10 Sv. Cells harvested 6 or 24 hours after IR. Dose applied in 1 or 4 fractions.	Co-expression
GDS722	Prostate adenocarcinoma response to radiation (HG-U95D)	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following ionizing radiation (IR) to a dose of 10 Sv. Cells harvested 6 or 24 hours after IR. Dose applied in 1 or 4 fractions.	Co-expression
GDS723	Prostate adenocarcinoma response to radiation (HG-U95E)	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following ionizing radiation (IR) to a dose of 10 Sv. Cells harvested 6 or 24 hours after IR. Dose applied in 1 or 4 fractions.	Co-expression
GDS724	Kidney transplant rejection expression profiling	Analysis of kidney transplant rejection by expression profiling of kidney biopsies and peripheral blood lymphocytes from patients. Results identify expression profiles unique to rejection, dysfunction without rejection, and well-functioning transplants.	Co-expression
GDS725	Prostate adenocarcinoma and ionizing radiation	Time course of androgen-independent LNCaP C4-2 prostate adenocarcinoma cells following a dose of 10 Sv ionizing radiation (IR). Cells harvested at several time points up to 24 hours after IR.	Co-expression
GDS731	Leukotriene LTD4 effect on macrophage and endothelial cells	Examination of gene expression in MonoMac6 macrophage and umbilical vein endothelial cells treated with 100 nM leukotriene LTD4 for 1 hour.  Results offer insight into autocrine action of LTD4 on macrophages and its paracrine action on endothelial cells.	Co-expression
GDS737	Lung tissue from smokers with severe emphysema	Comparison of lung tissue from smokers with severe emphysema (removed at lung volume reduction surgery) and  smokers with mild or no emphysema. Study provides insights into the pathogenesis of chronic obstructive pulmonary disease (COPD).	Co-expression
GDS738	Intervertebral disc cells and osmotic loading	Gene expression profiles of intervertebral disc cells (IVD) exposed to iso-osmotic, hyper-osmotic and hypo-osmotic conditions. Under physiological conditions, IVD are subject to osmotic stress.	Co-expression
GDS740	Chromosomally stable and unstable isogenic clone comparison	Expression profiling of 2 pools of chromosomally unstable Chinese hamster-human hybrid GM10115 clones referenced to an isogenic stable clone RT210B.  Clone Fe10-3 pooled with 10-56-11, and LS12 with 10-107-9. Chromosome instability induced by radiation.	Co-expression
GDS748	Beta-catenin S37A mutant effect on gene expression	Expression profiling of 293T cells infected with RCAS vector carrying beta-catenin S37A mutant.  Beta-catenin S37A mutant is oncogenic and more stable than the corresponding wild type protein.	Co-expression
GDS751	Natural killer cell expression profiling	Expression profiling of CD56dimCD16+, CD56brightCD16-, and in vitro activated CD56+CD16+ natural killer (NK) cells.  NK cells derived from purified peripheral blood  pooled from 9 healthy donors.	Co-expression
GDS756	Colon cancer progression	Comparison of gene expression in SW480, a primary tumor colon cancer cell line, to that in SW620, an isogenic metastatic colon cancer cell line.  Cell lines derived from one individual.  Results provide insight the progression of cancer from primary tumor growth to metastasis.	Co-expression
GDS761	Essential thrombocythemia expression profiling	Expression profiling of malignant megakaryocytes (MK) from 6 donors with essential thrombocythemia (ET).  MK derived from bone marrow CD34+ hematopoietic progenitor cells.  Progenitors induced to differentiate into MK by treatment with 100 ng/ml thrombopoietin.  Apoptotic pathway is impaired in ET.	Co-expression
GDS77	Macrophages infected with Salmonella (SHAD2)	Identification of host pathways affected by the Salmonella virulence transcription factor phoP. phoP found to play a role in Salmonella-induced human macrophage cell death.	Co-expression
GDS776	Interferon-alpha effect on monocytes primed with interferon-gamma	Expression profiling of monocytes cultured for 2 days with 150 pg/ml interferon (IFN) gamma and then stimulated with 25 ng/ml of IFN-alpha.  Monocytes obtained from 3 donors.  Results provide insight into mechanisms underlying the enhanced response of IFN primed monocytes to cytokines.	Co-expression
GDS78	Macrophages infected with Salmonella (SHAI2)	Identification of host pathways affected by the Salmonella virulence transcription factor phoP. phoP found to play a role in Salmonella-induced human macrophage cell death.	Co-expression
GDS781	CD14 cells from granulocyte colony stimulating factor mobilized peripheral blood: expression profile	Expression profiling of CD14+ cells isolated from granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (G-PBMC). Cells collected from normal donors after 3 days of G-CSF stimulation. G-PBMCs may confer a survival advantage to allogeneic transplant recipients.	Co-expression
GDS785	CD4+ T cell differentiation (HG-133A)	Analysis of CD4+ T cell differentiation by expression profiling of subpopulations of CD4+ cells representing 5 successive stages of differentiation: intrathymic T progenitors, double positive thymocytes, single positive thymocytes, naïve T cells from cord blood, and naïve T cells from adult blood.	Co-expression
GDS786	CD4+ T cell differentiation (HG-133B)	Analysis of CD4+ T cell differentiation by expression profiling of subpopulations of CD4+ cells representing 5 successive stages of differentiation: intrathymic T progenitors, double positive thymocytes, single positive thymocytes, naïve T cells from cord blood, and naïve T cells from adult blood.	Co-expression
GDS80	Macrophages infected with Salmonella (SHS)(I)	Identification of host pathways affected by the Salmonella virulence transcription factor phoP. phoP found to play a role in Salmonella-induced human macrophage cell death.	Co-expression
GDS806	Estrogen positive breast cancer recurrence during tamoxifen therapy: whole tissue tumor	Expression profiling of estrogen positive primary breast cancer tumors from 60 patients.  Patients subsequently treated with tamoxifen for 5 years, and tumors classified according to whether cancer recurred.  Results identify gene markers of disease-free survival that include HOXB13 and IL17BR.	Co-expression
GDS807	Estrogen positive breast cancer recurrence during tamoxifen therapy: microdissected tumor	Expression profiling of microdissected estrogen positive primary breast cancer tumors from 60 patients.  Patients later treated with tamoxifen for 5 years, and tumors grouped according to whether cancer recurred.  Results identify markers of disease-free survival that include HOXB13 and IL17BR.	Co-expression
GDS810	Alzheimer's disease at various stages of severity	Expression profiling of brain hippocampi from 22 postmortem subjects with Alzheimer's disease (AD) at various stages of severity.  7, 8, and 7 subjects diagnosed with incipient, moderate, and severe AD respectively.  Results provide insight into mechanisms underlying the early pathogenesis of AD.	Co-expression
GDS817	Breast cancer cell expression profiles (HG-U95A)	Expression profiling of breast cancer cell lines HCC 1954 and MDA-MB-436 in reference to mammary epithelial cells.  Results used to validate a method of comparing data generated from Affymetrix arrays to that from cDNA arrays.  The method uses DNA sequence to match probes between platforms.	Co-expression
GDS820	Breast cancer cell expression profiles (HG-U133A)	Expression profiling of breast cancer cell lines HCC 1954 and MDA-MB-436 in reference to mammary epithelial cells. Results used to validate a method of comparing data generated from Affymetrix arrays to that from cDNA arrays. The method uses DNA sequence to match probes between platforms.	Co-expression
GDS823	Breast cancer cell expression profiles (HG-U133B)	Expression profiling of breast cancer cell lines HCC 1954 and MDA-MB-436 in reference to mammary epithelial cells. Results used to validate a method of comparing data generated from Affymetrix arrays to that from cDNA arrays. The method uses DNA sequence to match probes between platforms.	Co-expression
GDS825	Breast cancer cell expression profiles (G4100A)	Expression profiling of breast cancer cell lines HCC 1954 and MDA-MB-436 in reference to mammary epithelial cells.  Results used to validate a method of comparing data generated from cDNA arrays to that from Affymetrix arrays.  The method uses DNA sequence to match probes between platforms.	Co-expression
GDS826	Erythroid differentiation of erythroleukemia cell line induced by hemin: time course	Expression profiling of K562 erythroleukemia cells induced to differentiate into erythroid-like cells by hemin.  K562 cells examined at various time points up to 72 hours following treatment with 50 uM hemin.  Results provide insight into mechanisms underlying hemoglobinization.	Co-expression
GDS829	Alternative pre-mRNA splicing in various tissues and cell lines (Rosetta/Merck Splicing Chip 1)	Monitoring of mRNA splice variants for more than 10,000 multi-exon genes using arrays with oligonucleotide probes positioned at exon-exon junctions.  mRNA from 52 tissues and cell lines examined.  Results provide tissue distribution of splice variants and identify novel splice variants.	Co-expression
GDS830	Alternative pre-mRNA splicing in various tissues and cell lines (Rosetta/Merck Splicing Chip 2)	Monitoring of mRNA splice variants for more than 10,000 multi-exon genes using arrays with oligonucleotide probes positioned at exon-exon junctions. mRNA from 52 tissues and cell lines examined. Results provide tissue distribution of splice variants and identify novel splice variants.	Co-expression
GDS831	Alternative pre-mRNA splicing in various tissues and cell lines (Rosetta/Merck Splicing Chip 3)	Monitoring of mRNA splice variants for more than 10,000 multi-exon genes using arrays with oligonucleotide probes positioned at exon-exon junctions. mRNA from 52 tissues and cell lines examined. Results provide tissue distribution of splice variants and identify novel splice variants.	Co-expression
GDS832	Alternative pre-mRNA splicing in various tissues and cell lines (Rosetta/Merck Splicing Chip 4)	Monitoring of mRNA splice variants for more than 10,000 multi-exon genes using arrays with oligonucleotide probes positioned at exon-exon junctions. mRNA from 52 tissues and cell lines examined. Results provide tissue distribution of splice variants and identify novel splice variants.	Co-expression
GDS833	Alternative pre-mRNA splicing in various tissues and cell lines (Rosetta/Merck Splicing Chip 5)	Monitoring of mRNA splice variants for more than 10,000 multi-exon genes using arrays with oligonucleotide probes positioned at exon-exon junctions. mRNA from 52 tissues and cell lines examined. Results provide tissue distribution of splice variants and identify novel splice variants.	Co-expression
GDS834	Sindbis virus-induced cell death	Comparison of 293 cells that are resistant to Sindbis virus-induced cell death (clones 9, 43) versus cells that are sensitive to Sindbis virus-induced cell death (wild type 293).	Co-expression
GDS838	Imatinib effects on chronic myelogenous leukemia CD34+ cells	Comparison of purified bone marrow CD34+ cells from imatinib-treated chronic myelogenous leukemia (CML) patients and healthy donors.	Co-expression
GDS841	Adult acute myeloid leukemia: bone marrow and peripheral blood expression profiles (SHCO)	Part of a study profiling 54 bone marrow and 65 peripheral blood samples from 116 adults with acute myeloid leukemia (AML). Results identify distinct gene expression signatures that correlate with clinical outcomes. Signatures used to construct a clinical outcome predictor using 133 genes.	Co-expression
GDS843	Adult acute myeloid leukemia: bone marrow and peripheral blood expression profiles (SHDJ)	Part of a study profiling 54 bone marrow and 65 peripheral blood samples from 116 adults with acute myeloid leukemia (AML). Results identify distinct gene expression signatures that correlate with clinical outcomes. Signatures used to construct a clinical outcome predictor using 133 genes.	Co-expression
GDS845	Breast cancer cell line ME16C response to chemotherapeutics: time course	Analysis of the response of the basal epithelium derived breast cancer line ME16C to either doxorubicin or 5-fluorouracil.  Cells examined 12, 24, and 36 hours following treatment.  Results provide insight into the response of breast cancers derived from different cell types to chemotherapeutics.	Co-expression
GDS846	Breast cancer cell line HME-CC response to chemotherapeutics: time course	Analysis of the response of basal epithelium derived breast cancer line HME-CC to either doxorubicin or 5-fluorouracil. Cells examined 12, 24, and 36 hours following treatment. Results provide insight into the response of breast cancers derived from different cell types to chemotherapeutics.	Co-expression
GDS847	Breast cancer cell line MCF-7 response to chemotherapeutics: time course	Analysis of the response of luminal epithelium derived breast cancer line MCF-7 to either doxorubicin or 5-fluorouracil. Cells examined 12, 24, and 36 hours following treatment. Results provide insight into the response of breast cancers derived from different cell types to chemotherapeutics.	Co-expression
GDS848	Breast cancer cell line ZR-75-1 response to chemotherapeutics: time course	Analysis of the response of luminal epithelium derived breast cancer line ZR-75-1 to either doxorubicin or 5-fluorouracil. Cells examined 12, 24, and 36 hours following treatment. Results provide insight into the response of breast cancers derived from different cell types to chemotherapeutics.	Co-expression
GDS849	Hereditary spastic paraparesis	Analysis of gene expression in skeletal muscle of three patients affected by hereditary spastic paraplegia (HSP) caused by mutations of spastin (SPG4). SPG4 is an ubiquitously expressed protein involved in microtubule regulation and vesicle traffic.	Co-expression
GDS85	Serum stimulation time course (10k_print2)	Temporal transcriptional program of primary fibroblasts in response to serum. Samples taken at various time points up to 24 hours.	Co-expression
GDS852	Alveolar epithelial cell line A549 response to acute lung injury causing stimuli: time course	Examination of alveolar epithelial A549 cells in models of pulmonary parenchymal cell activation: exposure to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), or cyclic stretch. Cells examined 1 and 4 hours after exposure to each acute lung injury-causing stimulus.	Co-expression
GDS854	Transforming growth factor beta effect on acute myelogenous leukemia cells	Analysis of M091 acute myelogenous leukemia cells after treatment with 200 pM transforming growth factor beta (TGFbeta) for 2 and 4 hours. Part of a study comparing M091 to hematopoietic stem cells. Reveals cytostatic role of TGFbeta in hematopoiesis and identifies p57 as a possible tumor suppressor	Co-expression
GDS855	Transforming growth factor beta effect on CD34+ hematopoietic stem cells	Analysis of CB-CD34 CD34+ hematopoietic stem cells after treatment with 200 pM TGFbeta for 2 and 4 hours. Part of a study comparing CB-CD34 cells to acute myelogenous leukemia cells. Reveals cytostatic role of TGFbeta in hematopoiesis and identifies p57 as a possible tumor suppressor.	Co-expression
GDS858	Mucoid and motile Pseudomonas aeruginosa infected lung epithelial cell comparison	Comparison of lung epithelial Calu-3 cells infected with the mucoid alginate-producing FRD1 strain to those infected with the isogenic motile flagellin-producing FRD440 strain of Pseudomonas aeruginosa. Mucoid and motile strains are associated with chronic and acute lung infections, respectively.	Co-expression
GDS86	Serum stimulation time course (10k_print1)	Analysis of a temporal transcriptional program in the response of primary fibroblast cultures to serum. Samples taken at 15 minutes and 2 hours.	Co-expression
GDS860	Endothelin-1 effect on fibroblasts	Cultured primary lung fibroblasts incubated 4 hours in the presence or absence of 100 nM endothelin-1 (ET-1). Results suggest that ET-1 is involved in matrix synthesis and connective tissue deposition during wound repair and in pulmonary fibrosis.	Co-expression
GDS88	Cancer cell lines (10k_print2)	Analysis of cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Gene expression is linked to phenotypic properties and drug sensitivity profiles of the cell lines.	Co-expression
GDS881	Breast cancer and selective estrogen receptor modulators	Analysis of gene stimulation and inhibition by the selective estrogen receptor modulators (SERMs) trans-hydroxytamoxifen (TOT) and raloxifene (Ral) or ICI 182,780 (ICI) and by estradiol (E2) in estrogen receptor-containing MCF-7 breast cancer cells. Cells were treated for 8 or 48 hours.	Co-expression
GDS884	Estradiol effect on osteosarcoma cells expressing estrogen receptor alpha or beta: time course	Expression profiling of U2OS osteosarcoma cells after treatment with 17beta-estradiol (E2) for various lengths of time up to 48 hours.  U2OS transfected with either estrogen receptor (ER) alpha or beta.  Results identify signaling pathways in bone regulated by E2 through ERalpha and ERbeta.	Co-expression
GDS885	Tumor cell response to topoisomerase poison camptothecin	HeLa tumor cells treated with 10 uM topoisomerase poison camptothecin (CPT) for 8 hours. This dose and time are sufficient to induce rapid apoptosis. Results identify potential targets for adjuvant cancer therapy.	Co-expression
GDS892	GATA3 ectopic expression in 293T cells	Examination of 293T epithelial kidney cells stably transfected with either wild type GATA3 or R367L mutant GATA3. GATA3 can be highly expressed in breast tumors. GATA3 variants may contribute to tumorigenesis.	Co-expression
GDS893	GATA3 ectopic expression in 293T cells (dye-swap)	Examination of 293T epithelial kidney cells stably transfected with either wild type GATA3 or R367L mutant GATA3. GATA3 can be highly expressed in breast tumors. GATA3 variants may contribute to tumorigenesis.	Co-expression
GDS894	Skeletal muscle response to exercise and circadian rhythms	Analysis of effects of resistance exercise (RE) and time of day in skeletal muscle. Biopsies of male vastus lateralis muscle obtained 6 and 18 hours after acute RE, or no RE. Results suggest that RE may directly modulate circadian rhythms in skeletal muscle.	Co-expression
GDS901	Estrogen receptor alpha L540Q mutation effect on gene induction by estradiol: time course	Analysis of breast cancer cell line 231/ERalpha expressing L540Q mutant estrogen receptor after 1 or 2 hour estradiol treatment. Mutant receptor is defective in binding steroid receptor coactivator (SRC) proteins. Results identify estrogen-regulated genes that require SRCs for expression.	Co-expression
GDS906	Bladder smooth muscle cell response to mechanical stretch	Expression profiling of cultured bladder smooth muscle cells subjected to repetitive mechanical stimulation for 4 hours.  Chronic overdistension results in bladder wall thickening, associated with loss of muscle contractility. Results identify genes whose expression is altered by mechanical stimuli.	Co-expression
GDS909	Alternative splicing in five tissues	Detection of tissue-specific regulation of alternative splicing for 316 genes in five normal tissues (brain, muscle, liver, bone marrow, testes) using array containing oligonucleotides spanning individual exons and splice junctions.	Co-expression
GDS910	Alternative splicing in five tissues (dye-swap)	Detection of tissue-specific regulation of alternative splicing for 316 genes in five normal tissues (brain, muscle, liver, bone marrow, testes) using array containing oligonucleotides spanning individual exons and splice junctions.	Co-expression
GDS911	Growth-arrested cell: serum deprivation and contact inhibition growth-arrest comparison	Expression profiling of T98G cancer cells in growth-arrest induced by 3 days of either serum deprivation or contact inhibition. Results show that targets of the p130- E2F4 repressor complex are downregulated under the two growth-arrest conditions.	Co-expression
GDS913	DNA damage from ultraviolet and ionizing radiation effect on peripheral blood lymphocytes	Analysis of peripheral blood lymphocytes exposed to ultraviolet (10 J/m^2) or ionizing radiation (5 Gy). Lymphocytes obtained from 15 healthy individuals from ages 21 to 36 years and immortalized with Epstein-Barr virus. Results provide insight into transcriptional response to DNA damage.	Co-expression
GDS915	Metabolic syndrome response to exercise intervention (HG-95A)	Analysis of skeletal muscle from overweight males with metabolic syndrome. Individuals subjected to chronic exercise training. Muscles examined prior to training, and after 1 and 14 days of recovery following 9 months training. Provides insight into effects of exercise intervention.	Co-expression
GDS916	Ewing family tumor histogenetic origin	Human embryonic kidney cells HEK293 transfected with the Ewing family tumor (EFT)-specific EWS-FLI1 fusion protein to investigate the histogenetic origin of EFTs. The observed EFT-specific gene expression profile supports the concept of a neural crest and endothelial origin of EFT stem cells.	Co-expression
GDS917	Whole blood RNA isolation and leukocyte RNA purification: comparison of methods	Comparison of RNA isolation from whole blood using the PAXgene system to that from leukocytes using the buffy coat procedure.  Blood of healthy subjects and trauma patients examined.  Results indicate that RNA isolated from whole blood produced more noise than that from leukocytes.	Co-expression
GDS918	Ewing family tumor cells: effect of transfection	Analysis of Ewing family tumor (EFT) cell line A673 response to interleukin-2 (IL-2) transfection to assess possible undesirable effects (e.g. tumor stimulation) of in vitro manipulation. Results impact the potential use of IL-2 transfection as an in vivo immunotherapy for EFT patients.	Co-expression
GDS940	Kaposi sarcoma-associated herpesvirus infection of primary human dermal endothelial cells	Primary human dermal endothelial cells (HDMEC) were infected with isolated Kaposi sarcoma-associated herpesvirus (KSHV) for 7 days. Infection of HDVECs with KSHV results in upregulation of lymphatic lineage-specific genes and downregulation of blood vascular genes.	Co-expression
GDS942	Skeletal myoblast cell line KM109 differentiation: time course (I)	Expression profiling of primary myoblast cell line KM109 obtained from muscle biopsy of a healthy individual and induced to differentiate by serum deprivation.  Cells examined at various time points up to 14 days following serum deprivation.  Results provide insight into late myogenesis.	Co-expression
GDS943	Skeletal myoblast cell line KM109 differentiation: time course (I, dye-swap)	Expression profiling of primary myoblast cell line KM109 obtained from muscle biopsy of a healthy individual and induced to differentiate by serum deprivation. Cells examined at various time points up to 14 days following serum deprivation. Results provide insight into late myogenesis.	Co-expression
GDS944	Skeletal myoblast cell line KM109 differentiation: time course (II)	Expression profiling of primary myoblast cell line KM109 obtained from muscle biopsy of a healthy individual and induced to differentiate by serum deprivation. Cells examined at various time points up to 14 days following serum deprivation. Results provide insight into late myogenesis.	Co-expression
GDS945	Skeletal myoblast cell line KM109 differentiation: time course (II, dye-swap)	Expression profiling of primary myoblast cell line KM109 obtained from muscle biopsy of a healthy individual and induced to differentiate by serum deprivation. Cells examined at various time points up to 14 days following serum deprivation. Results provide insight into late myogenesis.	Co-expression
GDS946	Familial combined hyperlipidemia	Expression profiling of lymphoblastic cell lines derived from the peripheral blood lymphocytes of patients with familial combined hyperlipidemia (FCHL), the most common form of genetically determined dyslipidemia.  Results provide insight into the pathophysiology of FCHL.	Co-expression
GDS961	Diabetic nephropathy	Comparison of glomeruli from kidneys with diabetic nephropathy (DN) and glomeruli from kidneys of healthy individuals. Progression of DN may be due to diminished tissue repair capability.	Co-expression
GDS962	Peripheral blood mononuclear cells and the effect of exercise	Peripheral blood mononuclear cells (PBMC) were isolated from blood samples taken from healthy male subjects before, immediately after, and 60 minutes after 30 minutes of exercise. Brisk activation and deactivation of genes associated with stress, inflammation, and tissue repair observed.	Co-expression
GDS963	Macular degeneration and dermal fibroblast response to sublethal oxidative stress	Expression profiling of dermal fibroblasts from patients with macular degeneration.  Fibroblasts subjected to sublethal oxidative stress.  This study tests the hypothesis that patients with macular degeneration have an abnormal response to cellular injury in sites other than the eye.	Co-expression
GDS968	Radiation therapy toxicity association with abnormal transcriptional response to DNA damage	Analysis of UV and IR irradiated lymphoblastoid cell lines derived from the peripheral blood of patients with acute radiation toxicity.  Samples taken 2 months after the completion of radiation therapy.  Results provide insight into the role of the response to DNA damage in radiation toxicity.	Co-expression
GDS969	Bone marrow prolonged storage effects	Analysis of impact of pre-analytical handling of bone marrow (BM). Time delays of 0, 24, or 48 hours between sample aspiration and RNA extraction examined. Storage of BM has dramatic effects on mRNA expression of individual transcripts.	Co-expression
GDS971	Rhabdomyosarcoma and Ewing's sarcoma comparison	Comparison of gene expression in 12 pediatric rhabdomyosarcomas (RMS) to that in 11 pediatric Ewing's sarcomas (EWS).   3 embryonic and 9 alveolar RMS tumors examined.  RMS and EWS appear similar in routine histology.  Results identify expression profiles that distinguish RMS from EWS.	Co-expression
GDS987	Kidney transplant response to calcineurin inhibitor-free immunosuppression using sirolimus	Analysis of kidneys from adult renal transplant recipients subjected to calcineurin inhibitor-free immunosuppression using sirolimus. Patients treated with sirolimus have a lower prevalence of chronic allograft nephropathy compared to those treated with cyclosporine, a calcineurin inhibitor.	Co-expression
GDS988	Kaposi's sarcoma-associated herpesvirus LANA overexpression in B lymphoid cells: time course	Expression profiling of B lymphoid cell lines overexpressing the latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus. B cells made to express LANA from a tetracycline inducible promoter.  Expression examined at various time points up to 48 hours after induction.	Co-expression
GDS989	Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus infected cell lines	Expression profiling of cell lines BCBL-1 and BC-3 infected by Kaposi's sarcoma-associated herpesvirus (KSHV), Raji infected by the Epstein-Barr virus (EBV), and BC-1 infected by both viruses.  Results identify expression patterns specific to KSHV-infected primary effusion lymphoma derived cells.	Co-expression
GDS992	Endoplasmic reticulum membrane-associated genes in breast cancer cell line MCF-7	Identification of genes whose mRNA are translated from the endoplasmic reticulum (ER) in the breast cancer cell line MCF-7.  Secreted and membrane-bound proteins are preferentially translated in the ER.  Results provide insight into the association of membrane-bound proteins and breast cancer.	Co-expression
GDS999	Bronchoalveolar lavage cells of lung transplant recipients with acute rejection	Expression profiling of bronchoalveolar lavage cells of lung transplant recipients with acute rejection. Rejection status determined from biopsies. Results identify possible gene markers of lung transplant rejection.	Co-expression
SRP000599	Genome-wide annotation of small RNAs expressed in HeLa and HepG2 cells	We report an applicaton of small RNA sequencing using high throughput next generation sequencing to identify the small RNA content of cell lines. By sequencing over 30 million reads we could identify a new class of small RNAs previousy observed with tiling arrays and mapping to promoter regions of coding genes. We also identified a large number of small RNAs corresponding to internal exons of coding genes. By using different enzymatic treatments and immunoprecipitation experiments, we have determined that both the promoter associated small RNAs as well as ones within the body of the genes bear 5'' cap structures. Overall design: Examination of the expression of small RNAs (<200nt).	Co-expression
SRP000931	Melanoma Cell Transcriptome	Paired end sequencing of cDNA isolated from individual melanoma samples via the Illumina sequencing platform to identify genetic aberrations that may play a role in melanoma genesis.	Co-expression
SRP001313	miRNA expression of human cancer and mouse cell lines	miRNA expression profile Keywords: small RNA profiling by high throughput sequencing Overall design: The small RNA fraction (18-30nt) was cloned and sequenced from total RNA of each cell line	Co-expression
SRP001381	Target RNA-directed destruction of miRNAs in Drosophila	In flies, small interfering RNAs (siRNAs) direct Argonaute2 (Ago2) to defend cells from viruses and transposons. In contrast, micro RNAs (miRNAs) mainly guide Ago1 to repress target mRNAs. A key step in the production of a functional Ago2/siRNA but not an Ago1/miRNA complex is Hen1-mediated methylation of the small RNA guide at the 2* hydroxyl of the 3*-terminal ribose. The function of this modification in animals is unknown. Here we show that highly complementary target RNAs decrease the steady-state level of Ago1-bound miRNAs. In vitro, the decline in miRNA levels requires high, but not complete complementarity between the target RNA and the small RNA; is accompanied by 3*-terminal nucleotide addition; and is blocked by Hen1-catalyzed 2*-O-methylation of small RNAs. The absence of Hen1 results in 3*-terminal uridylation and destabilization of Ago2-associated small RNAs in vivo. Our results suggest that small RNA-target RNA complementarity has shaped the coevolution of miRNAs and their target RNAs in flies and we present human cultured cell experiments that the target RNA-dependent small RNA tailing and degradation machinery may be conserved in mammals.	Co-expression
SRP001540	Understaning mechanisms underlying human gene expression variation with RNA sequencing	Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal. While all eQTL studies to date have assayed mRNA levels using expression microarrays, recent advances in RNA sequencing enable the analysis of transcript variation at unprecedented resolution. We sequenced RNA from 69 lymphoblastoid cell lines (LCLs) derived from unrelated Nigerian individuals that have been extensively genotyped by the International HapMap Project. Pooling data from all individuals, we generated a map of the transcriptional landscape of these cells, identifying extensive use of unannotated polyadenylation sites and over 100 novel putative protein-coding exons.  Using the genotypes from the HapMap project, we identified over a thousand genes at which genetic variation influences overall expression levels or splicing. We demonstrate that eQTLs near genes generally act via a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within or near the consensus splice sites. Our results illustrate the power of high-throughput sequencing for the joint analysis of variation in transcription, splicing, and allele-specific expression across individuals. Overall design: RNA-Seq in 69 lymphoblastoid cell lines from multiple Yoruban HapMap individuals in at least two replicate lanes per individual	Co-expression
SRP001558	Sex-specific and lineage-specific alternative splicing in primates	Comparative studies of gene regulation suggest an important role for natural selection in shaping gene expression patterns within and between species. Most of these studies, however, estimated gene expression levels using microarray probes designed to hybridize to only a small proportion of each gene. Here we used recently-developed RNA sequencing protocols, which side-step this limitation, to assess intra- and inter-species variation in gene regulatory processes in considerably more detail than was previously possible. Specifically, we used RNAseq to study transcript levels in humans, chimpanzees, and rhesus macaques, using liver RNA samples from three males and three females from each species. Our approach allowed us to identify a large number of genes whose expression levels likely evolve under natural selection in primates. These include a subset of genes with conserved sexually dimorphic expression patterns across the three species, which we found to be enriched for genes involved in lipid metabolism. Our data also suggest that while alternative splicing is tightly regulated within and between species, sex-specific and lineage-specific changes in the expression of different splice forms are also frequent. Intriguingly, among genes in which a change in exon usage occurred exclusively in the human lineage, we found an enrichment of genes involved in anatomical structure and morphogenesis, raising the possibility that differences in the regulation of alternative splicing have been an important force in human evolution. Keywords: Gene Regulation Study Overall design: Examination of gene expression levels in livers from three primate species (human, chimpanzee, and rhesus macaque), using 3 male and 3 female samples from each species.	Co-expression
SRP001563	Polymorphic cis- and trans-regulation of human gene expression	Expression levels of human genes vary extensive among individuals.  Gene expression determines cell function and characteristics thus this variation likely contributes to phenotypic variation.  Genetic studies have shown that there is a heritable component to gene expression variation, and have identified genomic regions that contain polymorphic regulators.  However, most of these regions are quite large, and few regulators have been identified.  In this genetic of gene expression study, we used a large sample to search the genome for polymorphic regulators that influence gene expression, and followed up the results with deep sequencing of transcriptomes and molecular analyses. Key word(s): Transcriptome Analysis Overall design: genetics of gene expression study, 41 Coriell cell line samples examined.	Co-expression
SRP001758	PTB CLIP-seq	Recent transcriptome analysis indicates that >90% of human genes undergoes alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells. The polypyrimidine tract binding protein PTB is a well-characterized splicing repressor, but PTB knockdown causes both exon inclusion and skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional RNA map now revealed that dominant PTB binding near a competing constitutive splice site generally induces exon inclusion whereas prevalent binding close to an alternative site often causes exon skipping. This positional effect was further demonstrated by disrupting or creating a PTB binding site on minigene constructs and testing their responses to PTB knockdown or overexpression. These findings suggest a mechanism for PTB to modulate splice site competition to produce opposite functional consequences, which may be generally applicable to RNA binding splicing factors to positively or negatively regulate alternative splicing in mammalian cells. Overall design: Examination of PTB-RNA binding in Hela cells using CLIP-seq (Cross-Linking ImmunoPrecipitation coupled with high-throughput sequencing) method. Peaks: The four alignment files (linked as supplementary files on Sample records) were combined together for peak finding, as we found that most of the monomeric and dimeric tags are similarly distributed in the genome with high pearson correlation coefficient. The method to detect the peaks above gene-specific randomized background was similar to (Yeo et al., 2009) and described in the paper (Xue et al., 2009).	Co-expression
SRP001893	Regulation of alternative splicing by histone modifications	Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. Overall design: To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.	Co-expression
SRP002079	Dynamic transcriptomes during neural differentiation of human embryonic stem cells	Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short long, and paired-end sequencing In order to examine the fundamental mechanisms governing neural differentiation, we analyzed the transcriptome changes that occur during the differentiation of human embryonic stem cells (hESCs) into the neural lineage. Undifferentiated hESCs as well as cells at three stages of early neural differentiation, N1 (early initiation), N2 (neural progenitor), and N3 (early glial-like) were analyzed using a combination of single read, paired-end read, and long read RNA sequencing. The results revealed enormous complexity in gene transcription and splicing dynamics during neural cell differentiation. We found previously unannotated transcripts and spliced isoforms specific for each stage of differentiation. Interestingly, splicing isoform diversity is highest in undifferentiated hESCs and decreases upon differentiation, a phenomenon we call “isoform specialization.” During neural differentiation, we observed differential expression of many types of genes including those involved in key signaling pathways, and a large number of extracellular receptors exhibit stage-specific regulation. These results provide a valuable resource for studying neural differentiation and reveal insights into the mechanisms underlying in vitro neural differentiation of hESCs, such as neural fate specification, NPC identity maintenance and the transition from a predominantly neuronal state into one with increased gliogenic potential Overall design: Characterization of changes in the transcriptome profiles during early stages of human neural differentiation from H1 !Series_overall_design=hESCs. 454 SFF files are missing. hESC_B_s9.fastq--> SRR037192 hESC_B_s8.fastq--> SRR037191 hESC_B_s7.fastq--> SRR037190 hESC_B_s6.fastq--> SRR037189 hESC_B_s5.fastq--> SRR037188 hESC_B_s4.fastq--> SRR037187 hESC_B_s3.fastq--> SRR037186 hESC_B_s2.fastq--> SRR037185 hESC_B_s16.fastq--> SRR037184 hESC_B_s15.fastq--> SRR037183 hESC_B_s14.fastq--> SRR037182 hESC_B_s13.fastq--> SRR037181 hESC_B_s12.fastq--> SRR037180 hESC_B_s11.fastq--> SRR037179 hESC_B_s10.fastq--> SRR037178 hESC_B_s1.fastq--> SRR037177 hESC_B_p6_2.fastq--> SRR037176 hESC_B_p6_1.fastq--> SRR037176 hESC_B_p5_2.fastq--> SRR037175 hESC_B_p5_1.fastq--> SRR037175 hESC_B_p4_2.fastq--> SRR037174 hESC_B_p4_1.fastq--> SRR037174 hESC_B_p3_2.fastq--> SRR037173 hESC_B_p3_1.fastq--> SRR037173 hESC_B_p2_2.fastq--> SRR037172 hESC_B_p2_1.fastq--> SRR037172 hESC_B_p1_2.fastq--> SRR037171 hESC_B_p1_1.fastq--> SRR037171 hESC_A_s3.fastq--> SRR037170 hESC_A_s2.fastq--> SRR037169 hESC_A_s1.fastq--> SRR037168 hESC_A_p3_2.fastq--> SRR037167 hESC_A_p3_1.fastq--> SRR037167 hESC_A_p2_2.fastq--> SRR037166 hESC_A_p2_1.fastq--> SRR037166 hESC_A_p1_2.fastq--> SRR037165 hESC_A_p1_1.fastq--> SRR037165 N3_A_s4.fastq--> SRR037226 N3_A_s3.fastq--> SRR037225 N3_A_s2.fastq--> SRR037224 N3_A_s1.fastq--> SRR037223 N3_A_p3_2.fastq--> SRR037222 N3_A_p3_1.fastq--> SRR037222 N3_A_p2_2.fastq--> SRR037221 N3_A_p2_1.fastq--> SRR037221 N3_A_p1_2.fastq--> SRR037220 N3_A_p1_1.fastq--> SRR037220 N2_B_s8.fastq--> SRR037219 N2_B_s7.fastq--> SRR037218 N2_B_s6.fastq--> SRR037217 N2_B_s5.fastq--> SRR037216 N2_B_s4.fastq--> SRR037215 N2_B_s3.fastq--> SRR037214 N2_B_s2.fastq--> SRR037213 N2_B_s1.fastq--> SRR037212 N2_B_p6_2.fastq--> SRR037211 N2_B_p6_1.fastq--> SRR037211 N2_B_p5_2.fastq--> SRR037210 N2_B_p5_1.fastq--> SRR037210 N2_B_p4_2.fastq--> SRR037209 N2_B_p4_1.fastq--> SRR037209 N2_B_p3_2.fastq--> SRR037208 N2_B_p3_1.fastq--> SRR037208 N2_B_p2_2.fastq--> SRR037207 N2_B_p2_1.fastq--> SRR037207 N2_B_p1_2.fastq--> SRR037206 N2_B_p1_1.fastq--> SRR037206 N2_A_s4.fastq--> SRR037205 N2_A_s3.fastq--> SRR037204 N2_A_s2.fastq--> SRR037203 N2_A_s1.fastq--> SRR037202 N2_A_p3_2.fastq--> SRR037201 N2_A_p3_1.fastq--> SRR037201 N2_A_p2_2.fastq--> SRR037200 N2_A_p2_1.fastq--> SRR037200 N2_A_p1_2.fastq--> SRR037199 N2_A_p1_1.fastq--> SRR037199 N1_A_s3.fastq--> SRR037198 N1_A_s2.fastq--> SRR037197 N1_A_s1.fastq--> SRR037196 N1_A_p3_2.fastq--> SRR037195 N1_A_p3_1.fastq--> SRR037195 N1_A_p2_2.fastq--> SRR037194 N1_A_p2_1.fastq--> SRR037194 N1_A_p1_2.fastq--> SRR037193 N1_A_p1_1.fastq--> SRR037193	Co-expression
SRP002105	Pol II and its associated epigenetic marks are present at pol III-transcribed non-coding RNA genes (II)	Epigenetic control is an important aspect of gene regulation.  Despite detailed understanding of many examples, the transcription of non-coding RNA genes by RNA polymerase (pol) III is less well characterized.  Here we profile the epigenetic features of pol III target genes  throughout the human genome.  This reveals that the chromatin landscape of pol III-transcribed genes resembles that of pol II templates in many ways, although there are also clear differences.  Our analysis also discovered an entirely unexpected phenomenon, namely that pol II co-localizes with the majority of genomic loci that are bound by pol III. Overall design: RNA-seq experiment for total RNA in CD4+ cells.	Co-expression
SRP002128	Human variation in PolII and NF-KappaB binding (RNA-seq study with TNF-alpha induced)	We examined genome-wide variation in transcription factor binding in different individuals and a chimpanzee using chromatin immunoprecipitation followed by massively-parallel sequencing (ChIP-Seq). The binding sites of RNA Polymerase II (Pol II) as well as a key regulator of immune responses, NFkB, were mapped in ten HapMap lymphoblastoid cell lines derived from individuals of African, European, and Asian ancestry, including a parent-offspring trio. We also mapped gene expression in all ten human cell lines for two treatment conditions: a) no treatment and b) following induction by TNF-alpha. Overall design: Genome-wide comparison of Pol II and NF-KappaB binding in ten individuals. RNA-seq study with TNF-alpha treatment.	Co-expression
SRP002184	Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis	Epidermal growth factor (EGF) is a key regulatory growth factor activating a myriad of processes affecting cell proliferation and survival that are relevant to normal development and disease. Here we have used a combined approach to study the EGF dependent transcriptome of HeLa cells. We obtained mRNA expression profiles using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, Febit, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer I (GA-I). By applying a procedure for cross-platform data meta-analysis based on rank product and global ancova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We used this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we found a whole new set of genes previously unrelated to the currently accepted EGF associated cellular functions, among which are metallothionein genes. We propose the use of global genomic cross-validation to generate more reliable datasets derived from high content technologies (microarrays or deep sequencing). This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data. Keywords: treated vs. untreated comparison, time course Overall design: Time course experiment comparing HeLa gene expression in response to EGF analyzed on different microarray platforms (Agilent, IMPPC, Illumina, and Operon) and by digital gene expression using short read high throughput tag sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6, and 24 h and harvested for RNA extraction. Technical dye swap duplicates were performed for each of the three biological replicates in both time points. Comparative genomic hybridization of HeLa cell genomic DNA versus  poooled genomic DNA from blood obtained from human females conducted on commercial oligonucleotide microarrays (Human Genome CGH Microarray Kit 244A, Agilent Technologies) in order to assess DNA dosage dependence of gene expression levels and response to EGF. Digital gene expression using short read high throughput tag sequencing data submitted to NCBI''s SRA	Co-expression
SRP002220	Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood (seq data)	MicroRNAs are a class of small non-coding RNAs that regulate mRNA expression at the post-transcriptional level and thereby many fundamental biological processes. A number of methods, such as multiplex polymerase chain reaction, microarrays have been developed for profiling levels of known miRNAs. These methods lack ability to identify novel miRNAs and accurately determine expression at a range of concentration. Deep or massively parallel sequencing methods are providing suitable platforms for genome wide transcriptome analysis and have the ability to identify novel transcripts. The results of analysis of small RNA sequences obtained by Solexa technology of normal peripheral blood mononuclear cells, tumor cell lines K562 (chronic myelogenous leukemia) and HL60 (acute promyelogenous leukemia) are presented. Custom computation pipelines were used to generate expression profiles of known and for identification of novel miRNAs. Some of the highly expressed miRNAs in the leukocytes include several members of the let 7 family, mir-21, 103, 185, 191 and 320a. Comparison of the miRNA profiles of normal versus K562 cells or HL60 revealed a specific set of differentially expressed molecules. Correlation of the miRNA with that of mRNA expression profiles, obtained by microarray, revealed a set of target genes showing inverse correlation with miRNA levels. Our computational pipeline also predicted a number of novel miRNAs. Some of the predictions were validated by realtime RT-PCR and or RNAase protection assay. Overall design: The small RNA population from four samples - Two Normal Peripheral blood mononuclear cells (PBMC) samples, K562 cell line (This cell line is used as a model to study Chronic Myelogenous Leukemia), HL60 (This cell line is used to study acute promyelogenous leukemia) was sequenced using Solexa technology.	Co-expression
SRP002272	Small RNA Solexa sequencing of human liver samples	We applied small RNA Solexa sequencing technology to identify microRNA expression in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver, a severe chronic hepatitis B liver, two HBV-related hepatocellular carcinoma (HCC), an hepatitis C virus (HCV)-related HCC, and an HCC without HBV or HCV infection. All samples were collected with the informed consent of the patients and the experiments were approved by the ethics committee of Second Military Medical University, Shanghai, China. We investigated the miRNome in human normal liver and suggested some deregulated abundantly expressed microRNAs in HCC. center_name: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. Overall design: Examination of miRNome in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver tissue, a severe chronic hepatitis B liver tissue, an HBV-related hepatocellular carcinoma (HCC) tissue and adjacent liver tissues of different regions,an HBV-related HCC tissue and adjacent liver tissue, an hepatitis C virus (HCV)-related HCC tissue and adjacent liver tissue, and an HCC without HBV or HCV infection and adjacent liver tissue. All 15 human liver tissue samples.	Co-expression
SRP002274	Next generation sequencing of human brain tissues transcriptome	Apply the Illumina next generaton sequencing technology to obtain 22 millions of 50-bp paired-end reads Overall design: High-throughput RNA-seq in human brain tissues. Mapping results on human genome (hg18) by SeqMap.	Co-expression
SRP002306	Elucidating the stromal expression pattern in response to tumor-derived Shh	Most tumors of the upper gastrointestinal tract are known to depend on an excessive expression of Shh. It was recently discovered that this Shh does not signal on the tumor cells, but rather the stromal cells that in turn produce an unknown set of reciprocal signals that act as growth- or survival cues for the tumor cells. This sequencing effort aims to identify the reciprocal signals. Overall design: Mouse fibroblasts and Shh-expressing human pancreatic adenocarcinoma cells were either grown alone, or in a non-adherent coculture system. To be able to assess the effect of Shh on fibroblast gene expression (being the reciprocal signal), 5E1 blocking antibody was added to the cells and after 5 days, RNA was isolated. n=1	Co-expression
SRP002347	Multi tissue small RNA	We sequenced the small RNA component from 2 individuals across 8 tissues: Lung, Kidney, Skeletal muscle, Heart, Pancreas, Frontal Orbital Gyrus, Spleen, Liver.	Co-expression
SRP002487	Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP: sequencing data	We applied 4-thiouridine to cultured cells expressing the FLAG/HA-tagged RNA-binding proteins (RBPs) followed by UV 365 nm irradiation. The crosslinked RNA-protein complexes were isolated by immunoprecipitation, and the covalently bound RNA was partially digested with RNase T1 and radiolabeled. The radiolabeled RNPs were subsequenctly separated by SDS-PAGE, the crosslinked RNA segments recovered and converted into a cDNA library and sequenced. Overall design: RBPs were UV-crosslinked to their RNA targets containing 4-thiouridine. The RNA segments were recovered after immunoprecipitation and seqeunced by Solexa.	Co-expression
SRP002543	Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases	Messenger RNAs are regulated by a variety of degradation mechanisms in mammalian cells.  In the canonical animal microRNA pathway, microRNAs in complex with Argonaute proteins bind to many mRNA targets with imperfect complementarity, leading to degradation of the mRNA through the regular decay machinery.  The ancestral “slicer” endonuclease activity of Argonaute2 itself, which requires more extensive complementarity with the target RNA, is not used in this pathway, and has only been observed in two microRNA-guided cases.  Nevertheless, the cleavage capacity of mammalian Ago2 is conserved and essential for viability.  Here, we assess the endonucleolytic function of Ago2 and other nucleases by identifying cleavage products retaining 5`-phosphate groups in mouse ES cells on a transcriptome-wide scale.  We detect a significant signature of Ago2-dependent cleavage events and validate several targets.  Unexpectedly, a broader class of Ago2-independent cleavage sites is also observed, indicating participation of additional nucleases in this mode of mRNA regulation.  Within this class, we identify a cohort of Drosha-dependent mRNA cleavage events, including one in the Dgcr8 mRNA, that functionally regulate mRNA levels in mES cells.  Together, these results highlight the underappreciated role of endonucleolytic cleavage in controlling mRNA fates in mammals. Overall design: Global 5`-phosphate-dependent RACE in WT, Ago2-KO and Drosha-excised mouse ES cells and human 293S cells	Co-expression
SRP002628	Comparative transcriptomic analysis of prostate cancer and matched normal tissue using RNA-seq	We used RNA-seq to interrogate prostate cancer specific gene fusions, alternative splicings, somatic mutations and novel transcripts. Overall design: We sequenced the transcriptome (polyA+) of 20 prostate cancer tumors and 10 matched normal tissues using Illumina GAII platform. Then we used bioinformatic approaches to identify prostate cancer specific aberrations which include gene fusion, alternative splicing, somatic mutation, etc.	Co-expression
SRP002640	Expanding the MicroRNA Targeting Code:  A Novel Type of Site with Centered Pairing	We present “centered sites,” a class of microRNA target sites that lacks both perfect seed pairing and 3'-compensatory pairing and instead has 11–12 contiguous Watson–Crick pairs to the center of the microRNA.  In elevated Mg2+, centered sites impart mRNA cleavage, but in cells, centered sites repress protein output without consequential Agronaute-catalyzed cleavage.  Our study also identified novel extensively paired sites that are cleavage substrates in cultured cells and human brain.  This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many microRNAs are evolutionarily conserved. Overall design: To study centered sites and identify miRNA cleavage targets, mRNA degradomes were sequenced from human brain and HeLa cells, and smallRNAs were sequenced from human brain and zebrafish embryo at 24 hours post fertilization (hpf). Replicates were combined before the analysis. Fastq files are not available for GSM548638 and GSM548639.	Co-expression
SRP002861	Deep Sequencing of Human Nuclear and Cytoplasmic Small RNAs Reveals an Unexpectedly Complex Subcellular Distribution of miRNAs and tRNA 3'' Trailers	Background: MicroRNAs (miRNAs) are 22-nt small non-coding regulatory RNAs that have generally been considered to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in the nucleus. Methodology/Principal Findings: To determine the number of miRNAs localized to the nucleus, we systematically investigated the subcellular distribution of small RNAs (sRNAs) by independent deep sequencing the nuclear and cytoplasmic pools of 18- to 30-nucleotide sRNAs from human cells. We identified 339 nuclear and 324 cytoplasmic known miRNAs, 300 of which overlap, suggesting that the majority of miRNAs are imported into the nucleus. With the exception of a few miRNAs evidently enriched in the nuclear pool, such as the mir-29b, the ratio of miRNA abundances in the nuclear fraction versus in the cytoplasmic fraction vary to some extent. Moreover, our results revealed that a large number of tRNA 3'' trailers are exported from the nucleus and accumulate in the cytoplasm. These tRNA 3'' trailers accumulate in a variety of cell types, implying that the biogenesis of tRNA 3'' trailers is conserved and that they have a potential functional role in vertebrate cells. Conclusion/Significance: Our results provide the first comprehensive view of the subcellular distribution of diverse sRNAs and new insights into the roles of miRNAs and tRNA 3'' trailers in the cell Overall design: Discovery and characterization of small RNA species through deep sequencing of nuclear and cytoplasmic small RNA fractions from 5-8F cells, a nasopharyngeal carcinoma cell line.	Co-expression
SRP002958	microRNA expression in human tonsillar B cell populations	small RNA profiles of 6 human tonsillar B cell populatios (naive B cells, pre-germinal center B cells, centrocytes, centroblasts, memory B cells, and plasma cells) were determined by deep sequencing.  These samples were compared to mouse developing lymphocytes, various hematopoietic cell lineages, and tissues. Overall design: small RNA expression profiles of 6 well defined B cell populations isolated from human tonsils.	Co-expression
SRP003021	Genome-wide analysis of RNAs associated with Lin28	We used immunoprecipitation to pulldown Lin28 associated RNA targets and used genome-wide high throughput deep sequencing to identified those Lin28-associated RNAs. Keywords: Lin28 IP-RNAseq Overall design: Examination of Lin28 immunoprecipitated RNA transcripts	Co-expression
SRP003483	Differential genome-wide profiling of tandem 3'UTRs among human breast cancer and normal cells by high-throughput sequencing	Tandem 3'UTRs produced by alternative polyadenylation (APA) sites in last exon play an important role in gene expression network by impacting mRNA stability, translation and translocation in cells. Several studies investigated APA sites switching in various physiological states, nevertheless they only focused on the genes with two known APA sites or several candidate genes. Here we developed a strategy to study APA sites in genome-wide fashion with the second generation sequencing technology, which could not only identify new polyadenylation sites but also analyze the APA sites switching in all genes especially those with more than two APA sites. We used this strategy to explore the profiling of APA sites in two human breast cancer cell lines (MCF7 and MB231) and one cultured mammary epithelial cell line (MCF10A). More than half of the identified polyadenylation sites are not reported in human poly(A) databases. While MCF7 showed shortening 3'UTR, more genes in MB231 switched to distal poly(A) sites. Several gene ontology terms and pathways were enriched in the list of genes with switched APA sites, including cell cycle, apoptosis, metabolism and so on. These suggest the more complex regulation of APA sites in cancer cells than the previous thought. Several motifs were found to possibly contribute to the APA sites switching. In short, our novel unbiased method can be a powerful approach to uncover the complex mechanism of 3'UTR switching in genome-wide fashion among various physiological processes and diseases cost-effectively like this study.	Co-expression
SRP003611	Deep transcriptional sequencing analysis of human prostate adenocarcinoma and reference samples	Prostate adenocarcinoma and matched adjacent normal samples were profiled by deep transcriptional sequencing to analyze transcription-induced chimeras and gene fusions.  Reference samples from the MAQC and brain and universal reference libraries were also sequenced. Overall design: Two-condition experiment plus reference samples: Prostate adenocarcinoma versus matched normal from three separate patients, plus brain and universal reference samples from the MAQC project.	Co-expression
SRP003672	Genome-wide characterization of long nonpolyadenylated RNAs, experiment II	We have used deep sequencing to explore the repertoire of both poly(A)+ and poly(A)- RNAs from two standard cell lines, HeLa cells and human embryonic stem cell (hESC) H9 cells. Overall design: Examination of nonpolyadenylated and polyadenylated in 2 cell types.	Co-expression
SRP003901	Digital gene expression (DGE) sequencing of 10 pairs samples between kidney normal tissue and cancer tissue	we combined their genome-wide profiles of tumors and normal adjacent tissues in 10 ccRCC patients. The results showed that 283 miRNAs were down-regulated and 187 up-regulated, meanwhile 7473 mRNAs were up-regulated and 3439 down-regulated in ccRCC. Expressions of 12 miRNAs and genes were validated in 10 patients we studied by RT-qPCR (validation rate from 60% to 100%). Differentially expressed gene analysis showed the collective change of miR-200 and SLC22A gene family, and pathway analysis revealed down-regulation of multiple metabolic pathways and up-regulation of focal adhesion, ECM-receptor interaction, etc. Moreover, A miRNA cluster located in chromosome Xq27.3 were significantly down-regulated in ccRCC, which were verified in 53 ccRCC patients by RT-qPCR (validation rate from 63.8% to 88.6%).56 and 586 potentially novel miRNAs and mRNA we detected according to statistical analyses. In addition, 14 miRNA candidates were randomly selected to validate using qRT-PCR and Sanger sequcencing technology, 10 of out 14 could be successfully amplified,.Plus, the sequences of all 5 randomly selected amplified products were confirmed by cloned Sanger sequencing.Our data demonstrated a combined profiling of miRNAs and mRNAs in ccRCC, which showed the decreased metabolism and the perturbation of renal cell function. Moreover, this study identified the expression alteration of a miRNA cluster on Xq27.3, which suggested its potential function in carcinogenesis of ccRCC Overall design: Examination of 10 pairs of kidney normal cells and cancer cells .	Co-expression
SRP003902	miRNA sequencing of 10 pairs samples between kidney normal tissues and cancer tissue	we combined their genome-wide profiles of tumors and normal adjacent tissues in 10 ccRCC patients. The results showed that 283 miRNAs were down-regulated and 187 up-regulated, meanwhile 7473 mRNAs were up-regulated and 3439 down-regulated in ccRCC. Expressions of 12 miRNAs and genes were validated in 10 patients we studied by RT-qPCR (validation rate from 60% to 100%). Differentially expressed gene analysis showed the collective change of miR-200 and SLC22A gene family, and pathway analysis revealed down-regulation of multiple metabolic pathways and up-regulation of focal adhesion, ECM-receptor interaction, etc. Moreover, A miRNA cluster located in chromosome Xq27.3 were significantly down-regulated in ccRCC, which were verified in 53 ccRCC patients by RT-qPCR (validation rate from 63.8% to 88.6%).56 and 586 potentially novel miRNAs and mRNA we detected according to statistical analyses. In addition, 14 miRNA candidates were randomly selected to validate using qRT-PCR and Sanger sequcencing technology, 10 of out 14 could be successfully amplified,.Plus, the sequences of all 5 randomly selected amplified products were confirmed by cloned Sanger sequencing.Our data demonstrated a combined profiling of miRNAs and mRNAs in ccRCC, which showed the decreased metabolism and the perturbation of renal cell function. Moreover, this study identified the expression alteration of a miRNA cluster on Xq27.3, which suggested its potential function in carcinogenesis of ccRCC Overall design: Examination of 10 pairs of kidney normal cells and cancer cells .	Co-expression
SRP004637	Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression (RNA-Seq data)	Noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer–associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencing of polyA+ RNA (RNA-Seq) from a cohort of 102 prostate tissues and cells lines. We characterized one ncRNA, PCAT-1, as a prostate-specific regulator of cell proliferation and show that it is a target of the polycomb repressive complex 2 (PRC2). We further found that patterns of PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1–repressed target genes. Taken together, our findings suggest that PCAT-1 is a transcriptional repressor implicated in a subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes. Overall design: 21 prostate cell lines sequenced on the Illumina Genome Analyzer and GAII.  Variable number of replicates per sample.  RNA-Seq data from prostate cancer tissues used in this study will be made available on dbGAP.	Co-expression
SRP004837	Altered antisense-to-sense transcript ratios in breast cancer: ASSAGE	Transcriptome profiling studies suggest that a large fraction of the genome is transcribed and many transcripts function independent of their protein coding potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological processes and in tumorigenesis is increasingly recognized. Here, we describe consistent and significant differences in the distribution of sense and antisense transcripts between normal and neoplastic breast tissues. Many of the differentially expressed antisense transcripts likely represent long ncRNAs. A subset of genes that mainly generate antisense transcripts in normal but not cancer cells is involved in essential metabolic processes. These findings suggest fundamental differences in global RNA regulation between normal and cancer cells that might play a role in tumorigenesis. Overall design: Global strand-specific transcriptome profilings of 2 samples in cancer and 1 sample in normal from clinical breast tissue using asymmetrical strand-specific analysis of gene expression (ASSAGE).	Co-expression
SRP005242	A Comparison of Single Molecule and Amplification Based Sequencing of Cancer Transcriptomes: RNA-Seq Comparison	The second wave of next generation sequencing technologies, referred to as single-molecule sequencing (SMS), carries the promise of profiling samples directly without employing polymerase chain reaction steps used by amplification-based sequencing (AS) methods. To examine the merits of both technologies, we examine mRNA sequencing results from single-molecule and amplification-based sequencing in a set of human cancer cell lines and tissues. We observe a characteristic coverage bias towards high abundance transcripts in amplification-based sequencing. A larger fraction of AS reads cover highly expressed genes, such as those associated with translational processes and housekeeping genes, resulting in relatively lower coverage of genes at low and mid-level abundance. In contrast, the coverage of high abundance transcripts plateaus off using SMS; Consequently, SMS is able to sequence lower- abundance transcripts more thoroughly, including some that are undetected by AS methods; however, these include many more mapping artifacts. A better understanding of the technical and analytical factors introducing platform specific biases in high throughput transcriptome sequencing applications will be critical in cross platform meta-analytic studies.	Co-expression
SRP005309	Genome-wide identification of micro-ribonucleic acids associated with human endometrial receptivity in natural and stimulated cycles by deep sequencing	In this study, we took advantage of deep sequencing approaches to investigate the miRNA expression profiles of human endometrium on days LH+2 and LH+7 in natural cycles, and compare them with those on days hCG+4 and hCG+7 in stimulated cycles during IVF treatment. Overall design: Examination of miRNA expression in human endometrium during natural and stimulated cycles	Co-expression
SRP005342	Regulation of alternative splicing by the core spliceosomal machinery	Abstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP protein SmB/B’ self-regulates its expression by promoting the inclusion of a highly-conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B’ in human cells results in reduced levels of snRNPs and in a striking reduction in the inclusion levels of hundreds of alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors. Overall design: HeLa cells were transfected with a control non-targeting siRNA pool (siNT), or with siRNA pools designed to knockdown SmB/B'' or SRSF1 (also known as SF2/ASF/SFRS1). Sequence reads were aligned to exon-exon junction sequences in a database of EST/cDNA-mined cassette-type alternative splicing events. Processed data files (.bed and .txt) provided as supplementary files on the Series record.  Processed data file build information: hg18.	Co-expression
SRP006474	A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins (CLIP)	Crosslinking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins (RBPs). We developed a method for CLIP data analysis and applied it to compare 254 nm CLIP with PAR-CLIP, which involves crosslinking of photoreactive nucleotides with 365 nm UV light. We found small differences in the accuracy of these methods in identifying binding sites of HuR, a protein that binds low-complexity sequences and Argonaute 2, which has a complex binding specificity. We show that crosslink-induced mutations lead to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect sufficiently their sites under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific ribonucleases strongly biases the set of recovered binding sites. We finally show that this bias can be substantially reduced by milder nuclease digestion conditions. Overall design: We performed duplicate experiments for each variant of the CLIP protocol (CLIP, PAR-CLIP), each protein (HuR, Ago2), and enzymatic digestion (complete T1 digestion, mild MNase digestion). In addition, we performed a single PAR-CLIP experiment with mild T1 digestion.	Co-expression
SRP006475	A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins (mRNA-seq)	Crosslinking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins (RBPs). We developed a method for CLIP data analysis and applied it to compare 254 nm CLIP with PAR-CLIP, which involves crosslinking of photoreactive nucleotides with 365 nm UV light. We found small differences in the accuracy of these methods in identifying binding sites of HuR, a protein that binds low-complexity sequences and Argonaute 2, which has a complex binding specificity. We show that crosslink-induced mutations lead to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect sufficiently their sites under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific ribonucleases strongly biases the set of recovered binding sites. We finally show that this bias can be substantially reduced by milder nuclease digestion conditions. Overall design: We performed duplicate mRNA-Seq experiments for cells grown in the presence of modified nucleotides or in normal medium, and following crosslinking at 365nm, 254nm or without crosslinking. In addition, we performed single mRNA-Seq experiments of cells transfected with anti-GFP or anti-HuR siRNA.	Co-expression
SRP006574	GSE28884: MicroRNA sequence and expression analysis in breast tumors by deep sequencing	No description.	Co-expression
SRP006575	Transcriptional profiling of lncRNAs and novel transcribed regions across a diverse panel of archived human cancers	Molecular characterization of tumors has been critical for identifying important genes in cancer biology and for improving tumor classification and diagnosis. Long non-coding RNAs (lncRNAs), as a new, relatively unstudied class of transcripts, provide a rich opportunity to identify both functional drivers and cancer-type specific biomarkers. However, despite the potential importance of lncRNAs to the cancer field, no comprehensive survey of lncRNA expression across various cancers has been reported. We used 3''-End Sequencing for Expression Quantification (3SEQ) to quantify transcript abundance across 64 solid tumors representing 17 diagnostic subtypes of adenocarcinomas, squamous cell carcinomas, and sarcomas. We identified hundreds of transcripts from among the known 1,065 lncRNAs surveyed that show variability in transcript levels between the tumor types, and therefore, make potential biomarker candidates. We discovered 1,071 novel intergenic transcribed regions and demonstrate that these show similar patterns of variability between tumor types. We find that many of these differentially expressed cancer transcripts are also expressed in normal tissues. One such novel transcript specifically expressed in breast tissue was further evaluated using RNA in situ hybridization on a panel of breast tumors and shown to correlate with low tumor grade and estrogen receptor expression, thereby representing a potentially important new breast cancer biomarker. This study provides the first large survey of lncRNA expression within a panel of solid cancers and also identifies a number of novel transcribed regions differentially expressed across distinct cancer types that represent candidate biomarkers for future research. Overall design: 3SEQ was performed on 64 formalin-fixed, paraffin-embedded (FFPE) human tumors representing 17 diagnostic cancer subtypes. Duplicate libraries were prepared for two of the tumors (ESS STT5520 and LMS STT516). 3SEQ was also performed on 27 normal human tissue samples. RNA-Seq was performed on 6 breast cancer cell lines for the examination of the breast-specific transcript on chr10. Series supplementary files: ''GSE28866_raw_counts_54511_peaks_cancer_and_normal.txt'': Raw_counts: Total 3SEQ reads in each peak for each sample. File includes read counts for 54,511 peaks for the 66 cancer libraries and the 27 normal libraries. ''GSE28866_36048_normalized_peaks_cancer_and_normal.txt'': Normalized_peaks: Normalized 3SEQ expression data for the 36,048 filtered peaks for the 66 cancer libraries and the 27 normal libraries. Peaks were classified as coding, lncRNA (Rinn, Bartel, Hughes, Gencode_lnc), other known transcripts (ref_known_Gencode_nc, all_mrna, other known), downstream, intron, promoter, or novel_intergenic. Peaks determined to be differentially expressed in one of the 17 cancer subtypes using a series of 2-Class SAM analyses are noted along with the type of cancer showing upregulation. Expression data was normalized using the sequencing depth of each sample by scaling the data using the mean value of each sample. Data was further compressed to reduce outliers by taking the square root of each value.	Co-expression
SRP006674	ChipSeq of FoxP3 bound regions and mRNAseq data of human Treg and CD4+ Th cells	Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4+ Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the Treg gene signature. Its ablation leads to severe immune deficiencies in human and mice. Recent developments in sequencing technologies have revolutionized the possibilities to gain insights into transcription factor binding by ChiP-Seq and into transcriptome analysis by mRNA-Seq. We combine FoxP3 ChiP-Seq and mRNA-Seq in order to understand the transcriptional differences between primary human CD4+ T helper and regulatory T-cells, as well as to study the role of FoxP3 in generating those differences. We show, that mRNA-Seq allows analyzing the transcriptomal landscape of T-cells including the expression of specific splice variants at much greater depth than previous approaches, whereas 50% of transcriptional regulation events have not been described before by using diverse array technologies.	Co-expression
SRP006676	mRNA-seq of Human Airway Epithelial Cells	mRNA expression was profiled from pooled bronchial airway epithelial cell brushings (n=3 patients/pool) obtained during bronchoscopy from healthy never (NS) and current smokers (S) and smokers with (C) and without (NC) lung cancer Overall design: 4 samples were sequened, each representing a pool of 3 patients.  The phenotypes of the 4 samples were as follows: healthy non-smoker, healthy smoker, smoker without lung cancer and smoker with lung cancer.	Co-expression
SRP006731	RNA-Seq anlalysis of prostate cancer cell lines using Next Generation Sequencing	Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. Overall design: Next generation Sequencing for Gene expression using the RNA-Seq methodology from LNCaP and PrEC cell lines	Co-expression
SRP006769	rRNA cleavage ensures translational cessation in the mature sperm	We report how unique RNA seq profiles of ribosomal RNA (18S, 28S) present in sperm indicate specific cleavage sites.  Additionally, these sequencing results reveal how overall character of RNA (GC content) can significantly affect overall distribution of mapped reads. Overall design: Examination of rRNA population and distribution in spermatozoa	Co-expression
SRP006908	Global analysis of previously unrecognized alternative splicing in BRCA1- related breast cancers	Background: Breast cancers arising from germline BRCA1 mutations are usually high grade, clinically aggressive tumors that are associated with a poor prognosis. Alterations in a number of pathways contribute to this phenotype including genomic stability, cell cycle and cell proliferation. RNA splicing is also often perturbed in cancers but it is not known whether this contributes to tumorigenesis in BRCA1-related breast cancers.  Methods: Using next-generation mRNA sequencing (RNA-Seq), we compared the transcriptome of four breast cancer cell lines and three primary breast cancers from BRCA1 germline mutation carriers to five breast cancer cell lines and two breast cancers occurring in non-BRCA mutation carriers. We created a systematic computational pipeline to detect potentially abnormal novel splice junctions (i.e. absent from RefSeq and UCSC) with irregular expression levels in BRCA1¬-related breast cancers compared to the non-BRCA control cancers.   Results: We found that a greater number of common splice junctions not annotated in RefSeq or UCSC databases were either up- or down-regulated in the BRCA1-related breast cancers than expected by chance. We present a list of highly recurrent splicing events, with the most discordant expression patterns compared to other breast cancers. Most of these are predicted to disrupt protein domains, cause frameshifts or are located in important regulatory genes. However, we were not able to detect any abnormally spliced transcripts which clearly contribute to the phenotype of the BRCA1-related breast cancers.  Conclusions: RNA-Seq is a powerful tool for analyzing abnormal transcripts on a genome-wide scale. With RNA-Seq, several potentially abnormal transcripts were found to be more highly expressed in the BRCA1-related breast cancers than in the non-BRCA1 breast cancer controls. However, we did not find evidence that highly recurrent, highly expressed abnormal alternative splice variants of specific genes are predominant drivers of tumorigenesis in BRCA1-related breast cancers.	Co-expression
SRP006970	Identification of allele-specific alternative mRNA processing via transcriptome sequencing	Establishing the functional roles of genetic variants remains a significant challenge in the post-genomic era. Here, we present a method, allele-specific alternative mRNA processing (ASARP), to identify genetically influenced mRNA processing events using transcriptome sequencing (RNA-Seq) data. The method examines RNA-Seq data at both single nucleotide and whole-gene/isoform levels to identify allele-specific expression (ASE) and existence of allele-specific regulation of mRNA processing. We applied the methods to data obtained from the human glioblastoma cell line U87MG and primary breast cancer tissues and found that 26–45% of all genes with sufficient read coverage demonstrated ASE, with significant overlap between the two cell types. Our methods predicted potential mechanisms underlying ASE due to regulations affecting either whole-gene-level expression or alternative mRNA processing, including alternative splicing, alternative polyadenylation and alternative transcriptional initiation. Allele-specific alternative splicing and alternative polyadenylation may explain ASE in hundreds of genes in each cell type. Reporter studies following these predictions identified the causal single nucleotide variants (SNVs) for several allele-specific alternative splicing events. Finally, many genes identified in our study were also reported as disease/phenotype-associated genes in genome-wide association studies. Future applications of our approach may provide ample insights for a better understanding of the genetic basis of gene regulation underlying phenotypic diversity and disease mechanisms. Overall design: Examine allele-specific gene expression and alternative RNA processing in U87MG cell line	Co-expression
SRP007169	RNA Sequencing Analysis Generates Comprehensive Transcriptomic Landscape and Identifies PTK6 as a Novel Tumor Suppressor Gene in Esophageal Squamous Cell Carcinoma	We performed the integrative transcriptome analysis of human esophageal squamous cell carcinoma (ESCC) using Illumina high-throughput sequencing. A total of 187 million 38bp sequencing reads were generated containing 7 billion bases for three pairs of matched patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues. By investigating the digital gene expression profiling, we found 1425 genes significantly differentially expressed and detected more than 9000 SNPs across all six samples. We also identified protein tyrosine kinase 6 (PTK6) as a novel tumor suppressor gene, which is critical in ESCC development. Overall design: Analysis of whole transcriptome from 3 paired patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues.	Co-expression
SRP007338	Widespread regulated alternative splicing of single codons accelerates proteome evolution	Thousands of human genes contain introns ending in NAGNAG motifs (N any nucleotide), where both NAGs can function as 3' splice sites, yielding isoforms differing by inclusion/exclusion of just three bases. However, the functional importance of NAGNAG alternative splicing is highly controversial. Using very deep RNA-Seq data from sixteen human and eight mouse tissues, we found that approximately half of alternatively spliced NAGNAGs undergo tissue-specific regulation and that regulated events have been selectively retained: alternative splicing of strongly tissue-specific NAGNAGs was ten times as likely to be conserved between species as for non-tissue-specific events. Further, alternative splicing of human NAGNAGs was associated with an order of magnitude increase in the frequency of exon length changes at orthologous mouse/rat exon boundaries, suggesting that NAGNAGs accelerate exon evolution. Together, our analyses show that NAGNAG alternative splicing constitutes a major generator of tissue-specific proteome diversity and accelerates evolution of proteins at exon-exon boundaries. Overall design: mRNA-Seq of sixteen human and eight mouse tissues. Supplementary files: human.nagnag.junctions.gff and mouse.nagnag.junctions.gff are the annotation files (in GFF3 format) corresponding to the 'bwtout' mapped reads files linked to the Sample records. Raw data files provided for Samples GSM742937-GSM742952 only.	Co-expression
SRP007351	GSE30222: RNA-seq of brain and various cell lines	No description.	Co-expression
SRP007412	The evolution of gene expression levels in mammalian organs	Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals. Our transcriptome data provide a valuable resource for functional and evolutionary analyses of mammalian genomes. Overall design: To study mammalian transcriptome evolution at high resolution, we generated RNA-Seq data (~3.2 billion Illumina Genome Analyser IIx reads of 76 base pairs) for the polyadenylated RNA fraction of brain (cerebral cortex or whole brain without cerebellum), cerebellum, heart, kidney, liver and testis (usually from one male and one female per somatic tissue and two males for testis) from nine mammalian species: placental mammals (great apes, including humans; rhesus macaque; mouse), marsupials (gray short-tailed opossum) and monotremes (platypus). Corresponding data (~0.3 billion reads) were generated for a bird (red jungle fowl, a non-domesticated chicken) and used as an evolutionary outgroup. Important note: Fluorophore intensity files were processed with the Ibis base caller (version 1.11). As illustrated in Supplementary Note Table 1 and Supplementary Note Figure 1 of Brawand et al. (Nature 2011), we found that Ibis significantly increased the number of usable reads and drastically reduced the error rate. However, Ibis quality values are not comparable to those from Illumina values, which should be taken into account when using our data and interpreting their quality relative to data established using other base calling approaches.	Co-expression
SRP007461	GSE30567: Long RNA-seq from ENCODE/Cold Spring Harbor Lab	No description.	Co-expression
SRP007481	Transposon-mediated gene regulatory network rewiring contributed to the evolution of pregnancy in mammals	We report the gene expression profile of human endometriual stromal cells and armadillo endometrial samples Overall design: We report the gene expression profile of human endometriual stromal cells and armadillo endometrial samples generated with Illumina GA2	Co-expression
SRP007483	Transcriptomic analysis of autistic brain reveals convergent molecular pathology [high-throughput sequence data]	Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. Overall design: To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.	Co-expression
SRP007494	Integrative Annotation of Human Large Intergenic Non-Coding RNAs Reveals Global Properties and Specific Subclasses	Large intergenic non-coding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-Seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalogue of over 8,000 human lincRNAs. Our catalogue unifies previously existing annotation sources with transcripts we assembled from RNA-Seq data collected from ~4 billion RNA-Seq reads across 24 tissues and cell types.  We characterize each lincRNA by a panorama of more than 30 properties, including sequence, structural, transcriptional, and orthology features. We find that lincRNA expression is strikingly tissue specific compared to coding genes, and that they are typically co-expressed with their neighboring genes, albeit to a similar extent to that of pairs of neighboring protein-coding genes. We distinguish an additional sub-set of transcripts that have high evolutionary conservation but may include short open reading frames, and may serve either as lincRNAs or as small peptides. Our integrated, comprehensive, yet conservative reference catalogue of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes. Overall design: We extracted profiled the transcriptome expression polyadenylated mRNA-Seq.  We then used these to reconstruct the transcriptome using de-novo assemblers and identify long non coding RNAs and their expression.	Co-expression
SRP007498	Unstressed HeLa cells and  ELAVL1/HuR knock down conditions: polyA RNA-Seq, small RNA-Seq, and PAR-CLIP	Post-transcriptional gene regulation relies on hundreds of RNA binding proteins (RBPs) but the function of most RBPs is unknown. The human RBP HuR/ELAVL1 is a conserved mRNA stability regulator. We used PAR-CLIP, a method based on RNA-protein crosslinking, to identify transcriptome wide ~26,000 HuR binding sites. These sites were on average highly conserved, enriched for HuR binding motifs and mainly located in 3'' untranslated regions. Surprisingly, many sites were intronic, implicating HuR in splicing. Upon HuR knock down, mRNA levels and protein synthesis of thousands of target genes was down regulated, validating functionality. HuR and miRNA binding sites tended to reside nearby but generally did not overlap. Additionally, HuR knock down triggered strong and specific up regulation of miR-7. In summary, we identified thousands of direct and functional HuR targets, found a human miRNA controlled by HuR, and propose a role for HuR in splicing. Overall design: PolyA mRNA was extracted from anti HuR siRNA treated and mock transfected HeLa cells to identify changes in mRNA expression and splicing. 2x100 paired end sequencing was performed according to the protocol on the Illumina HiSeq. PARCLIP was performed as in Hafner et. Al 2010 but with an antibody against endogenous HuR (3A2, Santa Cruz, sc-5261) in unstressed HeLa cells. We used, independently, 4-thiouridine (4SU) and 6-thioguanosine (6SG) to assess a possible nucleotide bias. As our proteomics measurements required labeling of cells in a special medium we also performed PAR-CLIP on cells grown in SILAC medium. Altogether we performed three PAR-CLIP experiments: 4SU labeling in standard DMEM medium, 4SU labeling in SILAC medium (as a replicate) and 6SG labeling in SILAC medium. Small RNA was extracted from anti HuR siRNA treated and mock transfected HeLa cells to identify changes in mRNA expression. Sequencing was performed on Illumina GAII using the standard sRNA 36cycle protocol.	Co-expression
SRP007560	Transcriptome for human liver cancer	No description.	Co-expression
SRP007569	SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset	Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. However, CD14++CD16+ monocytes remain the most poorly characterized subset so far. Therefore we analyzed the transcriptomes of the three monocyte subsets using SuperSAGE in combination with high-throughput sequencing. Analysis of 5,487,603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the two other monocyte subsets. CD14++CD16+ monocytes were linked to antigen processing and presentation (e.g. CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (e.g. TGFB1, AIF1, PTPN6), and to angiogenesis (e.g. TIE2, CD105). Therefore we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. Overall design: Human monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) were isolated from 12 healthy volunteers based on MACS technology. Total RNA from monocyte subsets was isolated and same aliquots from each donor and monocyte subset were matched for SuperSAGE. Three SuperSAGE libraries (CD14++CD16-, CD14++CD16+ and CD14+CD16++) were generated.	Co-expression
SRP007596	Genome-wide maps of polyadenylation sites in control and PABPN1kd cells	We applied deep-sequencing based technique, 3''-Seq, to obtain comprehansive maps of poly-A sites in human cells. 3''-Seq was applied to two cell lines (U2OS and RPE-1), in control and PABPN1 knockdown cells Overall design: Examination of poly-A sites in control and PABPN1kd cells (in two different cell lines)	Co-expression
SRP007605	Comprehensive analysis of RNA-Seq data reveals  extensive RNA editing in a human transcriptome	RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ~767 million sequencing reads from poly(A)+, poly(A)- and small RNA samples. We developed a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most changes (~93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential link between RNA editing and miRNA-mediated regulation. Our approach facilitates large-scale studies to profile and compare editomes across a wide range of samples.	Co-expression
SRP007641	small RNA profiling in human cell line following Dicer silencing	microRNAs (miRNAs) are a large class of small non-coding RNAs which post-transcriptionally regulate the expression of a large fraction of all animal genes and are important in a wide range of biological processes. Recent advances in high-throughput sequencing allow miRNA detection at unprecedented sensitivity, but the computational task of accurately identifying the miRNAs in the background of sequenced RNAs remains challenging. For this purpose we have designed miRDeep2, a substantially improved algorithm which identifies canonical and non-canonical miRNAs such as those derived from transposable elements and informs on high-confidence candidates that are detected in multiple independent samples. Analyzing data from seven animal species representing the major animal clades, miRDeep2 identified miRNAs with an accuracy of 98.6-99.9% and reported hundreds of novel miRNAs. To test the accuracy of miRDeep2, we knocked down the miRNA biogenesis pathway in a human cell line and sequenced small RNAs before and after. The vast majority of the >100 novel miRNAs expressed in this cell line were indeed specifically down-regulated, validating most miRDeep2 predictions.  Last, a new miRNA expression profiling routine, low time and memory usage and user-friendly interactive graphic output can make miRDeep2 useful to a wide range of researchers." Overall design: high-throughput sequencing was used to profile small RNA expression in a human MCF-7 cell line before and after Dicer knock-down	Co-expression
SRP007819	Comprehensive identification of edited miRNAs in the human brain	A-to-I editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the micro-RNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread others deem the reported events as rare. Utilizing a next-generation sequencing approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissue. Our algorithm successfully identified many of the known editing sites in mature miRNAs, and revealed additional novel sites, six of which are in the recognition sites of the miRNAs. The editing efficiency of most sites identified is very low. Thus, we find that A-to-I editing does alter several miRNAs but it is not widespread.	Co-expression
SRP007825	Small RNA sequencing in normal and psoriatic skin	We report the application of Illumina small RNA sequencing to normal human skin, as well as uninvolved and involved psoriatic skin. By obtaining over 600 million qualified reads from 20 healthy controls and 47 psoriasis biopsies (uninvolved/involved), we have generated a complete small RNA profile in normal and diseased human skin, with particular emphasis on miRNAs. We report the discovery of 284 putative novel miRNAs as well as 98 differentially expressed miRNAs in psoriatic skin. Overall design: miRNA discovery and expression profiling in 67 normal and psoriatic human skin biopsies	Co-expression
SRP007881	Analysis of the RNA-Seq data of castration resistant prostate cancer (CRPCa)	Prostate cancer is the second leading cancer that causes the death of American men. In this study, we  perform an integrative analysis of the whole-transcriptome of metastatic prostate cancer clinical samples. Specifically, we prepare our samples using an innovative protocol NuGEN, which captures the profile of the total RNA, rather than only the mRNA as the popular polyA selection protocol does. Unexpectedly high intronic expressions are observed including the gene AR (Androgen Receptor) and KLK3/PSA, a marker of prostate cancer. Further, certain amount of reads can be found to be across the intron-exon boundaries, suggesting that they come from unspliced pre-mRNAs.  Interestingly, we also observe high splicing on a non-coding RNA MALAT-1. We believe that the aberrant splicing patterns are associated with prostate cancer development. Overall design: Analysis of 8 clinical samples of metastatic prostate cancer patients	Co-expression
SRP007885	CTCF promotes RNA pol II pausing and links DNA methylation to alternative splicing [RNA-Seq]	The goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.	Co-expression
SRP007946	microRNA expression of cancer and matched adjacent tissues from 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder	Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of ''key'' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or therapeutic applications. Overall design: Examination of microRNA expression of cancer and matched adjacent tissues from 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder	Co-expression
SRP007947	mRNA expression of cancer and matched adjacent tissues of 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder	Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of ''key'' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or therapeutic applications. Overall design: Examination of mRNA expression of cancer and matched adjacent tissues of 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder	Co-expression
SRP008145	Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay	We apply a massively parallel reporter assay (MPRA) that relies on mRNA and plasmid tag sequencing (Tag-Seq) to compare the regulatory activities of more than 27,000 distinct variants of two inducible enhancers in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible interferon beta enhancer. The resulting data define accurate maps of functional transcription factor binding sites in both enhancers at single-nucleotide resolution and can be used the to train quantitative sequence-activity models (QSAMs). Overall design: Reporter Tag-Seq from HEK293 cells transfected with each of six MPRA plasmid pools, with and without stimulation (forskolin or Sendai virus). The reporter mRNAs contain unique 10 nucleotide tags that facilitates quantitation of their abundances. The same tags were also sequenced from each ransfected plasmid pool to facilitate normalization to plasmid copy numbers. The reporter constructs were designed according to two different mutagenesis strategies: 'single-hit scanning' and 'multi-hit sampling'. The specific variants are included in the processed data files.	Co-expression
SRP008216	microRNA Targetome Analysis of Latently KSHV-infected Primary Effusion Lymphoma Cell lines Using PAR-CLIP [Illumina]	Primary effusion lymphoma (PEL) is caused by Kaposi''s sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and, often, EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in viral latency and lymphomagenesis. Here we report the direct and transcriptome-wide identification of miRNA target sites for all miRNAs expressed in PEL cell lines. The resulting dataset revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs encoding proteins that function in pathways with relevance to KSHV pathogenesis. Moreover, ~50% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, these experiments identify an extensive list of mRNAs targeted by KSHV miRNAs and indicate that these are likely to strongly influence viral replication and pathogenesis. Overall design: small RNA sequencing, 3 samples Ago2 (EIF2C2) PAR-CLIP, 2 samples	Co-expression
SRP008225	An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq]	Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. However, the contribution of AS to the control of embryonic stem cell (ESC) pluripotency is not well understood. Here, we identify an evolutionarily conserved ESC-specific AS event that changes the DNA binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency including OCT4, NANOG, NR5A2 and GDF3, while concomitantly repressing genes required for ESC differentiation. Remarkably, this isoform also promotes the maintenance of ESC pluripotency and the efficient reprogramming of somatic cells to induced pluripotent stem cells. These results thus reveal that an AS switch plays a pivotal role in the regulation of pluripotency and functions by controlling critical ESC-specific transcriptional programs. Overall design: Exons 18 and 18b form a mutually exclusive splicing event. The FOXP1 (non-ES) isoform contains only exon 18 and not 18b, while the FOXP1-ES isoform contains only exon 18b and not 18. To investigate whether FOXP1 and FOXP1-ES control different sets of genes, we performed knockdowns using custom siRNA pools targeting FOXP1 exons 18 or 18b in undifferentiated H9 cells, followed by RNA-Seq profiling.	Co-expression
SRP008280	Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin hubs	We have analyzed publicly available K562 Hi-C data, which enables genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 46 transcription factors and 8 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into three types of chromatin hubs. The different clusters of loci display very different relationships with transcription factor binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 6, which is distinguished by marks of open chromatin but not by marks of active enhancers or promoters, was not bound by most transcription factors but was highly enriched for 3 transcription factors (GATA1, GATA2, and c-Jun) and 3 chromatin modifiers (BRG1, INI1, and SIRT6). To validate the identification of the clusters and to dissect the impact of chromatin organization on gene regulation, we performed RNA-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors greatly alters the expression of genes within cluster 6. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provide genome-wide evidence that Hi-C data identifies sets of biologically relevant interacting loci. Overall design: RNA-seq of control, siGATA1 and siGATA2 K562 cells	Co-expression
SRP008331	Transposon-based construction of strand-specific RNA-seq libraries	We have developed two methods for efficiently consructing RNA-seq libraries using transposition.  Each method constructs high quality RNA-seq libraries when compared to standard approaches. One of the methods (Directional Tn-RNA-seq) maintains strand-of-origin information and exhibits strand specificity comparable to current approaches. Overall design: RNA-seq libraries were constructed from ECC-1, a human cell line, and Universal Human Reference RNA using transposon-based and standard RNA-seq library construciton methods.	Co-expression
SRP008339	Immune-related microRNAs are enriched in breast milk exosomes	Breast milk is a complex liquid that enriched in immunological components and affect the development of the infant immune system. Exosomes, the membranous vesicles of endocytic origin, are ubiquitously in various body fluids which can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding small RNAs, in human breast milk are packaged inside exosomes. Here, we present the identification of miRNAs in human breast milk exosomes using deep sequencing technology. We found that the immune-related miRNAs are enriched in breast milk exosomes, and are resistant to the general harsh conditions. Overall design: Four small RNA libraries in human breast milk exosomes from four healthy women (30 +/- 0.9 years old, primiparity) when the infant were aged at 60 days were sequenced.	Co-expression
SRP008482	RNA-seq reveals novel transcriptome of genes and their isoforms in human pulmonary microvascular endothelial cells treated with Thrombin	The regulation of endothelial functions is essential for maintaining circulatory homeostasis and the physiological function of different organs. Thrombin can stimulate endothelial cells and regulate the expression, release and activation of a number of biological mediators. However, transcriptional regulation of vascular endothelial cells by thrombin is not completely understood. In the present study, Illumina RNA-seq was used to profile the transcriptome in human pulmonary microvascular endothelial cells (HMVEC-L) treated with thrombin to gain insight into thrombin''s direct effects on the endothelial function. Out of 100 million total reads from a paired end sequencing assay, 91-94% of the reads were aligned to over 16,000 genes in the reference human genome. Thrombin upregulated 150 known genes and 480 known isoforms, and downregulated 2,190 known genes and 3,574 known isoforms by at least 2 fold. Of note, thrombin upregulated 1,775 unknown isoforms and downregulated 12,202 isoforms by at least 2 fold. Many genes displayed isoform specific differential expression levels and different usage of transcriptional start sites after the thrombin treatment. Since the dysregulation of vascular endothelial cells by different agonists including thrombin has been implicated in the development of a number of pathologic disorders, such as inflammatory conditions, cancer, diabetes, coronary heart disease, further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on molecular pathogenic mechanisms underlying thrombin mediated endothelial dysfunction in those processes and provide new leads of potential relevant therapeutic targets.	Co-expression
SRP008496	Identification of a Novel Angiogenesis and Tumor Suppressor Gene   Rab25 in Esophageal Squamous Cell Carcinoma	Twelve clinical samples from human esophageal squamous cell carcinoma (ESCC) (seven tumors and five non-tumors) were sequenced using Illumina high-throughput sequencing and the RNA-Seq profiling was investigated with 1730 genes significantly differentially expressed. The gene Rab25 was found to be down-regulated in tumors (p-value < 1E-20) and identified as a novel candidate tumor suppressor gene. The down-regulation of Rab25 was examined in a large cohort of ESCC and non-tumor cases by qPCR and immunohistochemistry analyses. Aberrant methylation in the promoter region of Rab25 was studied by demethylation treatment with 5-aza-dC and bisulfite genomic sequencing (BGS). In order to assess the effect of Rab25 on tumor growth and angiogenesis, in vitro and in vivo functional studies in ESCC cell lines using lentiviral-based overexpression or knockdown models were also performed. Overall design: 7 tumor and 5 normal samples	Co-expression
SRP008552	Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing	In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Overall design: Examination of miRNA profile of two different ages	Co-expression
SRP008743	PrimSeq	RNA Sequencing of 12 primates and 4 mammals.	Co-expression
SRP008746	Identification of gene fusion transcripts by transcriptome sequencing in BRCA1-mutated breast cancers and cell lines	RNA sequencing was performed on ten breast cancer transcriptomes (five BRCA1-mutated breast cancer cell lines, three BRCA1-mutated primary tumours, two secretory breast cancer primary tumours and one non-tumorigenic breast epithelial cell line) using the Illumina Genome Analyzer. We sought to identify putative gene fusions using a bioinformatics approach. As a proof of concept, we were able to identify two previously characterized gene fusions in our samples using both single-end and paired-end approaches. In addition, we identified three novel in-frame fusions, but none were recurrent. Two of the candidates, WWC1-ADRBK2 in HCC3153 cell line and ADNP-C20orf132 in a primary tumour, were confirmed by Sanger sequencing and RT-PCR. RNA-Seq expression profiling of these two fusions showed a distinct overexpression of the 3' partner genes, suggesting that its expression may be under the control of the 5' partner gene's regulatory elements.	Co-expression
SRP008775	Comparison of the human oocyte to its sister polar body	Clinicians need additional metrics for predicting quality of human oocytes for IVF procedures. Human polar bodies reflect the oocyte transcript profile. Quantitation of polar body mRNAs could allow for both oocyte ranking and embryo preferences in IVF applications. The transcriptome of a polar body has never been reported, in any organism. Overall design: Eight total samples. There are 2 biological replicates of the following four conditions: pooled oocytes and their sister polar bodies and a single oocyte and its sister polar body.	Co-expression
SRP008930	Combinatorial role of two paralogous splicing factors, hnRNP L and L-like, in multiple-exon regulation of CD45 alternative splicing	The goal of this study was to investigate the role of hnRNP L-like in alternative pre-mRNA splicing in human B-cells through an RNA-Seq approach. Overall design: RNA-Seq was performed in DG75 cell line with over expression of hnRNP L-like or GFP as control.	Co-expression
SRP008976	Personal Omics Profiling Reveals Dynamic Molecular Phenotypes and Actionable Medical Risks	We have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311	Co-expression
SRP009067	The genetics and regulatory logic of alternative polyadenylation in human lymphoblastoid cells	We set out to investigate genomic mechanisms by which alternative polyadenylation impacts gene expression and its variation across genetically distinct human individuals. We used 3’-end RNA-seq to maximize genome coverage and precision of transcript end positions, and to measure quantitative expression levels of transcript forms. The results shed light on the architecture of transcript ends and regulatory elements in human 3’ UTRs and the principles of genetic variation in 3’ length form usage. Overall design: Survey of transcript 3'' end positions in B-lymphocyte cell lines derived from six human individuals (two biological replicates each)	Co-expression
SRP009094	RIPSEQ DNMT1 HL60	Identification of the all RNA species associated with DNMT1. Using a comparative genome-scale approach we identified and correlated the RNA species physically associated with DNMT1 and proximal to the annotated genes to the methylation status of the corresponding loci and expression levels of the respective genes. This comparative approach delineated the first -DNMT1 centered- 'epitranscriptome' map, a comprehensive map cross-referencing DNMT1-interacting transcripts to (i) DNA methylation and (ii) gene expression profile. Overall design: Relationship between DNMT1-RNA interactions, DNA methylation and gene expression	Co-expression
SRP009123	Transcriptome sequencing of human hepatocellular carcinoma	Deep high-throughput transcriptome sequencing (RNA-seq) performed on 3 pairs of matched tumor and adjacent non-tumorours (NT) tissues from HCC patients of Chinese origin generated 183.6-million reads that could be aligned. We discovered a number of differentially expressed genes and multiple types of somatic single nucleotide variations (SNVs) in expressed genes.  After the removal of the error alignments, high-quality reads were mapped to the human reference sequence (GRCh37/hg19) using three different softwares TopHat, Burrows-Wheeler Aligner (BWA) and CLC Genomics Workbench (CLC).  The high-quality variants were identified using VarScan with the following parameters: minimum coverage depth of 10, variation frequency of more than 30% and base quality of more than 15.  A total of 568, 545 and 494 potential somatic single nucleotide variants (SNVs), including 94, 89 and 101 coding somatic SNVs (cSNVs), were identified in 3 tumor samples HCC448T, HCC473T and HCC510T, respectively. Validation analysis was carried out for 10 of the intersected cSNVs (all are non-synonymous substitutions) within selected genes of interests with the majority confirmed. Overall design: Examination of 3 paired human hepatocellular carcinoma and matched non-tumor tissues	Co-expression
SRP009144	Transcriptomic profiling of a glioblastoma multiforme patient with matched control brain tissue	To investigate differential gene expression, we analyzed the entire transcriptomes of tumor and matched normal brain tissues obtained from a patient who had glioblastoma multiforme.  We extracted and sequenced the mRNA using Illumina GA2 platform. The raw data was analyzed using our recently developed program called RNASEQR, as well as ERANGE, MapSplice, SpliceMap, and TopHat. Overall design: Tumor and matched control brain tissues were obtained from a Han-Chinese patient.	Co-expression
SRP009246	High-resolution profiling and analysis of viral and host small RNAs during human cytomegalovirus infection	Small RNA deep sequencing analysis was conducted on primary human fibroblasts infected with human cytomegalovirus (HCMV). HCMV-encoded miRNAs accumulated to ~20% of the total smRNA population at late stages of infection, and our analysis led to improvements in viral miRNA annotations and identification of novel HCMV miRNAs. Through crosslinking and immunoprecipitation of Argonaute-bound RNAs from infected cells, followed by high-throughput sequencing (Ago CLIP-seq), we obtained direct evidence for incorporation of all HCMV miRNAs into the endogenous host silencing machinery. Additionally, significant upregulation was observed during infection for a host miRNA cluster containing miR-96, miR-182 and miR-183. We also identified novel non-miRNA forms of virus-derived smRNAs, revealing greater complexity within the smRNA population during HCMV infection. Overall design: High-throughput profiling of smRNAs,  Ago1-, and Ago2-associated miRNAs from HCMV-infected fibroblast cells. Wild-type HCMV Towne (Genbank FJ616285.1) was used for these studies.	Co-expression
SRP009247	Human-specific patterns of gene expression in the brain (RNA-Seq)	We identified human-specific gene expression patterns in the brain by comparing expression with chimpanzee and rhesus macaque. Overall design: DpnII tag-based libraries were generated from human, chimpanzee, and rhesus macaque brain (frontal pole, hippocampus, caudate nucleus), and sequenced using an Illumina Genome Analyzer.	Co-expression
SRP009251	Human transcriptome pattern of primary cutaneous lesions from patients with localized cutaneous leishmaniasis and mucosal leishmaniasis	We evaluated the trancriptome of primary cutaneous leisions caused by infection with Leishmania braziliensis. mRNA-seq technique was used to study the trancriptome of both host and parasite. A total of 10 samples was obtained from primary skin ulcers of two extreme clinical forms of American tegumentary leishmaniasis: (i) individuals that after antimonial treatment cured completely (localized cutaneous leishmaniasis - LCL, n=5) and (ii) individuals that developed mucosal lesions in naso and oropharynx areas long after initial healing of the cutaneous lesion (mucosal leishmaniasis - ML, n=5).  The sequencing generated an average of 13+ 5 million reads per samples. The reads were aligned to Homo sapiens (USCS - hg19) and to Leishmania braziliensis (Wellcome Trust Sanger Institute - V2_29072008) genomes. Approximately, 15,000 human genes could be detected in the samples. Low amount of L. braziliensis reads did not allow the evaluation of parasite gene expression. LCL and ML samples showed different patterns of gene expression, indicating a more robust immune response in LCL individuals. In summary, this study demonstrated that next-generation sequencing can be used for identification of potentially important biological pathways and drug targets in the host-response to L. braziliensis infection and for characterization of a gene expression signature that could be used to predict the disease outcome. Moreover, we also showed the ability of this technique in, simultaneously, sequence host and pathogen mRNA. Overall design: Examination of 10 fragments of cutaneous lesions: 5 from localized cutaneous leishmaniasis patients and 5 from mucosal leishmaniasis patients.	Co-expression
SRP009262	Identification of new viral genes and transcript isoforms during Epstein-Barr virus reactivation using RNA-seq.	Using an enhanced RNA-seq pipeline to analyze Epstein-Barr virus transcriptomes, we have  investigated viral and cellular gene expression in the Akata cell line following B-cell receptor mediated reactivation. Robust induction of EBV gene expression was observed, with most viral genes induced more than 200-fold and with EBV transcripts accounting for 7% of all mapped reads within the cell. Following induction, hundreds of candidate splicing events were detected using the junction mapper TopHat, including a novel non-productive splicing event at the gp350/gp220 locus and several alternative splicing events at the LMP2 locus. A more detailed analysis of lytic LMP2 transcripts showed an overall lack of the prototypical type III latency splicing events. Analysis of nuclear versus cytoplasmic RNA-seq data showed that the lytic forms of LMP2, EBNA-2, EBNA-LP, and EBNA-3A, B, and C have higher nuclear-to-cytoplasmic accumulation ratios than most lytic genes, including classic late genes. This data raises the possibility that at least some lytic transcripts derived from these latency gene loci may have unique, non-coding nuclear functions during reactivation. Our analysis has also identified two previously unknown genes, BCLT1 and BCRT2, that map to the BamHI C-region of the EBV genome. Pathway analysis of cellular gene expression changes following BCR activation identified inflammatory response as the top predicted function, and ILK and TREM1 as the top predicted canonical pathways.	Co-expression
SRP009276	Wide-scale analysis of alternative polyadenylation (APA) associated with proliferation and transformation using 3''-Seq	We mapped and quantified poly(A) sites in BJ and MCF10A cells under proliferative, arrested and transformed states Overall design: Two human cell lines (BJ and MCF10A) examined under proliferative, arrested and transformed states	Co-expression
SRP009310	Correlation of global micro RNA expression with basal cell carcinoma subtype	Basal cell carcinomas (BCCs) are the most common cancers in the US.  Histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior.  In this study global miRNA expression was quantified by high throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves.  Principal components analysis correctly classified seven out of eight infiltrative tumors on the basis of miRNA expression.  The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements.  Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs.  qPCR assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors.  The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness.  These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies. Overall design: Total RNA was extracted from eight nodular and eight infiltrative basal cell carcinomas. miRNA was then processed into libraries using the Illumina Small RNA Ver 1.5 protocol. Samples were then sequenced on the Illumina GAII system	Co-expression
SRP009316	Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics	Burkitt lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies.  We used high throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways that cooperate with MYC, the defining oncogene of this cancer.  In 38% of sporadic BL (sBL) cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression.  In 70% of sBL cases, mutations affecting the transcription factor TCF3 or its negative regulator ID3 fostered TCF3 dependency.  TCF3 activated the pro-survival PI(3) kinase pathway in BL, in part by augmenting constitutive B cell receptor signaling.  These findings suggest opportunities to improve therapy for patients with BL.	Co-expression
SRP009373	Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types	Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence.  By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order.  Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs.  Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a widespread and perhaps general feature of the gene expression program in human cells. Overall design: 3 samples of non-malignant primary human leukocytes, one replicate each	Co-expression
SRP009374	A novel post-translational mechanism controlling the oncogenic activity of c-Myc is enhanced in poor outcome breast cancer	Examination of Pin1-regulated Myc target genes in a human breast epithelial cell line. Overall design: Two samples: control GFP-expressing MCF10A-Myc cells and Pin1-expressing MCF10A-Myc cells.	Co-expression
SRP009408	MicroRNA expression profiles in lung cancer tissues versus adjacent lung tissues using next-gen sequencing	Background: MicroRNAs (miRNAs) are small noncoding RNAs about 22 nucleotides in length and regulate mRNA expression by binding to 3?UTR of mRNAs and causing translation repression or degradation of mRNAs. Recent studies have revealed that microRNAs play important regulatory roles in carcinogenesis. However, the complement of miRNAs involved in lung carcinogenesis and tumor biology is generally unknown. We used high-throughput sequencing technology to investigate miRNA expression profiles in a study of paired lung non-small cell carcinomas and remote noncancerous lung tissues. Methods: Total RNA was isolated by Trizol from patient lung tissues, including 1 non-pair of macroscopic lung adenocarcinoma tissue, and 20 pairs of macroscopic lung adenocarcinoma tissues and corresponding paired noncancerous lung tissues from the same patients, 1 non-pair of noncancerous lung tissues of squamous cell carcinoma patient, and 10 pairs of squamous cell carcinoma and corresponding paired noncancerous lung tissues from the same patients. Small RNA library of each total RNA was constructed with Illumina?s Small RNA Sample Prep Kit, followed by high-throughput sequencing. Statistical differences in microRNA expression between groups were analyzed by GenePattern software. Results: Using 2-fold threshold with FDR<0.05, there were ~90 miRNAs differentiated the lung cancers from nontumor lung tissues, both histologies.  (a) The sets of microRNAs differentiating adenocarcinoma from paired nontumor tissues are largely different from those differentiating squamous tumors. There were 40 upregulated and 23 downregulated microRNAs differentiating adenocarcinoma Tvs.NT .  For squamous cell, the numbers were 19 and 6, respectively.  (b) In common between the two tumor histologies, there were six common upregulated microRNAs (miR-21, 135b, 200a, 494, 708. 1259), and four common down-regulated microRNAs (miR-144, 184, 516a, 1251). (c) Comparing our 22 miRNAs in common with Yanaihara/Harris Cancer Cell 2006 using spotted microarrays, we found similar direction of change in 19/22.  (d) As a group, the top over-expressed miRNA in lung tumors (determined as fold change > 2, and comprising at least .01% of total miRNA) are able to predict mRNAs that are differentially expressed in those same samples (p=4.6x10^-6). Conclusions: This effort represents one of the more comprehensive surveys of the lung tumor micronome. (i) Tumor microRNA complement differs from far-adjacent lung; (ii) Histologies differ in their overall, and tumor-distinctive microRNA complement; (iii) Statistical correlations of individual microRNA:mRNA (putative) pairing from the same tissue sets are pending.  (iv) Experimental confirmation of microRNA:mRNA targeting, using our microRNA affinity pull down assay is also pending. Overall design: Examination of different microRNA expression profiles between lung cancer tissues and adjacent lung tissues. Our lung tissues were from 32 patients, including 21 adenocarcinoma patient (20 pairs of tumor and non-tumor and 1 non-pair tumor) and 11 squamous cell carcinoma patients (10 pairs of tumor and non-tumor and 1 non-pair non-tumor).	Co-expression
SRP009568	The SEC family of RNA Polymerase II elongation factors: gene target specificity and transcriptional output	The elongation stage of transcription is a highly regulated in metazoan. We previously purified the AFF1/AFF4-containing Super Elongation Complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical isolation of SEC-like 2 (SEC-L2) and SEC-like 3 (SEC-L3) containing AFF2 and AFF3 in association with P-TEFb, ENL, and AF9. The SEC family members demonstrate high levels of Pol II CTD kinase activity, however, only SEC is required for the proper induction of the HSP70 gene upon stress. Genome-wide mRNA-seq analyses demonstrate that SEC-L2-3 control the expression of different subsets of genes, while AFF4/SEC plays a more dominant role in rapid gene expression in cells. MYC is one of the direct targets of AFF4/SEC, and the SEC requirement to the MYC gene regulates its expression in different cancer cells bearing either acute myeloid or lymphoid leukemia. These findings suggest that AFF4/SEC could be a potential therapeutic target for the treatment of leukemia or other cancers associated with MYC overexpression. Overall design: RNA-seq in human embyonic kidney 293T cells of wild-type and after RNAi of AFF2, AFF3, AFF4.  ChIP-seq of AFF4 and Pol2 in human 293T cells.	Co-expression
SRP009615	GSE33816: RNA-seq analysis of K562 cells (K562-shX) with stable integration of a tet-inducible shRNA targeting a candidate (X) transcription factor from ENCODE/HudsonAlpha-MyersLab	Summary: K562-shX cells are made in an effort to validate TFBS data and ChIP-seq antibodies in Myers lab (GSE32465). K562 cells are transduced with lentiviral vector having Tet-inducible shRNA targeting a transcription factor gene. Cells with stable integration of shRNA constructs are selected using puromycin in growth media. Doxycycline is added to the growth media to induce the expression of shRNA and a red fluorescent protein marker.  A successful shRNA cell line shows at least a 70% reduction in expression of the target transcription factor as measured by qPCR. For identification, we designated these cell lines as K562-shX, where X is the transcription factor targeted by shRNA and K562 denotes the parent cell line.  For example, K562-shATF3 cells are K562 derived cells selected for stable integration of shRNA targeting the transcription factor ATF3 gene and showed at least a 70% reduction in the expression of ATF3 gene when measured by qPCR. Cells growing without doxycycline (uninduced) are used as a control to measure the change in expression of target transcription factor gene after induction of shRNA using doxycycline. For detailed growth and culturing protocols for these cells please refer to http://hudsonalpha.org/myers-lab/protocols . To identify the potential downstream targets of the candidate transcription factor, analyze the mRNA expression profile of the uninduced and induced K562-shX using RNA-seq.    For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf    Overall Design: Make K562-shX cells as described in the http://hudsonalpha.org/myers-lab/protocols . Measure the mRNA expression levels in uninduced K562-shX and induced K562-shX cells in two biological replicates using RNA-seq. Identify the potential downstream targets of the candidate transcription factor.	Co-expression
SRP009659	Accurate Identification of A-to-I RNA editing in human by transcriptome sequencing	RNA editing enhances the diversity of gene products at the post-transcriptional level. Approaches for genome-wide identification of RNA editing face two main challenges: separating true editing sites from false discoveries and accurate estimation of editing levels. We developed an approach to analyze transcriptome sequencing data (RNA-Seq) for global identification of RNA editing in cells for which whole-genome sequencing data are available. We applied the method to analyze RNA-Seq data of a human glioblastoma cell line, U87MG. Around 10,000 DNA-RNA differences were identified, the majority being putative A-to-I editing sites. These predicted A-to-I events were associated with a low false discovery rate (~5%). Moreover, the estimated editing levels from RNA-Seq correlated well with those based on traditional clonal sequencing. Our results further facilitated unbiased characterization of the sequence and evolutionary features flanking predicted A-to-I editing sites and discovery of a conserved RNA structural motif that may be functionally relevant to editing. Genes with predicted A-to-I editing were significantly enriched with those known to be involved in cancer, supporting the potential importance of cancer-specific RNA editing. A similar profile of DNA-RNA differences as in U87MG was predicted for another RNA-Seq data set obtained from primary breast cancer samples. Remarkably, significant overlap exists between the putative editing sites of the two transcriptomes despite their difference in cell type, cancer type and genomic backgrounds. Our approach enabled de novo identification of the RNA editome, which sets the stage for further mechanistic studies of this important step of post-transcriptional regulation. Overall design: Examine mRNA expression in U87MG cells following ADAR1 or control siRNA knockdown	Co-expression
SRP009840	Outgrowth of Clones Carrying Mutations in Cytosolic 5’-Nucleotidase II in Childhood Relapsed Acute Lymphoblastic Leukemia	We profiled the transcriptome of matched diagnosis and relapse samples from 10 pediatric B precursor Acute Lymphoblastic Leukemia (ALL) patients using massively parallel sequencing (RNA-Seq) technology to identify novel mutations specific at disease recurrence.	Co-expression
SRP010038	Molecular Effects of Doxycycline Treatment on Pterygium as Revealed by Massive Transcriptome Sequencing	A total of 332 genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in ten human pterygium samples.	Co-expression
SRP010041	Detecting splicing variants from non-differentially expressed genes of human idiopathic pulmonary fibrosis	Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown cause that lacks a proven therapy for altering its high mortality rate. Microarrays have been employed to investigate the pathogenesis of IPF, but are presented mostly at the gene-expression level due to technologic limitations. In as much as, alternative RNA splicing isoforms are increasingly identified as potential regulators of human diseases, including IPF, we propose a new approach with the capacity to detect splicing variants using RNA-Seq data. We conducted a joint analysis of differential expression and differential splicing on annotated human genes and isoforms, and 333 non-differentially expressed genes were identified with a high degree of “switch” between major and minor isoforms. Three cases with variant mechanisms for alternative splicing were validated using qRT-PCR, among the group of genes in which expression was not significantly changed at the gene level. We also identified 37 genes related to IPF specific novel transcripts using exon-exon junction evidence, and selected a representative for qRT-PCR validation. The results of our study are likely to provide new insight into the pathogenesis of pulmonary fibrosis and may eventuate in new treatment targets. Moreover, a similar approach can be applied to discovering novel splicing variants in other diseases.	Co-expression
SRP010054	Chromatin Accessibility Reveals Insight into Androgen Receptor Activation and Transcriptional Specificity	Using DNase-seq, mRNA-seq and publicly available ChIP-seq data sets, we examined the role of chromatin accessibility (DNase-seq) in androgen receptor binding to the genome (ChIP-seq) and AR-mediated transcriptional changes (mRNA-seq). Our data reveals genome-wide changes in chromatin structure that correspond to AR binding and  differential gene expression.  A focused examination of DNase-seq data around androgen receptor motifs within androgen receptor ChIP-seq peaks reveals distinct patterns of protection from DNaseI cleavage. Overall design: Examination of chromatin accessibility (DNase-seq), AR binding (AR ChIP-seq), and transcription (mRNA-seq) in LNCaP cells before and after 12 hours of 1 nM R1881 treatment This Series represents the RNA-Seq data only. Exon microarray data generated under the same conditions is available through GSE15805.  The DNase-seq data is publicly available through GSE32970 as well as the UCSC genome browser (genome.ucsc.edu) under Regulation::ENCODE DNase/FAIRE::Duke DNaseI HS:LNCaP and LNCaP + Andro.  The accession numbers for the ChIP-seq experiments used are GSE14097 and GSE28126.	Co-expression
SRP010061	K562 polyA RNA-Seq	RNA-Seq reads and TopHat (Trapnell et al. Bioinformatics 2009) alignments of K562 cell-line transcriptome.  These were used to validate the expression of short peptides idenitified by Mass-Spectrometry in K562 cells. Overall design: K562 polyA+ RNA (Batch 1) and total RNA (batch 2) was purchased from Ambion. We used oligo (dT)-selected polyA+ RNA to construct libraries for RNA-Seq.We then profiled the transcriptome of polyadenylated mRNA-Seq using Illumina sequencing platforms. We then used the sequenced reads to reconstruct the transcriptome using the Cufflinks de-novo assembler (Trapnell et al. Nat.Bio.Tech. 2010). Recent computational and ribosome profiling analyses suggest that many short open reading frames (sORFs) in eukaryotic genomes are translated. However, evidence that these sORFs produce stable polypeptides is lacking. Here we develop a strategy to discover and validate novel sORF-encoded polypeptides (SEPs) in human cells. In total, we detect 117 SEPs, 114 of which are novel, varying in length from 15 to 149 amino acids. Of these, 10 SEPs (0.5%) are derived from long intergenic non-coding RNAs (lincRNAs). We also observe the presence of polycistronic genes and the widespread use of non-AUG start codons, which is a phenomenon historically thought to be rare in the mammalian genome. Quantitative measurements reveal that SEPs can be found at concentrations between ~10-2000 copies per cell, which is within the range of typical cellular proteins. We confirm the translation of a number of these SEPs through heterologous expression of their encoding cDNAs. We also discover that several SEPs possess properties characteristic of functional proteins. These results demonstrate that human sORFs produce numerous stable polypeptides, revealing that the human proteome is larger and more diverse than previously appreciated.	Co-expression
SRP010129	Multicolor miRNA fluorescence in situ hybridization for tumor differential diagnosis	We profiled and quantitated miRNAs in two skin tumors (Basal cell carcinoma and Merkel cell carcinoma) and identified tumor-specific miRNAs. We used these tumor-specific miRNAs to guide development of miRNA fluorescence in situ hybridization. Overall design: 2 barcoded sequencing runs, including 40 unique samples (36 used in manuscript). The details of each sample can be found in Supplementary Tables S1 and S2.	Co-expression
SRP010166	Deep Sequence Analysis of non-small cell lung cancer: Integrated analysis of gene expression, alternative splicing, and single nucleotide variations in lung adenocarcinomas with and without oncogenic KRAS mutations	In this manuscript, we have used RNA-Sequencing experiment to obtain and integrate a variety of genomic features in order to identify signaling pathways that are associated to mutant KRAS lung tumors. Overall design: 8 lung adenocarcinomas with mutant KRAS in lung tumors and 8 lung adenocarcarcinomas without KRAS mutation of which one sample is ran twice for QC purposes.	Co-expression
SRP010181	Derivation of HLA types from shotgun sequence datasets	The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles directly from shotgun sequence datasets (http://www.bcgsc.ca/platform/bioinfo/software/hlaminer). This approach circumvents the additional time and cost of generating HLA-specific data and capitalizes on the increasing accessibility and affordability of massively parallel sequencing.	Co-expression
SRP010279	Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins  (CLIP-Seq)	Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS) in human cells. Using splicing-sensitive microarrays, cross-linking and immunoprecipitation coupled with high-throughput sequencing, and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins, and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and auto-regulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells. Overall design: CLIPseq for hnRNP A1, hnRNP A2/B1, hnRNP F, hnRNP M, and hnRNP U in human 293T cells	Co-expression
SRP010280	Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins (RNA-Seq)	Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS) in human cells. Using splicing-sensitive microarrays, cross-linking and immunoprecipitation coupled with high-throughput sequencing, and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins, and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and auto-regulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells. Overall design: RNAseq for control, hnRNP A1, hnRNP A2/B1, hnRNP H1, hnRNP F, hnRNP M, and hnRNP U siRNA treated human 293T cells	Co-expression
SRP010350	Effects of Cardiac Glycosides on RNA Expression in Prostate Cancer LNCaP-abl Cells	Prostate cancer is the most common cancer in men and cardiac glycosides inhibit prostate cancer cell proliferation. In order to investigate the mechanism by which cardiac glycosides inhibit  prostate cancer cells, we observed genome-wide RNA expression in prostate cancer LNCaP-abl cells, hormone resistant cells, after the cardiac glycoside treatment using RNA-Seq. In addition, we profiled LNCaP-abl cells after androgen receptor (AR) knockdown to observe whether cardiac glycoside effect on RNA expression is similar to that of  AR knockdown. Overall design: Observation of three cardioglycosides, Digoxin, Peruvoside and Strophanthidin,  and AR knockdown regulated RNA expression in LNCaP-abl with RNA-Seq (each triplicates)	Co-expression
SRP010384	Transcriptome of normal, paracancerouse and cancerous bladder tissues based on RNA-Seq method	In order to support our research of bladder cancer in human genome, we conducted massively parallel pyrosequencing of mRNAs (RNA-Seq) using normal, paracancerouse and cancerous human bladder tissues. We obtained a total of 30.0 million read pairs from normal, 33.1 million read pairs from paracancerous and 36.5 million read pairs from cancerous. The RNA-Seq data derived from the sample illustrated the differencially expression genes among normal, paracancerous and cancerous bladder tissues of human. Overall design: 3 samples examined: normal tissue, paracancerous tissue, cancerous tissue.	Co-expression
SRP010430	A protective strategy against hyperinflammatory responses requiring the non-transcriptional actions of GPS2	The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of TNFA-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFA target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis. Overall design: RNA-sequencing of polyA selected RNA molecules in 293T cells and ChIP-seq of GPS2, TBL1, and NCOR.	Co-expression
SRP010483	The human pancreatic islet transcriptome: impact of pro-inflammatory cytokines	We have used RNA-seq to identify transcripts, including splice variants, expressed in human islets of Langerhans under control condition or following exposure to the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interferon-? (IFN-?). A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets. 25/41 of the candidate genes for type 1 diabetes are expressed in islets, and cytokines modified expression of several of these transcripts. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)	Co-expression
SRP010644	Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells (RNA-seq)	Genome-wide gene expression was measured in peripheral blood mononuclear cells (PBMCs) from patients with cystic fibrosis (CF) after treatment in vitro with the flagellin protein fliC, and/or synthetic peptide IDR-1018 to assess patterns of gene expression. The patterns of gene expression suggest that CF cells have a hyperinflammatory phenotype including dysfunctional autophagy processes. The synthetic peptide IDR-1018 attentuates this hyperinflammatory phenotype. Overall design: Total RNA was obtained from PBMCs obtained from CF patients after treatment with the fliC flagellin protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.	Co-expression
SRP010647	Dosage imbalance of NMD genes is associated with intellectual disability	Nonsense-mediated mRNA decay (NMD) functions to degrade transcripts bearing premature stop codon (PTC) and is a crucial regulator of gene expression. NMD and the UPF3B gene have been implicated as the cause of various forms of intellectual disability (ID) and other neurological symptoms. Here, we reports three patients with global developmental delay carrying hemizygous deletions of the UPF2 gene, another important member of the NMD pathway and direct interacting partner of UPF3B. Overall design: Using RNA-SEQ on lymphoblastoid cells from UPF2 deletion patients, we identified 1009 differently expressed genes (DEGs). 38% of these DEGs overlapped with DEGs identified in UPF3B patients. More importantly, 95% of all DEGs in either UPF2 or UPF3B patients share the same trend of de-regulation. This demonstrates that the transcriptome deregulation in these two patient groups is similar and that UPF2 should be considered as a new candidate gene for ID in man. We expanded our inq`uiries and performed a comprehensive search for copy number variations (CNVs) encompassing all NMD genes in cohorts of ID patients and controls. We found that UPF2, UPF3A, Y14, SMG6 and EIF4A3 are frequently deleted and/or duplicated in ID patients. These CNVs are likely to be the root of the problems or to act as predisposing factors. Our results suggest that dosage imbalance of NMD factors is associated with ID and further emphasize the importance of NMD in normal learning and memory processes.	Co-expression
SRP010670	Genome-wide analysis of histone methylation reveals chromatin state-based regulation of host cellular gene expression induced by hepatitis B viruses (DGE dataset)	Hepatitis B virus (HBV) is a hepatotropic virus that can regulate many host cellular gene expressions participating in the HBV life cycle, liver inflammation and hepatocellular injury. However, the underlying mechanism of differential gene expression is not understood. We report here a genome-wide analysis of histone methylation on two histone H3 lysine residues (H3K4me3 and H3K27me3) and gene expression profiles in HepG2 and HepG2.2.15 cells. We found that specific correlation exists between gene expression and the amounts of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations displayed three distinct modes (repressive, active and poised), reflecting different functions of these genes in the HBV life cycle, liver inflammation and hepatocellular injury. Furthermore, a permissive chromatin state of each gene was established by a combination of different histone modifications. Our findings reveal a complex regulation by histone methylation in differential gene expression and suggest that histone methylation may be responsible for the HBV life cycle, liver inflammation and hepatocellular injury induced by HBV. Overall design: A large-scale analysis of gene expression of 2 different cell types (HepG2, HepG2.2.15) using a digital gene expression (DGE) tag profiling approach.	Co-expression
SRP010675	Small RNA profile of HeLa cells through the cell cycle	Dicer plays a key role in RNA silencing. By processing pre-miRNAs and dsRNAs, Dicer generates miRNAs and siRNAs that act as post-transcriptional regulators of gene expression. Dicer is also implicated in heterochromatin formation and toxic RNA degradation. Here we report that Dicer is controlled in cell cycle. The Dicer protein level drastically rises at late G1 phase and falls at early S phase. Interestingly, the protein stability of Dicer is decreased specifically at early S phase. MG132, an inhibitor of proteasome, increases Dicer protein level, suggesting that the stability of Dicer is controlled via ubiquitination-dependent proteasome pathway.	Co-expression
SRP010678	Transcriptome profiling of epidermal differentiation	The aim of this study was to establish a deeply sequenced transcriptome at multiple timepoints during the differentiation of human epidermal keratinocytes from the progenitor state (d0).  These transcriptomes were then assembled in order to discover novel genes and transcriptional events that are dynamically regulated during terminal differentiation of a human somatic tissue. Overall design: Paired-end RNA sequencing was performed on primary human keratinocytes at three timepoints during calcium-induced epidermal differentiation.	Co-expression
SRP010679	The translational landscape of mTOR signaling steers cancer initiation and metastasis	The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Employing ribosome profiling we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signaling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism, and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion mRNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signaling. We further develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings significantly extend our understanding of how the “cancerous” translation machinery steers specific cancer cell behaviors and may be therapeutically targeted. Overall design: Examination of mRNA translation in human prostate cancer upon differential inhibition of the mTOR signaling pathway.	Co-expression
SRP010712	miR-seq of human frontal lobe	Two normal frontal white matter samples, obtained from two pediatric patients (A boy of 3 year old and a girl of 3 mount old) undergoing focal brain resection for head injury, were obtained. miRVana miRNA Isolation Kit (Ambion, USA) was used following the manufacturing instruction to isolate miRNA from these two samples. Brain samples were collected during neurosurgery of the patients at the Policlinico Gemelli in Rome. The study was approved by the local ethical committee. The miRNA was sequenced using Illumina HiSeq2000 machine.	Co-expression
SRP010943	Small RNA profiles following TUT knock-down in HeLa	The precise control of microRNA (miRNA) biogenesis is important for various cellular functions, and its dysregulation is often associated with human diseases. We previously reported that Terminal uridylyl transferase 4 (TUT4) down-regulates let-7 miRNA biogenesis by oligo-uridylating let-7 precursor (pre-let-7) in mouse embryonic stem cells and that a pluripotency marker Lin28 promotes a processivity of TUT4. Here we find that TUT4 positively controls let-7 biogenesis by adding a uridine residue to the 3' end of pre-let-7 in the absence of Lin28. Such mono-uridylation enhances Dicer processing by generating an optimal end structure of pre-let-7 for Dicer recognition and may protect pre-miRNA from trimming. Moreover, TUT7, TUT4 and TUT2 redundantly regulate pre-let-7 processing and simultaneous knock down of these TUTs leads to the decrease of mature let-7 and the accumulation of pre-let-7 in cells. This study provides a novel regulation mechanism of miRNA biogenesis, which may function in development and tumorigenesis. Overall design: HeLa cells were transfected with siRNA two times over a 4~5 day period.	Co-expression
SRP010944	RIP-seq analysis of eukaryotic Sm proteins identifies three major categories of Sm-containing ribonucleoproteins	Background: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results: We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions: This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism. Overall design: RNA-Immunoprecipitation sequencing of RNA-Sm protein complexes.	Co-expression
SRP010961	Alternative Splicing Networks Regulated by Signaling in Human T Cells	The formation and execution of a productive immune response requires, among many things, the maturation of competent T cells and a robust change in cellular activity upon antigen challenge. Such changes in cellular function require regulated alterations of protein expression. Much work has previously gone into defining the transcriptional changes that regulate protein expression during T cell development and antigen stimulation. Here we describe a parallel pathway of gene regulation that occurs during T cell stimulation, namely alternative splicing. Specifically, we use RNA-Seq to identify 178 exons in 168 genes that exhibit robust changes in inclusion in response to a stimulation of a human T cell line. Interestingly, these signal-responsive genes are enriched for functions related to immune response including, cell trafficking, inflammatory and immune response, immunologic disease and several cell signaling pathways. The vast majority of these genes also exhibit different isoform expression in naive and activated primary T cells. Comparison of the responsiveness of splicing to various stimuli in the cultured and primary T cells reveal important insight into the diversity of signaling pathways that control splicing. Using this data we are able to classify signal-responsive exons into at least three distinct networks. Importantly, we find that each regulatory network is characterized by distinct sequence hallmarks, further suggesting independent regulatory mechanisms. Overall design: We utilize high-throughput RNA sequencing (RNA-Seq) to investigate global changes in alternative splicing in a cultured T cell line and in primary human T cells. We identify 178 genes that are predicted to exhibit robust signal-induced changes in isoform expression in cultured T cells.	Co-expression
SRP011054	iCLIP analysis of EZH2-interacting RNAs	RNAs directly interacting with EZH2 were isolated from human colorectal HCT116 cells using an in vivo crosslinking and immunoprecipitation strategy (iCLIP, König J et al, Nat Struct Mol Biol 2010) coupled to an ultrasequencing approach. Overall design: RIP sequencing for 1 Human sample	Co-expression
SRP011085	Characterization of transcriptome dynamics in response to contact with host cells	Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections which are often life threatening. Hematogenously disseminated candidiasis (HDC) has a 47% mortality rate despite current antifungal therapy. An increase in prevalence, as well as an increasing resistance to most of the clinically important antifungal therapies, provides a strong impetus to understand the molecular mechanisms of pathogenesis and the acquisition of drug resistance. This information holds promise to identify novel therapeutic targets. A complete and accurate characterization of how the transcriptome of C. albicans responds to its interaction with cells from the host is an absolute necessity to accomplish this goal. RNA-seq (deep-sequencing of cDNA) provides an unbiased method to define comprehensively and systematically the transcriptome of an organism. We propose a comprehensive characterization of the C. albicans transcriptome in two different human tissue culture models, using RNA-seq. Such a characterization will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. A major problem in the design of antifungal agents stems from the fact that fungi and mammals are both eukaryotic organisms. Pharmaceutical compounds that can kill fungal cells will often kill human cells resulting in a drug having toxic side effects. Since a successful antifungal drug must inhibit the function of a gene that is expressed during the course of an infection, this work will provide a list of potential novel therapeutic targets to treat candidiasis, as well as mycoses caused by other serious invasive fungal pathogens, in the clinic. This project is led by Vincent M. Bruno, Ph.D., Institute for Genome Sciences, in collaboration with Dr. Scott Filler, David Geffen School of Medicine at UCLA.	Co-expression
SRP011107	Two large groups of YB-1 associated RNAs reveal a novel RNA pathway	Identify YB1 associated RNAs	Co-expression
SRP011130	Next-generation sequencing and microarray-based interrogation of microRNAs from formalin-fixed, paraffin-embedded tissue: Assessment of cross-platform concordance.	We examine the concordance between miRNA-seq and cDNA-mediated annealing, selection, extension, and ligation (DASL) miRNA assays. Overall design: We profiled two technically replicated FFPE specimens on both DASL and RNA-seq. This submission represents the RNA-seq component of study. The DASL samples used in the study are GSM876557, GSM876558, GSM876564, and GSM876565.	Co-expression
SRP011233	Transcriptomic response to benzo[a]pyrene treatment in HepG2 cells (RNA-Seq)	Whole-genome transcriptome measurements are pivotal for characterizing carcinogenic mechanisms of chemicals and predicting toxic classes, such as genotoxicity, from in vitro and in vivo assays. DNA microarrays have evolved as the gold standard for this purpose. In recent years deep sequencing technologies have been developed that hold the promise of measuring the transcriptome with RNA-seq in a more accurate and unbiased manner than microarrays. So far, however, few applications have been published that assess the performance of RNA-seq within a toxicogenomics context. Here, we applied RNA-seq for the characterization of the in vitro transcriptomic responses in HepG2 cells upon exposure to benzo[a]pyrene (BaP), a well-known DNA damaging carcinogen. We demonstrate the performance of RNA-seq with respect to the identification of differentially expressed genes and associated pathways, in comparison with microarray technology. RNA-seq data generates more complete and thus accurate data on differentially expressed genes and affected pathways than microarrays. Additionally, we highlight the potential of RNA-seq for characterizing mechanisms related to alternative splicing and thereby gathering new information. Exposure to BaP alters the isoform distribution for many genes, including regulators of cell death and DNA repair such as TP53, BCL2 and XPA, which are relevant for genotoxic responses. Finally, we demonstrate that RNA-seq enables to investigate allele-specific gene expression, although no changes for that could be observed. Our results provide evidence that RNA-seq is a powerful tool for toxicology which, compared to microarrays, is capable of adding valuable information at the transcriptome level for characterizing toxic effects caused by chemicals. Overall design: Examination of 2 biological replicates at 2 different timepoints	Co-expression
SRP011278	Small RNA-seq and gene expression analysis reveal a miRNA profile of cancer-susceptibility in ATM deficient human mammary epithelial cells (Small RNA-Seq)	Deficiencies in the ATM gene are the underlying cause for ataxia telangiectasia, a congenital syndrome characterized by neurological, motor and immunological defects, as well as a predisposition to cancer risks. MicroRNAs (miRNAs) are small regulators of post-transcriptional gene expression and a useful tool for cancer diagnosis, staging, and prediction of therapeutic responses to clinical regimens. In particular, miRNAs have been used to develop signatures for breast cancer profiling.  We are interested in the consequences of ATM deficiency on miRNA expression in breast epithelial cells and the potential contribution to cancer predisposition. In this study we investigate the effects of ATM loss on the miRNA expression and related gene expression changes in normal human mammary epithelial cells (HME-CC). We have identified 81 significantly differently expressed miRNAs in the ATM-deficient HME-CCs using small RNA sequencing. Many of these differentially expressed miRNAs have been described and implicated in tumorigenesis and proliferation. These changes include down-regulation of tumor suppressor miRNAs, such as hsa-miR-29c and hsa-miR-16, as well as the over-expression of pro-oncogenic miRNAs hsa-miR-93 and hsa-mir-221. All 81 miRNAs were combined with genome wide gene expression profiles to investigate possible targets of miRNA regulation. We identified messenger RNA (mRNA) targets of these miRNAs that were also significantly regulated after the depletion of ATM. Predicted targets included many genes implicated in cancer formation and progression, including SOCS1 and the proto-oncogene MAF. Integrated analysis of miRNA and mRNA expression allows us to build a more complete understanding of the pathways and networks involved in the breast cancer predisposition observed in individuals deficient in ATM. This study highlights miRNA and predicted mRNA target expression changes in ATM-deficient HME-CCs and suggests a mechanism for the breast cancer-prone phenotype seen in ATM deficient cells and patients. Additionally, this study provides preliminary data for defining miRNA profiles that may be used prognostic biomarkers for breast cancer predisposition. Overall design: Examination of small RNA population in human mammary epithelial cell lines. Each condition was preformed in triplicate.	Co-expression
SRP011369	A Role for Small RNAs in DNA Double-Strand Break Repair	Here we identify a novel class of small RNAs that are ~21-nucleotide in length and are produced from the sequences in the vicinity of DNA double strand break (DSB) sites in Arabidopsis and humans. We named them diRNAs for DSB-induced small RNAs. In Arabidopsis, the biogenesis of diRNAs requires the PI3 kinase ATR, RNA polymerase IV (Pol IV), and Dicer-like proteins. Mutations in these proteins as well as in Pol V cause significant reduction in DSB repair efficiency. diRNAs are recruited by Argonaute 2 (AGO2) to mediate DSB repair. In humans, knocking down Dicer or Ago2 causes a significant reduction in DSB repair. Our findings reveal a novel biological function for small RNAs in the DSB repair pathway. We propose that diRNAs may function as guide molecules for chromatin modifications or recruitment of repair complexes at DSB sites to facilitate repair. Overall design: 28 samples from Arabidopsis thaliana in various genetic backgrounds and 5 samples from the human cells, small RNA sequencing	Co-expression
SRP011378	DNMT3B7, an aberrant DNMT3B isoform, suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma	In adult cancers, epigenetic changes and aberrant splicing of the DNMT3B is commonly observed, and the pattern of gene methylation and expression has been shown to be modified by DNMT3B7, a truncated protein of DNMT3B.  Much less is known about the mechanism of epigenetic changes in the pediatric cancer neuroblastoma.  To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression and tumor phenotype in neuroblastoma, we measured DNMT3B isoform expression in primary tumors and cell lines. Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas, suggesting that expression of DNMT3B7 may induce a less clinically aggressive tumor phenotype.  To test this hypothesis, we investigated the effects of forced DNMT3B7 in neuroblastoma cells.  We found that DNMT3B7 expression significantly inhibited neuroblastoma cell proliferation in vitro, and in neuroblastoma xenografts, DNMT3B7 decreased angiogenesis and tumor growth. DNMT3B7-positive cells had higher levels of total genomic methylation, and RNA-sequencing revealed a dramatic decrease in expression of FOS and JUN family members, AP1 complex components.  Consistent with the established antagonistic relationship between AP1 expression and retinoic acid receptor activity, decreased proliferation and increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all trans retinoic acid (ATRA) compared to controls. Our results demonstrate that high levels of DNMT3B7 modify the epigenome in neuroblastoma cells, induce changes in gene expression, inhibit tumor growth, and increase sensitivity to ATRA.    Further knowledge regarding mechanisms by which DNMT3B7 regulates gene methylation may ultimately lead to the development of therapeutic strategies that reverse the epigenetic aberrations that drive neuroblastoma pathogenesis. Overall design: DNMT3B7, a truncated DNMT3B isoform, was stably transfected into an N-type neuroblastoma cell line (LA1-55n) using a Tet-off inducible system. DNMT3B7 expressing cells were compared to vector control cells after 21 days of induction.	Co-expression
SRP011422	Small RNA sequencing of melanoma samples to deduce microRNA expression profiles	We report results on microRNA profiles revealing the distribution of "isomirs" of microRNA in a cancerous state. Deep sequencing was conducted at Stanford University and data analysis was conducted at the University of Connecticut Health Center. Overall design: Small RNA profiling to deduce differential microRNA expression levels along various stages of melanoma. Deep sequencing was performed on formalin-fixed paraffin-embedded (FFPE) archived tissue samples, fresh frozen samples from melanomas, and cell lines.	Co-expression
SRP011546	Tracing pluripotency of human early embryos and embryonic stem cells by single cell RNA-seq	Find the casual relationship between gene expression network and cellular phenotype at single cell resolution. We collected donated human pre-implatation embryos, and the embryonic stem cells derived from them, isolate individual cells, prepared single cell cDNAs, and sequenced them by HiSeq2000. Then we analyzed the expression of known RefSeq genes. Overall design: We get transcriptome of 124 individual cells from human pre-implantation embryos and human embryonic stem cells by applying single cell RNA-seq technique we recently developed[1][2][3][4]. We did in-depth bioinformatic analysis to these data and found very dynamic expression of protein-coding genes. [1] Tang, F. et al. (2010a) Tracing the Derivation of Embryonic Stem Cells from the Inner Cell Mass by Single-Cell RNA-Seq Analysis. Cell Stem Cell 6, 468-478. [2] Tang, F. et al. (2010b) RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protocols 5, 516-535. [3] Tang, F. et al. (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Meth 6, 377-382. [4] Tang, F. et al. (2011) Development and applications of single-cell transcriptome analysis. Nat Meth 8, S6-S11.	Co-expression
SRP011578	SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells	Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2 and NOTCH1 was detected in side population (SP) cells than in none side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2 and NOTCH1 in xenografted NOD/SCID mice. By RNA-Seq method, additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer. Overall design: Examination of mRNA profiles in A549 cells with SOX2 silencing	Co-expression
SRP011895	Comparison of stem-cell derived retinal pigment epithelia (RPE) with human fetal retina pigment epithelium	Retinal Pigment Epithelium (RPE) derived from two human embryonic stem cell lines, H1 and H9, were compared with human fetal RPE (hfRPE) using RNA-seq. Nominally, the transcriptome of H1-derived RPE showed greater overlap with hfRPE. For cells maintained in the medium used to differentiate RPE, 6.2% (H1-RPE) and 4.2% (H9-RPE) of the transcripts were expressed in amounts that were statistically different from hfRPE (false discovery rate: 5%).  After adaptation to the serum-free medium, SFM-1, only 1.0 % (H1-RPE) and 1.9% (H9-RPE) were expressed in amounts that were statistically different. For RPE signature genes, statistical differences were observed for 1.0 % (H1-RPE) and 1.9% (H9-RPE) of the transcripts. For some barrier-function related mRNAs the statistical differences were greater than these small differences would predict. For adhesion proteins and plasma membrane transporters, the differences were as great as 6.9% and 4.3%, respectively. After adaptation to SFM-1, the statistical differences between H1- and H9-RPE were only 0.4% for all transcripts, 1.4% for signature genes, and 0.7% for membrane transporters.  No statistical differences were observed for the transcripts related to tight junctions, adhesion junctions or ion channels. In summary, SFM-1 promoted the maturation of stem cell-derived RPE, and the statistical difference between two stem cell lines was minimal. Overall design: RNA sequencing of hfRPE from three fetuses (reference sample) and three independent isolates of RPE derived from the H1, and three from the H9, human embryonic stem cell (hESC) lines. The cultures were maintained in a serum-free medium, SFM-1.  Comparisons were also made to cultures maintained in the medium used to differentiate the cells, KSR.	Co-expression
SRP011903	RBFOX1 Splicing and Transcriptional Regulation in Neurons	We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation. We observe that RBFOX1 regulates a large set of alternative splicing events implicated in neurogenesis and cell maintenance. Subsequent alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Overall design: RNA sequencing at a 75bp single-end read scale was performed using polyA-enriched RNA from 5 biological replicates of primary human neural progenitor cell lines generated by lentiviral-mediated knockdown of GFP (control) or RBFOX1 and differentiated for 4 weeks.	Co-expression
SRP011924	mRNA expression profiling in patients with Tetralogy of Fallot and healthy unaffected individuals	Right ventricular mRNA profiles from 22 patients with Tetralogy of Fallot (TOF) and mRNA-seq profiles from the left and right ventricle (LV and RV, respectively) of 4 healthy unaffected individuals (NH) were generated. The total RNA was isolated from the 30 human heart samples using TRIzol. mRNAs were isolated from total RNA and prepared for sequencing using Illumina Kit RS-100-0801 according to the manufacturer''s protocol (Preparing Samples for Sequencing of mRNA Sept 2008). The sequencing libraries were generated using a non-strand-specific library construction method. The purified DNA fragments were used directly for cluster generation, and 36 cycles of single-end read sequencing were performed using the Illumina Genome Analyzer. Sequencing reads were extracted from the image files using the open source Firecrest and Bustard applications (Illumina Genome Analyzer pipeline 1.3.2, 1.4.0 and 1.5.0). Overall design: Right ventricular mRNA-seq profiles from 22 patients with Tetralogy of Fallot and mRNA-seq profiles from the left and right ventricle of 4 healthy unaffected individuals. Supplementary processed data files: GSE36761_gene_expression_levels.txt: Gene expression profiling data for all samples. GSE36761_gene_expression_levels_normalized.txt: Normalized gene expression profiling data for all samples. GSE36761_transcript_expression_levels.txt: Transcript expression profiling data for all samples. GSE36761_transcript_expression_levels_normalized.txt: Normalized transcript expression profiling data for all samples. Genome build: hg18	Co-expression
SRP011974	DEEP SEQUENCING OF MODELS OF BREAST DUCTAL CARCINOMA IN SITU REVEALS ALDH5A1 AS A NOVEL POTENTIAL THERAPEUTIC TARGET	We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation.  To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx.  Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A.  These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling.  Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation.  We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates	Co-expression
SRP011977	High-throughput transcriptome sequencing of an AML-M2 patient in two stages: primary tumor and remission.	In order to detect the transcriptomic differences during chemotherapy treatment of de novo AML, we adopted massively parallel pyrosequencing of mRNAs (RNA-seq) using blood tissues of an patient with AML (FAB subtype M2) in tumor stage and remission stage. We obtained a total of 34.6 and 30.8 million paired reads from the two samples. The RNA-seq data derived from the sample illustrated the differentially expression genes between the two stages. Overall design: Blood samples of an AML-M2 patient in two stages examined: primary tumor and chemotherapy induced remission.	Co-expression
SRP012015	Transcriptome wide analysis of  classically  and alternatively activated macrophages	Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived human M1- and M2-like macrophage profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to establish a high resolution transcriptome of human macrophages. Total RNA was isolated from classically and aternative activated human macrophages.mRNA profiles were generated by deep sequencing og M1 and M2 macrophages from 3 donors using Illumina HiSeqSQ. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Casava1.8 and TopHat followed by Cufflinks. qRT–PCR validation was performed using LightCycler and SYBR Green assays. Overall design: mRNA profiles were generated by deep sequencing og M1 and M2 macrophages from 3 donors using Illumina HiSeqSQ.	Co-expression
SRP012056	Genome-wide analysis of pre-mRNA 3'' end processing reveals a decisive role of human cleavage factor I in the regulation of 3'' UTR length: A-seq	Through alternative polyadenylation, human mRNAs acquire longer or shorter 3'' untranslated regions, the latter typically associated with higher transcript stability and increased protein production. To understand the dynamics of polyadenylation site usage, we mapped transcriptome-wide both binding sites of 3'' end processing factors CPSF-160, CPSF-100, CPSF-73, CPSF-30, Fip1, CstF-64, CstF-64tau, CF Im25, CF Im59, and CF Im68 and 3'' end processing sites in HEK293 cells. We found that although binding sites of these factors generally cluster around the poly(A) sites most frequently used in cleavage, CstF-64/CstF-64tau and CF Im proteins have much higher positional specificity compared to CPSF components. Knockdown of CF Im68 induced a systematic use of proximal polyadenylation sites, indicating that changes in relative abundance of a single 3'' end processing factor can modulate the length of 3'' untranslated regions transcriptome-wide, and suggesting a mechanism behind the previously observed increase in tumor cell invasiveness upon CF Im68 knockdown. Overall design: 3'' ends of transcripts were profiled by high-throughput sequencing in HEK 293 cells under normal conditions, and in HEK 293 cells depleted of 3'' end processing factors CF Im 68 and CstF-64.	Co-expression
SRP012062	RNA-sequencing analysis of NB4 cells overexpressing miR-125b	To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we proceeded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental NB4 myeloid cell line and that transiently transfected with miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Overall design: Compare the gene expression levels in miR control transfected cells with that in miR-125b transfected NB4 cells.Â	Co-expression
SRP012096	METTL3 KD in HepG2 cells	To gain insight into possible processes that require m6A for their function, METTL3 was knocked down (KD) in HepG2 cells by siRNA transfections Overall design: Differential expression analysis of METTL3 KD versus mock-transfected HepG2 cells, in 2 biological replicates	Co-expression
SRP012098	m6A mapping in human RNA (with treatments)	We developed a novel approach, m6A-seq, for high-resolution mapping of the transcriptome-wide m6A landscape, based on antibody-mediated capture followed by massively parallel sequencing. Overall design: Identification of m6A modified sequences in HepG2 cells. HepG2 cells were incubated with either IFNg (200ng/ml) or HGF/SF (10 ng/ml) over night. Stress effects were tested in HepG2 cells by either 30 minutes incubation at 43ºC (heat shock) or UV irradiation of 0.04 J/cm2 followed by 4 hours of recovery in normal growing conditions prior to harvesting using Trypsin.	Co-expression
SRP012099	m6A mapping in human RNA (untreated)	We developed a novel approach, m6A-seq, for high-resolution mapping of the transcriptome-wide m6A landscape, based on antibody-mediated capture followed by massively parallel sequencing. Overall design: Identification of m6A modified sequences in HepG2 cells.	Co-expression
SRP012100	m6A mapping in mouse RNA (mouse liver and human brain)	We developed a novel approach, m6A-seq, for high-resolution mapping of the transcriptome-wide m6A landscape, based on antibody-mediated capture followed by massively parallel sequencing Overall design: Identification of m6A modified sequences in mouse liver and human brain	Co-expression
SRP012167	DPN and Tamoxifen treatments of parathyroid adenoma cells	Stimulation of estrogen receptor beta in PHPT, genetic changes after 24 and 48h of treatments vs. Control Overall design: Treatment of parathyroid adenomas (4 patients, 4 adenomas) with DPN 24h (4 samples), DPN 48h (4 samples), OHT 24h (4 samples), OHT 48h (4 samples), control 24h (3 samples), control 48h (4 samples). Omission of 1 sample based on low RNA quality.	Co-expression
SRP012295	Vascular histone deacetylation by pharmacological HDAC inhibition [TSA, RNA-seq]	HDAC inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action, however, little is known of the extent of genome-wide changes of the mammalian genome when stimulated by the hydroxamic acids, TSA and SAHA. In primary human vascular endothelial cells we map the chromatin modifications, histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation mediated gene expression is often associated with modification of other lysine residues we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). Genome-wide mRNA sequencing indicates the differential expression of about 30% of genes, with almost equal numbers being up- and down- regulated. We observe deacetylation conferred by TSA and SAHA that are associated with decreased gene expression. Histone deacetylation is associated with the loss of p300/CBP binding at gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation. Overall design: HAEC mRNA profiles of TSA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP012461	RNA-Seq Analysis Reveals Different Dynamics of Differentiation of Human Dermis- and Adipose-derived Stromal Stem Cells	Background: Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation   of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to   differentiate into various cell types, have been isolated from the stromal fraction of virtually all   tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great   tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell   composition.   Methodology/Principal findings: Our aim was to analyze the dynamics of differentiation of two closely related stromal cell types,   adipose tissue-derived MSCs and dermal fibroblasts (FBs) along adipogenic, osteogenic and   chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated   donor-matched MSCs and FBs are distinct populations that stay different upon differentiation   into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression   occur early in differentiation and persist over time in both MSCs and FBs. Further, MSCs and   FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics   of chondrogenic differentiation.  Conclusion: Our findings suggest that stromal stem cells including adipose-derived MSCs and dermal FBs   exploit different molecular mechanisms of differentiation to reach a common cell fate. The early   mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic   differentiation but are distinct for chondrogenic differentiation between MSCs and FBs. Overall design: A total of 91 samples were analyzed by multiplex RNA-seq. Samples represented replicates from two patients, two cell types and three differentiation protocols, as indicated by the sample annotation. 5 barcodes were unused, but the corresponding FASTQ files are included for completeness.	Co-expression
SRP012463	Mixture models and wavelet transforms reveal high confidence RNA-protein interaction sites in MOV10 PAR-CLIP data	The Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. The strength of this versatile method results from induction of specific T to C transitions at sites of interaction. However, current analytical tools do not distinguish between non-experimentally and experimentally induced transitions. Furthermore, geometric properties at potential binding sites are not taken into account. To surmount these shortcomings, we developed a two-step algorithm consisting of a non-parametric two-component mixture model and a wavelet-based peak calling procedure. Our algorithm can reduce the number of false positives up to 24% thereby identifying high confidence interaction sites. We successfully employed this approach in conjunction with a modified PAR-CLIP protocol to study the functional role of nuclear MOV10, a putative RNA helicase interacting with Argonaute2 and Polycomb. Our method, available as the R package wavClusteR, is generally applicable to any substitution-based inference problem in genomics. Overall design: The data comprises one MOV10 PAR-CLIP data file and one nuclear RNA-seq file	Co-expression
SRP012546	Genome-wide microRNA expression analysis of clear cell Renal Cell Carcinoma by next generation deep sequencing	MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy.   Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis Overall design: Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis.	Co-expression
SRP012585	Identification of miRNA signatures during the differentiation of hESCs into retinal pigment epithelial cells	Retinal pigment epithelium (RPE) cells can be obtained through in vitro differentiation of both embryonic stem cell (ESC) and induced pluripotent stem cells (iPSC) for cell replacement therapy. We have previously identified 87 signature genes relevant to RPE cell differentiation and function through transcriptome analysis of both human ESC- and iPSC-derived RPE as well as normal fetal RPE. Here, we profiled miRNA expression through small RNA-seq in human ESCs and their RPE derivatives. Much like conclusions drawn from our previous transcriptome analysis, we found that the overall miRNA landscape in RPE is distinct from ESCs and other differentiated somatic tissues. We also profiled miRNA expression during intermediate stages of RPE differentiation and identified unique subsets of miRNAs that are gradually up- or downregulated, suggesting dynamic regulation of these miRNAs is associated with the RPE differentiation process. Indeed, the down-regulation of a subset of miRNAs during RPE differentiation is associated with up-regulation of RPE-specific genes, such as RPE65, which is exclusively expressed in RPE. We conclude that miRNA signatures can be used to classify different degrees of in vitro differentiation of RPE from human pluripotent stem cells. We suggest that RPE-specific miRNAs likely contribute to the functional maturation of RPE in vitro, similar to the regulation of RPE-specific mRNA expression. Overall design: Study miRNA in ESC-derived RPE	Co-expression
SRP012607	Differential analysis of HOXA1 in adult cells at isoform resolution by RNA-Seq [Illumina]	High-throughput RNA sequencing (RNA-Seq) has enabled accurate gene discovery and expression estimation, but robust differential analysis of gene and transcript abundances has proven difficult. We present a new algorithm, implemented in the freely available tool Cuffdiff, which integrates transcript-level expression estimation with a method to control for variability across replicate samples. Cuffdiff robustly identifies differentially regulated isoforms and genes and reveals differential splicing or promoter-preference changes. We demonstrate the accuracy of our approach through differential analysis of lung fibroblasts in response to loss of the developmental transcription factor HOXA1 and uncover a critical role for this gene in the maintenance of adult cells. We show that HOXA1 is required for lung fibroblast and HeLa cell cycle progression, and loss of HOXA1 results in significant expression level changes in thousands of individual transcripts, along with isoform switching events in key regulators of the cell cycle. Overall design: Lung Fibroblasts were transfected with either a HOXA1 directed siRNA pool or a scramble non-targeting siRNA control. RNA was collected 48 hours after transfection and changes in gene expression were assayed for using Agilent microarrays.	Co-expression
SRP012608	MiR-27a-3p in peripheral blood mononuclear cells as a potential marker for pancreatic cancer screening	Background & Aims: MicroRNAs have been shown to offer great potential in the diagnosis of cancer. We aimed to identify microRNAs in peripheral blood mononuclear cells (PBMCs) for diagnosing pancreatic cancer (PC). Methods: PBMCs microRNA expression was investigated in three independent cohorts including 352 participants (healthy, benign pancreatic/peripancreatic diseases (BPD), and PC). First, we used sequencing technology to identify differentially expressed microRNAs in 60 PBMCs samples for diagnosing PC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using an independent cohort. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: We found that PBMCs miR-27a-3p could efficiently discriminate PC from BPD (AUC=0.840; 95% CI, 0.787 to 0.885; sensitivity=82.2%, specificity=76.7%). A panel composed of PBMCs miR-27a-3p and serum CA19-9 provided a high diagnostic accuracy in differentiating PC from BPD in the clinical setting (AUC=0.886; 95% CI, 0.837 to 0.923; sensitivity=85.3%, specificity=81.6%). The satisfactory diagnostic performance of the panel persisted regardless of disease status (AUCs for tumour-node-metastasis stages?,?, and ? were 0.881, 0.884, and 0.893, respectively).  Conclusion: PBMCs miR-27a-3p could be a potential marker for PC screening. A panel composed of PBMCs miR-27a-3p and serum CA19-9 has considerable clinical value in diagnosing early-stage PC. Therefore, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy. Overall design: Examination of different MicroRNA profiles in 3 types of PBMCs samples	Co-expression
SRP012656	A high dimensional deep sequencing study of non-small cell lung adenocarcinoma in never-smoker Korean females [Seq]	One of the most fertile applications of next generation sequencing will be in the field of cancer genomics. Here, we report a high-throughput multi-dimensional sequencing study of primary non-small cell lung adenocarcinoma tumors and adjacent normal tissues of 6 never-smoker Korean female patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations including 47 somatic mutations and 20 fusion transcripts. We also characterized gene expression profiles which we sought to integrate with genomic aberrations and epigenetic regulations into functional networks. Importantly, among others the gene network module governing G2/M cell check point emerged as the primary source of disturbance in these patients. In addition, our study strongly suggests that microRNAs make key regulatory inputs into this gene network module. Our study offers a paradigm for integrative genomics analysis and proposes potential target pathways for the control of non-small cell lung adenocarcinoma. Overall design: Study of primary non-small cell lung adenocarcinoma tumors and normal tissues of 6 patients.	Co-expression
SRP012695	mRNA profiling of THP1 cell line	Analysis of mRNA in THP1 (human monocytic leukemia) cell line in order to correlate miRNA activity with target abundance. Overall design: THP1 mRNA profiles were generated in triplicates by deep-sequencing in Illumina HiSeq2000.	Co-expression
SRP013021	Poly-gene fusion transcripts and chromothripsis in prostate cancer	Complex genome rearrangements are frequently observed in cancer, but their impact on tumour molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumours exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly-gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly-gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumour with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data shows that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly-gene fusion transcripts is potentially of great significance to cancer genetics.	Co-expression
SRP013022	RNA-seq in breast cancer cell lines after manipulation of miR-23b expression	RNA sequencing technology has been carried out in order to evaluate mRNA expression changes after manipulation of miR-23b in both MCF-7 and MDA-MB-231 breast cancer cell lines Overall design: Our study implicates miR-23b in cytoskeletal remodeling in breast cancer. To evaluate the entire set of genes modulated by miR-23b we performed RNA-seq after ectopic manipulation of this miRNA in breast cancer cell lines. We over-expressed this miRNA in MCF-7 epithelial cancer cell lines and also reduced its activity by stably transfecting MDA-MB-231 mesenchymal-like cancer cell lines with a specific sponge vector. RNA-seq analysis revealed a number of candidate targets of this miRNA.	Co-expression
SRP013224	Next-generation sequencing reveals HIV-1-mediated suppression of T cell activation and RNA processing and the regulation of non-coding RNA expression in a CD4+ T cell line	We sequenced the total mRNA from infected cells and detected differences in the expression of both host mRNA. We detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi providing new possible markers of virus-induced T cell cytopathology. By 24 hpi the expression of over 50% of detectable host loci was also altered indicating widespread alteration of host processes including RNA processing, splicing, and transport to an extent not previously reported. In addition next-generation sequencing provided insights into the expression of non-coding RNAs including microRNA host genes. Overall design: We isolated polyadenylated RNA from SUPT1 cells infected with HIV-1 strain LAI at 12 and 24 hours post-infection (3 replicates for each time point). As controls we isolated polyadenylated RNA from mock-infected cells at 12 and 24 hours post-infection (2 replicates at 12 hours post-infection, 3 replicates at 24 hours post-infection).	Co-expression
SRP013239	Global Analysis of the Immediate Transcriptional Effects of Estrogen Signaling Reveals a Rapid, Extensive, and Transient Response	We report the immediate effects of estrogen signaling on the transcriptome of breast cancer cells using Global Run-On and sequencing (GRO-seq). We found that estrogen signaling directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein-coding genes, estrogen regulates the distribution and activity of all three RNA polymerases, and virtually every class of non-coding RNA that has been described to date. This data submission covers >95% of mapped reads comprising nearly all transcript classes described.  Reads mapping to intergenic and enhancer transcripts were removed from this data submission and will be reported separately (manuscripts in preparation). Bed files are tab-separated text files in which columns represent: chrom, chromStart (5'' End of the read), chromEnd (chromStart+1), name (unused always ''n''), score (the number of mismatches), and strand.  Note that because of the inclusion of reads mapping to the rRNA chromosome, bed files cannot be uploaded to the UCSC genome browser directly.  Instead, use the wiggle files (coming soon!) for this purpose. Overall design: Using GRO-seq over a time course (0, 10, 40, 160 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.	Co-expression
SRP013288	Examination of gene expression in wild type and USP49 knockdown cells [RNA-Seq]	Posttranslational histone modifications play important roles in regulating chromatin structure and function. Histone H2B ubiquitination and deubiquitination have been implicated in transcriptional regulation, but the function of H2B deubiquitination is not well defined, particularly in higher eukaryotes. Here we report the purification of USP49 as a histone H2B specific deubiquitinase and demonstrate that H2B deubiquitination by USP49 is required for efficient co-transcriptional splicing of a large set of exons. USP49 forms a complex with RVB1 and SUG1, and specifically deubiquitinates histone H2B in vitro and in vivo. USP49 knockdown results in small changes in gene expression, but affects the abundance of over 9,000 isoforms.  Exons down-regulated in USP49 knockdown cells show both elevated levels of alternative splicing and a general decrease in splicing efficiency.  Importantly, USP49 is relatively enriched at this set of exons.  USP49 knockdown increased uH2B levels at these exons as well as upstream 3’ and downstream 5’ intronic splicing elements.  Change in H2B ubiquitination level, as modulated by USP49, regulates U1A and U2B association with chromatin and binding to nascent pre-mRNA. Although H3 levels are relatively stable after USP49 depletion, H2B levels at these exons are dramatically increased, suggesting that uH2B may enhance nucleosome stability. Therefore, this study identifies USP49 as a histone H2B specific deubiquitinase and uncovers a critical role for H2B deubiquitination in co-transcriptional pre-mRNA processing events. Overall design: Examination of gene expression in wild type and USP49 knockdown cells [RNA-Seq]	Co-expression
SRP013299	Massive parallel single cell RNA Sequencing of human embryos reveals novel dynamic changes across development stages	Preimplantation human embryonic development is a highly dynamic cellular and molecular process, the correct execution of which is critical for successful development to occur. However the mechanism of this event remains largely unknown due to the scarcity of the material, legal restraints and limited techniques to  faithfully analyze small amounts of samples. The development of single cell RNA-seq technology to measure gene expression at single cell levels opens new avenues for investigations into preimplantation human embryonic development.	Co-expression
SRP013363	The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts [PAR-CLIP]	Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. Close to one third of these proteins, were neither previously annotated nor could be functionally predicted to bind RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3'' UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of unexpected mRNA-binders with novel molecular functions participating in combinatorial post-transcriptional gene-expression networks. Overall design: PARCLIP was performed as in Hafner et al. 2010 Cell 141, 129–141, with HEK293 cell lines stably expressing HIS/FLAG/HA-tagged ALKBH5, C17orf85, C22orf28, CAPRIN1, and ZC3H7B. We used 4-thiouridine (4SU) to enhance the crosslink and generated two PAR-CLIP cDNA libraries per protein.	Co-expression
SRP013389	Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of binding sites in a cell type-specific manner	To obtain an integrated view of gene regulation in response to environmental and endogenous estrogens on a genome-wide scale, we performed ChIP-seq, to identify estrogen receptor 1 (ER) binding sites, and RNA-seq in endometrial cancer cells exposed to bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 17ß-estradiol (E2; an endogenous estrogen).  GEN and BPA treatment induces thousands of ER binding sites and >50 gene expression changes, representing a subset of E2-induced gene regulation changes.  Genes affected by E2 were highly enriched for ribosome-associated proteins; however, GEN and BPA failed to regulate most ribosome-associated proteins and instead enriched for transporters of carboxylic acids.  Treatment-dependent changes in gene expression were associated with treatment-dependent ER binding sites, with the exception that many genes up-regulated by E2 harbored a BPA-induced ER binding site, but failed to show any expression change after BPA treatment.   GEN and BPA exhibited a similar relationship to E2 in the breast cancer line T-47D, where cell type specificity played a much larger role than treatment specificity.  Overall, both environmental estrogens clearly regulate gene expression through ER on a genome-wide scale, although with lower potency resulting in less ER binding sites and less gene expression changes compared to the endogenous estrogen, E2. Overall design: RNA-seq of human cancer cell lines treated with estradiol, bisphenol A, genistein or DMSO (control)	Co-expression
SRP013402	mRNA expression in iPS cells generated by a synthetic self-replicative RNA	We generated iPS cells with a synthetic self-replicative RNA that expresses four independent reprogramming factors (OCT4, KLF4, SOX2 and either c-MYC or GLIS1).  We performed whole genome RNA sequencing (RNA-seq) of iPS cell clones, parental BJ and HUES9 ES cell controls. All iPS cell clones analyzed by RNA-seq showed unsupervised hierarchical clustering and expression signatures characteristic of human HUES9 ES cells that were highly divergent from parental human fibroblasts. Overall design: RNA-seq in two OKS-iM iPS clones (generated from OCT4, KLF4, SOX2 and cMYC expressing RNA replicon), two OKS-iG clones (generated from OCT4, KLF4, SOX2 and GLIS1 expressing RNA replicon), HUES9 and BJ cells.	Co-expression
SRP013450	Study functions of ADAR proteins using next generation sequencing of genome and transcriptome	Adenosine deaminases, RNA specific (ADAR) are proteins that deaminate adenosine to inosine which is then recognized in translation as guanosine.  To study the roles of ADAR proteins in RNA editing and gene regulation, we carried out DNA and RNA sequencing, RNA interference and RNA-immunoprecipitation in human B-cells.  We also characterized the ADAR protein complex by mass spectrometry.  The results uncovered over 60,000 sites where the adenosines (A) are edited to guanosine (G) and several thousand genes whose expression levels are influenced by ADAR.  We also identified more than 100 proteins in the ADAR protein complex; these include splicing factors, heterogeneous ribonucleoproteins and several members of the dynactin protein family.  Our findings show that in human B-cells, ADAR proteins are involved in two independent functions: A-to-G editing and gene expression regulation.  In addition, we showed that other types of RNA-DNA sequence differences are not mediated by ADAR proteins, and thus there are co- or post-transcriptional mechanisms yet to be determined. Overall design: Here we studied human B-cells where ADAR proteins (ADAR1 and ADAR2) are expressed but APOBECs are not.  We identified the sequence differences between DNA and the corresponding RNA in B-cells from two individuals.  Then, we carried out RNA interference, RNA-immunoprecipitation and next generation sequencing to determine the contribution of ADAR proteins in mediating A-to-G editing and other types of RNA-DNA sequence differences.	Co-expression
SRP013456	The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts [protein occupancy profiling]	Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. Close to one third of these proteins, were neither previously annotated nor could be functionally predicted to bind RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3'' UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of unexpected mRNA-binders with novel molecular functions participating in combinatorial post-transcriptional gene-expression networks. Overall design: We generated protein occupancy cDNA libraries for two biological replicates. Briefly, we crosslinked 4SU-labeled cells and purified protein-mRNA complexes using oligo(dT)-beads. The precipitate was treated with RNAse I to reduce the protein-crosslinked RNA fragments to a length of about 30-60 nt. To remove non-crosslinked RNA, protein-RNA complexes were precipitated with ammonium sulfate and blotted onto nitrocellulose. The RNA was recovered by Proteinase K treatment, ligated to cloning adapters, and reverse transcribed. The resulting cDNA libraries were PCR-amplified and next-generation sequenced	Co-expression
SRP013463	The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts [RNA-seq]	Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. Close to one third of these proteins, were neither previously annotated nor could be functionally predicted to bind RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3'' UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of unexpected mRNA-binders with novel molecular functions participating in combinatorial post-transcriptional gene-expression networks. Overall design: To obtain a more detailed picture of the RNA present in the pooled precipitates of four consecutive oligo(dT)-purifications, we constructed a cDNA library by random priming of 4-thiouridine (4SU)- and 6-thioguanosine (6SG)-labeled RNA derived from UV-irradiated (365 nm)and non-irradiated cells. Digital gene expression analysis of the cDNA library of non-irradiated cells, labeled with 4SU and 6SG, was performed.  To monitor the incorporation of photoreactive nucleotides into mRNA, we isolated 4SU- and 6SG-labeled RNA from the oligo(dT) precipitate of non-crosslinked cells by biotinylation and streptavidin purification (Dolken et al., 2008).	Co-expression
SRP013473	Hi-seq 2000 sequencing facilitates quantitative analysis of transcriptomes in LNCaP cells with or without SiGATA2 treatment.	We obtained 1,367 GATA2 up-regulated and 759 GATA2 down-regulated genes (p< 0.001). Overall design: mRNA profiles of LNCaP cell treated with or without SiGATA2 were generated by deep sequencing  in duplicate using Hi-Seq 2000.	Co-expression
SRP013504	Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3	The TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding  to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in 6 human cell lines. We identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864  sites common to the 6 cell lines. Using ChIP-seq, we showed that many genomic regions that are marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer  activity. Bioinformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells. Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the genome via GATA3. Our studies demonstrate a novel relationship between GATA3 and TCF7L2,  and reveal important insights into TCF7L2-mediated gene regulation. Overall design: RNAseq analysis of MCF7 cells transfected with siCONTROL, siTCF7L2 or siGATA3. ChIP-seq analysis of H3K27ac, H3K4me1, H3K27me3, H3K9me3 in MCF7 cells; H3K4me1 and H3K27ac in HCT116 cells.	Co-expression
SRP013619	Homo sapiens Transcriptome or Gene expression	RNA-seq was performed on human PBMCs subjected to 0.004% and 0.04% cigarette smoke condensate to examine changes in gene expression levels.	Co-expression
SRP013621	Homo sapiens Transcriptome or Gene expression	RNA-Seq uncovers transcriptomic variations associated with the lethal phenotype conversion on LNCaP progression cell model	Co-expression
SRP013724	Expression Analysis of Normal and Cancerous Prostate Cells	Strand-specific RNA sequencing was done on a normal and a cancer cell line to examine how isoforms are used differently between these two states. Overall design: One PrEC sample, a normal cell line. One LNCaP sample, a cancer cell line.	Co-expression
SRP013725	Mapping of Transcription Start Sites of Normal and Cancerous Prostate Cells	Capped analysis of gene expression (CAGE) sequencing was done on a normal and a cancer cell line to examine how promoter usage changes between these two states. Overall design: One PrEC sample, a normal cell line. One LNCaP sample, a cancer cell line.	Co-expression
SRP013825	Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal.	The expansion of the neocortex during mammalian brain evolution results primarily from an increase in neural progenitor cell divisions in its two principal germinal zones during development, the ventricular zone (VZ) and the subventricular zone (SVZ). Using mRNA sequencing, we analyzed the transcriptomes of fetal human and embryonic mouse VZ, SVZ and cortical plate (CP). We describe sets of genes that are up- or down-regulated in each germinal zone. These data suggest that cell adhesion and cell-extracellular matrix (ECM) interactions promote the proliferation and self-renewal of neural progenitors in the developing human neocortex. Notably, relevant ECM-associated genes include distinct sets of collagens, laminins, proteoglycans and integrins, along with specific sets of growth factors and morphogens. Our data establish a basis for identifying novel cell-type markers and open up avenues to unravel the molecular basis of neocortex expansion during evolution. Overall design: Total RNA was isolated from the VZ, inner SVZ (ISVZ), outer SVZ (OSVZ) and CP of six 13-16 weeks post-conception (w.p.c.) human fetuses and from the VZ, SVZ and CP of five E14.5 mouse embryos using laser capture microdissection of Nissl-stained cryosections of dorsolateral telencephalon. Poly A+ RNA was used as template for the preparation of cDNA which were then subjected to single-end 76-bp RNA-Seq.	Co-expression
SRP013912	Intracellular and  extracellular microRNAs expressed by HEK293T cells	MicroRNAs (miRNAs) are a class of small RNA molecules that regulate expression of specific mRNA targets. They can be released from cells, often encapsulated within extracellular vesicles (EVs), and therefore have the potential to mediate intercellular communication. It has been suggested that certain miRNAs may be selectively exported, although the mechanism has yet to be identified. Manipulation of the miRNA content of EVs will be important for future therapeutic applications. We therefore wished to assess which endogenous miRNAs are enriched in EVs and how effectively an overexpressed miRNA would be exported. Small RNA libraries from HEK293T cells and vesicles before or after transfection with a vector for miR-146 overexpression were analysed by deep sequencing. A subset of miRNAs was found to be enriched in EVs. The global expression data provided by deep sequencing confirms that specific miRNAs are enriched in EVs released by HEK293T cells. Overall design: Cells were transfected with a plasmid to direct overexpression of miR-146a. Extracellular vesicles were isolated by ultracentrifugation from untreated and transfected cells. RNA was isolated from one sample each of untreated and transfected cells and vesicles.Small RNA libraries were prepared for sequencing.	Co-expression
SRP013935	Gene expression of three hepatocellular carcinoma cell lines with different organ-tropism.	In this study we investigated the gene expression profiling in three HCC cell lines with different organ-tropism.The parent cell line has low metastasis ability in nude mice model. Subclone 1 has higher metastasis ability specific to lung, and subclone 2 has dual metastasis ability to lung and celiac lymph node. We aimed to explore differentially expressed genes involved in process of HCC metastasis and organ-specific metastasis, and identify their biological functions. Overall design: Examination of different gene expression among the 3 cell types.	Co-expression
SRP013981	Small RNAs expression of three hepatocellular carcinoma cell lines with different organ-tropism.	In this study we investigated the small RNAs expression profiling of three HCC cell lines with different organ-tropism.The parent cell line has low mestastasis ability in nude mice model. Subclone 1 has higher metastasis ability specific to lung, and subclone 2 has dual metastasis ability to lung and celiac lymph node. We aimed to explore differentially expressed small RNAs involved in process of HCC metastasis and organ-specific metastasis, and identify their biological functions. Overall design: Examination of  different small RNAs expression among the 3 cell types.	Co-expression
SRP013984	Genetically-driven target tissue over-expression of CD40: A novel mechanism in autoimmune disease	The CD40 gene, an important immune regulatory gene, is also expressed and functional on non-myeloid derived cells, many of which are targets for tissue specific autoimmune diseases, including d thyroid follicular cells in Graves’ disease (GD). Whether target tissue CD40 expression plays a role in autoimmune disease etiology has yet to be determined. Here we show for the first time, that target-tissue over-expression of CD40 plays a key role in the etiology of autoimmunity. Using a murine model of GD, we demonstrated that thyroidal CD40 over-expression augmented the production of thyroid specific antibodies, resulting in more severe experimental autoimmune Graves’ disease (EAGD), whereas deletion of thyroidal CD40 suppressed disease. Using transcriptome and immune-pathway analyses we showed that in both EAGD mouse thyroids and human primary thyrocytes, CD40 mediates this effect by activating downstream cytokines and chemokines, most notably IL-6. To translate these findings into therapy, we blocked IL-6 during EAGD induction in the setting of thyroidal CD40 over-expression, and showed decreased levels of TSHR stimulating antibodies and frequency of disease. We conclude that target tissue over-expression of CD40 plays a key role in the etiology of organ specific autoimmune disease. Overall design: CD40 in Thyroid Autoimmunity: 1) Incubation of human thyroid cells with G28.5, a CD40 stimulating antibody, and purification of RNA, conversion to cDNA, measurement of mRNA expression using RNAseq. 2) Removal of thyroid tissues from CD40 over-expressing transgenic mice and wild type mice, purification of RNA, conversion to cDNA measurement of mRNA expression using RNAseq.	Co-expression
SRP013999	The transposable element composition of human lincRNAs reveals a role for HERVH elements to promote stem cell specific expression of lincRNAs	Numerous studies over the past decade have elucidated a substantial set of long intergenic noncoding RNAs (lincRNAs). It has since become clear that lincRNAs constitute an important layer of genome regulation across a wide spectrum of species. Yet, the factors governing their evolution and origins remain relatively unexplored. One possible factor that may have shaped lincRNA biology are transposable elements (TEs). Here we set out to comprehensively characterize the TE content of lincRNAs relative to genomic averages and protein coding transcripts. Our analysis of the TE composition across 9241 human lincRNAs revealed that, in sharp contrast to protein coding genes, a striking majority (83%) of lincRNAs contain a TE, and TEs comprise 42% of lincRNA transcript sequences. LincRNA TE composition varies significantly from genomic averages, being depleted of LI and Alu elements and enriched for a broad class of endogenous retroviruses (ERVs). Furthermore, specific TE families occur in biased positions and orientations within lincRNAs, particularly at their transcription start sites, suggesting a role in the origin of those lincRNAs. Finally, we find that TEs can drive gene expression regulation of lincRNAs—we observed a dramatic correlation between lincRNAs containing HERVH elements and almost exclusive expression in pluripotent cells. Conversely, those lincRNAs that are devoid of TEs are more highly expressed in testis. Collectively, TEs pervade lincRNAs and have shaped lincRNA evolution and function via bestowing tissue-specific expression from donated transcriptional regulatory signals. Overall design: We extracted profiled the transcriptome expression polyadenylated mRNA-Seq.  We then used these to reconstruct the transcriptome using de-novo assemblers and identify long non coding RNAs and their expression.	Co-expression
SRP014009	DGCR8 HITS-CLIP reveals novel functions for the Microprocessor (CLIP-seq)	The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 contains two double-stranded RNA binding motifs that recognize the RNA substrate, whereas Drosha functions as the endonuclease. We have used high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify endogenous RNA targets of DGCR8 in mammalian cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs comprised several hundred mRNAs as well as snoRNAs and long non-coding RNAs. We found that DGCR8 together with Drosha controls the abundance of several mRNAs, as well as long non-coding RNAs, such as MALAT-1. By contrast, the DGCR8-mediated cleavage of snoRNAs is independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Interestingly, binding of DGCR8 to cassette exons, acts as a novel mechanism to regulate the relative abundance of alternatively spliced isoforms.  Collectively, these data provide new insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs. Overall design: Comparison of RNAs associated to both endogenous (D8) and overexpressed (T7) DGCR8 in HEK293T cells	Co-expression
SRP014020	miRNA high-throughput sequencing of follicular thyroid tumors	We report data obtaibed from high-throughput sequencing of small RNAs in 20 samples of follicular thyroid tumors. We analyzed a total of 4.7±1.5million reads per sample with 3 different pipelines. The main goal was to evaluate the usefulness of next generation sequencing in small RNA profiling and the concordance of its results with microarrays and qPCR. Additionally we verified published follicular thyroid tumor biomarkers in the set of our samples. Overall design: Small RNA expression profiling  with High Throughput Sequencing of 20 thyroid tumor samples, performed on an Illumina HiScan-SQ.	Co-expression
SRP014027	Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX.	Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain cancers. How cell-lineage-restricted genes specifically influence metastasis is poorly defined. In lung cancers, we uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype. Overall design: mRNA profiles of human lung Adenocarcinoma PC9 cell lines infected with lentivirus harboring shRNA of control and shRNA of both GATA6 and HOPX were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.	Co-expression
SRP014142	Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene	To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer. Overall design: Sequencing of approximately 18-35 nt small RNAs from paired samples of normal, tumor and tumor-adjacent tissue for five breast cancer patients	Co-expression
SRP014146	Molecular Rejuvenation of Gene Expression Pattern of Photoaged and Intrinsically Aged Human Skin by Broadband Light Treatment	Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply deep sequencing of RNA 3'' ends ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging") and the impact of broadband light (BBL) treatment. We find that skin aging was associated with the significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment, i.e. more similar in expression level of youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long non-coding RNAs. Skin aging is not associated with systematic changes in 3'' end mRNA processing. Hence, BBL treatment can restore the gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveals a novel set of targets that may lead to new insights into the human skin aging process. Overall design: Examination of broadband light treated and untreated human skin transcriptomes of 5 women aged 50 years or more. They were compared to the skin transcriptomes of 5 young women aged 30 years or less.	Co-expression
SRP014157	Embedding siRNA sequences targeting Apolipoprotein B100 in shRNA and miRNA scaffolds results in differential processing and in vivo efficacy	Purpose: Identical predicted small interfering RNA (siRNA) sequences targeting Apolipoprotein B100 (siApoB) were embedded in shRNA (shApoB) or miRNA (miApoB) scaffolds and a direct compariso  of the possible aspecific off-target effects in vivo was performed. Next generation sequencing (NGS) of small RNAs originating from shApoB- or miApoB-transfected cells revealed substantial differences in processing, resulting in different siApoB length, 5' and 3' cleavage sites and abundance of the guide or passenger strands. Methods [1]: Total liver RNA sequencing libraries for the Illumina sequencing platform were generated using high-quality total RNA as input and the Illumina TrueSeq RNA v2 Sample preparation kit according to the manufacturer's protocol. Each read file (sample), in the FASTQ format, was individually aligned against the mouse reference genome (15 May 2012 NCBI build 38.1) using CLC Bio-Genomic Workbench and the expression abundance for each gene (RPKM) was calculated according to Montazavi et al. Result [1]s: Based on our previous observations that shApoB and miApoB are differentially processed and that miApoB has a different passenger, we checked for possible aspecific off-target effects in vivo. NGS liver transcriptome analysis was performed 8 weeks p.i. for animals injected with 1x1011 gc AAV encoding shScr, shApoB, miScr and miApoB. We investigated whether shApoB and miApoB processing differences translate into differences in gene expression in injected animals. A total number of 266 genes were significantly changing (p <0,05) in miApoB-injected mice compared to miScr. Additionally 106 genes were found to be significantly up or down-regulated in the shApoB mice compared to shScr. Off-target predictions using Smith-Waterman algorithm for the most abundant guide and passenger strand variants were performed to investigate if any of the observed changes results from aspecific interactions. None of the changing genes had predicted targets for the guide or passenger strands of shApoB or miApoB. Conclusions [1]: An important observation is that none of the changes in gene expression in AAV-miApoB and AAV-shApoB can be explained by possible aspecific down-regulation of non-target transcripts. Methods [2]: For NGS analysis cells were transfected with 4 µg shApoB- or miApoB-expression plasmids using Lipofectamine 2000 reagent and total RNA was isolated from cells 48 hr post-transfection using Trizol (Invitrogen, Carlsbad, CA) according to the manufacturer's protocol. Total RNA sequencing libraries for the Illumina sequencing platform were generated using high-quality total RNA as input and the Illumina TrueSeq RNA v2 Sample preparation kit according to the manufacturer's protocol. The NGS small RNA raw data set was analyzed using the CLC_bio genomic workbench (CLC Bio, Aarhus, Denmark). The obtained reads were adaptor-trimmed, which decreased the average read size from ~36bp to ~25bp. The custom adapter sequenced used for trimming all the bases extending 5' was: GTGACTGGAGTTCC-TTGGCACCCGAGAATTCCA. All reads containing ambiguity N symbols, reads shorter than 15 nt, longer than 55 nt in length and reads represented less than 10 times were discarded. Next, both data sets from shApoB and miApoB samples were grouped based on the match to the reference sequence and the obtained unique small RNAs were aligned to the sequence of pre-miApoB: GATCCTGGAGGCTTGC-TGAAGGCTGTATGCTGATGGACAGGTCAATCAATCTTGTTTTGGCCACTGACTGACAAGATTGAGACCTGTCCATCAGGACACAAGGCCTGTTACTAGCACTCACATGGAACAAATGGCCCAGATCTGGCCGCAG or shApoB: GATCCCCGATTGATTGACCTGTCCATTTCAAGAGAATGGACAGGTCAATCAATC-TTTTTCAGCTT sequence, respectively. To relatively represent the expression counts for the small RNAs obtained in the experiment, reads per million (rpm) or percentage of reads based on the total number of reads matching the reference shApoB or miApoB sequence were calculated Results [2]: The small RNAs were aligned against their reference sequence resulting in 541.939 reads matching shApoB and 1.525.211 reads matching miApoB (Fig S1 and S2). Analysis of the length distribution of the reads indicated that siApoB guide strand originating from shApoB ranged between 19 and 23 nt, with the most abundant one being 21 nt-long. Surprisingly, siApoB guide from miApoB scaffold ranged from 23 to 25 nt with the 24 nt-long strand being the predominant variant. This finding was rather unexpected considering that the predicted guide strand of siApoB was 21 nt long for both shApoB and miApoB scaffolds. Analysis of the processed 5' ends of the siApoB guide strand indicated that most of the reads matched position +1 relative to the predicted cleavage site for shApoB, while all the reads matched position 0 for miApoB. The 3' ends of the siApoB guide strand had a more heterogeneous pattern and ranged from -1 to +3 for shApoB and +1 to +4 for miApoB.   Next, we looked at the sequence distribution and percentage of reads for both the guide and passenger siApoB strands originating from the shApoB and miApoB scaffolds. A substantial difference between the two is that the guide from shApoB is in the 3' arm and hence Dicer or other endonuclease  defines the cleavage position while the guide is present in the 5' arm of miApoB, where Drosha defines the cleavage. Thus, defining the length and exact cleavage position for the guide and passenger strands is very important since even single nucleotide differences may result in significant changes in the predicted targets of the siRNAs. Moreover, the passenger siRNA* strand, if not degraded efficiently, may bind to unanticipated targets and cause off-target effects. As expected, 44.4% of the reads originating from shApoB matched the siApoB guide strand but processing was shifted at position +1 (Fig. 2d, upper panel). Surprisingly only 12.1% of the reads matched perfectly the predicted siApoB guide strand of 21 nt and starting at position 0. The reads matching the passenger siApoB* strand were represented in much lower percentage with the predominant one being only 5.3%.   Analysis of the guide strand from the siApoB reads originating from the miApoB scaffold indicated that they all started at the predicted cleavage site. Surprisingly, the predominant, 22.3% of reads were 24 nt-long. Furthermore 5.1% reads were 23 nt- and 1.9% were 25 nt-long. A substantial number of 62% of the reads was found matching the passenger siApoB* strand and ranged between 20 and 22 nt in length. In conclusion, both shApoB and miApoB scaffolds did not yield the predicted siApoB guide or siApoB* passenger sequences after processing from the cellular RNAi machinery. The guide from miApoB was cleaved much more precisely by Drosha at its 5' end compared to shApoB that gave more heterogeneous pools of sequences following processing. Conclusions[2]: An unexpected discovery in the current study was that siRNA processing by the cellular RNAi machinery did not follow the generally accepted and described cleavage sites for both molecules shApoB and miApoB siApoB guide strand originating from the shApoB scaffold was more heterogeneous in cleavage sites and length compared to the product originating from the miApoB scaffold. Most likely, differential cleavage mechanism defined the heterogeneity in the guide and passenger strands. Additionally, shRNAs with 19 bp stem or less are not necessarily recognized by Dicer and maybe be processed differently. The heterogeneity seen with the shApoB can also be explained by the potential for 2 or 3 uridines to be added following termination of pol III transcription. The main pool of guide sequences originating from miApoB was 24 nt-long although we used the scaffold of cellular pri-mir-155 that produces a 23 nt mature miRNA. However, a 24 nt-long siApoB sequence did not compromise efficacy because when placed in the miApoB scaffold, the ApoB target sequence was extended at the 3' end with 4 nt until the loop.   Another important observation is that the siApoB* Overall design: Liver mRNA profiles of C57BL/6 9 weeks after intravenous AAV injection of 1x1011 gc per animal (~4x1012 gc/kg) of AAV-shRNA, AAV-miRNA or PBS via the tail vein. Next Generation Sequencing on Illumina platform	Co-expression
SRP014213	A receptor tyrosine kinase network comprised of FGFRs, EGFR, ERBB2, and MET drives growth and survival of HNSCC cell lines.	We have previously shown that some gefitinib insensitive head and neck squamous cell carcinoma (HNSCC) cell lines exhibit dominant autocrine fibroblast growth factor receptor (FGFR) signaling. Herein, we deployed a whole genome loss-of-function screen to identify genes whose knockdown potentiated the inhibitory effect of the FGFR inhibitor, AZ12908010, in HNSCC cell lines. Three HNSCC cell lines expressing a genome-wide shRNA library were treated with AZ8010 and the abundance of shRNA sequences was assessed by deep sequencing. Synthetic lethal hits were validated through use of specific inhibitors and independent shRNAs. We found that multiple alternate receptors provided protection from FGFR inhibition, including the receptor tyrosine kinases (RTKs), epidermal growth factor receptor 2 (ERBB2) and hepatocyte growth factor receptor (MET).  We showed that specific knockdown of either ERBB2 or MET in combination with FGFR inhibition led to increased inhibition of growth relative to FGFR tyrosine kinase inhibitor (TKI) treatment alone. These results were confirmed using specific small molecule inhibitors of either ERBB family members or MET. Moreover, the combination of FGFR, MET and ERBB family inhibitors showed the largest inhibition of growth as compared to the double combinations. These results reveal a role for alternate RTKs in maintaining pro-growth and survival signaling in HNSCC cells in the setting of FGFR inhibition. Thus, improved therapies for HNSCC patients could involve rationally designed combinations of TKIs targeting FGFR, ERBB family members and MET. Overall design: Using a genome-wide shRNA library in combination with deep sequencing, we screened for gene targets that were synthetic lethal with the FGFR inhibitor, AZ12908010 in HNSCC cells. Three HNSCC cell lines were screened in triplicate and the abundance of shRNA sequences in drug treated cells was compared to control treated cells.	Co-expression
SRP014320	GSE33480: RNA-seq from ENCODE/Caltech	No description.	Co-expression
SRP014428	Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells	We assessed Smart-Seq, a new single-cell RNA-Seq library preparation method, on a variety of mouse and human RNA samples or cells. Overall design: We generated RNA-Seq libraries for dilution series of MAQC reference RNA and mouse brain RNA to assess technical reproducibility, and for a variety of individual cells including putative circulating tumour cells.	Co-expression
SRP014443	MicroRNA profiling and discovery by deep sequencing cord blood from Down syndrome fetuses	To investigate the expression characteristic of miRNAs during the development of Down syndrome (DS) fetuses and to identify whether another miRNA gene resides in the Hsa21, we employed high-throughput Solexa sequencing technology to comprehensively characterize the miRNA expression profiles of both DS and normal fetal cord blood mononuclear cells (CBMCs). In total, 200 of 395 identified miRNAs were significantly differentially expressed (fold change > 2.0 and P-value < 0.001) and 2 of 181 candidate novel miRNAs were identified as residing within the "Down syndrome critical region" of human chromosome 21 (chr21q22.2-22.3). Additionally, 7 of 14 Hsa21-derived miRNAs genes were detected that three miRNAs (hsa-miR-802, miR-3648, miR-3687) were up-regulated more than 50% and four miRNAs (hsa-miR-99a, let-7c, miR-125b-2, miR-155) were down-regulated in the DS fetal CBMCs compared with the control. Bioinformatics analyses revealed that abnormally expressed miRNAs were major associated with the regulation of transcription, gene expression, cellular biosynthetic process, macromolecule biosynthetic process and nucleic acid metabolic process. The data obtained in our study provides a considerable insight into understanding the expression characteristic of miRNAs in the DS fetal hemopoietic system and the differentially expressed miRNAs may be involved in the hemopoietic abnormalities and the immune defects of DS fetus and newborns. Overall design: A total of 6 DS and 6 matched control fetal cord blood samples (18-22 weeks of gestation) were collected. Three DS and 3 control cord blood samples were combined to form pooled DS and control cord blood samples, respectively, for small RNA library construction and Solexa sequencing. The remaining samples were used as the validation set to confirm the miRNA differential expression patterns by qRT-PCR.	Co-expression
SRP014487	Identification of microarray probe signals constantly present in multiple sample types (part 2)	The correlation of the RNA profiles obtained by microarray analysis was compared with that obtained from RNA-Seq by using reduced complexity sperm datasets. This resolved as a series of discordant probes. The extent of discordancy among other datasets was then determined. Overall design: A correlative study between probe’s signal intensity from Illumina bead arrays with its transcript level detected by next generation sequencing technique was performed. RNAs from sperm and testis samples were applied	Co-expression
SRP014542	Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting	So far, the annotation of translation initiation sites (TISs) has been based mostly upon bioinformatics rather than experimental evidence. We adapted ribosomal footprinting to puromycin-treated cells to generate a transcriptome-wide map of TISs in a human monocytic cell line. A neural network was trained on the ribosomal footprints at previously annotated AUG translation initiation codons (TICs), and used for the ab initio prediction of TISs in 5062 transcripts with sufficient sequence coverage. Functional interpretation suggested 2994 novel upstream open reading frames (uORFs) in the 5´ UTR (924 AUG, 2070 near-cognate codons), 1406 uORFs overlapping with the coding sequence (116 AUG, 1290 near-cognate) and 546 N-terminal protein extensions (6 AUG, 540 near-cognate). The TIS detection method was validated on the basis of previously published alternative TISs and uORFs. On average, TICs in newly annotated TISs were significantly more conserved among primates than control codons, both for AUGs (p<10-10) and near-cognate codons (p=3.8×10-3). The derived transcriptome-wide map of novel candidate TISs will help to explain how human proteome diversity is influenced by alternative translation initiation and regulation. Overall design: Examination of translational initiation in human cell lines using ribosomal footprinting	Co-expression
SRP014566	Site identification in high-throughput RNA-protein interaction data (Ago2_HITS-CLIP)	No description.	Co-expression
SRP014591	FMR1 targets distinct mRNA sequence elements to regulate protein expression [PAR-CLIP]	Fragile-X Syndrome (FXS) is a multi-organ disease leading to mental retardation, macro-orchidism in males, and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASD). FXS is typically caused by the loss of FRAGILE X-MENTAL RETARDATION 1 (FMR1) expression, which encodes for the RNA-binding protein (RBP), FMR1 (or FMRP). We report the discovery of the RNA recognition elements (RREs), binding sites, and mRNA targets for wild-type and I304N mutant FMRP isoforms as well as its paralogs, FXR1 and FXR2. RRE frequency, ratio, and distribution determine target mRNA association with FMRP. Among highly-enriched targets, we identified many genes involved in ASD and demonstrate that FMRP can affect their protein levels in cell culture, mice, and human brain. Unexpectedly, we discovered that these targets are also dysregulated in Fmr1-/- mouse ovaries, showing signs of premature follicular overdevelopment. These results indicate that FMRP targets shared signaling pathways across different cellular contexts. As it is become increasingly appreciated that signaling pathways are important to FXS and ASD, our results here provide an invaluable molecular guide towards the pursuit of novel therapeutic targets for these devastating neurological disorders. Overall design: PAR-CLIP profiling for wild-type and I304N mutant FMRP isoforms as well as paralogs, FXR1 and FXR2.	Co-expression
SRP014620	Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures	Hemogenic endothelium (HE) is the source of HSCs in the developing embryo. In this study we have identified the hemogenic endothelial progenitors and their precursors originating from differentiated H1 cells on OP9 stromal cells. Overall design: RNA-seq of  hemogenic endothelial progenitors and their precursors originating from differentiated H1 cells on OP9 stromal cells.	Co-expression
SRP014624	Argonaute proteins couple chromatin silencing to alternative splicing (RNA IP-Seq)	While Argonaute (AGO) proteins play a major role in transcriptional gene silencing (TGS) in many organisms, their role in the nucleus of somatic mammalian cells remains elusive. Here, we have purified AGO1 and AGO2 chromatin-embedded complexes, and found these proteins associated with previously described partners, but also with chromatin modifiers and, rather unexpectedly, with different splicing factors. Using the CD44 gene as a model for alternative splicing, we show that both AGO1 and AGO2 are required for Protein Kinase C (PKC)-dependent variant exon inclusion. AGO proteins facilitate the spliceosome recruitment and modulate the elongation rate of RNA polymerase II (RNAPII). The recruitment of AGO proteins to CD44 transcribed region is dependent on both the endonuclease Dicer and the chromodomain-containing protein HP1g, and results in locally increased levels of histone H3 lysine 9 (H3K9) methylation on variant exons. Genome wide analysis of splicing in either AGO2 or Dicer null cells showed that the two proteins have similar effects on many splicing events. Finally, sRNAs associated with nuclear AGO2 are mostly in sense orientation relative to protein-coding genes, supporting a role for intragenic antisense non-coding RNAs in the recruitment AGO and splicing factors. Together, our data demonstrate for the first time that the endogenous RNAi pathway is involved in alternative splicing decisions, unravelling a new model in which AGO proteins couple RNAPII elongation and chromatin modification. Overall design: Deep sequencing of small RNAs (approx. 15-80 nucleotides) bound to either cytoplasmic or chromatin-associated AGO2 complex.	Co-expression
SRP014629	Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution	Understanding translational control in gene expression relies on precise and comprehensive determination of translation initiation sites (TIS) across the entire transcriptome. The recently developed ribosome profiling technique enables global translation analysis, providing a wealth of information about both the position and density of ribosomes on mRNAs. Here we present an approach (global translation initiation sequencing, GTI-seq), by applying in parallel ribosome E site translation inhibitors lactimidomycin (LTM) and cycloheximide (CHX), to achieve simultaneous detection of both initiation and elongation events on a genome-wide scale.	Co-expression
SRP014635	Examination of gene expression in human placenta using RNA-seq	As genome-scale DNA methylation sequencing technologies have improved it has become apparent that tissue-specific methylation can occur not only at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). However, genomic sequencing of bisulfite-treated DNA (MethylC-seq) has revealed large partially methylated domains (PMDs) in some human cell lines. However, to date only cultured cells and some cancers have shown evidence for PMDs, suggesting that PMDs may not be observed in normal human tissues.  Here we performed MethylC-seq in a set of human tissues and found that full-term human placenta shows clear evidence of PMDs. Overall design: Examination of gene expression in human placenta using RNA-seq, with one biological replicate (taken from same placenta)	Co-expression
SRP014670	RNA-Seq of cKIT+ sorted cells from 16-16.5 week old fetal testes and ovaries and RNA-Seq of TRA-1-60+ H1 hESCs	Generation of research quality, clinically relevant cell types in vitro from human pluripotent stem cells (hPSCs) requires detailed understanding of the equivalent cell types in humans. Here we analyzed 130 human fetal samples at 6-20 weeks of development and identified the stages in which human cKIT+ primordial germ cells (PGCs), the precursors of gametes, undergo whole genome epigenetic reprogramming and ultimately initiation of imprint erasure with loss of both 5mC and 5-hydroxy-mC at differentially methylated regions. Using five alternate in vitro differentiation strategies combined with a single-cell microfluidic analysis, high throughput RNA sequencing and a bona fide human cKIT+ PGC signature, we show that hPSC differentiation generates a rare cKIT+ PGC subtype found in both the human fetal gonad and mouse embryo. Taken together, our study creates a resource of human germ line ontogeny that is absolutely essential for future studies aimed at interpreting in vitro differentiation of the human germ line. Overall design: cKIT+ cells analyzed from 2 biological samples for testes and 2 samples for ovaries at 16 and 16.5 weeks. 3 biological replicates of TRA-1-60+ cells sorted from H1 hESCs	Co-expression
SRP014671	LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance (HTS)	LIN28 is a conserved RNA binding protein implicated in pluripotency, reprogramming and oncogenesis. Previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through cross-linking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28 binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions. Overall design: CLIP-seq for LIN28-V5 in stable human Flp-In-293 cells, and LIN28 in hES cells; strand-specific mRNA-seq for uninfected, control KD, and LIN28 KD human H9 ES cells; and strand-specific smallRNA-seq for uninfected, control KD, and LIN28 KD human H9 ES cells.	Co-expression
SRP014675	YM500: An integrative small RNA sequencing (smRNA-seq) database for microRNA research	MicroRNAs (miRNAs) are small RNAs of ~22 nucleotides in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next generation sequencing applications, have reshaped the miRNA research landscape. In this study, we established an integrative database containing analysis pipelines and analysis results of 609 human and mice smRNA-seq results, including public data from GEO and private ones. YM500 collects analysis results for miRNA quantification, for isomiR identification (incl. RNA editing), for arm switching discovery, and, more importantly, for novel miRNA predictions. Wetlab validation on >100 miRNAs confirmed high correlation between miRNA profiling and RT-qPCR results (R=0.84). This database allows researchers to search these 4 different types of analysis results via our interactive web interface. YM500 allows researchers to define the criteria of isomiRs, as well as integrates the information of dbSNP to help researchers to distinguish isomiRs from SNPs. A user-friendly interface is provided to integrate miRNA-related information and existing evidences from hundreds of sequencing datasets. The identified novel miRNAs and isomiRs hold the potentials for both basic research and biotech applications. YM500 is now available on http://ngs.ym.edu.tw/ym500/. Overall design: There are 34 in-house datasets in YM500 . They are 9 human embryonal tumors, 9 human germ cell tumors, and 16 human gliomas.	Co-expression
SRP014739	A global analysis of tandem 3''UTRs in eosinophilic chronic rhinosinusitis with nasal polyps	Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3''-untranslated region (3''UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3''UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3''UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Overall design: Investigate the use of tandem APA sites of 3''ends of mRNAs using second-generation sequencing technology.	Co-expression
SRP014754	miR-146a promotes the initiation and progression of melanoma  by activating Notch signaling	Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. Overall design: WI-38 cells were either infected with BRAFV600E or Empty retroviral vectors and small RNA were prepared from these cells. As an additional control, WI-38 cells were serum starved and used to generate quiscent cells, which were also used to prepase small RNA.  The small RNA were then used to generate small RNA library and were used on Illumina genome analyzer.	Co-expression
SRP014790	The Small Molecule Genistein Increases Hepcidin Expression in Human Hepatocytes	Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals.  Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP) and interleukin-6 (IL-6) via effects on Smad4 or Stat3, respectively.  We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression.  We found that treatment with the isoflavone genistein from 28-52 hours post-fertilization in zebrafish embryos enhanced Hepcidin transcript levels as assessed by whole mount in situ hybridization and quantitative realtime RT-PCR.  Genistein’s stimulatory effect was conserved in human hepatocytes: genistein treatment of HepG2 cells increased both Hepcidin transcript levels and Hepcidin promoter activity.  We found that genistein’s effect on Hepcidin expression did not depend on estrogen receptor signaling or increased cellular iron uptake, but was impaired by mutation of either the BMP response elements or the Stat3 binding site in the Hepcidin promoter.  RNA-sequencing of transcripts from genistein-treated hepatocytes indicated that genistein upregulated 68% of the transcripts that were upregulated by BMP6, however genistein raised the levels of several transcripts involved in Stat3 signaling that were not upregulated by BMP6.  Chromatin-immunoprecipitation and ELISA experiments revealed that genistein enhanced Stat3 binding to the Hepcidin promoter and increased phosphorylation of Stat3 in HepG2 cells.  CONCLUSION:  Genistein is the first small molecule experimental drug that stimulates Hepcidin expression in vivo and in vitro.  These experiments demonstrate the feasibility of identifying and characterizing small molecules that increase Hepcidin expression.  Genistein and other candidate molecules may subsequently be developed into new therapies for iron overload syndromes. Overall design: RNA-seq of HepG2 cells treated with DMSO 1%, BMP6 50 ng/ml, or genistein 10 micromolar.  The numbers of biological replicates were 3, 2, and 3.	Co-expression
SRP014809	Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions	The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signalling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. While previous studies have focused on ligand-dependent AR signalling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that the AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a distinct gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal. Overall design: LNCaP, C4-2B, or 22RV1 cells were cultured in hormone-free media for 3 days and then treated with ethanol vehicle or DHT (10nM) for 4h or 16h prior to ChIP-seq or RNA-seq assays. For siRNA transfection, cells were transfected with AR siRNA or control siRNA for 3 days prior to RNA-seq assays.	Co-expression
SRP014856	Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation	Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defenses peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on macrophages/monocytes. Here we measured the effect of IDR-1018 on macrophage gene expression during differentiation. Differentiation in the presence of IDR-1018 induced a unique signature of immune responses suggesting that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. Overall design: RNA-seq was performed using the Illumina Genome Analyzer IIx platform. Monocytes were isolated from 3 healthy donors, and left unstimulated  or stimulated for 4 hours with 20 µg/ml IDR-1018. For library preparation, 500 ng of total RNA was processed according to the Illumina TruSeq RNA sample preparation guide (Illumina catalogue number FC-122-1002). Briefly, mRNA was purified using poly-dT beads, followed by synthesis of the first and second cDNA strands, end repair addition of an poly-A overhang, and ligation of adapters and unique barcodes, as per the manufacturer’s instructions. DNA enrichment was carried out via a 15-cycle PCR. Following quantification, 8 pM of dsDNA was used for cluster generation on a CBOT instrument (Illumina, San Diego, CA). RNA sequencing was done on a GAIIx instrument (Illumina), performed as a single read run with 51 amplification cycles. Data processing was carried out in house, using CASAVA to convert raw data and demultiplex to FASTQ sequence files. Reads were aligned to the reference genome using TOPHAT, and then mapped to genes using the Bioconductor package GenomeRanges.	Co-expression
SRP014867	Cleavage Factor Im as a key regulator of 3’ UTR length	In eukaryotes, the 3'' ends of RNA polymerase II-generated transcripts are made in the majority of cases by site-specific endonucleolytic cleavage, followed by the addition of a poly(A) tail. By alternative polyadenylation, a gene can give rise to multiple mRNA isoforms that differ in the length of their 3'' UTRs and hence in their susceptibility to post-transcriptional regulatory factors such as microRNAs. A series of recently conducted high-throughput studies of poly(A) site usage revealed an extensive tissue-specific control of 3’ UTR length and drastic changes in 3’ UTR length of mRNAs upon induction of proliferation in resting cells. To understand the dynamics of polyadenylation site usage, we recently identified binding sites of the major pre-mRNA 3’ end processing factors - cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and cleavage factor Im (CF Im) - and mapped cleaved polyadenylation sites in HEK293 cells. Our present study extends previous findings on the role of CF Im in alternative polyadenylation and reveals that subunits of the CF Im complex generally control 3’ UTR length. More specifically, we demonstrate that the  loss-of-function of CF Im68 and CF Im25 but not of CF Im59 leads to a transcriptome-wide increase of the use of proximal polyadenylation sites. Overall design: 3'' ends of transcripts were profiled by high-throughput sequencing in HEK 293 cells under normal conditions, and in HEK 293 cells depleted of 3'' end processing factors CF Im25, CF Im59, and CF Im68.	Co-expression
SRP014925	mRNA profiles following TUT knock-down in HeLa	The precise control of microRNA (miRNA) biogenesis is important for various cellular functions, and its dysregulation is often associated with human diseases.  We previously reported that Terminal   uridylyl transferase 4 (TUT4) down-regulates let-7 miRNA biogenesis by oligo-uridylating let-7 precursor (pre-let-7) in mouse embryonic stem cells and that a pluripotency marker Lin28 promotes   a processivity of TUT4.  Here we find that TUT4 positively controls let-7 biogenesis by adding a uridine residue to the 3' end of pre-let-7 in the absence of Lin28. Such mono-uridylation enhances Dicer   processing by generating an optimal end structure of pre-let-7 for Dicer recognition and may protect pre-miRNA from trimming. Moreover, TUT7, TUT4 and TUT2 redundantly regulate pre-let-7   processing and simultaneous knock down of these TUTs leads to the decrease of mature let-7 and the accumulation of pre-let-7 in cells. This study provides a novel regulation mechanism of miRNA   biogenesis, which may function in development and tumorigenesis. Overall design: HeLa cells were transfected with siRNA two times over a 4~5 day period.	Co-expression
SRP015003	Papillary Type 2B RCC - RNA SEQ	Papillary type 2B RNA sequencing.	Co-expression
SRP015013	A model system for assessing the ability of tag sequencing to detect genes specific for malignant B-cells	The purpose of this study was to develop a quantification method that can be used to assess the ability of tag-seq to detect malignant B-cell transcripts. The data support that tumour cell concentration is an important variable with fundamental impact on gene expression pattern. Overall design: We analysed eight serial dilutions of the malignant B-cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293, by tag-sequencing. No technical replicates were performed.	Co-expression
SRP015138	Hydroxymethylation at gene regulatory regions directs stem cell commitment during erythropoiesis	CD34 positive hematopoietic stem cells were differentiated into erythroid lineage. Next generation sequencing (NGS) of 5hmC affinity pulldown and RNAseq were performed in four time point of different stages of erythroid differentiation. Overall design: 4 RNA-Seq Samples (d0, d3, d7 and d10); 4 affinity-pulldown  (d0, d3, d7 and d10), and 4 input samples  (d0, d3, d7 and d10).	Co-expression
SRP015360	RNAseq analysis of the human neutrophil transcriptome, with and without in vitro cytokine stimulation	We report cytokine specific changes in gene expression in the human neutrophil transcriptome using TNF-alpha and GM-CSF stimulation of healthy neutrophils Overall design: Healthy human neutrophils were stimulated with TNF-alpha or GM-CSF for 1h in vitro. RNA was analysed by SOLiD and Illumina sequencing.  RNA from one biological donor was sequenced on both platforms, and two different biological donors were sequenced by Illumina.	Co-expression
SRP015370	Evolution of mammalian miRNA genes	MicroRNAs (miRNAs) are major post-transcriptional regulators of gene expression, yet their origins and functional evolution in mammals remain little understood due to the lack of appropriate comparative data. Using RNA sequencing, we have generated extensive and comparable miRNA data for five organs in six species that represent all main mammalian lineages and birds (the evolutionary outgroup), with the aim to unravel the evolution of mammalian miRNAs. Our analyses reveal an overall expansion of miRNA repertoires in mammals, with three-fold accelerated birth rates of miRNA families in placentals and marsupials, facilitated by the de novo emergence of miRNAs in host gene introns. Generally, our analyses suggest a high rate of miRNA family turnover in mammals, with many newly emerged miRNA families being lost soon after their formation. Selectively preserved mammalian miRNA families gradually evolved higher expression levels as well as altered mature sequences and target gene repertoires, and were apparently mainly recruited to exert regulatory functions in nervous tissues. However, miRNAs that originated on the X chromosome evolved high expression levels and potentially diverse functions during spermatogenesis, including meiosis, through selectively driven duplication-divergence processes. Overall, our study thus provides detailed insights into the birth and evolution of mammalian miRNA genes and the associated selective forces. Overall design: 30 main samples from five adult tissues (brain, cerebellum, heart, kidney and testis) collected in six species (human, macaque, mouse, opossum, platypus and chicken) + 5 biological replicates + 3 samples from spermatogenic cells in adult mouse testis  (Sertoli cells, spermatocytes and spermatids)	Co-expression
SRP015409	iMir: An integrated pipeline for high-throughput miRNA-Seq data analysis	We report a novel modular pipeline (iMir) for comprehensive analysis of miRNA-Seq data, from linker removal and sequence quality check to differential expression and biological target prediction, integrating multiple open source modules and resources linker together in an automated flow. Overall design: Development of an integrated pipeline (iMir) for comprehensive analysis of miRNA-Seq experiment.	Co-expression
SRP015439	Efficient direct reprogramming of c-Kit- mature amniotic cells into endothelial cells by ETS factors and TGFß suppression	ETS transcription factors ETV2, FLI1 and ERG1 specify pluripotent stem cells into endothelial cells (PSC-ECs). However, these PSC-ECs are unstable and often drift towards non-vascular cell fates. We show that human mid-gestation c-Kit- lineage-committed amniotic cells (ACs) can be reprogrammed into induced vascular endothelial cells (rAC-VECs). Transient ETV2 expression in ACs generated immature iVECs, while co-expression with FLI1/ERG1 endowed rAC-VECs with a vascular repertoire and morphology matching mature ECs. Brief TGFb-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and non-vascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Thus, short-term ETV2 expression and TGFb-inhibition along with constitutive ERG1/FLI1 co-expression reprogram mature ACs into generic rAC-VECs with clinical-scale expansion potential. Public banking of HLA-typed rAC-VECs would establish a vascular inventory for treatment of genetically diverse disorders. Overall design: Transcriptome sequencing of clonal and non-clonal rAC-VECs, HUVECs, LSECs, CD34+/Lin-, BMS	Co-expression
SRP015449	Integrative Analyses of Gene Expression and DNA Methylation Profiles in a Breast Cancer Cell Line Model of Tamoxifen-Resistance Indicate a Crucial Role of Cells with Stem-like Properties	Purpose: Development of resistance to tamoxifen is an important clinical issue in the treatment of patients with breast cancer. Tamoxifen resistance may be the result of the acquisition of epigenetic regulation such as DNA methylation within breast cancer cells resulting in changed mRNA expression of genes being pivotal for estrogen dependent growth. Alternatively, tamoxifen resistance may be due to selection of preexisting resistant cells, which may exhibit cancer stem-like characteristics or a combination of the two mechanisms. Methods: To evaluate the contribution of these possible mechanisms to tamoxifen resistance, we applied modified DNA methylation-specific digital karyotyping (MMSDK) and digital gene expression (DGE) in combination with massively parallel sequencing to analyze a well-established tamoxifen resistant cell line model: MCF-7/S0.5 (tamoxifen sensitive parental cell line) and 4 high-dosage tamoxifen selected resistant offspring sublines (MCF-7/TAMR-1, MCF-7/TAMR-4, MCF-7/TAMR-7 and MCF-7/TAMR-8). MMSDK uses BssHII as mapping enzyme (DNA methylation sensitive enzyme). Both MMSDK and DGE use NlaIII and MmeI to produce 20-21 bp tag. The indexed single-end sequencing was performed by Illumina HiSeq 2000 in BGI-Shenzhen. A dynamic programming algorithm-FASTX-Toolkit implemented in Perl was used to trim the adaptor sequence. The trimmed tags were subjected to quality filtering, so that only tags with sequencing quality higher than 30 for more than 80% of the nucleotides were used for subsequent analysis. For MMSDK tag mapping, we generated a simulated reference library, i.e., BssHII reference library, by in silico enzyme digestion of the human genome (hg19, UCSC) regardless of the methylation state. This library was used as reference for subsequent mapping of the tags in the MMSDK analysis. In the DGE analysis, refMrna (hg19, UCSC) was used as reference for mapping cDNA tags. Subsequently, the Burrows–Wheeler Aligner (BWA) procedure for aligning the MMSDK and DGE tags to the simulated BssHII reference library and refMrna reference library, respectively, was applied. Results: MMSDK libraries using BssHII/NlaIII were generated from the parental tamoxifen sensitive subline MCF-7/S0.5 and the 4 TAMR cell lines: TAMR-1, TAMR-4, TAMR-7 and TAMR-8. The 5 indexed MMSDK libraries were sequenced in one lane and 1.38 Gb clean tag data for all 5 cell lines were obtained, with an average sequencing amount of ~270 Mb per library. On average, 59.5 % of the tags with mapping quality = 20 were mapped back to the simulated BssHII/NlaIII reference library. DGE libraries were also generated from MCF-7/S0.5 and the 4 TAMR cell lines. The 5 indexed DGE libraries were sequenced in one lane and obtained 1.71 Gb clean tag data for all 5 cell lines with an average sequencing amount of ~340 Mb per library. On average, 40.8 % with mapping quality = 20 were mapped back to the simulated NlaIII human transcriptome (refMrna reference library). Our present study demonstrates large differences in global gene expression and DNA methylation profiles between parental tamoxifen-sensitive cell line and 4 high-dosage tamoxifen treatment selected resistant sublines. The tamoxifen resistant cell lines exhibited globally higher methylation level than the parental cell line and an inverse relationship between gene expression and DNA methylation in the promoter regions were noticed. High expression of SOX2 and alterations of other SOX gene family members, E2F gene family members and RB-related pocket protein genes as well as highlighted stem cell pathways imply that cancer initiating cells/stem cells are  involved in the resistance to tamoxifen. Overall design: DNA methylation and mRNA expression profiles from tamoxifen sensitive parental cell line MCF-7/S0.5 and 4 high dosage of tamoxifen selected resistant offspring sublines (MCF-7/TAMR-1, MCF-7/TAMR-4, MCF-7/TAMR-7 and MCF-7/TAMR-8) were analyzed by MMSDK and DGE methods, respectively, in combination of massively parallel sequencing, using Illumina HiSeq 2000	Co-expression
SRP015640	Comprehensive comparative analysis of RNA sequencing methods for degraded or low input samples	RNA-Seq is an effective method to study the transcriptome, but can be difficult to apply to scarce or degraded RNA from fixed clinical samples, rare cell populations, or cadavers. Recent studies have proposed several methods for RNA-Seq of low quality and/or low quantity samples, but their relative merits have not been systematically analyzed. Here, we compare five such methods using a comprehensive set of metrics, relevant to applications such as transcriptome annotation, transcript discovery, and gene expression. Using a single human RNA sample, we constructed and deeply sequenced 10 libraries with these methods and two control libraries. We find that the RNase H method performed best for low quality RNA, and can even effectively replace oligo (dT) based methods for standard RNA-Seq. SMART and NuGEN had distinct strengths for low quantity RNA. Our analysis allows biologists to select the most suitable methods and provides a benchmark for future method development. Overall design: Examination of 9 different RNA-Seq libraries starting from total RNA from 5 distinct methods; also 3 control RNA-Seq libraries	Co-expression
SRP015668	aSyn polyA-RNAseq in PD and unaffected cortical brain samples	We sought to more precisely characterize the different alpha-synuclein (aSyn) 3’UTR mRNA species in normal and PD human brain.  High-throughput, whole-transcriptome sequencing of the 3’UTR ends of polyadenylated mRNA transcripts (termed pA-RNAseq; see Methods) was performed on a cohort of 17 unaffected and 17 PD cerebral cortical tissue samples.  This revealed 5 aSyn 3’UTR isoforms, with lengths of 290, 480, 560, 1070 and 2520 nt.  Of these, the 560 nt and 2520 nt forms were predominant. The existence and relative preponderance of these species was further confirmed by Northern Blot. We next hypothesized, that aSyn 3’UTR selection might be altered in PD.  Comparison of pA-RNAseq profiles from PD and unaffected cerebral cortex samples revealed an increase in the preponderance of the long 3’UTR species (>560 nt) relative to shorter species (<560 nt).  Such a relative increase in aSynL was confirmed by Quantitative real-time RT-PCR (rt-qPCR) and appeared specific for PD, as the increase was also observed by comparison to RNA from amyotrophic lateral sclerosis patient samples.  We note that the modified aSyn 3’UTR selection associated with PD patient tissue was detected in cerebral cortex tissue, which typically harbors pathological evidence of the disease process without frank cell loss; thus, this phenotype is unlikely to be a secondary consequence of neurodegeneration. Overall design: Comparison of 3''UTR ends of alpha-synuclein in PD and unaffected brain cortex	Co-expression
SRP015670	Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis	Background: West Nile virus is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV. Results: From a total of 50 million reads per sample, we employed a Bayesian hierarchical mixture model to identify 4,026 transcripts that were differentially expressed after infection. Both predicted and novel gene changes were detected, as were gene isoforms, and while many of the genes were expressed by all donors, some were unique. Knock-down of genes not previously known to be associated with WNV resistance identified their critical role in control of viral infection. Conclusions: Our study distinguishes both common gene pathways as well as novel cellular responses. Such analysis will be valuable for translational studies of susceptible and resistant individuals -- and for targeting therapeutics -- in multiple biological settings. Overall design: Differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV were generated by RNA-Seq.	Co-expression
SRP015715	Revisiting Global Gene Expression Analysis (RNA-Seq)	Gene expression analysis is a widely used and powerful method for investigating the transcriptional behavior of biological systems, for classifying cell states in disease and for many other purposes.  Recent studies indicate that common assumptions currently embedded in experimental and analytical practices can lead to misinterpretation of global gene expression data.  We discuss these assumptions and describe solutions that should minimize erroneous interpretation of gene expression data from multiple analysis platforms. Overall design: Polyadenylated RNA depleted of ribosomal content was used for preparation of two independent sequencing libraries (low-Myc & high-Myc). A panel of synthetic RNA''s was added to these populations, based on cell number.	Co-expression
SRP015725	Differences in miRNA Detection Levels are Technology and Sequence Dependent [NGS]	We undertook an integrative technological approach to compare miRNA detection capability of three high-throughput commercial platforms. Overall design: We artificially introduced human precursor, 2’-O-methyl modified and mature spiked-in miRNAs in a controlled fashion into native human placenta total RNA.	Co-expression
SRP015733	EWS function in Ewing sarcoma	Identification of EWS regulated genes in Ewing sarcoma.	Co-expression
SRP015741	Transcriptome-wide analyses of CstF64-RNA interactions in global regulation of mRNA alternative polyadenylation	We mapped CstF64-RNA interactions at the transcriptome level and studied CstF64-mediated regulation of global mRNA alternative polyadenylation by using iCLIP-seq and direct RNA sequencing analyses. Overall design: CstF64 iCLIP-seq in HeLa cells;  direct RNA sequencing (DRS) of control HeLa cells, CstF64-RNAi cells and CstF64&CstF64tau-RNAi cells	Co-expression
SRP015764	Characteristics of Cross-Hybridization and Cross-Alignment in Pseudo-Xenograft samples by RNA-Seq and Microarrays [RNA-Seq]	In order to study molecular changes in the stroma from tissue samples it is recommended to separate tumor tissue from stromal tissue. This is particularly relevant to mouse tumor xenograft models where tumor, particularly metastatic tumors, can be small and difficult to separate from the host tissue. In our research we compared qualitatively the ability of high-throughput mRNA sequencing, RNA-Seq, and microarrays to detect tumor (human) and stromal (mouse) expression from mixed tumor-stromal samples in terms of the genes and pathways that are involved in cross-alignment (RNA-Seq) and cross-hybridization (microarrays). Overall design: Human samples consisted of total RNA obtained from MDA-MB-231 human breast carcinoma cell line and isolated from three independent cultures of sub-confluent MDA-MB-231 cell lines in exponential phase of growth.  Mouse samples were obtained from NOD scid gamma mice, and normal lung tissue was harvested from three independent age-matched mice.	Co-expression
SRP015799	BCL11B function in Ewing sarcoma	Gene regulation by BCL11B in Ewing sarcoma.	Co-expression
SRP015845	Next Generation Sequencing Facilitates Quantitative Analysis of Argonaute 2 (Ago2)-immunoprecipitation (IP) after miR-195 or miR-497 overexpression in HepG2	To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines.  The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines.  Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs.  Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest.  Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC.  Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Identification of miR-195 and miR-497 target genes by sequencing Ago2-binding mRNAs and total mRNAs of miR-195 or miR-497 overexpressed, or non-treated Hep G2 cell. Overall design: Deep sequencing of RNAs in Ago2-IP fraction and mRNAs extracted from miR-195 or miR-497 overexpressed, or non-treated Hep G2 cell.	Co-expression
SRP015853	Integrated detection of both 5-mC and 5-hmC by high-throughput tag sequencing technology highlights methylation reprogramming of bivalent genes during cellular differentiation [DGE]	5-methylcytosine (5-mC) can be oxidized to 5-hydroxymethylcytosine (5-hmC). Genome-wide profiling of 5-hmC thus far indicated 5-hmC may not only be an intermediate form of DNA demethylation but could also constitute an epigenetic mark per se. We describe a cost-effective and selective method to detect both the hydroxymethylation and methylation status of cytosines in more than 1.8 million MspI sites in the human genome. This method involves the selective glucosylation of 5-hmC residues, short-sequence tag generation and high-throughput sequencing. We tested this method by screening H9 human embryonic stem cells and their differentiated embroid body cells, and found that differential hydroxymethylation preferentially occur in bivalent genes during cellular differentiation. Especially, our results support hydroxymethylation can regulate key transcription regulators with bivalent marks through demethylation and affect cellular decision on choosing active or inactive state of these genes upon cellular differentiation. Overall design: In order to explore the role of methylation and hyroxymethylation in regulating gene expression upon cellular differentiation to EBs, we examined  the gene expression level in  H9 human embryonic stem cells and their differentiated embroid body cells by Digital gene expression (DGE), respectively.	Co-expression
SRP015909	mRNA profiles of WTAP siRNA-treated HUVECs	To examine the role of WTAP in splicing regulation, we performed high-throughput mRNA sequencing (RNA-seq) on RNA isolated from control, WTAP or Virilizer siRNA-treated HUVECs, yielding 12 million uniquely mapped 75nt pair-end tags from each sample. MapSplice software was used for differential expression and differences in transcript splice junctions . Overall design: mRNA profiles of control, WTAP or Virilizer siRNA-treated HUVECs were generated by deep sequencing using Illumina GAII.	Co-expression
SRP015943	YAP mediates crosstalk between the Hippo and PI3K-TOR pathway by suppressing PTEN via miR-29	We aimed to identify microRNAs that are regulated by YAP in human mammary epithelial cells. Overall design: We utilized deep sequencing technology to identify microRNAs that are induced by YAP overexpression and repressed by YAP knockdown.	Co-expression
SRP015976	The loop position of shRNAs and pre-miRNAs is critical for the accuracy of Dicer processing in vivo	Short-hairpin RNA (shRNA)-induced RNAi is used for biological discovery and therapeutics. Dicer, whose normal role is to liberate endogenous miRNAs from their precursors, processes shRNAs into different biologically active siRNAs, affecting their efficacy and potential for off-targeting. We found that in cells, Dicer induced imprecise cleavage events around the expected sites based on the previously described 5'/3'-counting rules. These promiscuous non-canonical cleavages were abrogated when the cleavage site was positioned 2 nt from a bulge or loop. Interestingly, we observed that the ~1/3 of mammalian endogenous pre-miRNAs that contained such structures were more precisely processed by Dicer. Implementing a new "loop-counting rule", we designed potent anti-HCV shRNAs with substantially reduced off-target effects. Our results suggest that Dicer recognizes the loop/bulge structure in addition to the ends of shRNAs/pre-miRNAs for accurate processing. This has important implications for both miRNA processing and future design of shRNAs for RNAi-based genetic screens and therapies. Overall design: Various shRNAs were expressed in Cell and processed by the RNase III enzyme Dicer.  The profiles of the siRNA products were generated by deep sequencing with or without the Ago2-IP.	Co-expression
SRP015989	EWS/FLI function in Ewing sarcoma	Gene regulation by EWS/FLI1 fusion in Ewing sarcoma.	Co-expression
SRP016003	Ago HITS-CLIP in KSHV-infected primary effusion lymphoma (PEL) cell lines BCBL-1 and BC-3	We performed Ago HITS-CLIP to identify targets of viral and human miRNAs in latently KSHV-infected PEL cells Overall design: Ago HITS-CLIP was performed in two latently infected PEL cell lines, BCBL-1 and BC-3; Argonaute-immunoprecipitation of UV cross-linked Ago-miRNA-mRNA complexes, followed by RNA isolation, library construction, and high-throughput sequencing (Illumina GAxII); we performed 3 biological replicates for each cell line, two technical (sequencing) replicates of BCBL-1 biological replicate 1	Co-expression
SRP016004	Multiple platform assessment and isomir analysis of the EGF dependent microRNA-ome by microarray and deep sequencing analysis [small RNA-seq]	We have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by RT-qPCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomirs) among regulated miRNAs. Overall design: Time course experiment comparing HeLa gene expression in response to EGF analyzed by small RNA-seq using Illumina 36-bp read massively parallel sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6h and harvested for RNA extraction.  Thus, a total of 6 samples were analyzed, 3 controls and the 3 respective treated counterparts. These same samples were also analyzed in parallel on two different microarray platforms.	Co-expression
SRP016059	RNA-seq for gastric cancer and normal tissues/cells	We performed RNA-seq experiments to identify differentially expressed intergenic transcripts between gastric cancer and normal tissues/cells. Overall design: Three primary cell culture samples from gastric cancer tissues, three gastric cancer cell lines and two normal tissue samples were used for the experiments.	Co-expression
SRP016118	Expression data for HT29 cells treated with 5-aza-deoxy-cytidine [RNA-Seq]	The RNA samples from HT-29 (ATCC) colon cancer cell line were reverse transcribed to build cDNA libraries and categorized into 3 groups with different concentrations of 5-aza-deoxy-cytidine (5-Aza); in each group three replicative 150 mm cultures were treated with: 1) dimethyl sulfoxide (vehicle alone, 0 µM 5-Aza); 2) 5µM 5-Aza and 3) 10 µM 5-Aza; for five days. This experiment was also performed parallel on a commercial Affymetrix microarray [GSE41364] and the aim of the study was to compare the two platforms on gene expression measurements and differentially expressed gene (DEG) detection. The results showed a strong correlation between the two platforms, yet it also confirmed the existence of fixed and proportional biases on the gene expression measurements between microarray and RNA-Seq. The DEG analysis indicated the relative superiority of DESeq method in terms of its performance; high consistency was confirmed between DESeq, baySeq methods from RNA-Seq and SAM/eBayes from microarray data. Overall design: Experiment on human colon cancer HT29 cell line treated with 3 concentrations of 5-aza-deoxy-cytidine	Co-expression
SRP016140	Identification of Novel Molecular Markers through Transcriptomic Analysis in Human Fetal and Adult Corneal Endothelial Cells	Corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs) in the inner layer of cornea, which is essential for maintaining corneal transparency. In order to better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other types of tissues, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are characteristic of CECs, involving in cell adhesion, proteoglycan and sulfur metabolic process. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. By comparing fetal and adult CECs, we also identified stage-specific markers associated with CEC maturation, such as the activation of the Wnt pathway genes in fetal, but not in adult CECs. Lastly, by immunohistochemistry of ocular tissues, we further confirmed the unique protein expression patterns for Wnt5a, S100A4, S100A6, and IER3, the four novel markers for either fetal or adult CECs.  The identification of a new panel of molecular markers for fetal and mature CECs would be very useful for characterizing and quality controlling CECs through ex vivo expansion or stem cell differentiation for cell replacement therapy. Overall design: mRNA profile between adult and fetal CECs by high-throughput sequencing	Co-expression
SRP016568	Somatic copy-number mosaicism in human skin revealed by induced pluripotent stem cells (sequencing)	Reprogramming human somatic cells into induced pluripotent stem cells (iPSC) has been suspected of causing de novo copy number variations (CNVs). To explore this issue, we performed a whole-genome and transcriptome analysis of 20 human iPSC lines derived from primary skin fibroblasts of 7 individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two CNVs not apparent in the fibroblasts from which the iPSC was derived. Using qPCR, PCR, and digital droplet PCR (ddPCR) to amplify across the CNVs'' breakpoints, we show that at least 50% of those CNVs are present as low frequency somatic genomic variants in parental fibroblasts and are manifested in iPSC colonies due to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSC, since most of line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically. Overall design: We have generated and characterized hiPSC lines derived from skin fibroblasts collected from seven members of two families, which were competent to be differentiated into neuronal progenitors and neurons	Co-expression
SRP016583	Transcriptional Profiling of Psoriasis Using RNA-seq Reveals Previously Unidentified Differentially Expressed genes	The transcriptomic profiling of psoriasis has led to an increased understanding of disease pathogenesis. Although microarray technologies have been instrumental in this regard, it is clear that these tools detect an incomplete set of DEGs. RNA-seq can be used to supplement these prior technologies. Here, the use of RNAseq methods substantially increased the number of psoriasis-related DEGs. Furthermore, DEGs that were uniquely identified by RNA-seq, but not in other published microarray studies, further supported the role of IL-17 and tumor necrosis factor-a synergy in psoriasis. Examination of one of these factors at the protein level confirmed that RNA-seq is a powerful tool that can be used to identify molecular factors present in psoriasis lesions, and may be useful in the identification of therapeutic targets that to our knowledge have not been reported previously.  Further studies are in progress to determine the biological significance of DEGs uniquely discovered by RNA-seq. Overall design: To define the transcriptomic profile of psoriatic skin, three pairs of lesional and nonlesional skin biopsy specimens were taken from patients with untreated  moderate-to-severe plaque psoriasis.	Co-expression
SRP016626	Specific miRNA Stabilization by Gld2-catalyzed Monoadenylation	miRNAs are small non-coding RNAs that inhibit translation and promote mRNA decay.  The levels of mature miRNAs are the result of different rates of transcription, processing, and turnover. The non-canonical polymerase Gld2 has been implicated in the stabilization of miR-122 possibly by catalyzing 3’ monoadenylation, however, there is little evidence that this relationship is one of cause and effect.  Here, we biochemically characterize Gld2 involvement in miRNA monoadenylation and its effect on miRNA stability.  We find that Gld2 directly monoadenylates and stabilizes specific miRNA populations in human fibroblasts and that sensitivity to monoadenylation-induced stability depends on nucleotides in the miRNA 3‘ end.  These results establish a novel mechanism of miRNA stability and resulting post-transcriptional gene regulation. Overall design: Sequencing of miRNAs to assess amount and 3'' end monoadenylation state upon Gld2 knock-down.	Co-expression
SRP016629	Accelerated high-yield generation of limb-innervating motor neurons from human stem cells	Human pluripotent stem cells are a promising source of diverse cells for developmental studies, cell transplantation, disease modeling, and drug testing.  However, their widespread use even for intensely studied cell types like spinal motor neurons, is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that induce up to 50% motor neurons within 3 weeks from human pluripotent stem cells with defined subtype identities that are relevant to neurodegenerative diseases.  Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord.  Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3-). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. Overall design: We analyzed 3 samples including 2 positive samples and 1 negative sample. Descriptions are as follows: a) Positive Sample 1: SHH-derived, day 21 GFP-high FACS-purified motor neurons. b) Positive Sample 2: S+P-derived, day 21 GFP-high FACS-purified motor neurons. c) Negative: S+P condition, day 21 GFP-off FACS-purified non-motor neurons. Initial analysis of data was performed on ~40% of fastq reads (Amoroso et al., J Neurosci 2013 Jan 9;33(2):574-86. PMID: 23303937).  Further processing of the full dataset has since been carried out and the updated rpkm file and expression analysis reflecting all aligned reads can be accessed at: http://scholar.harvard.edu/amorosornaseq/	Co-expression
SRP017019	Translatome of A549, H1299 and HBE cells	We performed translatome and transcriptome sequencing of A549, H1299 and HBE cells and analyzed the translation ratio (TR) of all genes Overall design: Total RNA and ribosome-bound RNA were extracted from A549, H1299 and HBE cells, and the polyA+ mRNA was sequenced using Illumina GAIIx and HiSeq-2000. The reads were mapped to RefSeq RNA reference sequences and the expression level were quantified by rpkM calculation.	Co-expression
SRP017123	Global DNA Hypermethylation in Down Syndrome Placenta [RNA-Seq]	We have performed genome-wide DNA methylation analysis at single base resolution and gene expression analysis, resulted in hypermethylation in all autosomes in DS samples, mediated by down-regulation of all three TET family genes, and down-regulation of REST/NRSF. Genes located on chr21 were up-regulated by a median of 45% in DS compared to normal villi, while genes with promoter hypermethylation were down regulated. Overall design: Comparison of RNA expression in human placenta between 5 normal and 4 Trisomy 21 samples.	Co-expression
SRP017138	RECURRENT SETBP1 MUTATIONS IN ATYPICAL CHRONIC MYELOID LEUKEMIA	RNA-Seq analysis of atypical chronic myeloid leukemia samples Overall design: We sequenced leukemic mRNA from 13 Atypical Cronic Mieloid Leukemia (aCML) samples  by Illumina GAIIx. Transcriptomic profiles, differentially expressed genes and pathway enrichment analysis were obtained comparing 7 SETBP1-mutated samples and 6 non-mutated (WT) samples by using TopHat aligner and SAMMate gene expression quantifier. We focused on the gene expression profile of known coding transcripts. A dataset of 20,907 protein-coding Ensembl Genes was obtained from the RNA-Seq by using the Human Ensembl GTF annotation file vs54 dowloaded from ftp://ftp.ensembl.org/pub/release-54/gtf/homo_sapiens/.	Co-expression
SRP017142	Quantitative analysis of proliferative and Ras-induced senescent human primary fibroblasts transcriptomes	The goals of this study is to analyse transcriptionnal changes  in senescent cells and to compare them with ChIPseq data for several histones marks and proteins of the SUMO machinery Overall design: mRNA profiling of proliferative versus Ras-induced senescent humain primary fibroblasts 5 days post-infection	Co-expression
SRP017190	Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration	The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer.  miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer. Overall design: Sequencing miRNAs from Human breast cancer cells: MCF10A, MCF7, MDA-MB-231, MDA-MB-LM2	Co-expression
SRP017199	Stability, Delivery and Functions of Human Sperm RNAs at Fertilization	We report on abundance and transcript profile characteristics of sperm RNAs. Overall design: Examination of RNA population and distribution in spermatozoa	Co-expression
SRP017262	Homo sapiens Transcriptome or Gene expression	Therapy-related and de novo acute myeloid leukemia transcriptome sequencing	Co-expression
SRP017263	Co-Translational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes	Translational control permits cells to respond swiftly to changing environment. Rapid attenuation of global protein synthesis under stress conditions has been largely ascribed to the inhibition of translation initiation. To monitor the co-translational response to proteotoxic stress especially during elongation stage, we performed ribosome profiling (deep sequencing of ribosome-protected mRNA fragments) and investigated the roles of chaperone molecules in this process.	Co-expression
SRP017294	Genomewide analysis of U1C-dependent alternative splicing	To investigate whether U1C plays a role in splicing regulation in human system, we performed siRNA-mediated knockdown of U1C in HeLa cells and analyzed alternative splicing patterns by high-throughput RNA sequencing (RNAseq) Overall design: RNAseq performed with poly(A)+ selected total RNA from U1C-knockdown and control-treated HeLa cells	Co-expression
SRP017330	DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation (RNA-seq)	Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. Overall design: RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).	Co-expression
SRP017352	Homo sapiens Transcriptome or Gene expression from infant epithelial cells in stool	Having developed a noninvasive method to sequence epithelial cells shed from the intestinal lining, this allowed testing of infants. We compared pooled RNA isolated from full term infants and pretern infants. This allowed for comparison of the differences in the healthy full term infant transcriptome and the extremely preterm infant transcriptome.	Co-expression
SRP017378	Transcriptome-profiling (RNA-seq) and Ribosome-profiling (Ribo-seq) in proliferation, quiescence, senescence and transformed states.	We applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells under the following conditions: normal proliferation, quiescence (induced by serum depletion), senescence (induced by activation of the oncogenic RASG12V gene, and examined at early (5 days; pre-senescent state) and late (14 days; fully senescent state) time points), and neoplastic transformation (induced by RASG12V in the background of stable p53 and p16INK4A knockdowns and SV40 small-T expression. Overall design: RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed. Ribosome profiling, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed.	Co-expression
SRP017395	Homo sapiens Genome sequencing	Submit for publication for Ting Ni	Co-expression
SRP017411	Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated microRNA Circuits	The induction of pluripotency or trans-differentiation of one cell type to another  can be accomplished with cell lineage-specific transcription factors. Here we report that  repression of a single RNA binding protein PTB, which occurs during normal brain  development via the action of miR-124, is sufficient to induce trans-differentiation of  fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we  show that PTB has a previously undocumented function in the regulation of microRNA  functions, suppressing or enhancing microRNA targeting by competitive binding on  target mRNA or altering local RNA secondary structure. A key event during neuronal  induction is the relief of PTB-mediated blockage of microRNA action on multiple  components of the REST complex, thereby de-repressing a large array of neuronal genes,  including miR-124 and multiple neuronal-specific transcription factors, in non-neuronal  cells. This converts a negative feedback loop to a positive one to elicit cellular  reprogramming to the neuronal lineage. Overall design: Examination of PTB regulated  AGO2/microRNA targeting in Hela cells by CLIP-seq (two biological replicates) , paired-end RNA-seq (control and PTB knockdown) and 3’end stability RNA-seq  (control and PTB knockdown)	Co-expression
SRP017413	Transcriptome profiling of primary uveal  melanomas	Uveal melanoma is the most common primary malignancy of the eye. By studying the expression of genes in primary uveal melanoma tumors we hope to gain an understanding of the underlying molecular biology. Expression analysis between uveal melanoma classes may make particularly important contributions to diagnosis and treatment decisions.	Co-expression
SRP017435	Genome-wide transcriptome profiling of SK-Mel-28, UACC-62 and HCT-116 cells stably expressing scrambled shRNA and RAB7 shRNA	Purpose: Asess the transcritpional changes induced upon RAB7 knock-down in melanoma (SK-Mel-28 and UACC-62) and in colon cancer (HCT-116) cell lines. Methods: mRNA profiles of tumor cell lines (SK-Mel-28, UACC-62, HCT-116) stably expressing scrambled shRNA or RAB7 shRNA (harvested at day 3 after lentiviral infection) were generated by deep sequencing, using three biological replicates per condition. The sequence reads that passed quality filters were analyzed with TopHat and Cufflinks. Validation of induced / silenced genes was performed by western blot. Results show a differential impact of RAB7 expression in the transcriptomic profile of melanoma vs non-melanoma cell lines, and support a lineage-specific role of this small GTPase in melanoma. Overall design: Examination of the mRNA profiles RAB7-depleted vs wild type cells, performed in parallel in 3 different tumor cell lines (Melanomas: SK-Mel-28 and UACC-62, Non-melanoma: HCT-116) harvested at day 3 after lentiviral infection.	Co-expression
SRP017465	RNA sequencing results	RNA sequencing data for human cell lines.	Co-expression
SRP017575	Two New Stromal Signatures Stratify Breast Cancers with Different Prognosis	Purpose:  Multiple studies from last decades have shown that the microenvironment of carcinomas plays an important role in the initiation, progression and metastasis of cancer.  Our group has previously identified novel cancer stroma gene expression signatures associated with outcome differences in breast cancer by gene expression profiling of two tumors of fibroblasts as surrogates for physiologic stromal expression patterns.  The aim of this study is to find additional new types of tumor stroma gene expression patterns. Results:  53 tumors were sequenced by 3SEQ with an average of 29 million reads per sample.  Both the elastofibroma (EF) and fibroma of tendon sheath (FOTS) gene signatures demonstrated robust outcome results for survival in the four breast cancer datasets.  The EF signature positive breast cancers (20-33% of the cohort) demonstrated significantly better outcome for survival.  In contrast, the FOTS signature positive breast cancers (11-35% of the cohort) had a worse outcome.  The combined stromal signatures of EF, FOTS, and our previously identified DTF, and CSF1 signatures characterize, in part, the stromal expression profile for the tumor microenvironment for between 74%-90% of all breast cancers. Conclusions:  We defined and validated two new stromal signatures in breast cancer (EF and FOTS), which are significantly associated with prognosis. Overall design: Gene expression profiling by 3SEQ was performed on 8 additional types of fibrous tumors, to identify different fibrous tumor specific gene expression signatures.  We then determined the significance of the fibrous tumor gene signatures in four publically available breast cancer datasets (GSE1456, GSE4922, GSE3494, NKI Dataset).	Co-expression
SRP017580	The effect of nicotinamide on dysregulated genes associated with frataxin deficiency in FRDA.	To investigate the efficacy of nicotinamide treatment using our ex-vivo primary lymphocyte model, we performed high-throughput RNA sequencing on libraries generated from untreated and nicotinamide treated samples. Overall design: PBMC isolated from FRDA affected individuals were cultured to prepare the primary lymphocyte cell lines. The primary cultured cells were either treated with 10mM nicotinamide or without the addition of drug during the 3-days treatment. RNA was extracted after the treatment and then RNA-seq libraries were generated by standard protocols.	Co-expression
SRP017583	Transcriptome landscape of the human placenta	The placenta is a key component in understanding the physiological processes involved in pregnancy. Characterizing genes critical for placental function can serve as a basis for identifying mechanisms underlying both normal and pathologic pregnancies. Detailing the placental tissue transcriptome could provide a valuable resource for genomic studies related to placental disease. We have conducted a deep RNA sequencing (RNA-Seq) study on three tissue components (amnion, chorion, and decidua) of 5 human placentas from normal term pregnancies. Our data demonstrate unique aspects of gene expression and splicing in placental tissues that provide a basis for disease investigation related to disruption of these mechanisms.	Co-expression
SRP017670	Next Generation Sequencing Facilitates Quantitative Analysis of CNE1-mock, CNE1-BART1, CNE-BART3, CNE1-BART7 cells	By using  NGS-derived retinal transcriptome profiling (RNA-seq) to compare the gene expression profiling between 4 differently treated NPC cells Overall design: Examination of different gene expression in EBV-miRNA-BART1/3/7 lentivirus and their control infected nasopharyngeal carcinoma cells.	Co-expression
SRP017684	RNA-Seq analysis of neurons derived from induced pluripotent stem cells reprogrammed from dental pulp	In this study, we investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs). Overall design: Comparison of expression profiles of iPSC derived from dental pulp and skin-fibroblast	Co-expression
SRP017699	Small RNA analysis of ADAR1-knock down HeLa cells by RNAi	Small RNA expression was analysed in total RNA of HeLa cells treated with siRNA toward Luciferase (negative cotrol) or ADAR1. Overall design: Small RNA: 2 samples examined: HeLa cell with siLuc (negative cotrol), with siADAR1	Co-expression
SRP017777	Identification of in vivo, conserved, TAF15 RNA binding sites and the impact of TAF15 on the neuronal transcriptome	TAF15, an RNA binding protein was recently implicated in Amyotrophic Lateral Sclerosis (ALS). ALS is a fatal neurodegenerative disease. We report the identification of  the conserved neuronal RNA targets of TAF15 and the assessment of the impact of TAF15 depletion on the neuronal transcriptome. Our study uncovers regulation of splicing of sets of neuronal RNAs encoding proteins with essential roles in synaptic activities including glutamergic receptors such as zeta-1 subunit of the glutamate N-methyl-D-aspartate (NMDA) receptor (Grin1). Overall design: Identification of TAF15 neuronal targets using normal human brain samples and mouse neurons.  Mouse background: E14Tg2a.4 wildtype cells derived from 129P2/OlaHsd.	Co-expression
SRP017788	Polysome-associated mRNA profiling of cancer cells in response to CXCL12 and IGF1	CXCL12 and IGF1 are key secreting molecules produced by cancer-associated fibroblasts in breast cancer. These factors promote the survival of disseminated cancer cells in the bone marrow. To assess the combined responses elicited by CXCL12 and IGF1, we examined the translating transcriptome of cancer cells in response to these two factors by Translating Ribosome Affinity Purification (TRAP)-RNAseq. Overall design: MDA-MB-231 cells were engineered to express an EGFP-tagged version of ribosomal protein L10a. This allows the retrieval of polysome-associated mRNA by anti-GFP pull down (TRAP) and profiling the translating transcriptome by RNAseq. EGFP-L10a+ cancer cells were serum starved (0.2% serum) for 24 hours, and then treated with CXCL12 (30ng/mL) + IGF1 (10ng/mL) or CXCL12 (300ng/mL) + IGF1 (100ng/mL) for 6hrs. Two biological replicates were profiled for each condition.	Co-expression
SRP017789	Translating transcriptome of cancer cells in situ in mesenchymal-rich tumor microenvironment	A mesenchymal rich stroma such as cancer-associated fibroblasts (CAFs) in breast tumors favors the selection of cancer clones with enhanced bone metastatic ability. To determine the cancer cell transcriptomic response to the mesenchymal stroma, we supplemented experimental mammary tumours with or without exogenous mesenchymal cells. We used bone marrow-derived human mesenchymal stem cells (MSCs) as a source of mesenchymal stroma, as MSCs have been shown to undergo CAF-like differentiation. We engineered the cancer cells to express an EGFP-tagged version of ribosomal protein L10a (EGFP-L10a). This allows the retrieval of cancer cell specific transcripts rapidly from whole tumor lysates by translating ribosome affinity purification (TRAP) and direct profiling of cancer cell gene expression patterns when they are in situ. Overall design: EGFP-10a+ MDA-MB-231 cells were orthotopically injected into the mammary fat pad with or without 1:1 ratio of MSCs. The mammary tumors were retrieved for TRAP-RNAseq profiling after 3 weeks.	Co-expression
SRP017809	Small RNA-seq of undiseased human brain	The surprising observation that virtually the entire human genome is transcribed means we know very little about the function of many emerging classes of RNAs, except their astounding diversity. Traditional RNA function prediction methods rely on sequence or alignment information, which are limited in their ability to classify classes of non-coding RNAs (ncRNAs). To address this, we developed CoRAL, a machine learning-based approach for classification of RNA molecules. CoRAL uses biologically interpretable features including fragment length, cleavage specificity, and antisense transcription to distinguish between different ncRNA classes. We evaluated CoRAL using genome-wide small RNA sequencing (smRNA-seq) datasets from two human tissue types (brain and skin [GSE31037]), and were able to classify six different types of RNA transcripts with 79~80% accuracy in cross-validation experiments, and with 71~73% accuracy when CoRAL uses one tissue type for training and the other as validation. Analysis by CoRAL revealed that long intergenic ncRNAs, small cytoplasmic RNAs, and small nuclear RNAs show more tissue specificity, while microRNAs, small nucleolar, and transposon-derived RNAs are highly discernible and consistent across the two tissue types. The ability to consistently annotate loci across tissue types demonstrates the potential of CoRAL to characterize ncRNAs using smRNA-seq data in less characterized organisms. Overall design: Four samples were sequenced, each one coming from frozen brain tissue (frontal cortex) of a deceased female human patient with no remarkable pathology.	Co-expression
SRP017843	Transcriptional profiles of PA1 teratoma cells transfected by RIPK1, RIPK2, RIPK3, or RIPK4	RIPK4 but not the related kinases RIPK1, RIPK2, and RIPK3 caused similar transcriptional changes to Wnt3a. Overall design: PA1 cells were transfected by 8ug RIPK1, RIPK2, RIPK3, or RIPK4 for 48h, RNA were extracted and sequenced.	Co-expression
SRP017933	Regional Differences in gene expression and promoter usage in aged human brains	Cap analysis of gene expression (CAGE) and massive parallel sequencing were used to profile the promoterome of aged human brains from five regions, namely: caudate, frontal cortex, hippocampus, putamen and temporal cortex. Overall design: 25 RNA  libraries from post-mortem brain tissue (five caudate, five frontal, 5 hippocampus, 5 putamen, five temporal RNA libraries from seven individuals) were processed using CAGE protocol and CAGE tags derived from the 25 libraries were sequenced with Illumina.	Co-expression
SRP017942	Widespread regulation of translation by elongation pausing in heat shock	RNA-seq and ribosome footprinting libraries of mouse 3T3 and human 293T cellsrelated to Shalgi et al.  2013 Overall design: 36bases paired-end RNA-seq, and ribosome footprinting libraries for: 3T3 cells - Control, 8 hours of mild heat shock (42) and 2 hours of severe heat shock (44) - in replicates, as well as 3T3 cells treated by mild followed by severe heat shock. In addition, 3T3 cells treated with Hsp70 inhibitor VER-155008 (Massey et al. 2010), and 293T cells transfected with Hspa1a or GFP, before and after 2 hours of severe heat shock.	Co-expression
SRP017959	The evolution of lncRNA repertoires and expression patterns in tetrapods	Only a minuscule fraction of long non-coding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but comparative analyses have been precluded by our ignorance of lncRNAs in non-model organisms. Here, we use RNA sequencing to identify lncRNAs in eleven tetrapod species and we present the first large-scale evolutionary study of lncRNA repertoires and expression patterns. We identify ~11,000 primate- specific lncRNA families, which show evidence for selective constraint during recent evolution, and ~2,400 highly conserved lncRNAs (including ~400 genes that likely originated more than 300 million years ago). We find that lncRNAs, in particular ancient ones, are generally actively regulated and may predominantly function in embryonic development. lncRNA X-inactivation patterns reveal an extremely female-biased monotreme-specific lncRNA, which may partially compensate X-dosage in this lineage. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but global patterns like tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network, which surprisingly contains many lncRNA hubs, suggests potential functions for lncRNAs in fundamental processes like spermatogenesis or synaptic transmission, but also in more specific mechanisms such as placenta growth suppression through miRNA production. Overall design: [Batch 1 and 2] To broaden our understanding of lncRNA evolution, we used an extensive RNA-seq dataset to establish lncRNA repertoires and homologous gene families in 11 tetrapod species. We analyzed the poly- adenylated transcriptomes of 8 organs (cortex/whole brain without cerebellum, cerebellum, heart, kidney, liver, placenta, ovary and testis) and 11 species (human, chimpanzee, bonobo, gorilla, orangutan, macaque, mouse, opossum, platypus, chicken and the frog Xenopus tropicalis), which shared a common ancestor ~370 millions of years (MY) ago. Our dataset included 47 strand-specific samples, which allowed us to confirm the orientation of gene predictions and to address the evolution of sense-antisense transcripts. See also GSE43721 (Soumillon et al, Cell Reports, 2013) for three strand-specific samples for mouse brain, liver and testis.	Co-expression
SRP017972	Heterokaryon RNA Sequencing	We report the application of bi-species RNAseq for investigating mechanisms of reprogramming towards pluripotency using heterokaryons (mouse embryonic stem cell X human fibroblast cell fusions). The use of mixed species allows one to monitor reprogramming of the human somatic nuclei independently of contributions from the mouse nuclei using nucleotide differences. We used RNAseq to monitor heterokaryon reprogramming over a 3-day timecourse, generating transcriptome-wide data for cell fusion based reprogramming of human fibroblasts towards pluripotency. Overall design: Examination of cellular reprogramming over a heterokaryon timecourse (mouse embryonic stem cells X human fibroblasts)	Co-expression
SRP017979	Small RNA Solexa sequencing of colorectal tumor and adjancent normal tissues	A pair of stage III colorectal cancer (CRC) tumor and adjacent normal tissue were collected from a patient without Transcatheter Arterial Infusion chemotherapy (TAI) during surgical resection of CRC tumors. Another pair of stage III CRC tumor and adjancent normal tissue were collected from another patient who had been treated with TAI one week before surgical resection. Total RNA of the collected tissues were extracted using TRIzol reagent (Invitrogen) according to the manufacturer''s instructions. The integrity of the RNA was checked with an ultraviolet spectrophotometry and 2100 BioAnalyzer (Agilent Technologies, Santa Clara, CA, USA). Construction of small RNA libraries from size fractionated RNA was carried out by following Solexa protocol and the obtained libraries were sequenced by Illumina HiSeq 2000 sequencer. We identified some de-regulated miRNAs in CRC tumor tissues. The expression levels of miR-142-5p were significantly reduced in tumor tissues of stage III CRC, then were increased significantly in tumor tissues receiving TAI and higher than tumor tissues without TAI. miR-142-5p is a potential tumor suppressor in CRC and is upregulated in tumor tissues after TAI, suggesting its potential clinical values for testing the functionality of TAI and predicting progress of CRC. Overall design: Examination of small RNA transcriptomes in colorectal tumor and adjancent normal tissues without and with Transcatheter Arterial Infusion chemotherapy using Illumina HiSeq2000 sequencer.	Co-expression
SRP018008	Homo sapiens Transcriptome or Gene expression	We sequenced the RNA of 42 bladder cancer patients.	Co-expression
SRP018010	DNA topoisomerase I and antisense transcription	DNA Topoisomerase I (Top1) relaxes DNA supercoiling and is inhibited with high specificity by camptothecin, a natural product of chinese tree Camptotheca acuminata with anticancer activity. Topoisomerase activity is required at transcribing regions to modulate DNA supercoils generated by RNA polymerases. However, Top1 functions at promoters and molecular responses to CPT are not fully understood. We found that camptothecin increases antisense RNA polymerase II transcripts at active divergent CpG-island promoters in a replication-independent manner. Kinetics investigations of the formation of Top1-DNA cleavage complexes and non-B DNA structures showed that CPT interferes with Top1 modulation of negative DNA supercoiling at promoters. The present findings will be a resource to establish the role of such antisense RNAs in transcription regulation and to discover additional components of the response pathway. Moreover, the transcriptional camptothecin effects can be the molecular basis of the therapeutic activity in cancer as well as neurological syndromes.	Co-expression
SRP018020	Evaluation of the effectiveness of semen collection and sperm purification methods for spermatozoa transcript profiling	RNA-Seq technique was applied to investigate the effects of two semen collection methods (Pelleted vs Liquefied) and two sperm purification methods (SCLB vs PS) to the integrity of isolated RNAs at different perspectives. Overall design: The same set of semen samples were applied to investigate the qualitative and quantitative effect of semen collection methods and sperm cell purification methods on sperm transcript profiling.	Co-expression
SRP018022	GLI1 function in Ewing sarcoma	Gene regulation by GLI1 in Ewing sarcoma.	Co-expression
SRP018104	Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing	Background: In recent years, a variety of small RNAs derived from other RNAs with well-known functions such as tRNAs and snoRNAs, have been identified. The functional relevance of these RNAs is largely unknown. To gain insight into the complexity of snoRNA processing and the functional relevance of snoRNA-derived small RNAs, we sequenced long and short RNAs, small RNAs that co-precipitate with the Argonaute 2 protein and RNA fragments obtained in photoreactive nucleotide-enhanced crosslinking and immunoprecipitation (PAR-CLIP) of core snoRNA-associated proteins. Results: Analysis of these data sets revealed that many loci in the human genome reproducibly give rise to C/D box-like snoRNAs, whose expression and evolutionary conservation are typically less pronounced relative to the snoRNAs that are currently catalogued. We further found that virtually all C/D box snoRNAs are specifically processed inside the regions of terminal complementarity, retaining in the mature form only 4-5 nucleotides upstream of the C box and 2-5 nucleotides downstream of the D box. Sequencing of the total and Argonaute 2-associated populations of small RNAs revealed that despite their cellular abundance, C/D box-derived small RNAs are not efficiently incorporated into the Ago2 protein. Conclusions: We conclude that the human genome encodes a large number of snoRNAs that are processed along the canonical pathway and expressed at relatively low levels. Generation of snoRNA-derived processing products with alternative, particularly miRNA-like, functions appears to be uncommon. Overall design: PAR-CLIP profiling for snoRNP core proteins NOP56, NOP58, Fibrillarin, and Dyskerin in HEK293 cells. Small RNA profiling using RNA-seq in HEK293 and HeLa cells, small RNA profiling using IP-seq of Ago2 associated small RNAs.	Co-expression
SRP018218	Vitamin d receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy	The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) has been attributed to intrinsic resistance to chemotherapy and a growth-permissive tumor microenvironment.  Quiescent pancreatic stellate cells (PSCs) are neuroendocrine, nestin-positive, lipid-accumulating cells whose homologues in the liver are the principal repository of Vitamin A esters.  Upon activation, lipid droplets are lost and via transdifferentiation they become the key cell type responsible for driving the severe desmoplasia that characterizes PDA.  Despite their critical role in PDA progression and chemoresistance, therapeutic strategies targeting PSCs are lacking.  Here we identified the vitamin D receptor (VDR) as a master genomic regulator of PSC activation and function.  In vitro we demonstrate that VDR activation reduces expression in PSCs of genes implicated in activation, inflammation, and extracellular matrix production, as well as restoring lipid droplet integrity. In vivo, the VDR ligand calcipotriol enhances the anti-tumor effects of gemcitabine by increasing intratumoral concentration 5-fold, reducing tumor volume to near baseline and lowering metastases by more than 65%.  These findings implicate VDR as a master regulator of PSC activation and identify a novel therapeutic approach for the treatment of pancreatic cancer. Overall design: RNA-Seq analyses was used to characterize cancer-associated changes between pre-activated (3-day culture) and activated (7-day culture) primary mouse PSCs, as well as control and PDA human PSCs.  RNA-Seq was also used to assess the impact of VDR activation (DMSO vs calcipotriol) in a human PSC line (MiaPaCa-2), the mouse primary PSCs	Co-expression
SRP018221	RNA-sequencing (RNA-seq) in breast cancer cell lines after ectopic manipulation of miR-26a expression	RNA sequencing technology has been carried out in order to evaluate mRNA expression changes after manipulation of miR-26a in both MCF-7 and MDA-MB-231 breast cancer cell lines. Overall design: To evaluate the entire set of genes modulated by miR-26a in breast cancer, we performed RNA-seq after ectopic manipulation of this miRNA. We over-expressed miR-26a in MCF-7 epithelial cancer cell lines and also reduced its activity by stably transfecting MDA-MB-231 mesenchymal-like cancer cell lines with a specific sponge vector. GO terms and pathway enriched analysis of the transcripts that significantly change upon miR-26 ectopic manipulation implicates miR-26ab in cell cycle, apoptosis, cell spreading and cell adhesion in breast cancer	Co-expression
SRP018234	Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor [RNA-Seq]	Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF.  In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone.  This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity. Overall design: Examination of PR target genes in human umbilical vein endothelial cells (HUVECs) using RNA-seq (PR infected only -PR only and PR infected followed by ligand treatment-PR+P)	Co-expression
SRP018242	Enrichment of processed pseudogene transcripts in L1-ribonucleoprotein particles	We explored the RNA binding properties of LINE-1 ORF1p, both free and in the L1 RNP, using a recently developed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation technique (PAR-CLIP) to comprehensively identify ORF1p binding sites in the transcriptome of human cells (HEK293T). Our results show that ORF1p binds to a wide range of cellular mRNAs, with an enrichment for binding at the 3’ UTR. Our data also show that ORF1p binds very strongly with retrotransposable RNA, i.e., L1, Alu and SVA. Overall design: PAR-CLIP analysis of L1 RNPs and free ORF1p RNA binding profiles, comparison to HuR RNA binding profile	Co-expression
SRP018254	A Stable Transcription Factor Complex Nucleated by Dimeric AML1-ETO Controls Leukaemogenesis	AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukemia, is a transcription factor implicated in both gene repression and activation. We now show that, in leukemic cells, AML1-ETO resides in and functions through a stable protein complex (AETFC) that contains several hematopoietic transcription factors and cofactors. In conjunction with biochemical and leukemia pathological studies, the ChIP-seq and RNA-seq analyses of the AETFC components in leukemic cells reveal that these components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, colocalize genome-wide, cooperatively regulate gene expression, and contribute to leukemogenesis. Overall design: RNA-seq analyses gene expression upon knockdown of each AETFC component, including AML1-ETO, HEB, E2A, LYL1, LDB1 and LMO2, and double-knockdown of HEB and E2A, in Kasumi-1 cells. ChIP-seq analyses of four AETFC components, namely AML1-ETO, HEB, E2A and LMO2, in Kasumi-1 cells.	Co-expression
SRP018256	Enhancer Transcripts Mark Active Estrogen Receptor Binding Sites	In this study, we used Global Run-On sequencing (GRO-seq), a method that assays the genome-wide location and orientation of all active RNA polymerases. We generated a global profile of active transcription at ERa binding sites in MCF-7 human breast cancer cells in response to short time course of E2 treatment. This method enabled us to detect active transcription at enhancers and define a class of primary transcripts transcribed uni- or bidirectionally from the ERa binding sites. The raw data used in this study is from GSE27463 but sequenced to a greater depth. Overall design: Using GRO-seq over a time course (0, 10, 40 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.	Co-expression
SRP018284	Identification of differentially expressed small RNAs of colon cancer stem cells.	Colorectal carcinoma (CRC) is one of the most common cancers worldwide. Re-evaluating our current knowledge on CRC and developing novel therapeutic strategies is still crucial. Accumulating evidence suggests that cancer cells possess characters reminiscent of those of normal stem cells. Unveiling small RNAs responsible for cell stemness and chemoradioresistance should eventually lead to the development of novel therapeutic approaches. Overall design: Expression profiles of parental CRC cells and cancer spheres expanded under stem cell medium cultivation were generated for identifying key regulators.	Co-expression
SRP018312	RNA-Sequencing Analysis of High Glucose Treated Monocytes Reveals Novel Transcriptome Signatures and associated Epigenetic Profiles	We report high throughput transcriptomic profiling with RNA-Sequencing (RNA-Seq) to uncover network responses in human THP-1 monocytes treated with high glucose (HG). Overall design: Examination of differential expression between normal and high glucose condition in THP1 cells.	Co-expression
SRP018317	AGO-PAR-CLIP of DG75 and BCBL-1	AGO-PAR-CLIP was employed to identify microRNA binding sites in BCBL-1, a Kaposi's sarcoma-associated herpesvirus (KSHV) infected B-cell line and DG75, a KSHV negative B-cell line as a control. By using our novel computational method (PARma) and differential analysis of PAR-CLIP data, highly accurate target sites of KSHV microRNAs can be defined. Overall design: Examination of microRNA target sites in two different cell lines using replicate PAR-CLIP experiments	Co-expression
SRP018359	Transcriptome analysis of human sinusoidal endothelial cells, hepatocyte	We report the transcriptome human primary hepatocytes and liver sinusoidal endothelial cells. Hepatocytes were obtained from commercial sources.  LSECs were isolated based on the coexpression of Tie2 and CD32b, te strategy of purification controlled by RNA-Seq. Overall design: Comparison of the expression of the Tie-2, CD32b, SELP, FVIII, VWF, Alb, Fg, F7genes	Co-expression
SRP018377	The Estrogen receptor alpha regulated NEAT1 long non-coding RNA promotes prostate cancer progression [RNA-Seq]	Prostate glands predominantly exhibit androgen dependence, but increasing evidence suggests that estrogen receptor signaling is involved in its development and pathogenesis. By integrating ChIP sequencing for estrogen receptor alpha (ERa) with transcriptome sequencing data from prostate cancer samples, we found ERa to significantly influence the noncoding transcriptome in prostate cancer. We identified one such long noncoding RNA, NEAT1, to play an important role in prostate cancer progression through direct regulation of transcription of its target genes. NEAT1, in an ERa dependent manner, promotes prostate tumorigenesis by interacting with and modulating chromatin state at promoters of prostate cancer specific signature genes. NEAT1 expression is positively correlated with PSMA in prostate adenocarcinoma and with B3GAT1 in neuroendocrine prostate cancer. This study identifies NEAT1 as a novel biomarker or therapeutic target in prostate cancer and also suggests that co-targeting ERa and androgen receptor (AR) may be effective for a subset of patients with advanced prostate cancer and with NEAT1 overexpression. mRNA profiles of MEF cell lines prepared from E13.5 embryos of wild-type (WT) and NEAT1 knockout (KO; NEAT1-/-) mice  were generated by deep sequencing, using Illumina HiSeq 2000. Strand specific mRNA profiles of VCaP and VCaP ERa cell lines were generated by deep sequencing, using Illumina GA IIx. Overall design: RNA sequencing of MEF (WT vs NEAT1 KO) and VCaP (control vs ERa)	Co-expression
SRP018552	Probing the off-target effect of EGFP siRNA and pro-siRNA in the HeLa-d1EGFP cell line	We have develped a novel method of making siRNAs (named pro-siRNA for prokaryotic siRNA). To evaluate off-targeting of pro-siRNA, we compared the mRNA expression profiles of HeLa-d1EGFP cells transfected with 4 nM EGFP siRNAs and pro-siRNAs by microarray. Overall design: We used microarray to study the off-target effect of siRNAs in the HeLa-d1EGFP cell line. After transfection of siRNAs for 24 hrs, RNA were extracted using Trizol. Deep sequencing libraries were generated using the NEBNext Ultra RNA Library Prep Kit for Illumina (NEB #E7530). HeLa-d1EGFP cells are HeLa cells stably expressing d1EGFP gene. EGFP siRNA is a siRNA made by chemical synthesis. EGFP100 and EGFPFL are pro-siRNAs made from either a 100 bp hairpin or a full length hairpin targeting EGFP coding sequence.	Co-expression
SRP018716	Remodeling of Ago2-mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates (part 1)	When adapting to environmental stress, cells attenuate and reprogram their translational output.  In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs.  The Ago2/microRNA machinery has been shown to participate in stress-induced translational upregulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking.  Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by CLIP-seq.  Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3` UTR and CDS sites exhibiting stronger interaction.  Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction.  To compare the changes in Ago2 binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA-seq.  Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated.  Taken together, these data point to a role for Ago2 and the mammalian microRNAs in mediating the translational component of the stress response. Overall design: In this sub-series, CLIP and RNAseq data from the arsenite treatment experiment are presented.  Experiments on 293S cells +/- arsenite treatment, in 4 biological replicates.  On each treatment/replicate biological sample, both a CLIP-seq protocol and an RNA-seq protocol were performed, so these datasets are “paired” in addition to the treatment pairing.	Co-expression
SRP018717	Remodeling of Ago2-mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates (part 2)	When adapting to environmental stress, cells attenuate and reprogram their translational output.  In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs.  The Ago2/microRNA machinery has been shown to participate in stress-induced translational upregulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking.  Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by CLIP-seq.  Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3` UTR and CDS sites exhibiting stronger interaction.  Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction.  To compare the changes in Ago2 binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA-seq.  Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated.  Taken together, these data point to a role for Ago2 and the mammalian microRNAs in mediating the translational component of the stress response. Overall design: In this sub-series, CLIP and RNAseq data from the emetine treatment experiment are presented.  Experiments on 293S cells +/- emetine treatment, in 1 biological replicate.  Here, for each treatment/replicate sample, an aliquot was used for RNA-seq, and the rest was split into three aliquots to perform 3 parallel CLIP-seq protocols with different antibodies.  So, each RNA-seq dataset here corresponds to 3 CLIP-seq datasets.	Co-expression
SRP018718	Remodeling of Ago2-mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates (part 3)	When adapting to environmental stress, cells attenuate and reprogram their translational output.  In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs.  The Ago2/microRNA machinery has been shown to participate in stress-induced translational upregulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking.  Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by CLIP-seq.  Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3` UTR and CDS sites exhibiting stronger interaction.  Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction.  To compare the changes in Ago2 binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA-seq.  Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated.  Taken together, these data point to a role for Ago2 and the mammalian microRNAs in mediating the translational component of the stress response. Overall design: In this sub-series, CLIP and RNAseq data from the hippuristanol treatment experiment are presented.  Experiments on 293S cells +/- hippuristanol treatment, in 2 biological replicates.  Here, for each treatment/replicate sample, an aliquot was used for RNA-seq, and the rest was split into three aliquots to perform 3 parallel CLIP-seq protocols with different antibodies.  So, each RNA-seq dataset here corresponds to 3 CLIP-seq datasets.	Co-expression
SRP018719	Remodeling of Ago2-mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates (part 4)	When adapting to environmental stress, cells attenuate and reprogram their translational output.  In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs.  The Ago2/microRNA machinery has been shown to participate in stress-induced translational upregulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking.  Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by CLIP-seq.  Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3` UTR and CDS sites exhibiting stronger interaction.  Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction.  To compare the changes in Ago2 binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA-seq.  Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated.  Taken together, these data point to a role for Ago2 and the mammalian microRNAs in mediating the translational component of the stress response. Overall design: In this sub-series, RNAseq data from sucrose gradient fractions with arsenite treatment are presented.	Co-expression
SRP018723	NSun2-mediated cytosine-5 methylation in Vault non-coding RNA determines its processing into small RNAs [iCLIP]	Autosomal-recessive loss of the NSUN2 gene has been recently identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNA). Whether NSun2 methylates additional RNA species is currently debated. Here, we adapted the individual-nucleotide resolution UV cross-linking and immunoprecipitation method (iCLIP) to identify NSun2-mediated methylation in RNA transcriptome. We confirm site-specific methylation in tRNA and identify messenger and non-coding RNAs as potential methylation targets for NSun2. Using RNA bisulfite sequencing we establish Vault non-coding RNAs as novel substrates for NSun2 and identified six cytosine-5 methylated sites. Furthermore, we show that loss of cytosine-5 methylation in Vault RNAs causes aberrant processing into argonaute-associating small RNA fragments (svRNA). Thus, impaired Vault non-coding RNA processing may be an important contributor to the etiology of NSUN2-deficieny human disorders. Overall design: Identification of Nsun2 targets by miCLIP in Embryonic kidney (HEK293) cells	Co-expression
SRP018779	Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap	Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including “vascular disease,” “disorder of artery,” and “occlusion of artery” as well as disease-related cellular functions including “cellular movement,” and “cellular growth and proliferation.” In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall. Overall design: RNA-Seq: 3 versus 3 technical replicates, siControl versus siTCF21	Co-expression
SRP018786	NSun2-mediated cytosine-5 methylation in Vault non-coding RNA determines its processing into small RNAs [RNA-seq]	Autosomal-recessive loss of the NSUN2 gene has been recently identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNA). Whether NSun2 methylates additional RNA species is currently debated. Here, we adapted the individual-nucleotide resolution UV cross-linking and immunoprecipitation method (iCLIP) to identify NSun2-mediated methylation in RNA transcriptome. We confirm site-specific methylation in tRNA and identify messenger and non-coding RNAs as potential methylation targets for NSun2. Using RNA bisulfite sequencing we establish Vault non-coding RNAs as novel substrates for NSun2 and identified six cytosine-5 methylated sites. Furthermore, we show that loss of cytosine-5 methylation in Vault RNAs causes aberrant processing into argonaute-associating small RNA fragments (svRNA). Thus, impaired Vault non-coding RNA processing may be an important contributor to the etiology of NSUN2-deficieny human disorders. Overall design: mRNA-seq in Embryonic kidney (HEK293) cells transfected with siRNA against Nsun2 vs control	Co-expression
SRP018815	RNA helicase A is necessary for KIF1Bß tumor suppression in neuroblastoma	During development neuronal progenitors compete for growth factors such as nerve growth factor NGF and require the prolyl hydroxylase EglN3 and the kinesin KIF1Bß for developmental apoptosis. Inherited KIF1Bß loss-of-function mutations in neuroblastomas and pheochromocytomas implicate KIF1Bß as a 1p36.2 tumor suppressor, however the mechanism of tumor suppression is unknown. We found that KIF1Bß interacts with the RNA helicase A (DHX9) resulting in DHX9 nuclear accumulation to regulate apoptosis. KIF1Bß-dependent DHX9 nuclear localization leads to transcription of the apoptotic target XIAP-associated factor 1. DHX9 is induced when NGF is limiting and required for apoptosis in cells deprived of NGF. Overall design: NB1 cells were transduced to incorporate shRNA against DHX9 or a scrambled control, and transfected with a KIF1Bß expression vector or control, then transfected cells were isolated and lysed after 48h.	Co-expression
SRP018836	Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition [RNA-Seq]	Human LIN28A and B are RNA-binding proteins (RBPs) conserved in animals with important roles during development and stem cell reprogramming. We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HEK293 cells and identified a largely overlapping set of ~3,000 mRNAs at ~9,500 sites located in the 3’UTR and CDS. In vitro and in vivo, LIN28 preferentially bound single-stranded RNA containing a uridine-rich element and one or more flanking guanosines, and appeared to be able to disrupt base-pairing to access these elements when embedded in predicted secondary structure. In HEK293 cells, LIN28 protein binding mildly stabilized target mRNAs and increased protein abundance. The top targets were its own mRNAs and those of other RBPs and cell-cycle regulators. Alteration of LIN28 protein levels also negatively regulated the abundance of some, but not all let-7 miRNA family members, indicating sequence-specific binding of let-7 precursors to LIN28 proteins and competition with cytoplasmic miRNA biogenesis factors. Overall design: To assess whether miRNAs are regulated by LIN28B we analyzed the miRNA levels of LIN28B overexpressing and LIN28B-depleted cells using small RNA cDNA library sequencing. The RBP LIN28B was depleted by siRNAs and the expression levels was compared to mock-transfected HEK293 cells.	Co-expression
SRP018837	Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition [PAR-CLIP]	Human LIN28A and B are RNA-binding proteins (RBPs) conserved in animals with important roles during development and stem cell reprogramming. We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HEK293 cells and identified a largely overlapping set of ~3,000 mRNAs at ~9,500 sites located in the 3’UTR and CDS. In vitro and in vivo, LIN28 preferentially bound single-stranded RNA containing a uridine-rich element and one or more flanking guanosines, and appeared to be able to disrupt base-pairing to access these elements when embedded in predicted secondary structure. In HEK293 cells, LIN28 protein binding mildly stabilized target mRNAs and increased protein abundance. The top targets were its own mRNAs and those of other RBPs and cell-cycle regulators. Alteration of LIN28 protein levels also negatively regulated the abundance of some, but not all let-7 miRNA family members, indicating sequence-specific binding of let-7 precursors to LIN28 proteins and competition with cytoplasmic miRNA biogenesis factors. Overall design: LIN28 protein PAR-CLIP	Co-expression
SRP018838	Single Cell RNA-Seq	RNA-seq transcriptome measurements are typically performed by isolating RNA from large numbers of cells in culture or tissues. While highly informative, such experiments mask the variability in gene expression patterns that exists between individual cells. To gain insight into the dynamics of gene expression on the level of single-cells, we have carried out the transcriptomes of single-cells from the GM12878 cell line using RNA-seq. Overall design: Single GM12878 cells were picked and RNA-seq libraries were generated using the SMART-seq protocol. We also carried out RNA-seq experiments on pools of 10, 30 and 100 cells, on 100pg and 10ng of total RNA, and on pools of 10 cells that were subsequently split into 10 separate sample and processed as if they were single cells in order to assess technical variation in our experiments.	Co-expression
SRP018853	Altered microRNA expression in individuals at high risk of type 1 diabetes	Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic insulin-producing ß cells. CD4+ T cells are integral to the pathogenesis of T1D, but biomarkers that define their pathogenic status in T1D are lacking. miRNAs have essential functions in a wide range of tissues/organs, including the immune system. We reasoned that CD4+ T cells from individuals at high risk for T1D (pre-T1D) might be distinguished by an miRNA signature. We sorted CD4+ T cells from 9 healthy and 7 pre-T1D individuals into 6 subsets, namely naïve, resting regulatory (rTreg), activated regulatory (aTreg), transitional memory (Ttm), central memory (Tcm) and effector memory (Tem) cells, and then compared miRNA profiles between these subsets and between pre-T1D and healthy individuals by deep sequencing. Differential expression of miRNAs was detected in each of the CD4+ T cell subsets. For example, expression of miRNAs that induce apoptosis (miR-15a) or FOXP3 instability (miR-31) was increased in rTreg and aTreg cells, respectively, in pre-T1D individuals, whereas miR-150 was increased in Tem cells of pre-T1D individuals. Importantly, increased miR-150 expression could be detected by qRT-PCR in total CD4+ T and PBMCs of pre-T1D individuals. Consistent with it being a marker of pathogenic CD4+ T cells, we showed that miR-150 regulates IFN-? production in mouse CD4+ T cells. Thus, comprehensive profiling identifies miRNA profiles that not only distinguish CD4+ T cell subsets but also discriminate individuals with preclinical T1D. The ability to detect differentially expressed miRNAs in total CD4+ T cells or PBMCs should facilitate clinical application of miRNAs as biomarkers. Overall design: CD4+T cells from healthy and individuals at high risk for autoimmune type 1 diabetes were sorted into 6 subsets, which resulted in 80 samples, 38 for healthy and 42 for high risk individuals. Each sample was barcoded and miRNA libraries were constructed and subsequently subjected to deep-sequencing on the Illumina GAII or HiSeq platform. The Fastq files are have deconvoluted and stripped of the barcode adaptor sequences.	Co-expression
SRP018883	Multiple roles for Grainyheadlike transcription factors in the establishment and maintenance of human mucociliary airway epithelium	The airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ basal cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis, differentiation, remodeling and repair. However, little is known about their function in the adult lung. Here, we focus on the role of GRHL2 in primary human bronchial epithelial (HBE) cells, using either shRNA or a dominant negative protein (DN-GRHL2) to inhibit its function. We follow changes in epithelial phenotype, and in gene transcription using RNA-seq or microarray analysis, both in undifferentiated basal cells and in cells differentiating in air-liquid interface culture into a mucociliary epithelium with transepithelial electrical resistance. We identify several hundreds of genes that are directly or indirectly regulated by GRHL2. Using ChIP-seq to map sites of GRHL2 binding in the basal cells we identify 7,687 potential primary targets, and confirm that GRHL2 binding is strongly enriched near GRHL-regulated genes. Different subsets of the large cohort of potential GRHL2 targets appear to be active in basal and differentiated cells. Taken together, the results strongly support the hypothesis that GRHL2 plays a key role in regulating many physiological functions of human airway epithelium, including those involving cell adhesion, polarity and morphogenesis. Overall design: Frozen primary human bronchial epithelial (HBE) cells were obtained from three donors. Passage 2 cells at 40% confluence were infected with H2B-GFP or DN-GRHL2 lentivirus and 1 mg/ml puromycin added 48 h later. At confluence, Doxycycline 0.5 mg/ml was added for 24 h. RNA-seq was performed on all six samples, as well as samples from two donors that were not infected.	Co-expression
SRP019207	Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types (RNA-seq)	We report the design and implementation of a "breakpoint analysis" pipeline to discover novel gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes.  We use this method to prioritize candidate rearrangements from high density array CGH datasets as well as exon-resolution expression microarrays.  We mine both publicly available data as well as datasets generated in our laboratory.  Several gene fusion candidates were chosen for further characterization, and corresponding samples were profiled using paired end RNA sequencing to discover the identity of the gene fusion.  Using this approach, we report the discovery and characterization of novel gene fusions spanning multiple cancer subtypes including angiosarcoma, pancreatic cancer, anaplastic astrocytoma, melanoma, breast cancer, and T-cell acute lymphoblastic leukemia.  Taken together, this study provides a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. Overall design: Breakpoint analysis for the discovery of novel gene fusions across human cancers	Co-expression
SRP019222	Epstein-Barr virus maintains lymphomas via its miRNAs	Epstein-Barr virus (EBV) has evolved exquisite controls over its host cells, human B lymphocytes, not only directing these cells during latency to proliferate and thereby expand the pool of infected cells, but also to survive and thereby persist for the lifetime of the infected individual.  Although these activities ensure the virus is successful, they also make the virus oncogenic, particularly when infected people are immunosuppressed. Here we show, strikingly, that one set of EBV’s miRNAs both sustain BL (Burkitt’s lymphoma) cells in the absence of other viral oncogenes and promote the transformation of primary B lymphocytes.  Burkitt’s Lymphoma cells were engineered to lose EBV and found to die by apoptosis and could be rescued by constitutively expressing viral miRNAs in them.  Two of these EBV miRNAs were found to target Caspase 3 to inhibit apoptosis at physiological concentrations. Overall design: Examination of RISC associated transcripts under 4 conditions in Sav S1-1 cells	Co-expression
SRP019241	LncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression	Long non-coding RNAs (lncRNAs) regulate diverse biological processes including cell lineage specification. Here we report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allowed the identification of hundreds of lncRNAs exhibiting differentiation stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an endoderm-specific lncRNA DEANR1 (Definitive Endoderm Associated long Non-coding RNA1) and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating endoderm factor FOXA2 expression. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by helping SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation stage-specific lncRNAs, but also characterizes a novel lncRNA important for endoderm differentiation. Overall design: Here we perform RNA-seq based transcriptome profiling using undifferentiated human ESCs (one sample), definitive endoderm (two replicates), pancreatic progenitors(three replicates) as well as sorted human primary alpha cells (two replicates), beta cells (two replicates) and exocrine cells (one sample). Moreover, we perform RNA-seq based transcriptome profiling for WT, FOXA2 knockdown, and DEANR1 knockdown of differentiated definitive endoderm samples (two replicates for each).	Co-expression
SRP019248	Interleukin-27 treated human macrophages induce the expression of novel miRNAs which may mediate anti-viral properties (RNA-seq)	In this study, we hypothesized that IL-27 could induce the expression of novel miRNAs in macrophages which may have functional relevance in terms of anti-viral activity. In this study, primary monocytes were differentiated into macrophages using M-CSF (M-Mac) or with a combination of M-CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted from these cells and deep sequencing was performed, in parallel with gene expression microarrays. Using the novel miRNA discovery software, miRDeep, seven novel miRNAs were discovered in the macrophages, four of which were expressed higher in I-Mac (miRNAs 2.1, 8.1, 9.1 and 14.2) whilst three were detected in both M-Mac and I-Mac (miRNAs 9.3, 13.6 and 15.8). The expression of six of the seven novel miRNAs was highly correlated with qRT-PCR using specific primer/probes designed for the novel miRNAs. Gene expression microarray further demonstrated that a number of genes were potentially targeted by these differentially expressed novel miRNAs. Overall design: screening novel and known miRNAs which may have antiviral properties in 2 different treatments in 2 donors.	Co-expression
SRP019250	Global analysis of alternative splicing regulated by RBM10	RBM10 is an RNA binding protein that was identified as a component of spliceosome complex, suggesting its potential role in splicing regulation. However, the direct experimental evidence for this function has been lacking. Here we characterized in vivo RBM10-RNA interactions and investigated the role of RBM10 in splicing regulation at the global level. We observed significant RBM10-RNA interactions in the vicinity of splice sites and identified hundreds of splicing changes following perturbation of cellular RBM10 abundance. A RNA splicing map integrating the binding pattern and splicing profiles revealed a significant correlation between RBM10-enhanced exon skipping events and its binding close to the splicing sites of both upstream and downstream introns. Furthermore, we demonstrated the splicing defects in a patient carrying a RBM10 mutation. Overall, our data provided insights into the mechanistic model of RBM10-mediated splicing regulation and established genomic resources for future studies on its function  in different pathophysiological contexts. Overall design: We sequenced the mRNA of HEK293 cells and LCL cells, and we determined the RBM10 binding sites using PARCLIP in HEK293 cells. In total we sequenced four mRNA-Seq libraries for KD and two for OE in HEK293 cells; for each of these libraries, we also sequenced one control library. We also sequenced the mRNA of one patient LCL and two normal LCL libraries. Two replicates of PARCLIP sequencing were perfomed.	Co-expression
SRP019270	Trans-chromosomal regulation by a novel lincRNA required for adipogenesis that escapes X-chromosome inactivation	Long noncoding RNAs (lncRNAs) have emerged as an important layer of genome regulation with common mechanistic themes including the formation of ribonucleoprotein complexes. Here, we present a novel X-linked lncRNA termed linc-Firre that escapes X-chromosome inactivation and forms trans-chromosomal interactions required for adipogenesis. Linc-Firre is exclusively nuclear and forms punctate expression foci on chromatin near its site of transcription on both X-chromosomes in human and mouse. Both the localization of linc-Firre and the association with the nuclear matrix protein hnRNPU require a conserved repeating RNA domain, R2D2. Collectively, these results reveal a lincRNA that escapes X-chromosome inactivation with a critical role in driving cell fate decisions by trans-chromosomal interactions. Overall design: Replicate RNA-Seq analyses of oligo-mediated knockdowns of linc-FIRRE and hnRNPU in two different cellular contexts; HeLa cells and mouse embryonic stem cells.  Also included are Firre knockout and wild-type mouse embryonic stem cells.	Co-expression
SRP019272	Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits	The genetics of messenger RNA expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to microRNA (miRNA) expression. We examined natural variation of miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for metabolic syndrome phenotypes as part of the METSIM study. We genotyped the subjects using high-density SNP microarrays and quantified the mRNA abundance using genome-wide expression arrays and miRNA abundance using next generation sequencing. We reliably quantified 356 miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed miRNAs. We mapped the miRNA abundance as an expression quantitative trait and determined cis regulation of expression for 9 of the miRNAs and of the processing of one miRNA (miR-28). The degree of genetic variation of miRNA expression was substantially less than that of mRNAs. For the majority of the miRNAs, genetic regulation of expression was independent of the host mRNA transcript expression. We also showed that for 108 miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24 miRNAs to be significantly associated with metabolic syndrome traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit ACACB, a key fatty acid oxidation enzyme that has been shown to play a role in regulating body fat and insulin resistance in adipose tissue. Overall design: miRNA expression profiling of adipose tissue isolated from 200 humans	Co-expression
SRP019275	Mutational activation of a mechanosensitive megachannel drives metastatic cell survival.	Next-generation sequencing has revolutionized cancer biology by accelerating the unbiased discovery of novel mutations across human cancers. Transforming such discoveries into a conceptual framework of cancer progression requires narrowing the vast number of mutations down to the driver elements, and further reducing these to mutations that govern cancer progression as opposed to tumor initiation. By integrating next-generation RNA-sequencing (RNA-seq) with in vivo selection, we devise an approach that identifies a series of novel recurrent non-synonymous amino acid mutations that are enriched in metastatic breast cancer cells and predicted to significantly alter protein function. These mutations, found in PANX1, RBFA, REST, KRIT1 and ZSWIM6, are detected at higher frequencies in the transcriptomes of two patients’ highly metastatic sub-lines relative to their poorly metastatic parental lines. We functionally characterize the cellular and molecular roles of one of these mutations—a nonsense alteration that yields a truncated pannexin-1 (PANX11-89) plasma membrane megachannel subunit—in metastatic progression. PANX11-89 interacts with full-length PANX1 and augments PANX1 channel activity to promote the survival of cancer cells as they are mechanically deformed. Protection from deformation-induced cell death requires PANX1 channels to release ATP, which acts as a cell autonomous survival signal during mechanical stress. Functional characterization of additional nonsense and missense PANX1 mutations detected in epithelial cancers of the colon, lung, and prostate reveals that these mutants also enhance PANX1-mediated ATP release. In vivo testing of one such truncating mutation detected in a metastatic colorectal tumor also enhances early survival, dissemination and liver metastatic colonization by human colon cancer cells. Finally, pharmacological inhibition of PANX1 inhibits breast cancer metastasis, implicating PANX1 as a novel therapeutic target in cancer. Our findings reveal that ATP release through mechanosensitive PANX1 channels enables cancer cells to overcome a major metastasis suppressive barrier—deformation-induced death in the microvasculature. Overall design: To systematically identify base-pair mutations present in metastatic cells that may drive cancer progression, we performed whole-transcriptome RNA-sequencing (RNA-seq) of in vivo-selected, highly metastatic human breast cancer cell sub-lines, CN-LM1A and MDA-LM2, as well as the CN34 and MDA-MB-231 parental lines from which they were derived. To minimize the false positive rate and allow for subsequent statistical analysis, we sequenced biological replicates of each cell line. Mutations conferring enhanced metastatic capacity should be enriched in the transcriptomes of highly metastatic cells relative to their less metastatic parental populations.	Co-expression
SRP019374	RNA-seq expression analysis to determine expression profile similarities between fibroblasts, induced endothelial cells from fibroblasts, and human dermal microvascular endothelial cells	The goal of this study was to determine the similarity between human dermal microvascular endothelial cells, induced endothelial cells from fibroblasts, and fibroblasts through RNA-seq expression analysis.  RNA samples from independently induced cultures, plus fibroblast and human dermal microvascular endothelial cultures were converted into individual cDNA libraries using Illumina TruSeq methods and subjected to single-end 50 base-sequence analysis at 20-30 million read depths. Overall design: Examination of one fibroblast culture, one human dermal mibrovascular endothelial cell culture, and two induced endothelial cell cultures.	Co-expression
SRP019498	Amplitude modulation of androgen signaling by c-MYC [RNA-Seq]	Androgen-stimulated growth of the molecular apocrine breast cancer is mediated by an androgen receptor (AR)-regulated transcriptional program.  Through profiling the genomic licalizations of AR and its co-regulators FOXA1 and TCF7L2 in MDA-MB-453 breast cancer cells, we revealed the molecular details of the AR-centered regulatory network. We further identified that  c-MYC is a key downstream target co-regulated by AR, FOXA1 and TCF7L2, and reinforces the transctiopnal activation of androgen-responsive genes in this subtype of breast cancers. Overall design: MDA-MB-453 breast cancer cells were transfected with control of MYC siRNA for 48 h, followed by treatment with 10nM DHT or vehicle for 6 h. The cells were subjected to mRNA purification and library praparation for RNA-seq on Illumina HiSeq2000 platform.	Co-expression
SRP019503	Homo sapiens Transcriptome or Gene expression	VCaP Xenografts in mice.	Co-expression
SRP019758	RNA-seq analysis of HT-29, MCF10A, and MDA-MB-436 cells	RNA-seq data from HT-29 cells treated with IFN-? for 24 hr, MCF10A cells, and MDA-MB-436 cells. Overall design: mRNA profiles of HT-29, MCF10A, and MDA-MB-436 were generated by deep sequencing using Illumina HiSeq 2000. All RNA sequencing data was generated by the Genomics Services Lab at the HudsonAlpha Institute for Biotechnology (Huntsville, AL).	Co-expression
SRP019762	Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans	While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence. Overall design: 14 human and 6 chimpanzee samples were sequenced.	Co-expression
SRP019807	Identification of expressed and conserved human non-coding RNAs	Methods: RNA profiles of 12 tissues were generated by deep sequencing using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. Results: This work has focused on identification of non-coding RNAs expressed in human tissues. We have identified a set of non-coding RNAs that are both expressed and conserved, as described in the manuscript accompagnying this work. Overall design: total RNA profiles of 12 normal human tissues, no replicates.	Co-expression
SRP019810	Genome-wide total RNA and MBD-sequencing in HCT116 and DKO cells as a global re-expression model [RNA-Seq]	Genome-wide view of the interplay between methylation and RNA expression in this colorectal cancer model was obtained. Overall design: RNA-sequencing of HCT116 cell line, the DNMT1 and DNMT3B double knock-out HCT116 cell line (DKO), and 7 additional colorectal cell lines.	Co-expression
SRP019817	Genome-wide methylation and expression analysis of two breast cancer cell lines [RNA-Seq]	To improve our understanding of the relationships between methylation and expression we profiled mRNA expression and single-base resolution methylation levels for two breast cancer cell lines, MCF7 and T47D. Expression was profiled using RNA-seq.  Methylation was assayed using Methyl-MAPS, which uses methylation-sensitive and -dependent restriction enzyme digests followed by high-throughput sequencing to identify methylation levels at individual CpGs (Edwards et al. 2010, Genome Research). Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7 and T47D cells under standard growth conditions.	Co-expression
SRP019936	An Integrated Model of the Transcriptome Landscape of HER2-Positive Breast Cancer	The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. Overall design: We analyzed RNA-seq data from a survey panel consisting of 8 benign breast lesions, 8 ER+, 8 triple negative, and 8 HER2-positive primary breast tumors to identify genomic features that were uniquely associated with HER2-positive tumors	Co-expression
SRP019939	Using RNA-Seq to create sample-specific proteomic databases that enable mass spectrometric discovery of splice junction peptides	Many new alternative splice forms have been detected at the transcript level using next generation sequencing (NGS) methods, especially RNA-Seq, but it is not known how many of these transcripts are being translated.  Leveraging the unprecedented capabilities of NGS, we collected RNA-Seq and proteomics data from the same cell population (Jurkat cells) and created a bioinformatics pipeline that builds customized databases for the discovery of novel splice-junction peptides. Results: Eighty million paired-end Illumina reads and ~500,000 tandem mass spectra were used to identify 12,873 transcripts (19,320 including isoforms) and 6,810 proteins. We developed a bioinformatics workflow to retrieve high-confidence, novel splice junction sequences from the RNA data, translate these sequences into the analogous polypeptide sequence, and create a customized splice junction database for MS searching. Overall design: Jurkat T-cell mRNA was analyzed on an Illumina HiSeq2000.  ~80 million paired end reads (2x200bp, ~350bp lengths) were collected.	Co-expression
SRP019946	SFMBT1 Functions with LSD1 to Regulate Expression of Canonical Histone Genes and Chromatin-Related Factors [RNA-Seq]	SFMBT1 is a poorly characterized mammalian MBT domain-containing protein homologous to Drosophila SFMBT, a Polycomb group protein involved in epigenetic regulation of gene expression. Here, we show that SFMBT1 regulates transcription in somatic cells and during spermatogenesis through the formation of a stable complex with LSD1 and CoREST.  When bound to its gene targets, SFMBT1 recruits its associated proteins and causes chromatin compaction and transcriptional repression.  SFMBT1, LSD1, and CoREST share a large fraction of target genes including those encoding replication-dependent histones.  Simultaneous occupancy of histone genes by SFMBT1, LSD1, and CoREST is regulated during the cell cycle and correlates with the loss of RNA polymerase II at these promoters during G2, M, and G1. The interplay between the repressive SFMBT1–LSD1–CoREST complex and RNA polymerase II contributes to the timely transcriptional regulation of histone genes in human cells. SFMBT1, LSD1, and CoREST also form a stable complex in germ cells and their chromatin binding activity is regulated during spermatogenesis. Overall design: RNA-seq in HeLaS3 cells ctrl compared to triple knockdown for SFMBT1, CoREST, and LSD1	Co-expression
SRP019961	Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity; implications for possible immune adjuvant therapy	Our goal of this study was to perform quantitative and global assessment of EBV gene expression in gastric carcinomas and assess EBV associated cellular pathway alterations. Overall design: Examination of a gastric carcinoma cell line naturally infected with EBV, SNU-719 using poly-A and ribodepletion RNA-seq data sets	Co-expression
SRP019968	Homo sapiens Transcriptome or Gene expression	RNA sequencing data for four cell lines representing different stages during malignant transformation.	Co-expression
SRP019989	Muscleblind-like proteins regulate embryonic stem cell-specific alternative splicing and reprogramming II	Previous investigations of the core gene regulatory circuitry that controls embryonic stem cell (ESC) pluripotency have largely focused on the roles of transcription, chromatin and non- coding RNA regulators. Alternative splicing (AS) represents a widely acting mode of gene regulation, yet its role in the regulation of ESC pluripotency and differentiation is poorly understood. Here, we identify the Muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of AS events that are differentially regulated between ESCs and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ESC-like AS pattern for at least half of these AS events. Among the events is an ESC-specific AS switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells (iPSCs) during somatic cell reprogramming. Overall design: mRNA profiles of various embryonic stem cells, tissues and cell lines from human and mouse using high-throughput sequencing data and the role of MBNL proteins in regulation of ESC-differential alternative splicing	Co-expression
SRP019990	miRNAs associated with the different human Argonaute proteins	microRNAs (miRNAs) are small non-coding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3’ untranslated region (UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer-independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected. Overall design: Examination of miRNAs associated with endogenous human Ago1-4 in HeLa cells	Co-expression
SRP019994	Stratification of Leiomyosarcoma molecular subtypes by 3'' end RNA-sequencing: Toward precision medicine	Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation.  Little is known about its molecular heterogeneity and no targeted therapy currently exists for LMS.  We demonstrate the existence of 3 molecular subtypes in a cohort of 99 cases and an independent cohort of 82 LMS.  Two new FFPE tissue-compatible diagnostic immunohistochemical markers are identified: LMOD1 for subtype I LMS and ARL4C for subtype II LMS. Subtype I and subtype II LMS are associated with good and poor prognosis, respectively.  The LMS subtypes show significant differences in expression levels for genes for which novel targeted therapies are being developed. Overall design: Gene expression profiling was performed by 3'' End RNA Sequencing (3SEQ), a next generation sequencing approach that does not rely on frozen tissue but can be performed on archival FFPE tissue. Samples included 99 LMS, 6 Undifferentiated Pleomorphic Sarcomas (UPS), 3 leiomyomas, 4 normal myometrium samples, and 1 case of Lymphangioleiomyomatosis (LAM). This study only includes the 99 LMS Samples. After gene expression levels were quantified by 3SEQ analysis pipeline, Consensus Clustering with bootstrap method was used to determine that the dataset contained three robust subtypes, and Silhouette analysis was performed to validate the subtype assignments. Two class SAM analysis (Significance Analysis of Microarrays) was performed to identify genes expressed differentially between each subtype of LMS with FDR of 0.05. Immunohistochemical staining was used to validate the potential diagnostic and prognostic markers from 3SEQ data on a tissue microarray.	Co-expression
SRP020470	RNA-sequencing of the human milk fat layer during colostrum, transitional, and mature stages of lactation	Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA sequencing technology to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. We find that transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during the same postpartum time frame could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (105-fold) in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding ß-casein (CSN2) and a-lactalbumin (LALBA), make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, PTPRF may serve as a biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data set to enable future targeted research on the physiological contributors to sub-optimal lactation in humans. Overall design: Milk fat mRNA profiles were generated from Day 2 and mature milk samples obtained from lactating mothers	Co-expression
SRP020486	Characterization of human plasma-derived exosomal RNAs	Exosomes, endosome-derived membrane microvesicles, contain a specific set of RNA transcripts that are involved in cell-cell communication and hold a great potential as disease biomarkers. To systemically characterize exosomal RNA profiles, we performed RNA sequencing analysis using three human plasma samples and evaluated efficacies of small RNA library preparation protocols from 3 manufacturers. Overall design: We tested the six samples (A1 and A2, B1 and B2, C1 and C2) using two small RNA library preparation kits: NEBNext Multiplex Small RNA library Prep Set from New England Biolab (NEB) and NEXTflex Small RNA Sequencing Kit from Bioo Scientific (BS). We also tested Illumina’s TrueSeq Small RNA Sample Preparation Kit (ILMN) in sample A1 and A2. Together, we tested these plasma samples by sequencing 14 indexed libraries. This study allowed direct comparison of current small RNA library preparation protocols and identified the most suitable strategy for future exosomal RNA sequencing analysis.	Co-expression
SRP020491	Changes in gene expression profiles of circulating B cells after influenza vaccination in healthy human subjects	Daily sampling of peripheral blood from human subjects vaccinated for influenza was done immediately before vaccination and for 10 days after vaccination. In B cells, 90% of transcriptomic variation in subjects who received influenza vaccine within the previous three years was explained by a single temporal pattern unique to the individual. A common set of 742 genes was strongly correlated with the migration of differentiating plasma cell subtypes. Overall design: Five subjects, 11 time points per subject (pre-vaccination and daily for 10 days post-vaccination)	Co-expression
SRP020492	Changes in PBMC gene expression profiles after influenza vaccination in healthy human subjects	Daily sampling of peripheral blood from human subjects vaccinated for influenza was done immediately before vaccination and for 10 days after vaccination. Temporal patterns of gene expression, determined by RNA-seq, in unfractionated PBMC suggested migration of myeloid/dendritic cell lineage cells one day after vaccination. Overall design: Five subjects, 11 time points per subject (pre-vaccination and daily for 10 days post-vaccination)	Co-expression
SRP020493	Gene expression analysis of breast cancer cell-lines	Recurrent mutations in histone modifying enzymes in multiple cancer types imply key roles in tumorigenesis. However, the functional relevance of these mutations remains unknown. Here we show that the JARID1B histone H3 lysine 4 demethylase is frequently amplified and overexpressed in luminal breast tumors and a somatic point mutation of JARID1B leads to the gain of luminal-specific gene expression programs. Downregulation of JARID1B in luminal breast cancer cells induces the expression of basal cell-specific genes and growth arrest, which is partially rescued by the inhibition of TGFBR thereby indicating a key role for TGFb signaling. Integrated genome-wide analysis of JARID1B chromatin binding, histone H3 lysine trimethyl (H3K4me3) and dimethyl (H3K4me2) patterns, and gene expression profiles in luminal and basal-like breast cancer cells suggest a key role for JARID1B in luminal cell-specific gene expression programs. A significant fraction of JARID1B binding-sites overlaps with CTCF in both luminal and basal-like breast cancer cells. CTCF also co-immunoprecipitates with JARID1B and it may influence its histone demethylase (HDM) activity as the H3K4me3/me2 ratio is lower at the CTCF-overlapping compared to JARID1B-unique sites. Additionally, a heterozygous JARID1B missense mutation (K1435R) in the HCC2157 basal-like breast cancer cell line is associated with unique JARID1B chromatin-binding and gene expression patterns implying gain of luminal features. In line with this, exogenous expression of this mutant in basal-like breast cancer cells leads to a gain of JARID1B binding at many luminal-specific genes. A PARADIGM score reflecting JARID1B activity in luminal breast cancer cells is associated with poor clinical outcome in patients with luminal breast tumors. Together, our data imply that JARID1B is a luminal lineage-driving oncogene and that its therapeutic targeting may represent a novel therapeutic strategy in treatment-resistant luminal breast tumors. Overall design: RNA-Seq in breast cancer cell-lines transfected with JARID1B/CTCF/control siRNA. 50 cycles of sequencing on Illumina platform.	Co-expression
SRP020499	Chromatin architecture of the NF-kB/RelA regulatory network	RNA-Seq of TNFa time course in human A549 cancer cell line.	Co-expression
SRP020544	Transcriptome-profiling (RNA-seq) and Ribosome-profiling (Ribo-seq) of BJ cells treated with Nutlin-3a, an MDM2 inhibitor, which induces p53.	We applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells in which p53 was induced by Nutlin-3a Overall design: RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs Ribosome profiling was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs	Co-expression
SRP020556	Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo	We present an approach for globally monitoring RNA structure in native conditions in vivo with single nucleotide precision. This method is based on in vivo modification with dimethyl sulfate (DMS), which reacts with unpaired adenine and cytosine residues9, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known mRNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome10. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast reveals that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding, thermodynamics play an incomplete role in determining mRNA structure in vivo. We use Dimethyl Sulfate to probe the structure of rRNA and mRNA in yeast in vivo, in vitro, and at different temperatures in vitro. We obtain a great agreement between in vivo data and known mRNA structures as well as the ribosome crystal structure. We find that in contrast  to ribosomal rna, mRNAs are less structured in vivo than in vitro, and the structures present in vivo can only partially be explained by thermodynamic stability. In addition, we identify new regulatory structures present in vivo. Overall design: Examination of RNA structure in yeast under different conditions - in vivo and in vitro at five different temperatures (30,45,60,75,95) We adapt our DMS-seq assay for use in mammalian cells and probe RNA structure genome-wide in K562 cells. We probe the RNA structure of primary fibroblast using DMS on a genome-wide scale to confirm the presence of more structures in vitro. In addition we probe the RNA structure in yeast upon ATP depleted conditions to investigate whether active (ATP-dependent) processed are modulating RNA structure in vivo.	Co-expression
SRP020646	Retroelements and DUX4 Create Primate-specific Promoters for Germline Genes	The human double-homeodomain retrogene DUX4 is normally expressed at high levels in germ cells of the testis. When aberrantly expressed in muscle its protein product causes facioscapulohumeral muscular dystrophy (FSHD), perhaps partly by inducing inappropriate expression of germline genes. DUX4 can bind >60,000 locations in the human genome that contain a strongly enriched sequence motif. Numerous long terminal repeat (LTR) class repetitive elements are enriched among DUX4 binding sites, including many from the mammalian apparent LTR-retrotransposon (MaLR) family as well as some ERVL and ERVK types, with MaLRs comprising ~1/3 of DUX4’s binding sites. We performed RNA-seq on myoblasts over-expressing DUX4 and find that DUX4 binding activates transcription of some but not all bound repeat types. Some of these activated repetitive elements comprise novel promoters for genes, long non-coding RNAs and antisense transcripts. We show that some of these chimeric repeat-initiated transcripts are expressed in testis and FSHD patient myotubes. The acquisition of MaLR-LTR elements during mammalian evolution may therefore have allowed rewiring of the transcriptional network. We also find that the pericentromeric satellite HSATII can be bound by DUX4 and that its transcription is massively induced by DUX4 over-expression. Our findings suggest a role for repetitive element transcripts in muscle disease and in the biology of normal testis. Overall design: RNA-seq of two myoblast cell lines transduced with lentivirus carrying DUX4, and two control myoblast lines	Co-expression
SRP020661	Apparently Balanced Chromosomal Rearrangements (BCRs) as a model for random mutagenesis in humans	Transcribed regions in adult temporal lobe, hippocampus and frontal lobe were assesed by strand specific next generation sequencing of polyA RNA. Overall design: Strand specific mRNA expression profiles of three human adult brain regions were generated by next generation sequencing using Illumina GAIIx	Co-expression
SRP021048	Homo sapiens whole pancreatic islet mRNA during culture in alternate media	Two islet preparations (from different donors) were subjected to RNA-sequencing. Within each preparation, subsets of islets were treated with 5 or 8 mM glucose, or 8 mM glucose in a specialized, conditioned medium containing Wnt and R-spondin ligands with Rho and ROCK inhibitors (L-WRN+) for 48 h immediately after initial receipt and hand-selection. L-WRN+ promotes proliferation with undue de-differentiation. Polyadenylated mRNA was obtained from 1 mcg of human islet total RNA and 50 nt, single-end sequencing reads were obtained from an Illumina HiSeq 2500.	Co-expression
SRP021085	RNAseq of PRMT4KD in human cord blood derived CD34+ cells	Defining the role of epigenetic regulators in normal hematopoiesis has become critically important, as recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We have found that PRMT4, a type I arginine methyltransferase, whose function in normal and malignant hematopoiesis is unknown, is overexpressed in AML patient samples. In support of an oncogenic role for PRMT4, we find that its overexpression blocks the myeloid differentiation of human stem/progenitor cells (HSPCs) while its knockdown (KD) is sufficient to induce myeloid differentiation of HSPCs and multiple AML cell lines. Although classically thought of as a co-activator, we found that PRMT4 functions to repress the expression of miR-223 in HSPCs via the methylation of RUNX1, which triggers the assembly of a multi-protein repressor complex that includes DPF2. As part of a feedback loop, PRMT4 expression is repressed post-transcriptionally by miR-223 during the normal differentiation process. These data reveal an unidentified role of PRMT4 in myeloid differentiation and its unexpected repressive role in transcriptional regulation. Furthermore, depletion of PRMT4 results in the differentiation of myeloid leukemia cells in vitro and their decrease proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia. Overall design: Purified human primary CD34+ cells were transduced with lentiviruses carrying PRMT4KD or scramble control shRNAs. Total RNA was extrated. RNAseq was performed to identify target genes that are regulated by PRMT4. Experiments were performed in triplicate.	Co-expression
SRP021130	A Study of Small RNAs from Cerebral Neocortex of Pathology-Verified Alzheimer’s Disease, Dementia with Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, and Non-Demented Human Controls	MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent ND subtypes. All cases had short postmortem intervals, relatively high-quality RNA, and state-of-the-art neuropathological diagnoses. The resulting data (over 113 million reads in total, averaging 5.6 million reads per sample) and secondary expression analyses constitute an unprecedented look into the human cerebral cortical miRNome at single nucleotide resolution. While we find no apparent changes in isomiR or miRNA editing patterns in correlation with ND pathology, our results validate and extend previous miRNA profiling studies with regard to quantitative changes in NDs. In agreement with this idea, we provide independent cohort validation for changes in miR-132 expression levels in AD (n = 8) and FTLD (n = 14) cases when compared to controls (n = 8). The identification of common and ND-specific putative novel brain miRNAs and/or short-hairpin molecules is also presented. The challenge now is to better understand the impact of these and other alterations on neuronal gene expression networks and neuropathologies. Overall design: Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent ND subtypes.	Co-expression
SRP021193	Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNA in Failing Human Heart and Remodeling with Mechanical Circulatory Support	Complete transcriptome profiling in human failing and non-failing control hearts using next-gen sequencing Overall design: Poly-A selected RNA and small RNA sequencing carried out in 5 groups of samples: NF, ICM, NICM, ICM+LVAD, NICM+LVAD	Co-expression
SRP021214	Widespread Transcription beyond mRNA 3' Ends Yields Abundant Regulatory RNAs	Through RNA-seq analyses of nascent transcripts, we found large numbers of RNA transcripts that extend beyond the 3' ends of protein-coding genes; we refer to these extended transcripts as geRNAs. These findings demonstrate that transcription of most human protein-coding genes does not terminate within close proximity to poly(A) signals; rather, it terminates at sites far beyond these signals (up to 50 kb). Overall design: Examination of different RNA species in HelaS3 cells by strand-specific RNA-seq. The 4sU-labeled RNA was isolated by using organomercurial affinity matrix.	Co-expression
SRP021221	Homo sapiens Transcriptome or Gene expression	No description.	Co-expression
SRP021459	Detection of small RNAs generated during early infection of human HEK 293 cells by the alphavirus Sindbis virus	A time course of infection of the alphavirus Sindbis virus (SINV) was used to investigate the presence of viral specific vsRNA and the changes in miRNAs profiles in human embryonic kidney 293 cells (HEK293) by high throughput DNA sequencing. Deep sequencing of small RNAs early in SINV infection (4 and 6 hpi) showed low abundance (0.8%) of viral specific RNAs (vsRNAs) , with a random uniform distribution not typical of Dicer products, suggesting they arise from non-specific degradation. Sequencing showed little variation of cellular microRNAs (miRNAs) at 4 and 6 hpi compared to uninfected cells. Twelve miRNAs exhibiting some minor differential expression by sequencing, showed insignificant modulation by Northern blot analysis. Overall design: RNA was isolated from mock infected and SINV inoculated HEK 293 cells at 4hpi and 6hpi cDNA libraries were generated for the small RNA (sRNA) content of the cells and sequenced using Illumina GA II, which yielded between 29.1M and 30.5M reads per sample	Co-expression
SRP021478	Evaluating the Impact of Sequencing Depth on Transcriptome Profiling in Human Adipose	Recent advances in RNA sequencing (RNA-Seq) have enabled the discovery of novel transcriptomic variations that are not possible with traditional microarray-based methods. Tissue and cell specific transcriptome changes during pathophysiological stress, in disease cases versus controls and in response to therapies are of particular interest to investigators studying cardiometabolic diseases. Thus, knowledge on the relationships between sequencing depth and detection of transcriptomic variation is needed for designing RNA-Seq experiments and for interpreting results of analyses. Using deeply sequenced RNA-Seq data derived from adipose of a healthy individual before and after systemic administration of endotoxin (LPS), we investigated the sequencing depths needed for studies of gene expression and alternative splicing (AS). We found that to detect expressed genes and AS events, ~100 million (M) filtered reads were needed. However, the requirement on sequencing depth for the detection of LPS modulated differential expression (DE) and differential alternative splicing (DAS) was much higher. To detect 80% of events, ~300M filtered reads were needed for DE analysis whereas at least 400M filtered reads were necessary for detecting DAS. Although the majority of expressed genes and AS events can be detected with modest sequencing depths (~100M filtered reads), the estimated gene expression levels and exon/intron inclusion levels were less accurate. We report the first study that evaluates the relationship between RNA-Seq depth and the ability to detect DE and DAS in human adipose. Our results suggest that a much higher sequencing depth is needed to reliably identify DAS events than for DE genes. Overall design: Random sampling the RNA-seq data in different depth for gene and alternative-splicing analysis	Co-expression
SRP021509	EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation	The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B-cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets in B-cells, and in human B-cell lymphomas. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GCB-type DLBCLs are mostly addicted to EZH2, regardless of mutation status, but not the more differentiated ABC-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. Overall design: RNA sequencing and H3K27me3 ChIP sequencing of human DLBCL cell lines and murine BCL1 cell line. RNA sequencing, H3K27me3 and H3K4me3 ChIP sequencing of B cells from de-identified human tonsills.	Co-expression
SRP021524	Human PA-1 cells treated with scrambled or specific ASOs	We describe the discovery of sno-lncRNAs, a class of nuclear-enriched intron-derived long noncoding RNAs (lncRNAs) that are processed on both ends by the snoRNA machinery. During exonucleolytic trimming, the sequences between the snoRNAs are not degraded, leading to the accumulation of lncRNAs flanked by snoRNA sequences but lacking 5'' caps and 3'' poly(A) tails. Such RNAs are widely expressed in cells and tissues and can be produced by either box C/D or box H/ACA snoRNAs. Importantly, the genomic region encoding one abundant class of sno-lncRNAs (15q11-q13) is specifically deleted in Prader-Willi Syndrome (PWS). The PWS region sno-lncRNAs do not colocalize with nucleoli or Cajal bodies, but rather accumulate near their sites of synthesis. These sno-lncRNAs associate strongly with Fox family splicing regulators and alter patterns of splicing. These results thus implicate a previously unannotated class of lncRNAs in the molecular pathogenesis of PWS. Overall design: We have used deep sequencing to explore the gene expression from poly(A)+ RNAs in embryonal carcinoma (EC) line PA-1 cells treated with scrambled or specific antisense oligodeoxynucleotides (ASOs).	Co-expression
SRP021908	Selective suppression of endothelial cytokine production by progesterone receptor [RNA-seq]	Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues Overall design: Examination of PR target genes in human umbilical vein endothelial cells (HUVECs) using RNA-seq PR infected only (PR); PR infected followed by ligand treatment (PR+P); PR infected followed by 4h LPS treatment (PR+LPs_4h); PR infected followed by 8h LPS treatment (PR+LPs_8h); PR infected followed by 4h LPS and progesterone treatment (PR+LPS+P_4h); PR infected followed by 8h LPS and progesterone treatment (PR+LPS+P_8h)	Co-expression
SRP021911	Small RNA sequencing of human preovulatory cumulus and mural granulosa cells	The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on miRNA level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Libraries of all 6 samples were sequenced twice, generating 2 technical replicates for each sample. Differential gene expression study was performed on the pooled results of technical replicates.	Co-expression
SRP021912	High-throughput RNA sequencing of human preovulatory cumulus and mural granulosa cells (mRNA)	The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. The current study determined the mRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Differential gene expression study was performed. The identified gene expression profile was also used for predicting targets for miRNAs that were also identified from the same samples (GSE46489).	Co-expression
SRP021917	RNA-sequencing analysis of 5'' capped RNAs identifies novel differentially expressed genes in sessile serrated colon polyps (SSPs)	RNA-sequencing of SSP RNA from patients with serrated polyposis syndrome identifies VSIG1 and MUC17 as potential diagnostic markers for SSPs Overall design: 5'' capped RNA from seven ascending SSPs, six patient matched uninvolved right colon and two normal right colon samples was used for RNA sequencing (15 samples total)	Co-expression
SRP021918	The permanent reduction of TIA proteins molds expression transcriptome in HeLa cells	This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1- and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenotypes. The data of differential expression were validated by using genome-wide microarrays and QPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Taken together, these results indicate that differential gene expression, alternative pre-mRNA isoforms, promoter usage and microRNA profiling contribute to define the molecular expression phenotypes implied in the progression of proliferative phenotypes associated to the absence of TIA proteins and prioritize candidates for future study. Overall design: Each library was run on one RNASeq Multiplex of 76 bp using sequencing from Illumina Genome Analyzer (GAIIx). Three samples were analyzed in this manner, taken from control, TIA1 and TIAR shRNA-depleted HeLa cells.	Co-expression
SRP021924	Whole transcriptome RNA-seq of undiseased human prefrontal cortex	We report the application of high-throughput RNA sequencing to the human prefrontal cortex. The brain dataset was obtained by sequencing total RNAs extracted from the dorsolateral prefrontal cortex of five deceased human patients with no apparent pathology, followed by depletion of ribosomal RNA to obtain all non-rRNA coding and non-coding RNAs in the human brain transcriptome. Overall design: Five samples were sequenced, four coming from frozen brain tissue (frontal cortex) of deceased female human patients with no remarkable pathology, and one from a male patient with no remarkable pathology.	Co-expression
SRP022025	A genome-wide map of transcription start sites specific for acute promyelocytic leukemia reveals deregulation of full-length transcripts	Transcription start sites are the focal points of transcriptional regulation, where information from regulatory elements is integrated to stabilize initiation of transcription. In humans, most genes have more than one transcription start site, and these often exhibit different tissue specificity, serving as distinct regulatory frameworks for the same gene.  Usage of such promoters can also result in differential gene function manifested on the protein level. Alternative promoter usage has been shown to be increased in several disease states, especially cancer.   In this study, we have applied the nanoCAGE method to create a genome-wide map of TSS usage in sorted leukemic blasts from acute myeloid leukemia patients, and corresponding normal controls.   We show that the nanoCAGE method can replace similar experiments made with microarrays in terms of expression, but also that it uniquely, allow for the identification of alternative promoter usage in cancer cells. We identify 2,162 putative promoters that are significantly differentially regulated between APL and controls. Interestingly, promoters whose usage is upregulated in APL have an increased propensity to be downstream alternative promoters, and conversely, the promoters producing the annotated longest gene variants are commonly downregulated in cancer. We show examples of genes with upregulated downstream promoters, and demonstrate protein domain loss that could contribute to leukemic induction and maintenance. In conclusion, we present the first genome wide promoterome study from rare purified human leukemic cells. Overall design: nanoCAGE-seq of human acute myeloid leukemia samples vs. normal hematopoietic counterparts, both in replicates	Co-expression
SRP022028	RNA-seq in neurons derived from iPSCs in controls and patients with schizophrenia and 22q11 del	Individuals with 22q11.2 Deletion Syndrome (22q11.2 DS) are a specific high-risk group for developing schizophrenia (SZ), schizoaffective disorder (SAD) and autism spectrum disorders (ASD). Several genes in the deleted region have been implicated in the development of SZ, e.g., PRODH and DGCR8. However, the mechanistic connection between these genes and the neuropsychiatric phenotype remains unclear. To elucidate the molecular consequences of 22q11.2 deletion in early neural development, we carried out RNA-seq analysis to investigate gene expression in differentiating human neurons derived from induced pluripotent stem cells (iPSCs) of 22q11.2 DS SZ and SAD patients. Eight cases (ten iPSC-neuron samples in total including duplicate clones) and seven controls (nine in total including duplicate clones) were subject to RNA sequencing. Using a systems level analysis, differentially expressed genes/gene-modules and pathway of interests were identified. We observed ~2-fold reduction in expression of almost all genes in the 22q11.2 region in SZ (37 genes reached p-value < 0.05, 36 of which reached a false discovery rate < 0.05). Outside of the deleted region, 745 genes showed significant differences in expression between SZ and control neurons (p<0.05). Function enrichment and network analysis of the differentially expressed genes uncovered converging evidence on abnormal expression in key functional pathways, such as apoptosis, cell cycle and survival, and MAPK signaling in the SZ and SAD samples. Overall design: Eight cases (ten iPSC-neuron samples in total including duplicate clones) and seven controls (nine in total including duplicate clones)	Co-expression
SRP022043	A blood based 12-miRNA signature of Alzheimer patients	We applied Next-Generation Sequencing (NGS) to miRNAs from blood samples of 48  AD (Alzheimer''s Disease) patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression level. Of these, 82 were higher and 58 lower abundant in samples from AD patients. We selected a panel of 12 miRNAs for a qRT-PCR analysis on a larger cohort of 202 samples including not only AD patients and healthy controls but also patients with other CNS illnesses: Multiple Sclerosis, Parkinson''s Disease, Major Depression, Bipolar Disorder, Schizophrenia, and Mild Cognitive Impairment, which is assumed to represent a transitional period before the development of AD. MiRNA target enrichment analysis of the selected 12 miRNAs indicated an involvement of miRNAs in nervous system development, neuron projection, neuron projection development, and neuron projection morphogenesis, respectively. Using this 12-miRNA signature we were able to differentiate between AD and controls with an accuracy of 93.3%, a specificity of 95.1%, and a sensitivity of 91.5%. The differentiation of AD from other neurological diseases was possible with accuracies between 73.8% and 77.8%. The differentiation of the other CNS disorders from controls yielded even higher accuracies. Overall design: Examination of the miRNA profile in blood samples of 48 AD patients and 22 controls	Co-expression
SRP022052	MicroRNA Target Site Identification by Integrating Sequence and Binding Information	High-throughput sequencing has opened numerous possibilities for the identification of regulatory RNA-binding events. Cross-linking and immunoprecipitation of Argonaute protein members can pinpoint microRNA target sites within tens of bases, but leaves the identity of the microRNA unresolved. A flexible computational framework that integrates sequence with cross-linking features reliably identifies the microRNA family involved in each binding event, considerably outperforms sequence-only approaches, and quantifies the prevalence of noncanonical binding modes. Overall design: Ago2 (Argonaute 2) PAR-CLIP and RNA deep sequencing of Epstein-Barr virus B95.8-infected Lymphoblastoid Cell Lines (LCLs)	Co-expression
SRP022054	High-throughput sequencing of matched colorectal normal, tumor and metastasis tissues and proof-of principal bioinformatics modeling of therapeutic consequences of miRNA applications	MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are so far hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We identified miRNA-1 as top candidate differentially expressed in tumor and metastasis. Furthermore, miRNA-1 was de-regulated in 16 additional tumor entities underscoring its central role in tumor pathogenesis. Functional analyses showed an additive effect of miRNA-1 with camptothecin treatment. We used a systems-biology simulation of cellular cancer models implemented in PyBios to investigate miRNA-1 function and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. Overall design: Examination of miRNA expression values by Illumina sequencing of matched benign, tumor and metastasis tissues of 8 colorectal cancer patients. For 4 of these patients all tissues have been resequenced to obtain mRNA expression values.	Co-expression
SRP022131	Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer	To understand epigenetic changes in the distal regulatory as well as proximal regions, we performed RNA-seq, MBD-seq, and H3K27ac ChIP-seq on gastric tissues and cell lines. Overall design: mRNA sequencing profiles of normal tissue (n), purified gastric cancer (sc), and cultured gastric cancer cell (dc) were generated by deep sequencing, in five samples from three patients (csc1, csc2, csc3) and two replicates (csc1_sc2, csc1_sc3), using Illumina GAIIx and HiSeq2000.	Co-expression
SRP022133	Identification of differentially expressed transcripts and pathways one week and six months following implant of left ventricular devices	A specific set of genes involved in regulating cellular immune response, antigen presentation, and T cell activation and survival were down-regulated 7 days after LVAD placement. 6 months following LVAD placement, the expression levels of these genes were significantly increased; yet importantly, remained significantly lower than age and sex-matched samples from healthy controls. Overall design: Examination of the effect of LVAD implant on peripheral blood transcriptome.  Blood was drawn before LVAD placement, 7 days post implant, and 180 days post implant.  RNA sequencing was performaed on all samples.	Co-expression
SRP022166	WTAP is a novel oncogenic protein in Acute Myeloid Leukemia	Acute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down	Co-expression
SRP022260	Expression data from 7 Human Melanomas	Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence, including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi. Overall design: We used RNA-Seq to detail the global programme of gene expression in human melanoma cell lines	Co-expression
SRP022361	ZEB2 function in Ewing sarcoma	A673 Ewing sarcoma cells were transfected with siRNAs targeting ZEB2 (siZEB2-5 and siZEB2-6) or a control siRNA (siControl) and RNAseq was performed to identify ZEB2 regulated genes in Ewing sarcoma.	Co-expression
SRP022591	Identification of LIN28-bound mRNAs reveals features of target recognition and regulation	The conserved human LIN28 RNA-binding proteins function in development, maintenance of pluripotency and oncogenesis. We used PAR-CLIP and a newly developed variant of this method, iDo-PAR-CLIP, to identify LIN28B targets as well as sites bound by the individual RNA binding domains of LIN28B in the human transcriptome at nucleotide resolution. The position of target binding sites reflected the known structural relative orientation of individual LIN28B binding domains, validating iDo-PAR-CLIP. Our data suggest that LIN28B directly interacts with most expressed mRNAs and members of the let-7 microRNA family. The Lin28 binding motif detected in pre-let-7 was enriched in mRNA sequences bound by LIN28B. Upon LIN28B knock down, cell proliferation and the cell cycle were strongly impaired. Quantitative shotgun proteomics of LIN28B depleted cells revealed significant reduction of protein synthesis from its RNA targets that function in translation, mRNA splicing and cell cycle control. Computational analyses provided evidence that the strength of protein synthesis reduction correlated with the location of LIN28B binding sites within target transcripts. Overall design: We used PAR-CLIP and a newly developed variant of this method, iDo-PAR-CLIP, to identify LIN28B targets as well as sites bound by the individual RNA binding domains of LIN28B in the human transcriptome at nucleotide resolution.	Co-expression
SRP022772	miR-146a-5p circuitry uncouples cell proliferation and migration, but not differentiation, in human mesenchymal stem cells	Administration of mesenchymal stem cells (MSCs) has the potential to ameliorate degenerative disorders and to repair damaged tissues. The homing of transplanted MSCs to injured sites is a critical property of engraftment. Our aim was to identify microRNAs involved in controlling MSC proliferation and migration. MSCs can be isolated from bone marrow and umbilical cord Wharton''s jelly (BM-MSCs and WJ-MSCs, respectively), and WJ-MSCs show poorer motility yet have a better amplification rate compared to BM-MSCs. Overall design: One human BM-MSC (pooled sample of 4 independent donors), one human WJ-MSC (pooled sample of 3 independent donors), and differentiated osteocytes and adipocytes derived from BM-MSCs after 2 weeks induction.	Co-expression
SRP022871	Discovery of the p53 targetome in MCF7 cells from RNA-seq data	RNA-seq and ChIP-seq on MCF-7 breast cancer cell line upon activation of p53 by the non-genotoxic small molecule Nutlin-3a Overall design: RNA-seq on MCF7 without (NS) or with Nutlin-3a stimulation (S), in duplicate, using illumina HiSeq 2000	Co-expression
SRP022876	Differential gene expression by suppression of either SOX2 or TP63 in KYSE70 human esophageal squamous carcinoma cell line.	SOX2 is a transcription factor essential for pluripotent stem cells, and development and maintenance of squamous epithelium. We previously reported SOX2 an oncogene subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs)1.  Here we demonstrate in SCCs that SOX2 interacts with another master squamous transcription factor p63, and through ChIP-seq show that genomic occupancy of SOX2 overlaps with that of p63 at a large number of loci and that they cooperatively regulate gene expression including ETV4, which we find essential for SOX2-amplified SCC cell survival. Furthermore, SOX2 binds to distinct genomic loci in SCCs than in embryonic stem cells and the SOX2-p63 coordinate binding is unique to SCC.  In addition, a subset of SOX2 genomic binding sites in SCC that lack p63 co-occupancy are co-occupied by the AP-1 transcriptional complex.  These demonstrate that SOX2’s actions in SCC differ substantially from its role in pluripotency and identify novel SOX2 interactions that will enable deeper characterization of SOX2’s function in SCC. Overall design: KYSE70 cells with stable expression of either pLKO-Tet-Op-shSOX2 or pLKO-Tet-Op-shTp63 were treated with 50ng/ml of doxycyline for 4 days. Total RNA was extracted, polyA+ selected, reverse transcribed, library constructed and sequencing was performed with Illumina HiSeq 2000. Differencial gene expression between the stable cell lines with Dox-induced and non-Dox treated was analyzed to determine the effects by suppression of either SOX2 or TP63 in KYSE70 cells.	Co-expression
SRP022892	RC3H1 posttranscriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kB pathway [PARCLIP]	The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3''UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3''UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway. Overall design: One PAR-CLIP Sample with human HEK293 cells	Co-expression
SRP022913	RNA-Guided Human Gene Activation by Cas9/CRISPR-Based Engineered Transcription Factors	Synthetic transcription factors can be applied in many areas of biotechnology, medicine, and basic research.  In contrast to current methods based on engineering new DNA-binding proteins, we show that Cas9 fused to a transcriptional activation domain can be targeted by combinations of guide RNA molecules to induce the expression of endogenous human genes. This simple approach for targeted gene activation circumvents the need for engineering new proteins and will enable widespread synthetic gene regulation. Overall design: HEK293T cells were transfected with plasmid expressing Cas9-VP64 fusion protein and a guide RNA. As a control, empty guide RNA was transfected. Gene expression was then measured using mRNA-seq, and differential expression calculated using DESeq. All experiments were performed in biological duplicates or triplicates.	Co-expression
SRP022920	3'' RNA-Seq (3''SEQ) analysis gene expression profiling at G1-S transition in human embryonic stem cells (hESCs) and hESC-derived endoderm cells	In this report, we examine transcripts on a genome-wide level between the synchronized cell cycles of hESCs and hESC-derived endoderm cells. We found 10347, 10299 and 10362 genes expressed in the G1, G1/S, and S phase of hESCs, respectively; 10333, 10227 and 10215 genes expressed at the G1, G1/S and S phase of derived endoderm. We compared the transcriptome between these data sets and identified genes with differentiated phase expression between hESCs and hESC-derived endoderm cells. Overall design: Examination of the transcriptome at the G1-S transition in hESCs compared to hESC-derived endoderm cells.	Co-expression
SRP022925	Improved genome-wide mapping of uncapped and cleaved transcripts in eukaryotes—GMUCT 2.0	The advent of high-throughput sequencing has led to an explosion of studies into the diversity, expression, processing, and lifespan of RNAs.  Recently, three different high-throughput sequencing-based methods have been developed to specifically study RNAs that are in the process of being degraded.  All three methods—genome-wide mapping of uncapped and cleaved transcripts (GMUCT), parallel analysis of RNA ends (PARE), and degradome sequencing—take advantage of the fact that Illumina sequencing libraries use T4 RNA ligase 1 to ligate an adapter to the 5’ end of RNAs that have a free 5’-monophosphate.  This condition for T4 RNA ligase 1 substrates means that mature mRNAs are not substrates of the enzyme because they have a 5’-cap.  As a result, these sequencing libraries are specifically made up of clones of decapped or degrading mRNAs and the 3’ fragment of cleaved miRNA and siRNA targets.  In this paper, we present a massively streamlined protocol for GMUCT that takes 2-3 days and can be initiated with as little as 5 µg of starting total RNA and involves only one gel size-selection step.  We show that the results are similar to libraries made using the previous GMUCT protocol and PARE. Overall design: GMUCT libraries were made from flower buds of the Arabidopsis thaliana accession Columbia (Col-0) and three human cell lines—the cervical cancer cell line HeLa, human embryonic kidney 293 T (HEK293T) cell line, and the human chronic myelogenous leukaemia cell line K562—two replicates of each.  Matched mRNA-seq libraries were made for each Col-0 GMUCT replicate. These libraries were sequenced on the Illumina HiSeq 2000 and the reads were trimmed to remove the adapter sequences (TGGAATTCTCGGGTGCCAAGGAACTCCAGTCA). The abundance of each unique read was determined, and unique reads were mapped to the Arabidopsis and human genomes, respectively.	Co-expression
SRP023199	mRNA sequencing identifies differential gene expresssion profiles between ASCC3 knock-down cells and control cells	We sequenced mRNAs from HeLa cells transduced with either scrambled shRNA or shRNA targeting ASCC3. The results have shown differential gene expression in ASCC3 knockdown cells, suggesting a regulatory role for ASCC3 in certain cellular pathway. Overall design: mRNA from HeLa cells transduced with either scrambled shRNA (ni) or shRNA targeting ASCC3 (ai) were harvested and used for deep sequencing by Illumina HiSeq 2000 sequencing instruments.	Co-expression
SRP023262	A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions	The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations.  To characterize the transcriptional changes of early breast neoplasia, we sequenced 3''- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene  expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns.  This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. Overall design: 3SEQ was performed on 72 FFPE human breast samples from 25 patients:  24 normal, 25 early neoplasia, 9 carcinoma in situ, and 14 invasive cancer	Co-expression
SRP023270	Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition [RNA-Seq]	Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs) and inhibiting DNA methylation results in aberrant splicing of ASEs. The methyl-CpG binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly DNA methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased nucleosome acetylation and aberrant skipping events of ASEs. We further show that inhibition of histone deacetylases leads to a highly significant overlap of exon skipping events caused by knocking-down MeCP2. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through its established interaction with HDACs. Overall design: RNA-Seq in IMR90 and HCT116	Co-expression
SRP023533	Integrated analysis of microRNA and mRNA expression and association with HIF binding in MCF-7 cells under hypoxia (miRNA-Seq)	Purpose: We aimed to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression. Methods: microRNA sequencing data and gene expression microarray data were generated from MCF-7 cells submitted to an hypoxia timecourse (16h, 32h and 48h at 1% Oxygen). Data was integrated to 500 published high-stringency HIF binding sites identified in MCF-7 cells. Results: We identified 41 microRNAs significantly up- and 28 down- regulated, of which 38 mature and 20 star forms are reported in conjunction with hypoxia for the first time. HIF-1a and HIF-2a binding sites within 50kb distance of microRNA loci were found by integration of HIF ChIP-seq data, showing overall association between binding sites and up-regulation. Gene expression profiling analysis showed no full coordination between pri-miRNA and microRNA expression, pointing towards additional levels of regulation. Several transcripts playing a role in microRNA processing were found regulated by hypoxia, of which two were HIF dependent. Conclusions: The data support the hypothesis that microRNA expression under hypoxia is regulated at transcriptional and post-transcriptional level. HIF is involved at both levels, regulating the transcription of certain microRNAs and also the expression of key elements of the microRNA processing pathway. Overall design: microRNA-seq profiles of MCF-7 exposed to hypoxia (1% Oxygen) for 16h (2 replicates), 32h (2 replicates) and 48h (2 replicates) and to normoxia (2 replicates) were generated using Illumina sequencing platform.	Co-expression
SRP023548	Homo sapiens strain:U-251 MG Transcriptome or Gene expression	Degraded RNA - RNA with low RIN.  U-251 MG brain gliablastoma cell line.	Co-expression
SRP023550	Differential LINE-1 retrotransposition in induced pluripotent stem cells between humans and great apes	Understanding cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic comprehension of the evolution and diversity of our own species. Until now, preserved tissues have been the main source of most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behavior, are not amenable to genetic manipulation and do not allow translation of observed differences into phenotypical divergence. We hypothesized that induced pluripotent stem cells (iPSCs) could provide a unique biological resource to elucidate relevant phenotypical differences between human and the great apes and that those differences could have potential adaptation and speciation value. Here, we describe the generation and initial characterization of iPSCs from chimpanzees and bonobos as novel tools to explore our most recent evolution. Comparative gene expression analysis of human and NHP iPSCs revealed differences in regulation of Long Interspersed Nuclear Element (LINE-1 or L1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. We observed decreased levels of L1 restricting factors APOBEC3B (A3B)7 and PIWIL28 in NHP iPSCs which was correlated with increased human and chimpanzee L1 mobility and endogenous L1 mRNA levels. Moreover, results from manipulation of A3B and PIWIL2 levels in iPSCs suggested a causal inverse relationship between levels of these proteins and L1 activity. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPSCs in culture and may have also occurred in the germline during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have had an adaptive significance. Overall design: polyA RNA-Seq profiling of iPS cells from human, chimpanzee, and bonobo, and small RNA-Seq profiling of human iPS cells.	Co-expression
SRP024244	Transcriptional profiling of FOXP3+ Treg cells and corresponding FOXP3-losing cells	Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion. Overall design: mRNA profiles of in-vitro-expanded FOXP3+ Treg and FOXP3-losing Treg cells generated by deep sequencing.	Co-expression
SRP024268	ALDH2, CCNE1 and SMAD3 are Potential Prognostic Markers for Upper Tract Urothelial Carcinoma Revealed by Massively Parallel Sequencing.	Purpose: upper tract urothelial carcinoma (UTUC) is the predominant subtype of the renal pelvis carcinoma but current knowledge about the molecular properties and prognostic markers is sparse. In this study, we examined the genome-wide mRNA expression spectrum of UTUC aiming to characterize the molecular basis of this cancer, and identify potential prognostic markers and thus facilitate the clinical practices. Experimental Design: we compared the whole mRNA expression spectrum of cancer and matched normal tissues in 10 patients with UTUC using massively parallel sequencing, thereafter the protein levels and prognostic roles of ALDH2, CCNE1 and SMAD3 were evaluated under an independent validation set comprising of 104 patients. Results: mRNA down-regulation of ALDH2 and up-regulation of SMAD3 and CCNE1 in UTUC were revealed by expression profiling. And low protein expression of ALDH2 was associated with an adverse outcome for patients (p < 0.0001). Whereas high CCNE1 and SMAD3 were associated with adverse clinical outcome (p < 0.0001). And multivariate analysis revealed that all these three molecular markers were independent prognostic predictors. Besides, compared to the pathological TNM classification, All ALDH2, CCNE1 and SMAD3 were more competent in identifying patient subgroup with high mortality risk, and the molecular markers were able to predict the survival difference in the patients of T2 and T3 subgroup (p < 0.001), which could not be achieved by TNM staging. Conclusions: This is the ?rst prospective study that characterizes genome-wide mRNA expression profile of UTUC. We revealed the prognostic significance of ALDH2, CCNE1 and SMAD3, and these molecular marker were more robust than TNM system in clinical outcome prediction. Overall design: Whole mRNA expression spectrum of cancer and matched normal tissues in 10 patients with UTUC was obtained by using massively parallel sequencing	Co-expression
SRP024274	Smoking Dysregulates the Human Airway Basal Cell Transcriptome at COPD-linked Risk Locus 19q13.2	Rationale: Genome-wide association studies (GWAS) and candidate gene studies have identified a number of loci linked to susceptibility of chronic obstructive pulmonary disease (COPD), a smoking-related disorder that originates in the airway epithelium. Objectives: Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome linked, in part, to known GWAS/candidate gene loci. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n=10) and smokers (n=7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS and candidate gene studies to confer risk for COPD. Measurements and Main Results: Smoker BC have 676 known genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10-4 compared to chance), including TGFB1, LTBP4, EGLN2 and NFKBIB, genes associated with risk for COPD. Conclusions: These observations provide the first direct link of known genetic risks for smoking-related lung disease with the specific population of lung cells that undergoes the earliest changes associated with smoking. Overall design: The human airway basal cell transcriptome of 7 smokers versus 10 nonsmokers was compared using massive parallel RNA sequencing (Illumina HiSeq 2000).	Co-expression
SRP024669	LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs [GRO-seq I]	While thousands of long non-coding RNAs (lncRNAs) are expressed in higher eukaryotes, the potential regulatory roles of lncRNAs in regulated gene transcription programs remain rather poorly understood. Here, we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1, bind successively to the androgen receptor (AR) and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the C-terminally acetylated AR on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM, to the N-terminally methylated AR. Unexpectedly, recognition of the H3K4me3 promoter  mark by the PHD finger-domain of Pygopus2, recruited by PCGEM1, proves to enhance selective looping of AR-bound enhancers to target gene promoters in these cells, revealing a novel aspect of ligand-induced enhancer-promoter interactions. In “resistant” prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for the robust activation of both truncated and full length AR, causing DHT-independent activation of the AR transcriptional program and cell proliferation. Conditionally-expressed short hairpin RNA (shRNA)-mediated targeting of these lncRNAs in these resistant cancer cell lines strongly suppressed xenograft growth in vivo. Together, these results suggest that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumors. Overall design: Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq); after knocking down PYGO2 LNCaP cells were grown to 30-50% confluence and siRNA/ASO transfections were carried out using Lipofectamine 2000 (Invitrogen) according to the  manufacturer’s instructions. Control samples were transfected with scramble  ASO and control siRNA, respectively. On the following day of transfection,  the cells were cultured in UltraCULTURE (Phenol red free) + 5% Charcoal  Dextran Stripped (CDS) serum for 48 hours. For androgen induction, we treat  cells with DHT from a 100 uM stock in 70% ethanol to a final concentration of 100 nM for 1 hour Control siRNA, -DHT Control siRNA, +DHT Pygo2 siRNA, -DHT Pygo2 siRNA, +DHT	Co-expression
SRP024674	LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs [GRO-seq II]	While thousands of long non-coding RNAs (lncRNAs) are expressed in higher eukaryotes, the potential regulatory roles of lncRNAs in regulated gene transcription programs remain rather poorly understood. Here, we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1, bind successively to the androgen receptor (AR) and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the C-terminally acetylated AR on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM, to the N-terminally methylated AR. Unexpectedly, recognition of the H3K4me3 promoter  mark by the PHD finger-domain of Pygopus2, recruited by PCGEM1, proves to enhance selective looping of AR-bound enhancers to target gene promoters in these cells, revealing a novel aspect of ligand-induced enhancer-promoter interactions. In “resistant” prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for the robust activation of both truncated and full length AR, causing DHT-independent activation of the AR transcriptional program and cell proliferation. Conditionally-expressed short hairpin RNA (shRNA)-mediated targeting of these lncRNAs in these resistant cancer cell lines strongly suppressed xenograft growth in vivo. Together, these results suggest that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumors. Overall design: Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq); after knocking-down lincRNAs PCGEM1 and PRNCR1. LNCaP cells were grown to 30-50% confluence and siRNA/ASO transfections were carried out using Lipofectamine 2000 (Invitrogen) according to the  manufacturer’s instructions. Control samples were transfected with scramble  ASO and control siRNA, respectively. On the following day of transfection,  the cells were cultured in UltraCULTURE (Phenol red free) + 5% Charcoal  Dextran Stripped (CDS) serum for 48 hours. For androgen induction, we treat  cells with DHT from a 100 uM stock in 70% ethanol to a final concentration of 100 nM for 1 hour Scramble ASO, -DHT Scramble ASO, +DHT PRNCR1 ASO, -DHT PRNCR1 ASO, +DHT PCGEM1 ASO, -DHT PCGEM1 ASO, +DHT	Co-expression
SRP025977	Homo sapiens Transcriptome or Gene expression	The condensin complex is required for chromosome condensation during mitosis. However its role in interphase is not clear. Neuroblastoma is the most common extracranial childhood tumor of sympathetic neuron. In human neuroblastoma, MYCN amplification correlates with poor prognosis. Results identify the genes that increased/decreased when Smc2 knockdowned in MYCN-overexperssing or control SH-EP neuroblastoma cell line.	Co-expression
SRP025982	A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequence Quality Control consortium	We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the United States Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for sequence discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed, for these and qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcriptlevel profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings. Overall design: The well-characterized reference RNA samples A (pooled cell lines) and B (human brain) from the MAQC consortium, adding spike-ins of synthetic RNA from the External RNA Control Consortium (ERCC).  Samples C and D were then constructed by combining A and B in known mixing ratios, 3:1 and 1:3, respectively.  All samples were distributed to several independent sites for RNA-Seq library construction and profiling by Illumina HiSeq 2000 and LifeTech SOLiD 5500 platforms.  Also, vendors created their own cDNA libraries that were then distributed to each test site, in order to examine the degree of a ?site effect? that was independent of the library preparation process.  To support an assessment of gene models, samples A and B were also sequenced at independent sites by the Roche 454 platform, providing longer reads.  For comparison to other technologies, these data were also compared to the MAQC-I Affymetrix U133 Plus2 microarray, several current microarray platforms, and also assessed by 20,801 PrimePCR reactions. Sample A: Universal Human Reference RNA (UHRR) from Stratagene and ERCC Spike-In controls Sample B: Human Brain Reference RNA (HBRR) from Ambion and ERCC Spike-In controls Sample C: Mix of A and B (3:1) Sample D: Mix of A and B (1:3) Sample E: Ambion ERCC Spike-In Control Mix 1 Sample F: Ambion ERCC Spike-In Control Mix 2	Co-expression
SRP026013	Impact of library preparation on downstream analysis and interpretation of RNA-seq data: comparison between Illumina PolyA and NuGEN Ovation protocol	Objectives: The sequencing by the PolyA selection is the most common approach for library preparation. With limited amount or degraded RNA, alternative protocols such as the NuGEN have been developed. However, it is not yet clear how the different library preparations affect the downstream analyses of the broad applications of RNA sequencing. Methods and Materials: Eight human mammary epithelial cell (HMEC) lines with high quality RNA were sequenced by Illumina’s mRNA-Seq PolyA selection and NuGEN ENCORE library preparation. The following analyses and comparisons were conducted: 1) the numbers of genes captured by each protocol; 2) the impact of protocols on differentially expressed gene detection between biological replicates; 3) expressed single nucleotide variant (SNV) detection; 4) non-coding RNAs, particularly lincRNA detection; and 5) intragenic gene expression. Results: Sequences from the NuGEN protocol had lower (75%) alignment rate than the PolyA (over 90%). The NuGEN protocol detected fewer genes (12-20% less) with a significant portion of reads mapped to non-coding regions. A large number of genes were differentially detected between the two protocols. About 17-20% of the differentially expressed genes between biological replicates were commonly detected between the two protocols. Significantly higher numbers of SNVs (5-6 times) were detected in the NuGEN samples, which were largely from intragenic and intergenic regions. The NuGEN captured fewer exons (25% less) and had higher base level coverage variance. While 6.3% of reads were mapped to intragenic regions in the PolyA samples, the percentages were much higher (20-25%) for the NuGEN samples. The NuGEN protocol did not detect more known non-coding RNAs such as lincRNAs, but targeted small and “novel” lincRNAs. Conclusion: Different library preparations can have significant impacts on downstream analysis and interpretation of RNA-seq data. The NuGEN provides an alternative for limited or degraded RNA but it has limitations for some RNA-seq applications. Overall design: Eight human mammary epithelial cell (HMEC) lines with high quality RNA were sequenced by Illumina’s mRNA-Seq PolyA selection and NuGEN ENCORE library preparation. The goal was to look the impacts of protocols on results and intepretation.	Co-expression
SRP026033	Transcriptome of embryonic stem cells cultured in enzymatic and mechanic passaging methods [RNA-seq]	hESC have morphologic, genetic and genomic alternatiions when cells cultured in different passaging condition. Overall design: Cells had initially mechanic passaging. From the initiating passage p13, cell were switched to enzymatic passaging after 15 passage (p13+EP15). Another sample was from cells after 15 mechanic passages (p13+MP15) which was designed as control. The transcripome of p13, p13+EP15 and p13+MP15 was analyzed with RNA sequencing by Illumina HiSeq2000 next-generation sequencer.	Co-expression
SRP026042	Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation [RNA-Seq]	Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Overall design: Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist	Co-expression
SRP026052	Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3’ UTRs	The RNA helicase UPF1 is best known for its key function in mRNA nonsense-mediated mRNA decay (NMD), but has also been implicated in additional mRNA turnover mechanisms, telomere homeostasis, and DNA replication. In NMD, UPF1 recruitment to target mRNAs is thought to occur through interaction with release factors at terminating ribosomes, but evidence for translation-independent interaction of UPF1 with the 3’ untranslated region (UTR) of mRNAs has also been reported. To map UPF1 binding sites transcriptome-wide, we performed individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) in human cells, untreated or after inhibiting translation by puromycin. We found a strong association of UPF1 with 3’ UTRs in undisturbed, translationally active cells and a significant increase in UPF1 binding to coding sequence (CDS) after translation inhibition. These results indicate that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. This evidence for translation-independent UPF1-RNA interaction, which is corroborated by RNA immunoprecipitations experiments and by our observation that UPF1 also crosslinks to long non-coding RNAs, suggests that the decision to trigger NMD occurs after association of UPF1 with the mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination. Overall design: Examination of Upf1 binding preferences via iCLIP in untreated HeLa cells and HeLa cells, where translation is blocked by puromycin treatment in vivo crosslinking and immunoprecipitation strategy (iCLIP)	Co-expression
SRP026084	Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR) [RNA-seq]	Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing only rarely targets canonical splicing acceptor, donor, and branch sites, it was found to affect splicing regulatory elements (SREs) within exons. Cassette exons were found to be significantly enriched with A-to-I RNA editing sites compared with constitutive exons. RNA-seq and exon-specific microarray revealed that ADAR knockdown in hepatocarcinoma and myelogenous leukemia cell lines leads to global changes in gene expression, with hundreds of genes changing their splicing patterns in both cell lines. This global change in splicing pattern cannot be explained by putative editing sites alone. Genes showing significant changes in their splicing pattern are frequently involved in RNA processing and splicing activity. Analysis of recently published RNA-seq data from glioblastoma cell lines showed similar results. Our global analysis reveals that ADAR plays a major role in splicing regulation. Although direct editing of the splicing motifs does occur, we suggest it is not likely to be the primary mechanism for ADAR-mediated regulation of alternative splicing. Rather, this regulation is achieved by modulating trans-acting factors involved in the splicing machinery. Overall design: HepG2 and K562 cell lines were stably transfected with plasmids containing siRNA designed to specifically knock down ADAR expression (ADAR KD). This in order to examine how ADAR affects alternative splicing globally.	Co-expression
SRP026125	The ABRF Next-Generation Sequencing Study (ABRF-NGS): Multi-platform and cross-methodological reproducibility of transcriptome profiling by RNA-seq [Ion Torrent Proton]	Next-generation sequencing (NGS) technology applications like RNA-sequencing (RNA-seq) have dramatically expanded the potential for novel genomics discoveries, but the proliferation of various platforms and protocols for RNA-seq has created a need for reference data sets to help gauge the performance characteristics of these disparate methods.  Here we describe the results of the ABRF-NGS Study on RNA-seq, which leverages replicate experiments across multiple sites using two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS).  These results show high (R2 >0.9) intra-platform consistency across test sites, high inter-platform concordance (R2 >0.8) for transcriptome profiling, and a large set of novel splice junctions observed across all platforms.  Also, we observe that protocols using ribosomal RNA depletion can both salvage degraded RNA samples and also be readily compared to polyA-enriched fractions.  These data provide a broad foundation for standardization, evaluation and improvement of RNA-seq methods. Overall design: Two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). Please note that the samples were named following the ABRF-Platform-Site-Sample-Replicate# format. For example, ABRF-454-CNL-A-1 means Sample A was run on 454 platform at Cornell and this is the first replicate, and  ABRF-454-CNL-A-2 means the same exact sample was ran with same machine at same location and is 2nd replicate.	Co-expression
SRP026126	The ABRF Next-Generation Sequencing Study (ABRF-NGS): Multi-platform and cross-methodological reproducibility of transcriptome profiling by RNA-seq [Illumina HiSeq 2500]	Next-generation sequencing (NGS) technology applications like RNA-sequencing (RNA-seq) have dramatically expanded the potential for novel genomics discoveries, but the proliferation of various platforms and protocols for RNA-seq has created a need for reference data sets to help gauge the performance characteristics of these disparate methods.  Here we describe the results of the ABRF-NGS Study on RNA-seq, which leverages replicate experiments across multiple sites using two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS).  These results show high (R2 >0.9) intra-platform consistency across test sites, high inter-platform concordance (R2 >0.8) for transcriptome profiling, and a large set of novel splice junctions observed across all platforms.  Also, we observe that protocols using ribosomal RNA depletion can both salvage degraded RNA samples and also be readily compared to polyA-enriched fractions.  These data provide a broad foundation for standardization, evaluation and improvement of RNA-seq methods. Overall design: Two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). Please note that the samples were named following the ABRF-Platform-Site-Sample-Replicate# format. For example, ABRF-454-CNL-A-1 means Sample A was run on 454 platform at Cornell and this is the first replicate, and  ABRF-454-CNL-A-2 means the same exact sample was ran with same machine at same location and is 2nd replicate.	Co-expression
SRP026144	Characterization of miRNomes in acute and chronic myeloid leukemia cells	An in-depth analysis of miRNomes in 3 human myeloid leukemia cell lines was carried out to comprehensively identify miRNAs that distinguish acute and chronic myeloid leukemias and relate to myeloid cell differentiation. Overall design: Characterization the miRNomes in 3 myeloid leukemia cell lines.	Co-expression
SRP026204	Mapping ERß genomic binding sites reveals unique genomic features and identifies EBF1 as an ERß interactor [Gro-Seq]	The C4-12/Flag.ERß cell line which stably expressed Flag.ERß is used to study ERß genomic functions without ERa interference. Mapping ERß binding sites in these cells reveals ERß unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERß target genes. Gene ontology analysis reveals that ERß targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERß binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERß binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERß binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERß genomic functions in our cell model, we confirm the anti-proliferative role of ERß and discover the novel cross talk of ERß with EBF1 which has various implications in normal physiology. Overall design: C4-12/Flag.ERß cells were treated with 10nM E2 (or ethanol as vehicle control) for 1 hour. Nuclei were extracted and processed with run-on assay. The resultant run-on RNA was reverse-transcribed to generate cDNA library which was subsequently sequenced by Illumina Genome Analyzer II or HiSeq2000. Two samples for each treatment were included in this experiment.	Co-expression
SRP026208	RNA-seq identifies novel transcript elements and transcript processing in the normal and failing hearts	Changes in gene expression contribute to the pathogenesis of heart failure. The sequence, expression level, and structure of the human cardiac transcriptome are incompletely described, as are their changes in heart disease. High throughput transcriptome sequencing (RNA-seq) is a quantitative and unbiased approach to measure transcript level and to identify novel transcribed elements or transcript splicing. Here we acquired 975.2 x 106 mapped RNA-seq reads in 15 control and 15 ischemic cardiomyopathy (ICM) hearts, obtained at the time of heart transplantation. We identified over 1000 differentially expressed transcripts, and thousands of novel transcribed elements, some of which were differentially expressed in between control and ICM groups. We found that transcript processing of several cardiac genes was deranged in ICM. For instance, the ratio between specific MYH6 exons was significantly changed in ICM compared to controls, while this type of inter-exon variation was not observed for the adjoining gene MYH7. This RNA-seq study of the human heart failure transcriptome revealed the diversity of transcripts expressed in the human heart and their complex patterns of expression in the diseased heart. Overall design: Transcriptome profiling (RNA-seq) of 15 control and 15 ischemic cardiomyopathy (ICM) hearts using Illumina GAII and SOLiD	Co-expression
SRP026256	Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer	This paper shows, for the first time, a novel function of the OVO-like proteins (OVOL1and OVOL2) as critical inducers of mesenchymal to epithelial transition (MET) in human cancer. Overall design: Examination of the effects of OVOL1 and OVOL2 overexpression in a prostate cancer model.	Co-expression
SRP026257	HeLa cell infection with Vaccinia virus	RNA samples were extracted before and after infection at different timepoints (0.5hpi, 2hpi, 6hpi, 18hpi)	Co-expression
SRP026315	High-throughput sequencing of PROMPT-enriched samples.	Sequencing of 5' and 3'ends and RNA-seq of PROMPT and mRNA molecules from control and exosome-depleted cells. Overall design: CAGE, 3'TAG and RNAseq library construction from RNA extracted from control and exosome-depleted cells.	Co-expression
SRP026331	Orchestrated intron retention regulates normal granulocyte differentiation [RNA-Seq]	Using mRNA-seq, we determined intron retaining genes that were differentially regulated in FACS purified cells at three progressive stages of mouse granulopoiesis; CD34+Kit+Gr-1low promyelocytes, CD34-Kit-Gr-1mid myelocytes and CD34-Kit-Gr-1high granulocytes. We found that IR affects 86 genes, including those specific to granulocyte (Lyz2 and MMP8) and nuclear architecture (Lmnb1 and Lbr). IR was associated with the decrease in protein levels measured by mass spectrometry (P=0.0015, binomial test). There was a significant overlap of IR between human and mouse (P=2.85E-22, hypergeometric test), showing that IR is conserved.Inhibition of NMD in granulocytes resulted in marked accumulation of 39/86 intron retaining mRNAs (P<0.05, RUV procedure with Holm-Bonferroni correction), indicating that IR triggers NMD to downregulate mRNA and protein expression. Overall design: Sequencing of polyadenylated RNA from three types of myeloid cells (promyelocytes, myelocytes and granulocytes) using Illumina GAIIx	Co-expression
SRP026333	Long Noncoding RNA HNF1A-AS1 Regulates Proliferation and Migration in Esophageal Adenocarcinoma  Cells	Objectives: Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of esophageal adenocarcinoma (EAC) and its progression. Design: lncRNAs that are abnormally upregulated in EACs were identified by RNA-seq analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 31 EAC patients. Cell biological assays in combination with siRNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. Results: We discovered that a lncRNA, HNF1A-AS1, is markedly upregulated in human primary EACs relative to their corresponding normal esophageal tissues (mean fold change 7.2, p<0.01). We further discovered that HNF1A-AS1 knockdown significantly inhibited cell proliferation and anchorage independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p<0.05). A gene ontological analysis revealed that HNF1A-AS1 knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well-known cancer-related lncRNA, H19, was the gene most markedly inhibited by HNF1A-AS1 knockdown. Consistent to this finding, there was a significant positive correlation between HNF1A-AS1 and H19 expression in primary EACs (p<0.01). Overall design: In order to identify novel oncogenic lncRNAs in esophageal adenocarcinogenesis, we carried out RNA-seq of a matched NE-BE-EAC tissue pair	Co-expression
SRP026359	T2D Transcriptome study	Strand specific RNA-Seq of T2D	Co-expression
SRP026387	The Wnt/ß-catenin-signaling pathway is modulated by androgen ablation therapy for advanced clinical prostate cancer and contributes to androgen independent cell growth	Androgen ablation therapy (AAT) is standard treatment for locally-advanced/metastatic prostate cancer (PCa).  Many patients develop castration-resistance (CRPCa) after ~2-3 years, with a poor prognosis.  The molecular mechanisms underlying CRPCa progression are unclear.  mRNA-Seq was performed on tumours from 7 patients with locally-advanced/metastatic PCa before and ~22 weeks after AAT initiation.  Differentially regulated genes were identified in treatment pairs. Overall design: Tumour biopsies from 7 patients were taken before and after AAT treatment	Co-expression
SRP026389	Homo sapiens strain:PBMC Transcriptome or Gene expression	Transcriptome Profiling of Activated T Cells	Co-expression
SRP026537	Transcriptional profiling of a breast cancer cell line panel using RNAseq technology	56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Overall design: Cell lines were profiled in their baseline, unperturbed state.	Co-expression
SRP026553	Homo sapiens Transcriptome or Gene expression	Sequencing from Ovarian Cancer cell lines	Co-expression
SRP026562	Alteration of the microRNA network during the progression of Alzheimer’s disease	We report the high-throughput profiling of microRNAs (miRNAs) from the prefrontal cortex of controls, early and late-stages Alzheimer''s disease subjects. We show miRNA expression changes between the two groups and down-regulation of miR-132-3p in the late-stages group. Overall design: Deep-sequencing of microiRNAs in 6 controls/early-stages and 6 late-stages Alzheimer''s disease patients	Co-expression
SRP026597	ieASV transcriptome project	ieASV transcriptome project.	Co-expression
SRP026620	RNA-seq of Tumor Initiating Cells (TICs) from Lung Squamous Cell Carcinoma (LSCC) lines reveals PRKCI dependent Hedgehog (HH) Signalling	RNA-seq analysis was performed on TICs and the parental counterparts of 4 LSCC cell lines. In addition, PRKCI knock down (KD) variants of these cells were sequenced. Subsequent analysis revealed that activation of HH signaling, a known driver of the TIC phenotype, is dependent on PRKCI expression. Overall design: Examination of TICS, parental cells, parental PRKCI KD cells, and TIC PRKCI KD cells	Co-expression
SRP026621	Transcriptome and Translatome Profiling of Caco-2 cells	This experiment performed RNA-seq of transcriptome and translatome (translating mRNA) of Caco-2 cells Overall design: We extracted transcriptome and translatome from Caco-2 cells and deep sequenced them	Co-expression
SRP026648	Homo sapiens Transcriptome or Gene expression	Human innate lymphoid cells: insights into function at homeostasis and during filarial infection.	Co-expression
SRP026690	Genome-Wide Transcriptional Effects of the Anti-Cancer Agent Camptothecin	The anti-cancer drug camptothecin inhibits replication and transcription by trapping DNA topoisomerase I (Top1) covalently to DNA in a “cleavable complex”. To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment affected transcription initiation, elongation, termination, splicing and enhancer activity. Following removal of camptothecin, transcription spread as a wave from the 5’-end of genes with no recovery of transcription apparent from RNA polymerases stalled in the body of genes. As a result, camptothecin preferentially inhibited the expression of large genes such as proto-oncogenes, and anti-apoptotic genes while smaller ribosomal protein genes, pro-apoptotic genes and p53 target genes showed relative higher expression. In addition, a set of mitotic regulator genes and histone genes were inhibited in a size-independent manner. Cockayne syndrome group B fibroblasts showed a very similar RNA synthesis recovery profile to normal fibroblasts suggesting that transcription-coupled repair is not involved in the repair of transcription-blocking TOP1 lesions. These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons. Overall design: Analysis of the effect of Camptothecin (CPT) on transcription. Normal fibroblasts and Cockayne syndrome group B fibroblasts were exposed to CPT for 60 minutes, after which a washout was performed. Nascent RNA was labeled using bromouridine for 15 minutes starting at time points: 1) 15 minutes before the washout; 2) Immediately after the washout; 3) 15 minutes after the washout. Test samples are compared to control cells that were not exposed to CPT.	Co-expression
SRP027015	Global response to chemotherapy-induced apoptosis	Here we use an integrated systems-level examination of transcription, translation, and proteolysis to explore how cancer cells struggle with a chemotherapeutic drug prior to succumbing to apoptosis. As a model system we study myeloma cells exposed to the proteasome inhibitor bortezomib, a first-line clinical treatment. Despite robust transcriptional changes, unbiased quantitative proteomics detects production of only a few critical anti-apoptotic proteins against a background of general translation inhibition. Ribosome profiling further reveals potential translational regulation of stress response genes following bortezomib treatment. Once the apoptotic machinery is engaged, degradation by caspases is largely independent of changes at the transcriptional level. Moreover, previously uncharacterized non-caspase proteolytic events also participate in cellular deconstruction. As suggested by these data, we find that inhibition of the anti-apoptotic response regulator HSF1 promotes cell death by bortezomib. Thus, monitoring global cellular dynamics after chemotherapy offers in-depth insight into apoptosis and can also guide potential therapeutic combinations. Overall design: We examined MM1.S myeloma cells exposed to 20 nM bortezomib across a time course with independent samples of poly(A) mRNA and ribosome footprints isolated at each of six time points (0h (untreated), 1.5h, 3h, 6h, 9h, 12h). Sequencing was performed on a Illumina HiSeq 2000 with single-end.	Co-expression
SRP027258	Genome-wide transcriptome analysis of the dietary chemopreventive phytochemical sulforaphane on normal and prostate cancer cells.	Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells.  Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Overall design: Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane	Co-expression
SRP027345	Viral small RNAs in Sindbis virus-infected mammalian cells	Small RNAs play a critical role in host-pathogen interaction. In insects, for instance, small RNA-mediated silencing or RNA interference (RNAi) represents the main antiviral defense system. However, the antiviral role of RNAi has not been clearly proven in higher vertebrates. On the contrary, it is well established that the cell response relies on the recognition of viral RNAs by host pattern recognition receptors (PRR) to trigger the activation of the interferon pathway. Based on this evidence, we wished to contribute to this research field by identifying and characterizing small non-coding RNAs produced in mammalian cells upon RNA virus infection. We focused on Sindbis virus (SINV), the prototypical arbovirus, which by definition, is able to infect both vertebrate hosts and invertebrate vectors and triggers the interferon pathway or RNAi, respectively. Overall design: Taking advantage of large scale sequencing, we cloned and sequenced small RNAs from both mock and SINV-infected mammalian cells (HEK 293 and VERO). We identified a novel population of viral small RNAs (vsRNAs) that accumulate as 20 to 30 nt species during infection. We assessed that this viral small RNA population is modified in 3'end and derived from the activation of the cellular antiviral endoribonuclease RNaseL. Altogether our results indicate a potential role for the SINV-derived small RNAs in the host defense mechanism.	Co-expression
SRP027358	Transcriptome of Primitive Human Hematopoietic Cells: A New Resource to Find hHSC-Specific Genes	We analysed the transcriptome of different HSC-enriched subpopulations of cells sorted from human umbilical cord blood and isolated from several individuals with different genetic backgrounds. We aim at identifying new cell surface markers associated with human HSC and downstream mature hematopoietic cell activity. Overall design: RNA-seq of CD34+CD45RA- cord blood cells from 17 non-pooled individuals.	Co-expression
SRP027364	Novel kinase fusion oncogenes in post-Chernobyl radiation-induced pediatric thyroid cancers	Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We identified non-overlapping somatic driver mutations in all 26 cases of post-Chernobyl thyroid cancers we studied through candidate gene assays and next generation RNA-sequencing. We found that 22/26 harbored fusion oncogenes arising primarily through intrachromosomal rearrangements. Altogether 23/26 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the two novel somatic rearrangements ETV6-NTRK3 and AGK-BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPAR?. A lower prevalence of fusion oncogenes was found in a cohort of pediatric thyroid cancers from children from the same geographical regions that were not exposed to radiation. Radiation-induced thyroid cancers are a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPAR?-driven transcriptional program. Overall design: Examination of transcriptome profiles and genetic somatic changes in thyroid cancer.	Co-expression
SRP027383	Whole transcriptome sequencing in 274 glioma patients reveals gene fusion profiling and novel candidate fusion genes	We detected fusion genes in 274 fresh surgical samples of gliomas using whole transcriptome sequencing. Using this approach we screened a panel of glioma samples and identified a number of activating novel fusion transcripts. Overall design: Fusion detection in 274 glioma patients	Co-expression
SRP027508	Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides	We developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses. Overall design: RNA-seq of human B lymphoblasts derived from peripheral blood mononuclear cells from 2 HLA-identical female siblings.	Co-expression
SRP027530	Deep Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Generalized Immune Suppression in BRAF (V600E) mutant vs. BRAF wild-type Papillary Thyroid Carcinoma	CONTEXT:  BRAF V600E mutation (BRAF-mut.) confers aggressiveness in papillary thyroid carcinoma, but unidentified genomic abnormalities may be required for full phenotypic expression.  OBJECTIVE:  To perform deep sequencing to identify genes differentially expressed between BRAF-mut. and BRAF-wild-type (BRAF-WT) tumors, and to compare to patient clinical status.  DESIGN:  BRAF-mut. and BRAF-WT tumors were identified in patients with T1N0 and with T23N1 tumors.  Expression levels of genes were determined from RNA sequencing (RNA-Seq) data and fusion transcripts were detected.  NanoString was used to validate the RNA-Seq data for immune genes.  SETTING:  Patients were seen at two sites of a major referral medical center.  PATIENTS:  Twenty patients were studied.  BRAF-mut. patients included 9 women, 3 men; 9 were TNM stage I and 3 were stage III; 3 (25%) had lymphocytic thyroiditis.  BRAF-WT included 5 women; 3 men; all were stage I; 5 (62.5%) had lymphocytic thyroiditis.  RESULTS:  560 of 13,085 genes were differentially expressed by RNA-Seq, and MetaCore analysis identified  55 immune function genes that were differentially expressed as a function of  BRAF mutational status.  Immune function genes were broadly underexpressed in BRAF-mut. tumors, with only 4 genes (HLA-G, CXCL14, TIMP1, IL1RAP) more highly expressed.  NanoString validated the RNA Seq data for immune genes.  Eleven high confidence fusion transcripts were detected, four being inter-chromosomal and seven intra-chromosomal.  CONCLUSION:  BRAF-mut. papillary thyroid cancers have less expression of immune and inflammatory response genes than BRAF-WT tumors.  Thirteen of 20 (65%) tumors had between one and three fusion transcripts.  Functional studies will be required to determine the potential role of the newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-mut. and wild-type tumors. Overall design: RNA-seq was performed on 20 thyroid carcinoma tumors	Co-expression
SRP027589	De novo sequencing of circulating microRNAs in locally advanced breast cancer	MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Overall design: The pre-treatment sera of 42 stage II–III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs.	Co-expression
SRP028118	Derivation of endothelial colony forming cells from human pluripotent stem cells	Human induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells differentiate into cells of the endothelial lineage, but derivation of cells with human umbilical cord blood endothelial colony forming cell (ECFC)-like properties has not been reported. Here we describe a novel serum- and stromal cell-free ECFC differentiation protocol for the derivation of clinically relevant numbers of ECFCs (> 108) from hiPS and hES cells. We identified NRP-1+CD31+ selected cells that displayed a stable endothelial phenotype exhibiting high clonal proliferative potential, extensive replicative capacity, formation of human vessels that inosculated with host vasculature upon transplantation, but lacking in teratoma formation in vivo. We also identified NRP-1-VEGF165-KDR-mediated activation of KDR as a critical mechanism for the emergence and derivation of ECFCs from hiPS and hES cells.  This protocol advances the field by generating highly replicative but stable endothelial cells for use as a potential cell therapy for human clinical disorders. Overall design: Transcriptome sequencing of undifferentiated day 0 hiPS cells, Day 3 differentiated hiPS-derived mesoderm proginator cells, Day 12 hiPS-derived NRP-1+CD31+ cells, Day 12 H9-hES-derived NRP-1+CD31+ cells and cord blood-derived Endothelial colony forming cells.	Co-expression
SRP028155	Transcriptomic analysis of ERR alpha orphan nuclear receptor	Determination of the genes regulated by ERRalpha nuclear receptor in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for ERRalpha using siRNA. Three different siRNAs were used (siE1, siE2, siE3). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq	Co-expression
SRP028170	Mapping of nascent RNA upon release of DRB in WT and KD of RECQL5	Global Run-On has been performed on WT or KD for RECQL5 cells after release from DRB.  When RECQL5 is knocked-down the transcriptional wave front is more advanced, suggesting that transcription is faster. Overall design: Constitutive knock-down cell lines expressing or not endogenous levels of shRNA resistant RECQL5 under a Doxycycline inducible promoter were treated with high doses of DRB to block transcription. Upon release into fresh medium we were able to follow how much and how fast the RNA Pol II progresses through genes by mapping nascent RNA by Run-On.  The experiment was performed in two cell line clones.	Co-expression
SRP028180	Profiling premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis	Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium, therefore studying these lesions is critical for understanding lung carcinogenesis. We performed RNA sequencing on laser-microdissected representative cell populations along the SCC pathological continuum of patient-matched normal basal cells, premalignant lesions, and tumor cells. We discovered transcriptomic changes and identified genomic pathways altered with initiation and progression of SCC within individual patients. We used immunofluorescent staining to confirm gene expression changes in premalignant lesions and tumor cells, including increased expression of SLC2A1, CEACAM5, and PTBP3 at the protein level and increased activation of MYC via nuclear translocation. Cytoband enrichment analysis revealed coordinated loss and gain of expression in chromosome 3p and 3q regions, respectively, during carcinogenesis. This is the first gene expression profiling of airway premalignant lesions with patient-matched samples that provides insight into the mechanisms of stepwise lung carcinogenesis. Overall design: Profiling of mRNA expression in laser-microdissected normal airway basal cells, premalignant airway lesions, and lung SCC tumor cells by massively parallel RNA sequencing.	Co-expression
SRP028190	mRNA differential expression analysis in a human ex vivo model of chronic wounds	To study the fibroblast to myofibroblast differentiation in a normal or pathological situation, NHDF (Normal human dermal fibroblast) obtained from two different healthy donors (donors A and B) were either left untreated (T-E-) either treated with TGF-beta alone (T+E-), or with exudate from chronic wounds (T-E+) or both (T+E+). For each different treatment we performed mRNA deep sequencing 3 times : twice with cells from donor A and once with cells from donor B.We focused our study on gene expression profile as a representation of cell fate. We performed mRNA deep sequencing analysis of the 4 different conditions. For each condition, mRNA deep sequencing was performed 3 times : twice with cells from donor A and once with cells from donor B.Comparing the mRNA abundance between the different treatments, we identified 3 lists of genes characterizing the different gene expression states: 171 genes in List I representing the genes differentially expressed during normal fibroblast to myofibroblast differentiation, 409 genes in List II representing the genes differentially expressed upon exudate-only treatment and 1006 genes in List III representing the genes differentially expressed upon the combination of exudate and TGF-beta treatments. Overall design: 4 different treatments are compared : (T-E-) NHFD left untreated, (T+E-) NHDF treated with TGFbeta  for 4 days, (T-E+) NHDF treated with exudate for 4 days and (T+E+) NHDF treated with both TGFbeta and exudate. NHDF : Normal Human Dermal Fibroblast	Co-expression
SRP028282	Inhibition of Androgen Receptor and ß-catenin activity in prostate cancer	Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective new approach to treating prostate cancer. Here we provide proof-of-concept that a small molecule inhibitor of nuclear ß-catenin activity (called C3) can inhibit both the AR and ß-catenin signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both ß-catenin/TCF and ß-catenin/AR protein interaction, reflecting the fact that TCF and AR have overlapping binding sites on ß-catenin. Given that AR interacts with, and is transcriptionally regulated by ß-catenin, C3 treatment also resulted in decreased occupancy of ß-catenin on the AR promoter and diminished AR and AR/ß-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and ß-catenin cofactor, CARM1, providing new insight into the unrecognized function of ß-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model, and blocked renewal of bicalutamide-resistant sphere forming cells, indicating the therapeutic potential of this approach. Overall design: Compare and contrast the expression profile of prostate cancer cells treated with a Wnt inhibitor (C3) with respect to ß-catenin and AR knockdown (all samples in duplicates).	Co-expression
SRP028291	Micro-RNA sequencing from 78 adrenocortical carcinomas	Micro-RNA sequencing of adrenocortical tumors and normal adrenal samples. Overall design: miRNA sequencing of  45 adrenocortical carcinomas (ACC), 30 adrenocortical adenomas (ACA) and 3 normal adrenal samples.	Co-expression
SRP028301	Improved Smart-Seq for sensitive full-length transcriptome profiling in single cells	Improved Smart-Seq for sensitive full-length transcriptome profiling in single cells. Overall design: Cells of four different origins were profiled using commercial SMARTer and compared to five variants of an improved protocol (Smart-Seq2).	Co-expression
SRP028336	Large-scale multi-species survey of metabolome and lipidome	This dataset was generated with the goal of comparative study of gene expression in three brain regions and two non-neural tissues of humans, chimpanzees, macaque monkeys and mice. Using this dataset, we performed studies of gene expression and gene splicing evolution across species and search of tissue-specific gene expression and splicing patterns. We also used the gene expression information of genes encoding metabolic enzymes in this dataset to support a larger comparative study of metabolome evolution in the same set of tissues and species. Overall design: 120 tissue samples of prefrontal cortex (PFC), primary visual cortex (VC), cerebellar cortex (CBC), kidney and skeletal muscle of humans, chimpanzees, macaques and mice. The data accompanies a large set of metabolite measurements of the same tissue samples. Enzyme expression was used to validate metabolite measurement variation among species.	Co-expression
SRP028340	LSD1 inhibitor HCI-2509 and gene expression in Ewing sarcoma (A673)	EWS/ERG function in Ewing sarcoma	Co-expression
SRP028344	EWS/ERG function in Ewing sarcoma	Gene regulation by EWS/ERG in Ewing sarcoma	Co-expression
SRP028346	LSD1 inhibitor HCI-2509 and gene expression in Ewing sarcoma (TTC-466)	The effect on gene regulation in Ewing sarcoma cells treated with LSD1 inhibitor HCI-2509	Co-expression
SRP028526	Stretch responsive miRNAs in human aortic valve interstitial cells	miRNA-Sequencing was performed on human aortic valve interestitial cells (AVICs) exposed to 14% stretch at 1 hz or static conditions for 24h. Overall design: Six static control and six samples exposed to cyclic stretch 14% for 24h	Co-expression
SRP028528	Homo sapiens Transcriptome or Gene expression	Transcriptome sequencing of Chronic Phase and Blast Crisis CML, normal cord blood cells, and normal cord blood cells transduced with lentiviral vectors	Co-expression
SRP028530	Ribosome Associated Tags (RAT) and Ribosme Protected Tags (RPT) Profiling in ovarian cancer	Ribosome pofile	Co-expression
SRP028554	Leucegene: ALL sequencing	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human T ALL (acute lymphoblastic leukemia). Methods: T ALL cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an Illumina HiSeq 2000 sequencer.	Co-expression
SRP028567	RNA-Seq analysis of primary AML specimens exposed to AhR modulating agents	The goal of the study was to identify genes that are directly or indirectly coregulated by the AhR pathway in primary human AML cells. Patient AML cells were treated for 16 hours with the two indirubin derivatives 6-bromoindirubin-3''oxime (BIO), 1-Methyl-6-bromoindirubin-3''oxime (MeBIO), the AHR-antagonist SR1 (StemReginin1), combinations of BIO+SR1 and MeBIO+SR1 or DMSO alone at indicated concentrations prior to RNA extraction for sequencing. Overall design: RNA-Seq performed on 5 primary AML samples fresh (t0) and after exposure to AhR-agonists (2), -antagonist (1), and DMSO Contributor: Leucegene Project, IRIC	Co-expression
SRP028570	Differential transcript stability measurements in MDA-MB-231 vs. MDA-LM2 cells	We performed whole-genome stability measurements for MDA-MB-231 and its highly metastatic derivative MDA-LM2. Our goal was to identify post-transcriptonal regulons that are deregulated en route to higher metastatic capacity. Overall design: Cells were pulsed with 4-thiouridine for 2 hours and then RNA was extracted at 0, 2, 4, and 7 hr time-points in quadruplicate from each cell line. 4sU labeling followed by RNA-seq was then used to measure the abundance of transcripts in each population. A decay rate was estimated based on the rate at which transcript abundance was reduced at these time-points.	Co-expression
SRP028594	Leucegene: AML sequencing (part 1)	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an Illumina HiSeq 2000 sequencer.	Co-expression
SRP028612	Primate transcript and protein expression levels evolve under compensatory selection pressures	Variation in gene regulation is thought to have played an important role in the evolution of primates, and many studies have documented differences in mRNA expression levels across primate species. However, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are more directly tied to phenotypic differences. To address this question, we used high-resolution, quantitative mass spectrometry to collect thousands of protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (LCLs). We also used RNA sequencing to collect transcript expression data from the same samples. Considering the two datasets jointly we found that there is much more inter-species divergence at the mRNA level than at the protein level. Remarkably, we found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest a much stronger evolutionary constraint on protein expression levels than on mRNA levels. We conclude that inter-species mRNA expression differences may often have limited functional consequences due to either buffering or compensatory changes in post-transcriptional or posttranslational regulation of proteins. Overall design: Gene expression patterns were compared between human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (5 individuals from each species) using RNA-Seq. These gene expression patterns were also compared to protein expression patterns based on mass-spec data, which are available separately (see publication for details).	Co-expression
SRP028705	Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data	A large number of computational methods have been recently developed for analyzing differential gene expression (DE) in RNA-seq data. We report on a comprehensive evaluation of the commonly used DE methods using the SEQC benchmark data set and data from ENCODE project. We evaluated a number of key features including: normalization, accuracy of DE detection and DE analysis when one condition has no detectable expression. We found significant differences among the methods. Furthermore, computational methods designed for DE detection from expression array data perform comparably to methods customized for RNA-seq. Most importantly, our results demonstrate that increasing the number of replicate samples significantly improves detection power over increased sequencing depth. Overall design: The Sequencing Quality Control Consortium generated two datasets from two reference RNA samples in order to evaluate transcriptome profiling by next-generation sequencing technology. Each sample contains one of the reference RNA source and a set of synthetic RNAs from the External RNA Control Consortium (ERCC) at known concentrations. Group A contains 5 replicates of the Strategene Universal Human Reference RNA (UHRR), which is composed of total RNA from 10 human cell lines, with 2% by volume of ERCC mix 1. Group B includes 5 replicate samples of the Ambion Human Brain Reference RNA (HBRR) with 2% by volume of ERCC mix 2. The ERCC spike-in control is a mixture of 92 synthetic polyadenylated oligonucleotides of 250-2000 nucleotides long that are meant to resemble human transcripts.	Co-expression
SRP028738	Evaluation of quantitative miRNA gene expression platforms in the microRNA Quality Control (miRQC) study	MiRNAs are important negative regulators of protein coding gene expression, and have been studied intensively over the last few years. Several measurement platforms, designed to determine their relative RNA abundance levels in biological samples, have been developed. In this study, we systematically compared 12 commercially available miRNA expression platforms by measuring an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples, and synthetic spikes from miRNA family members with varying homology. We developed novel and robust quality metrics to objectively assess platform performance of very different technologies such as small RNA sequencing, RT-qPCR and (microarray) hybridization. We assessed reproducibility, sensitivity, accuracy, specificity, and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which helps to guide informed selection of a quantitative miRNA gene expression platform in function of particular study goals. Overall design: Sequencing of 20 miRQC samples on Illumina Genome Analyzer IIx System	Co-expression
SRP028822	RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome [RNA-Seq]	The second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis. Fewer gene transcripts were observed using RNA-Seq than microarray (4,158 vs 8,842). Correlation of total expression within each sample ranged from R=0.43 to R=0.57. On average, there was 59% concordance in gene identity among the top 10% of genes ranked by expression. The RNA-Seq data yielded more significant pathways enrichment within the ?Physiological Systems Development and Function? categories of IPA. Alternative splicing of many well-known genes, including those previously studied in fetal development, such as H19 and IGF2  is detected by RNA-Seq. Also included in this paper is discussion of the technical challenges inherent to working with cell-free fetal RNA and possible solutions. Overall design: Cell-free fetal RNA from the amniotic fluid supernatant of five second trimester fetuses was divided and prepared in tandem for analysis using either the Illumina HiSeq 2000 or Affymetrix HG-U133 Plus 2.0 GeneChip microarray.	Co-expression
SRP028887	Differential Protein Occupancy Profiling of the mRNA Transcriptome	Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation and translation. We have developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing (Baltz and Munschauer et al. 2012). Our current work focuses on streamlining and extending protein occupancy profiling on poly(A)-RNA. Our objectives are to identify previously unknown protein-bound transcripts and, more importantly, to assess global and local differences in protein occupancy across different biological conditions. To this end, we have implemented poppi, the first pipeline for differential analysis of protein occupancy profiles. We have applied our analysis pipeline to pinpoint changes in occupancy profiles of MCF7 cells against already published HEK293 cells [GSE38157]. Overall design: We generated protein occupancy cDNA libraries for two biological replicates. Briefly, we crosslinked 4SU-labeled MCF7 cells and purified protein-mRNA complexes using oligo(dT)-beads. The precipitate was treated with RNAse I to reduce the protein-crosslinked RNA fragments to a length of about 30-60 nt. To remove non-crosslinked RNA, protein-RNA complexes were precipitated with ammonium sulfate and blotted onto nitrocellulose. The RNA was recovered by Proteinase K treatment, ligated to cloning adapters, and reverse transcribed. The resulting cDNA libraries were PCR-amplified and next-generation sequenced.	Co-expression
SRP028902	mRNA and RNC-mRNA deep sequencing of three hepatocellular carcinoma cell lines	We sequenced the total mRNA and translating mRNA (RNC-mRNA) of three hepatocellular carcinoma cell lines Hep3B, HCCLM3 and MHCC97H Overall design: For each cell line, samples prepared from three independent and identical cell cultures were pooled with equal amounts. C-HPP China Team	Co-expression
SRP028912	SnapShot-Seq: a method for extracting genome-wide, in vivo mRNA dynamics from a single total RNA sample	mRNA synthesis, processing, and destruction involve a complex series of molecular steps that are incompletely understood.  Because the RNA intermediates in each of these steps have finite lifetimes, extensive mechanistic and dynamical information is encoded in total cellular RNA.  Here we report the development of SnapShot-Seq, a set of computational methods that allow the determination of in vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay from a single RNA-Seq snapshot of total cellular RNA.  SnapShot-Seq can detect in vivo changes in the rates of specific steps of splicing, and it provides genome-wide estimates of pre-mRNA synthesis rates comparable to those obtained via labeling of newly synthesized RNA.  We used SnapShot-Seq to investigate the origins of the intrinsic bimodality of metazoan gene expression levels, and our results suggest that this bimodality is partly due to spillover of transcriptional activation from highly expressed genes to their poorly expressed neighbors.  SnapShot-Seq dramatically expands the information obtainable from a standard RNA-Seq experiment. Overall design: These data are total RNA-Seq data, from RNA sequencing of rRNA-depleted total cellular RNA -- except the LCL 4SU data, which derive from 4SU-labeled RNA.  Please see the associated paper for more details.	Co-expression
SRP028952	Human colon cancer tumors and xenografts in mice - Transcriptome or Gene expression	RNA-seq data from human colon cancer tumors and xenografts in mice	Co-expression
SRP028963	p53 shapes genome-wide changes in small non-coding RNA expression during the human DNA damage response	Small RNA-seq on MCF10A, HCT116 and HCT116p53-/- cell lines after induction of DNA damage (5 Gy Irradiation). Overall design: Small RNA-seq on MCF10A, HCT116 and HCT116p53-/- at 4 and 24 hours after induction of DNA damage (5 Gy Irradiation), done in duplicate with respective control (0 hour) using illumina Genome Analyzer IIx	Co-expression
SRP029207	Characterization of the human cumulus cell transcriptome during final follicular maturation and ovulation	Purpose:  The goal of this study was to identify differentially expressed genes and pathways between the cumulus of compact/unstimulated cumulus-oocyte-complex  (COC) and the cumulus of expanded/stimulated COC. Methods: mRNA profiles of  Compact/unstimulated cumulus cells (CCs) from germinal vesicle (GV) COC obtained from two patients undergoing unstimulated IVM procedure and  expanded/stimulated CCs from metaphase 2 (MII) COC obtained from three patients undergoing IVF/ICSI were generated by deep sequencing using Illumina HiSeq 2000. The sequence reads that passed quality filters were mapped to the human genome (hg19) using Tophat software. Differential expression analysis was done using DESeq bioconductor package. qRT–PCR validation was performed using SYBR Green assays. Results: A total of 40-80 million sequence reads per sample were mapped to the human genome (hg19). A total of 1746 differentially expressed genes between compact and expanded CCs with fold change > 2, and adjusted p value < 0.05 were identified. Gene ontology analysis of differentially expressed genes revealed a number of cellular processes regulated during the periovulatory interval including cellular movement, inflammatory response, immune cell trafficking, tissue development, lipid metabolism,  tissue morphology, DNA replication and cell cycle.  A total of 116 of the differentially expressed genes were annotated as long non-coding RNAs, 10 of them coded from introns of genes known to be involved in granulosa cell processes suggesting that unique non coding RNA transcripts may contribute to the regulation of cumulus expansion and oocyte maturation. Results were validated using qRT-PCR. Conclusions: Using global transcriptome sequencing we identified new important genes and non coding RNAs involved in COC maturation and cumulus expansion, which may contribute to improve the process of in vitro maturation of immature oocytes utilized in IVM cycles Overall design: mRNA profiles of  Compact/unstimulated cumulus cells (CCs) from germinal vesicle (GV) COC obtained from two patients undergoing unstimulated IVM procedure and  expanded/stimulated CCs from metaphase 2 (MII) COC obtained from three patients undergoing IVF/ICSI were  generated by deep sequencing using Illumina HiSeq 2000.	Co-expression
SRP029262	Global transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism [RNA-seq]	Here we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.	Co-expression
SRP029334	IVT-seq reveals extreme bias in RNA-sequencing	Background: RNA-seq is a powerful technique for identifying and quantifying transcription and splicing events, both known and novel. However, given its recent development and the proliferation of library construction methods, understanding the bias it introduces is incomplete but critical to realizing its value. Results: We present a method, in vitro transcription sequencing (IVT-seq), for identifying and assessing the technical biases in RNA-seq library generation and sequencing at scale. We created a pool of over 1,000 in vitro transcribed RNAs from a full-length human cDNA library and sequenced them with polyA and total RNA-seq, the most common protocols. Because each cDNA is full length, and we show in vitro transcription is incredibly processive, each base in each transcript should be equivalently represented. However, with common RNA-seq applications and platforms, we find 50% of transcripts have more than two-fold and 10% have more than 10-fold differences in within-transcript sequence coverage. We also find greater than 6% of transcripts have regions of dramatically unpredictable sequencing coverage between samples, confounding accurate determination of their expression. We use a combination of experimental and computational approaches to show rRNA depletion is responsible for the most significant variability in coverage, and several sequence determinants also strongly influence representation. Conclusions: These results show the utility of IVT-seq for promoting better understanding of bias introduced by RNA-seq. We find rRNA depletion is responsible for substantial, unappreciated biases in coverage introduced during library preparation. These biases suggest exon-level expression analysis may be inadvisable, and we recommend caution when interpreting RNA-seq results. Overall design: 5 rRNA-depleted samples with duplicates, 1 polyA selected, 1 total RNA, and 1 plasmid library all without replicates.	Co-expression
SRP029341	Homo sapiens Targeted Locus (Loci)	No description.	Co-expression
SRP029365	Regulation of the KEAP1/NRF2 oxidative stress response pathway by BRD4 in prostate and colorectal cancer	To identify genes regulated by BRD4 and to provide insight into new mechanisms de-regulated by BRD4, such as the response to oxidative stress, we integrated BRD4-binding regions with BRD4 gene expression data. For this analysis we performed BRD4 chromatin immunoprecipitation  experiments and BRD4 knock down experiments followed by RNA-Seq analyses. By integration of both gene lists we identified top candidate genes regulated by BRD4. Overall design: HEK cells have been investigated for genomewide BRD4 binding sites and expression changes after knock down of BRD4. Illumina sequencing was used to gather data of the type ChIP Seq and mRNA Seq.	Co-expression
SRP029367	FMRP-associated MOV10 facilitates and antagonizes miRNA-mediated regulation	The fragile X mental retardation protein FMRP is an RNA binding protein that regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway and we show here that it is associated with MOV10, a putative helicase that is also associated with the microRNA pathway.  We show that FMRP associates with MOV10 in an RNA-dependent manner and facilitates MOV10-association with RNAs in brain. We identified the RNA sequences recognized by MOV10 using iCLIP and found an increased number of G-quadruplexes in the CLIP sites. We provide evidence that MOV10 facilitates microRNA-mediated translation regulation and also has the novel role of increasing the expression of a subset of RNAs by sterically hindering Argonaute2 association. In summary, we have identified a new mechanism for FMRP-mediated translational regulation through its association with MOV10. Overall design: Comparison of MOV10 siRNA knockdown, irrelevant siRNA control and MOV10 overexpression on total RNA levels	Co-expression
SRP029401	Deep sequencing of exosomal and cellular miRNAs in MDA-MB-231 and MCF-10A cells	To identify the miRNAs that are differentially expressed and secreted between the MDA-MB-231 metastatic breast cancer cells and the MCF-10A non-cancerous human mammary epithelial cells, we profiled the cellular and exosomal small RNAs (between 17 and 52 nt) isolated from these two cell lines by Solexa deep sequencing.  MiRNAs that are significantly different between the two cell lines are identified. Overall design: RNA was extracted from cultured MDA-MB-231 and MCF-10A cells or purified exosomes secreted by these cells, and subjected to library construction and Solexa deep sequencing.	Co-expression
SRP029434	RNA-seq melanoma	Using a chromatin regulator-focused shRNA library, we found that suppression of sex determining region Y-box 10 (SOX10) in melanoma causes  resistance to BRAF and MEK inhibitors. To investigate how SOX10 loss leads to drug resistance, we performed transcriptome sequencing (RNAseq) of both parental A375 (Ctrl. PLKO) and A375-SOX10KD (shSOX10-1, shSOX10-2) cells. To ask directly whether SOX10 is involved indrug resistance in BRAF(V600E) melanoma patients, we isolated RNA from paired biopsies from melanoma patients (pre- and post- treatment) , that had gained  BRAF or MEK inhibitor resistance . We performed RNAseq analysis to determine changes in transcriptome upon drug resistance. Overall design: Investigate genes regulated by SOX10 and differntial gene expression between pre- and post-treatment biopsies. We use short hairpin RNA to suppression SOX10 in A375 cells and cells were harvested with trizol reagent for RNA isolation. For paired biopsies (patient samples) we collected the first biopsy before the initiation of treatment and the second biopsy after drug resistance developed. RNA was isolated from FFPE samples and subjected for RNA sequencing.	Co-expression
SRP029452	Non-IG Aberrations of FOXP1 in B-Cell Malignancies Lead to an Aberrant Expression of N-Truncated Isoforms of FOXP1	The transcription factor FOXP1 is implicated in the pathogenesis of B-cell lymphomas through immunoglobulin heavy chain (IGH) locus-related chromosomal translocations leading to dysregulated expression of FOXP1. Translocations of FOXP1 with non-IG gene sequences have been also reported, but the molecular consequences of such aberrations remain undetermined. Here, using molecular cytogenetics and molecular biology studies, we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas without underlying t(3p13/FOXP1). We found that non-IG rearrangements are usually acquired during evolution of lymphoma and constantly target the coding region of FOXP1, promiscuously fusing with coding and non-coding gene sequences at various reciprocal breakpoints (2q36, 10q24 and 3q11). Intriguingly, these rearrangements do not generate functional chimeric genes but commonly disrupt the full-length FOXP1 transcript leading to an aberrant expression of N-truncated FOXP1 isoforms, as shown by QRT-PCR and Western blot analysis. In contrast, cases with t(3;14)(p13;q32)/IGH-FOXP1 overexpress the full-length FOXP1. Collectively, our findings point to a dual mechanism through which FOXP1 is implicated in B-cell lymphomagenesis. The primary t(3;14)(p13;q32)/IGH-FOXP1 produces the full-length protein with potent oncogenic activity, whereas the secondary non-IG 17 rearrangements of FOXP1 generate N-truncated FOXP1 isoforms, likely driving progression of disease. Overall design: Using molecular cytogenetics and molecular biology studies (including RNA-seq), we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas without underlying t(3p13/FOXP1).	Co-expression
SRP029515	Transcriptomics analysis of gene expression in normal and METTL3 or WTAP deficient Human HeLa cells	RNA was isolated from and METTL3,WTAP deficient Human HeLa cells using the TRIzol (Invitrogen) reagent by following the company manual. For all samples the RNA integrity was checked using an Agilent Bioanalyzer 2100. All samples showed a RIN (RNA integrity number) of higher than 9. Approximately 2.5 µg of total RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer’s protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read mode, creating reads with a length of 50 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Overall design: Examination of gene expressive levels in normal and METTL3,WTAP deficient Human HeLa cells	Co-expression
SRP029589	Hela cell cycle ribosome profiling	This study sought to characterize changes in mRNA translation during cell cycle progression. Understanding how translation is regulated during each phase of the cell cycle will provide a greater understanding of normal cell growth and division as well as guide the development of potential cancer therapies.	Co-expression
SRP029592	RNA-seq transcriptomes of term not in labour and term in labour human myometrial tissue	Purpose: To chart the human myometrial transcriptomes before and after the onset of labour. Methods: Tophat splice junction mapping of paired-end reads, HTSeq to generate counts, cufflinks to track transcripts, DESeq, edgeR and baySeq to detect differentially expressed genes and principal component analysis for clustering analyses. Results: We mapped on average 14 million paired-end reads per sample (counting each end individually) to the human genome (build hg19) and covered the expressed transcriptome about 13 times with a TopHat-HTSeq workflow. We performed a comparative analysis with an analogous microarray study (Mittal et al., 2010) and found some overlap between the RNA-seq and the microarray data. Conclusions: Our study is the first RNA-seq study of the human myometrium before and after the onset of labour. We show that while microarray and RNA-seq studies may complement each other, RNA-seq has a much greater resolution. Overall design: At term with and at term without labour human myometrial mRNA profiles were generated by deep sequencing, using Illumina GAIIx (five biological replicates each).	Co-expression
SRP029603	Whole Transcriptomic Sequencing of Metastatic Castration Resistant Prostate Cancer Samples	We report the gene expression profile of 8 metastatic castration resisistant prostate cancer samples analyzed by paired-end RNA-seq. We found evidence of extensive abnormal splicing as well as several novel fusion genes. Finally, we also observed several recurrent high-confidence somatic mutations. Overall design: Paired-end RNA-seq by rRNA depletion	Co-expression
SRP029656	Landscape and variation of RNA secondary structure across the human transcriptome	In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. The ability of RNA to base pair with itself and other nucleic acids endow RNA with the capacity to form extensive structures, which are known to influence practically every step in the gene expression program1. Yet the nature of most RNA structures or effects of sequence variation on structure are not known.  Here we report the initial landscape and variation of RNA secondary structures (RSS) in a human family trio, providing a comprehensive RSS map of human coding and noncoding RNAs. We identify unique RSS signatures that demarcate open reading frames, splicing junctions, and define authentic microRNA binding sites.  Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over one thousand transcribed single nucleotide variants (~15% of all transcribed SNVs) alter local RNA structure; these “RiboSNitches”2 occur in disease-associated variants.  We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSS. Selective depletion of RiboSNitches versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3’UTRs, binding sites of miRNAs and RNA binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation. Overall design: RNA structure probing is performed at 37°C on poly(A)+ selected RNAs from GM12878, GM12891 and GM12892 cell lines, as well as on native proteinized RNAs from GM12878.  The structure probed RNAs is then cloned into a sequencing library using modied Ambion RNA sequencing kit compatible with the Illumina platform.  The samples were deep sequenced using Illumina''s Hi-Seq platform. AGO CLIP was performed as reported. Cells were crosslinked with UV and lysed using published protocols. AGO2 was enriched using immunopurification. The RNA-protein complex was digested with ribonuclease and purified by gel electrophoresis. Purified RNA was reverse transcribed and cDNA molecules were amplified and sequenced as described.	Co-expression
SRP029739	Whole transcriptome profiling of the two major subtypes of diffuse large B cell lymphoma	The goal of this study is to identify the transcriptome differences between the two major subtypes of diffuse large B cell lymphoma (DLBCL).  DLBCL is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC).  When compared to the GCB form, ABC lymphomas respond much more poorly to current therapies. To investigate how gene expression changes might contribute to this aggressive phenotype, we have used RNA-Seq to profile the whole transcriptome in 8 DLBCL cell lines (4 GCB subtype, 4 ABC) that are derived from patient tumors.  1,545 genes are differentially expressed between subtypes (FDR < 0.05), approximately 7% of the transcriptome.  The vast majority of these genes (81%, n = 1251) are more highly expressed in the ABC cell lines.  In contrast, only 294 genes (19%) are more highly expressed in the GCB cell lines.  Half (n = 765) of the genes with greater ABC subtype expression demonstrate very low read counts (< 5) in the GCB cell types.  Conversely, only 21 genes that are more highly expressed in GCB are unique to that subtype.  The prevalence of such “on/off” genes indicates that the major differences between ABC and GCB DLBCL are due almost exclusively to additional gene expression in ABC, rather than the two subtypes having divergent but equally active genetic programs. Overall design: Measurement and comparison of gene expression in 8 cell lines representing the 2 subtypes of DLBCL.  4 cell lines are subtyped as ABC and 4 are subtyped as GCB.  2 replicates are present for each cell line.  (Cell line OCI-Ly19 was not included in the analysis because its gene expression clustered in between the subtypes, probably due to its EBV+ status.  However, its sequencing runs have been included for completeness.)	Co-expression
SRP029880	Gene expression profiling study by RNA-seq in colorectal cancer	The objective of this study is to identify a prognostic signature in colorectal cancer (CRC) patients with diverse progression and heterogeneity of CRCs. We generated RNA-seq data of 54 samples (normal colon, primary CRC, and liver metastasis) from 18 CRC patients and, from the RNA-seq data, identified significant genes associated with aggressiveness of CRC. Through diverse statistical methods including generalized linear model likelihood ratio test, two significantly activated regulators were identified. In the validation cohorts, two activated regulators were independent risk factors and potential chemotherapy-sensitive agenets in colorectal cancers. Overall design: RNA-seq data of 54 samples (normal colon, primary CRC, and liver metastasis) were generated from 18 CRC patients. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x100 bp) using Hiseq-2000 (Illumina).	Co-expression
SRP029888	Primate iPS cells as tools for evolutionary analyses	Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from closely related species should be a central tool to understand human evolution and to identify conserved and variable patterns of iPSC disease models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs. We show that these cells are well comparable in their differentiation potential and generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analysed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes. Contributors: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany Overall design: We used expression profiling to characterize five gorilla, two bonobo and three macaque iPS clones as well as three iPS clones from two human individuals, three human embryonic stem (ES) cell lines and three macaque ES cell lines. We generated tagged RNA-Seq libraries from these 19 samples including four technical replicates (23 samples). Over 100 million single end reads were generated on the Illumina platform.	Co-expression
SRP029899	Tissue-specific RNA-seq in human evoked inflammation identifies novel blood and adipose lincRNA signatures of cardio-metabolic diseases	Inappropriate or sustained activation of innate immunity is a pathologic feature of several common cardio-metabolic disorders. Little is known, however, about transcriptomic modulation during inflammatory stress in disease-relevant human tissues. We applied deep RNA sequencing (RNA-seq) during low-dose experimental endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner, inflammatory tissue-level transcriptome responses of relevance to complex cardio-metabolic diseases. We utilized adipose and blood samples from three individuals who underwent a standardized inpatient endotoxemia protocol. Our comprehensive analysis revealed substantial, highly tissue- and subject-specific LPS-modulated changes in the expression of protein-coding genes and linc-RNAs as well as alternative splicing (AS). We also confirmed adipocytes and macrophages as potential cell sources of selective LPS-modulated linc-RNAs and AS events. Finally, we defined disease relevance of a subset of findings in obese adipose tissue and through interrogation of overlap with genome-wide association study loci for cardio-metabolic traits. Our findings provide novel insights into tissue-level genomic regulation, not detectable through analysis of DNA variations alone, of relevance to common cardio-metabolic diseases. Overall design: Using RNA-seq data to study LPS-modulated changes in lincRNA expression for adipose and blood of a healthy individual.	Co-expression
SRP029953	Homo sapiens strain:Several cell lines and primary RNA Targeted Locus (Loci)	More than half of human genes use alternative cleavage and polyadenylation (ApA) to generate mRNA transcripts that differ in the length of their 3' untranslated region (3'UTR), thus altering the post-transcriptional fate of the message and hence the protein output. The extent of 3'UTR variation across tissues and the functional role of ApA remain poorly understood. We developed a sequencing method to quantitatively map the 3' ends of the transcriptome of diverse human tissues and isogenic transformation systems. We found that cell type-specific gene expression is accomplished by two complementary programs. Tissue-restricted genes tend to have single 3'UTRs whereas a majority of ubiquitously transcribed genes generate multiple 3'UTRs. During transformation and differentiation, single-UTR genes change their mRNA abundance levels while multi-UTR genes mostly change 3'UTR isoform ratios to achieve tissue-specificity. However, both regulation programs target genes that function in the same pathways and processes that characterize the new cell type. Instead of finding global shifts in 3'UTR length during transformation and differentiation, we identify tissue-specific groups of multi-UTR genes that change their 3'UTR ratios – these changes in 3'UTR length are largely independent from changes in mRNA abundance. Finally, tissue-specific usage of ApA sites appears to be mechanism for changing the landscape targetable by ubiquitously expressed microRNAs.	Co-expression
SRP029987	Homo sapiens strain:293T cells Transcriptome or Gene expression	RBFOX over-expression in 293T cells	Co-expression
SRP029990	Molecular Hallmarks of Experimentally Acquired Immunity to Malaria [Pilot Study]	Sterile immunity to Plasmodium falciparum infection can be induced experimentally in humans after few exposures. An example is the induction of immunity using whole parasites by exposure of malaria-naive volunteers to infectious mosquito bites while using chloroquine prophylaxis (CPS immunization). Chloroquine kills blood-stage parasites but leaves liver-stage parasites unaffected, thereby exposing the liver-stage and early blood-stage antigens to the immune system. Upon subsequent challenge, volunteers are completely protected from infection, but protective efficacy decreases when fewer infectious mosquito bites are used for CPS immunization. Efforts to understand the mechanisms of this immunity, and how it differs from naturally-acquired immunity, may provide critical insights that could aid malaria vaccine development.  In this pilot study, transcriptomic features are derived from blood samples collected before and after challenge with infectious mosquito bites. Overall design: 12 samples; paired pre- and post-challenge for 5 individuals, plus two controls	Co-expression
SRP030027	Next generation sequencing of advanced non-castrate prostate cancer treated with docetaxel chemotherapy	Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival.  We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa.  As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Overall design: Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks	Co-expression
SRP030040	Homo sapiens Transcriptome or Gene expression	RNAseq human HCC	Co-expression
SRP030401	Gene expression, single nucleotide variant and fusion transcript discovery in archival material from breast tumors	Advantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs) and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. We measured gene expression in a set of manually degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from breast tumor with the hybridization based, NanoString nCounter, (226 gene panel) and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library preparation kits. We performed correlation analyses of gene expression between samples and across platforms. We then specifically assessed whole transcriptome expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE RNA-Seq data. For gene expression in the manually degraded samples, we observed Pearson correlation of >0.94 and >0.80 with NanoString and ScriptSeq protocols respectively. Gene expression data for matched fresh-frozen and FFPE samples yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes) and ScriptSeq whole transcriptome protocols respectively. Specifically for lincRNAs, we observed superb Pearson correlation (0.988) between matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we detected 53.4% of high confidence SNVs and 24% of high confidence fusion transcripts. Sensitivity of fusion transcript detection was not overcome by an increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million reads). Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene expression data for degraded and FFPE material. The high degree of correlation between NanoString and RNA-Seq platforms suggests discovery based whole transciptome studies from FFPE material will produce reliable expression data. The RiboZeroGold ScriptSeq protocol performed particularly well for lincRNA expression from FFPE libraries but detection of eSNV and fusion transcripts was less sensitive. Overall design: We performed RNASeq on RNA from nine matched pairs of fresh-frozen and FFPE tissues from breast cancer patients. The goal was to test the RiboZeroGold ScriptSeq complete low input library preparation kit for degraded RNA samples.	Co-expression
SRP030475	TALEN-based knockout of mir-141 and mir-200c in SK-BR-3 cells	We used transcription activator-like effector nucleases (TALENs) to generate knockout cells for two related microRNAs (miRNAs), mir-141 and mir-200c, which belong to the deeply conserved mir-200 family. By carrying out deep sequencing, we identified the target genes of each miRNA. Interestingly, miR-141 and miR-200c, despite their overall similarity, suppressed largely non-overlapping groups of targets. Overall design: Analysis of global mRNA level change in mir-141 and mir-200c knockout compared to wild type cells	Co-expression
SRP030617	Quantitative assessment of single-cell RNA sequencing methods	We generated single-cell transcriptomes from a large number of single cells using several commercially available platforms, in both microliter and nanoliter volumes, and compared performance between them. We benchmarked each method to conventional RNA-seq of the same sample using bulk total RNA, as well as to multiplexed qPCR, which is the current gold standard for quantitative single-cell gene expression analysis. In doing so, we were able to systematically evaluate the sensitivity, precision, and accuracy of various approaches to single-cell RNA-seq.  Our results show that it is possible to use single-cell RNA-seq to perform quantitative transcriptome measurements of individual cells, that it is possible to obtain quantitative and accurate gene expression measurements with a relatively small number of sequencing reads, and that when such measurements are performed on large numbers of cells, one can recapitulate the bulk transcriptome complexity, and the distributions of gene expression levels found by single-cell qPCR. Overall design: 109 single-cell human transcriptomes were analyzed in total; 96 using nanoliter volume sample processing on a microfluidic platform, Nextera library prep (biological replicates); 3 using the SMARTer cDNA synthesis kit, Nextera library prep (biological replicates); 3 using the Transplex cDNA synthesis kit, Nextera library prep (biological replicates); 7 using the Ovation Nugen cDNA synthesis kit (biological replicates) where 3 used Nextera library prep and 4 used NEBNext library prep. In addition, 4 bulk RNA samples were sequenced: bulk RNA generated using ~1 million pooled cells was used to make bulk libraries, 2 of which were made using SMARTer cDNA synthesis kit (technical replicates) and 2 made using Superscript RT kit with no amplification (technical replicates). All 4 bulk samples were made into libraries using Nextera.	Co-expression
SRP030628	Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation	78 tissue samples from prefrontal cortex (PFC) in human and macaque Overall design: The data from human and macaque PFC samples with different ages were used to estimate gene expression changes, including both protein-coding genes and lincRNAs, in PFC along lifespan in the two species.	Co-expression
SRP030639	A histone H3.3 Lysine 36 Trimethylation Reader Connects Chromatin to Regulated Pre-mRNA Processing	BS69 (aka ZMYND11) was initially discovered as a direct target of adenoviral E1A oncoprotein1. Subsequent studies implicated BS69 as a tumor suppressor and a transcriptional regulator2. But exactly how BS69 regulates gene expression has remained elusive. BS69 contains tandemly arranged PHD, BROMO and PWWP domains, which are known to function as chromatin recognition modalities. Here we show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via these chromatin recognition modules. Using a proteomics approach, we further identified association of BS69 with a host of RNA splicing regulators including EFTUD2 and other U5 snRNP components of the spliceosome. Remarkably, RNA-seq analysis shows that BS69 mainly regulates intron retention (IR), which is one of the least well-understood RNA alternative splicing events in mammalian cells. Specifically, loss of BS69 results in a decrease in IR, while in contrast, knockdown of EFTUD2 leads to an increase in IR, consistent with its role as a core member of the splicesome machinery. Importantly, wildtype BS69, but not a BS69 mutant defective in its interaction with EFTUD2, rescues the IR events. We also show that knockdown of SETD2, the main enzyme that mediates H3K36 trimethylation3, similarly results in a decreased retention of the same introns regulated by BS69. Significantly, a BS69 mutant unable to bind H3.3K36me3 in vitro fails to rescue the reduced IR phenotype associated with the loss of BS69. Taken together, our findings identify an antagonistic relationship between BS69 and the core splicing machinery and demonstrate that BS69-mediated RNA splicing regulation is dependent both on its ability to bind chromatin decorated by H3K36me3 and its ability to physically interact with the core spliceosome machinery. Our study reveals a novel and unexpected role of BS69 in connecting histone H3.3K36 trimethylation to regulated RNA splicing, providing significant new insights into chromatin regulation of RNA splicing. Overall design: HeLa cells were infected with lentiviruses carrying control and BS69 shRNA and deep sequencing data were generated, in triplicate, using Illumina HiSeq 2000	Co-expression
SRP031459	MicroRNA profiling of primary cutaneous large B-cell lymphomas	High-throughput sequencing of primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and in vitro activated peripheral blood B-cells. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Overall design: Lymphoma miRNA profiles of were generated by deep sequencing, using Illumina Genome Analyzer II.	Co-expression
SRP031476	RNA-seq differential expression studies: more sequence, or more replication?	Motivation: RNA-seq is replacing microarrays as the primary tool for gene expression studies. Many RNA-seq studies have used insufficient biological replicates, resulting in low statistical power and inefficient use of sequencing resources. Results: We show the explicit trade-off between more biological replicates and deeper sequencing in increasing power to detect differentially expressed (DE) genes. In the human cell line MCF-7, adding more sequencing depth after 10M reads gives diminishing returns on power to detect DE genes, while adding biological replicates improves power significantly regardless of sequencing depth. We also propose a cost-effectiveness metric for guiding the design of large scale RNA-seq DE studies. Our analysis showed that sequencing less reads and perform more biological replication is an effective strategy to increase power and accuracy in large scale differential expression RNA-seq studies, and provided new insights into efficient experiment design of RNA-seq studies Overall design: Treatment (10nM E2 treatment for 24h) and control MCF7 cells are both replicated 7 times, and collected for mRNA-seq. Reads are then subsampled for statistical analysis.	Co-expression
SRP031478	Altered Epigenetic Regulation of Homeobox Genes in Human Oral Squamous Cell Carcinoma Cells	To gain insight into the molecular changes during OSCC carcinogenesis, we performed unbiased, whole genome deep sequencing (RNA-seq) using RNA isolated from cultured, human TERT-immortalized, non-tumorigenic OKF6-TERT1R and OSCC SCC-9 cells. Overall design: OKF6-TERT1R cells and SCC-9 cells were  plated in 10 cm2 tissue culture plates at the density of 2 × 106 cells/plate and treated with 1 µM RA or vehicle (0.1% ethanol) for 48 hours. Experiment includes 3 independent biological replicates.	Co-expression
SRP031496	Transcriptome-based network analysis reveals a spectrum model of human macrophage activation [miRNA-seq]	Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. Overall design: Since transcriptional programs are further modulated on several levels including miRNAs we assessed the global spectrum of miRNA expression by miRNA-Seq in macrophages stimulated with IFN?, IL4 or with the combination of TNFa, PGE2 and P3C	Co-expression
SRP031507	Identification of the cellular RNAs bound by MOV10	Using the iCLIP protocol we have identified the cellular RNA entities that are bound by MOV10. We report the location and sequence of the MOV10 binding region on each RNA entity. Overall design: To identify the RNAs that bound MOV10, we UV-cross-linked HEK293F cells and immunoprecipitated with an irrelevant antibody (ir or "control") followed by a MOV10-specific antibody (MOV10) to isolate associated RNAs after stringent washing.	Co-expression
SRP031620	Homo sapiens strain:HeLa cells Transcriptome or Gene expression	Functional characterization of an identified physical connection between the cap-binding complex and the RNA exosome	Co-expression
SRP031698	Comparison of microRNA Profiling Platforms (HTS)	Global miRNA expression profiling of human malignancies is gaining popularity in both basic and clinically driven research. But to date, the majority of such analyses have used microarrays and quantitative real-time PCR.  With the introduction of digital count technologies, such as next-generation sequencing (NGS) and the NanoString nCounter System, we have at our disposal, many more options. To make effective use of these different platforms, the strengths and pitfalls of several miRNA profiling technologies were assessed, including a microarray platform, NGS technologies and the NanoString nCounter System.  These results were compared to gold-standard quantitative real-time PCR. Overall design: Comparison of non-small cell lung cancer cell lines grown in vitro (n = 5) and in vivo (n = 5) as xenograft models.	Co-expression
SRP031776	RNA-seq from primary skin fibroblasts, derived of matched pairs of middle and late donor age	Aging signatures developed from a longitudinal study design are dominated by reduced transcription of genes involved in protein synthesis Aging is a multifactorial process where the impact of singular components still remains unclear. Furthermore, previous studies were focused on measuring specific traits such as DNA -methylation and used categorical group-wise designs, unable to capture intra-individual signature changes. Here we have developed a new method for a longitudinal, age-related analysis combining the merits of a pair-wise design with the statistical power of gene set enrichment analysis. We present an integrated analysis, including transcriptional changes and genome-wide epigenetic changes in DNA- methylation, H3K4- and H3K27- histone methylation in promoter regions.  We tested our method on a rare collection of paired skin fibroblast samples from male middle age to old age transitions and obtained functional, age-related clusters. By using a set of only ten individuals, we could demonstrate a high overlap of functional terms to previously established tissue-independent age signatures including extracellular matrix, apoptosis and oxidative stress. Importantly, we identify protein translation-related processes as the main cluster of age-driven, specific down regulation. Overall design: Evaluation of transcriptional changes in matched sample pairs of primary skin fibroblasts from middle and old age.	Co-expression
SRP031849	Expanded identification and characterization of mammalian circular RNAs	The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type–specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their flanking linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a primate-specific zinc-finger gene, ZNF91. These results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs. Overall design: Examination of 9 samples in 1 cell type Note: The ENCODE data we used are under GEO SuperSeries GSE26284 (all samples labeled "_cell_total"). But they were not used in the processing of the U2OS data.	Co-expression
SRP031858	Transcriptional regulation in pluripotent stem cells by Methyl CpG binding protein 2 (MeCP2)	Rett syndrome (RTT) is one of the most prevalent female mental disorders. De novo mutations in methyl CpG binding protein 2 (MeCP2) are a major cause of RTT. MeCP2 regulates gene expression as a transcription regulator as well as through long-range chromatin interaction. Because MeCP2 is present on the X chromosome, RTT is manifested in a X-linked dominant manner. Investigation using murine MeCP2 null models and post-mortem human brain tissues has contributed to understanding the molecular and physiological function of MeCP2. In addition, RTT models using human induced pluripotent stem cells derived from RTT patients (RTT-iPSCs) provide novel resources to elucidate the regulatory mechanism of MeCP2. Previously, we obtained clones of female RTT-iPSCs that express either wild type or mutant MECP2 due to the inactivation of one X chromosome. Reactivation of the X chromosome also allowed us to have RTT-iPSCs that express both wild type and mutant MECP2. Using these unique pluripotent stem cells, we investigated the regulation of gene expression by MeCP2 in pluripotent stem cells by transcriptome analysis. We found that MeCP2 regulates genes encoding mitochondrial membrane proteins. In addition, loss of function in MeCP2 results in de-repression of genes on the inactive X chromosome. Furthermore, we showed that each mutation in MECP2 affects a partly different set of genes. These studies suggest that fundamental cellular physiology is affected by mutations in MECP2 from very early fetal development and that a therapeutic approach targeting to unique forms of mutant MeCP2 is needed. Overall design: RNA samples from normal ESCs/iPSCs, RTT-iPSCs and MeCP2 KD iPSCs were obtained. Gene expression of those cells were analyzed.	Co-expression
SRP031868	Bilaterality of Human Neocortical Topographic Gene Expression	We performed RNA-seq to identify differentially expressed genes between left and right hemispheres. This datased contains raw mRNA sequencing data of superior temporal cortices from both left and right hemispheres of eleven human brains.	Co-expression
SRP032165	Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (Multiplex Analysis of PolyA-linked Sequences)	Purpose: The purpose of this experiment is to identify a C9-ALS/FTD specific genomic profile in fibroblast lines that is distinct from sporadic ALS without C9orf72 expansion and non-neurologic control cells. The study will then evaluate the effect on this identified profile of ASO treatment targeting the sense strand RNA transcript of the C9orf72 gene. Methods: Expression profiling was performed on RNAs from fibroblasts of four C9orf72 patients, four control individuals and four sporadic ALS patients using Multiplex Analysis of PolyA-linked Sequences method. Results: Hierarchical clustering of expression values for all genes showed that the four C9orf72 patient lines had an expression profile distinct from control and sporadic ALS lines. Statistical comparison of expression values between the four C9orf72 lines and the four control lines revealed that 122 genes were upregulated (defined by a False Discovery Rate FDR<0.05) and 34 genes were downregulated (defined by a False Discovery Rate FDR <0.05) in C9orf72 patient fibroblasts. Conclusions: A genome wide RNA signature can be defined in fibroblasts with C9orf72 expansion. ASO-mediated reduction of C9orf72 RNA levels in fibroblasts with the hexanucleotide expansion efficiently reduced accumulation of GGGGCC RNA foci. This did not, however, generate a reversal of the C9orf72 RNA profile. Overall design: Use of Multiplex Analysis of PolyA-linked Sequences to identify expression changes in fibroblasts from amyotrophic lateral sclerosis and frontotemporal dementia patients harboring an hexanucleotide expansion in the C9orf72 gene.	Co-expression
SRP032168	HERV Abundance in Human Brain	HERV abundance in Human brain	Co-expression
SRP032279	Huntington’s disease biomarker progression profile identified by transcriptome sequencing in peripheral blood	In this study we investigated the suitability of blood to identify HD transcriptomic biomarkers, validated the outcome in an independent cohort and derived a first empiric panel of biomarkers capable of predicting HD motor scores. Finally we examined whether patient gene expression profiles could provide information about HD affected biological pathways. Overall design: Examination of differentially expressed genes in peripheral whole blood using linear modelling of  gene expression data (3'' DGE) against UHDRS total motor scores of Huntington''s Disease mutation carriers and controls.	Co-expression
SRP032363	Identification and Initial Functional Characterization of SENCR, a Long Non-Coding RNA Enriched in Human Vascular Cells	RNA sequencing (RNA-seq) analysis revealed 31 novel lncRNAs in HCASMC, including a vascular cell-enriched lncRNA called SENCR (for Smooth muscle and Endothelial cell long Non-Coding RNA). RT-PCR and hybridization studies show SENCR exists in two isoforms and is transcribed antisense from the 5’ end of the FLI1 gene. Knockdown of SENCR has no effect on FLI1 mRNA or protein expression. Biochemical fractionation and RNA fluorescence in situ hybridization (FISH) studies indicate SENCR is a cytoplasmic lncRNA. RNA-seq experiments in HCASMC where SENCR is attenuated disclose decreased expression of Myocardin and many SMC contractile genes; conversely a pro-migratory gene signature is increased. RT-PCR and Western blotting validated several differentially expressed genes following SENCR knockdown. Loss-of-function studies in scratch wound and Boyden chamber assays support SENCR as an inhibitor of vascular cell migration. Overall design: Total RNAs of 3 replicates of normal human coronary artery smooth muscle cells (Mock1, Mock2 and Mock3) were sequenced and analyzed for identification of novel lncRNAs. One of identified novel lncRNAs from that experiment is SENCR. To study its function, SENCR knock-down experiment were performed and then RNA-seq profiles of 3 replicates of both SENCR-knockdown samples and corresponding controls were compared.	Co-expression
SRP032455	RNA-Seq analysis of human adult peripheral blood populations	Generate transcriptomic atlas of healthy peripheral blood subpopulations Overall design: RNA-Seq performed on sorted granulocytes, monocytes, B-cells, T-cells, total WBC, CD34+ cells Leucegene Project, IRIC	Co-expression
SRP032456	A bioinformatics approach reveals novel mechanisms of the OVOL transcription factors in the regulation of epithelial-mesenchymal cell programming and cancer progression.	We find significant evidence of the OVOL, AP1, STAT1, STAT3, and NFKB1 TFs having important roles in MET. We prioritize known gene/drug targets for follow-up in the clinic, and show that the AP1/MYC TF pair is a strong candidate for intervention. Overall design: Examination of the effects of OVOL1 and OVOL2 overexpression common to prostate cancer and breast cancer models.	Co-expression
SRP032476	ETMR RNA-Seq	RNA sequencing data for patients with Embryonal tumor with multilayered rosettes and Primitive neuroectodermal tumor as controls.	Co-expression
SRP032510	RNA-seq analysis reveals endogenous aryl hydrocarbon receptor regulation is highly associated with eicosanoid synthesis and tumor necrosis factor activity in MCF-7 cancer cells	Background: The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is activated by xenobiotic chemicals that function as AHR ligands.  The response to xenobiotic AHR ligands is toxicity and the induction of drug metabolizing enzymes. The impact of AHR knockdown on gene expression and pathways in human breast cancer cells in absence of xenobiotic AHR ligands has not been investigated on a genome-wide scale. Methods: MCF-7 cells were used as a model of human breast cancer.  The AHR was silenced with short interfering RNA against AHR (siAHR).  RNA-sequencing coupled with Ingenuity pathway analysis (IPA) was used to determine the impact of AHR knockdown on gene expression and pathways in the absence of xenobiotic AHR ligands.  Western blot analysis and recombinant tumor necrosis factor (TNF) was used to investigate the impact of AHR knockdown on TNF induction of MNSOD expression. Results: We found that the AHR is transcriptionally active in MCF-7 breast cancer cells in the absence of xenobiotic AHR ligands.  In total, the expression of 634 genes was significantly changed in AHR knockdown cells compared to controls at a false discovery rate of < 10%. The analysis confirmed that drug metabolizing enzymes were AHR targets; however, we found that AHR also promoted the expression of genes that were not directly related to the metabolism of xenobiotics, such as those involved in lipid and eicosanoid synthesis.  Gene pathway analysis of the AHR regulated gene dataset predicted TNF activity to be reduced in AHR knockdown cells.  Our finding that AHR knockdown inhibited TNF-stimulated increases in MNSOD expression confirmed this IPA prediction. Conclusions: This is the first gene expression profiling study of AHR knockdown breast cancer cells.  Several known and novel AHR targets were identified.  The results suggest that endogenous AHR regulation impacts eicosanoid synthesis by regulating gene expression.  The IPA prediction of reduced TNF activity in AHR knockdown cells was confirmed by showing that TNF-induced increases in MNSOD expression was inhibited in AHR knockdown cells.   The requirement of AHR for MNSOD activation is novel and provides a new link by which AHR may impact reactive oxidative species (ROS) signaling. Overall design: Expression profiles by mRNA sequencing were generated for human MCF-7 cells transfected with cRNAi (6 replicates) or AHR-siRNA (5 replicates) for 36hr. Sequencing was performed on an Illumina HiSeq 1000 using a 2x100 base paired-end strategy.	Co-expression
SRP032539	Transcriptome-wide discovery of microRNA binding sites in human brain by Ago2 HITS-CLIP [Ago2-miRNA-target mRNA complexes]	Here, seeking to gain insight into the array of transcripts engaged with miRNAs in human brain, we performed HITS-CLIP to profile transcriptome-wide Ago2:RNA interactions in a panel of eleven post-mortem adult human brain samples harvested from adult motor cortex and cingulate gyrus, regions associated with movement and psychiatric disorders . Overall design: High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) Eleven post-mortem adult human brain tissues were subjected to ultraviolet radiation to crosslink proteins with nucleic acids, and HITS-CLIP was performed as previously described by Chi et al Nature. 2009 Jul 23;460(7254):479-86 using an anti-Ago2 polyclonal antibody and some additional modifications.	Co-expression
SRP032540	Transcriptome-wide discovery of microRNA binding sites in human brain by Ago2 HITS-CLIP [Ago2-miRNA complexes]	Here, seeking to gain insight into the array of transcripts engaged with miRNAs in human brain, we performed HITS-CLIP to profile transcriptome-wide Ago2:RNA interactions in a panel of eleven post-mortem adult human brain samples harvested from adult motor cortex and cingulate gyrus, regions associated with movement and psychiatric disorders . Overall design: High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) Eleven post-mortem adult human brain tissues were subjected to ultraviolet radiation to crosslink proteins with nucleic acids, and HITS-CLIP was performed as previously described by Chi et al Nature. 2009 Jul 23;460(7254):479-86 using an anti-Ago2 polyclonal antibody and some additional modifications.	Co-expression
SRP032559	Identification of miR-181a target genes in Epithelial Ovarian Cancer	We have identified a single miRNA, miR-181a, that can modulate TGF-ß signaling to induce and maintain EMT, and effect further downstream events of tumour cell survival, altered response to chemotherapy, migration, invasion and dissemination in vivo. Our present study provides an understanding of how enhanced expression of miR-181a can confer malignant and invasive traits through the modulation of a canonical signaling pathway and a consequent maintenance of a mesenchymal state. Furthermore, inhibition of miR-181a led to a reversion of EMT and subsequent events through decreased TGF-ß signaling. Our data confirmed Smad7 as a functional target through which TGF-ß-mediated EMT occurs; re-expression of Smad7 lacking its 3'UTR was able to rescue miR-181a-mediated phenotypes, deeming Smad7 as a critical mediator of miR-181a-induced EMT. Other recent studies support the crucial role(s) that miRNAs play in mediating EMT and consequent aggressive disease traits. For example, the miR-106b-25 cluster has also been shown to target Smad7 and mediate TGF-ß-induced EMT downstream to Six1 in breast cancer34. miR-9 directly targets E-cadherin and inhibition of miR-9 had led to an inhibition of metastasis35. Conversely, the miR-200 and -205 family was shown to target transcriptional repressors of E-cadherin, ZEB1 and SIP1, and re-expression of these miRNAs led to a mesenchymal-to-epithelial transition and prevented TGF-ß -induced EMT36. Overall design: A2780 ovarian cancer cell lines stably expressing either pBABE (control vector), p181a#1( clone 1 expressing miR-181a) or p181a#2( clone 2 expressing miR-181a)	Co-expression
SRP032743	Identification of transcripts altered upon LIN-41 knockdown in human embryonic stem cells	To identify transcripts altered upon LIN-41 knockdown, we transfected either a control siRNA or one of two different LIN-41 siRNAs into human embryonic stem cells and collected total RNA 72 hours after transfection. Overall design: We compared transcript levels between control siRNA or LIN-41 siRNA treated cells.	Co-expression
SRP032754	High resolution ChIP sequencing reveals novel bindings targets and prognostic role for SOX11 in Mantle cell lymphoma (RNA-Seq)	SOX11 (Sex determining region Y-box 11) expression is specific for MCL as compared to other Non-Hodgkin’s lymphomas. However, the function and direct binding targets of SOX11 in MCL are largely unknown. We used high-resolution ChIP-Seq to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11 target genes. qCHIP confirmed that SOX11 directly binds to individual genes in these pathways in both MCL cell lines and patients. Interrogation of an eighty-two patient  gene-expression dataset demonstrated that SOX11 mRNA expression was inversely proportional to Ki-67, a marker of cell proliferation. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT signaling and modulates chemotherapy sensitivity to cytarabine in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolina Institute and British Columbia Cancer Agency (BCCA). Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy incorporating cytarabine. Transcriptional regulation of WNT and other biological pathways affects by SOX11 target genes may help explain the impact of SOX11 expression on patient outcomes. Overall design: RNA-seq experiments studying SOX11-mediated regulation of gene transcription by examining genes differentially expressed following SOX11 depletion in 3 MCL cell lines, Granta-519, Z138 and JEKO-1	Co-expression
SRP032775	Molecular Hallmarks of Naturally Acquired Immunity to Malaria	Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. Overall design: 108 samples; paired pre- and post-challenge for 54 individuals 198 samples; paired pre- and post-challenge for 99 individuals	Co-expression
SRP032789	mRNA-sequencing of breast cancer subtypes and normal tissue	Goal: To define the digital transcriptome of three breast cancer subtypes (TNBC, Non-TNBC, and HER2-positive) using RNA-sequencing technology. To elucidate differentially expressed known and novel transcripts, alternatively spliced genes and differential isoforms and lastly expressed variants in our dataset. Method: Dr. Suzanne Fuqua (Baylor College of Medicine) provided the human breast cancer tissue RNA samples. All of the human samples were used in accordance with the IRB procedures of Baylor College of Medicine. The breast tumour types, TNBC, Non-TNBC and HER2-positive, were classified on the basis of immunohistochemical and RT-qPCR classification. Results: Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast.  We also report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. Additionally we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer Overall design: mRNA profiles of 17 breast tumor samples of three different subtypes (TNBC, non-TNBC and HER2-positive) and normal human breast organoids (epithelium) samples (NBS) were sequenced using Illumina HiSeq.	Co-expression
SRP032798	iPSC derived motor neuron cultures from C9ORF72 carriers	Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat–containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-a, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS. Overall design: Transcriptome profiling from iPSC derived motor neurons compared to controls	Co-expression
SRP032812	Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants (RNA-seq)	Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (=3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type-specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type-specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases. Overall design: Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project. NISC Comparative Sequencing Program	Co-expression
SRP032833	Identification of mRNAs and lincRNAs associated with lung cancer progression using next-generation RNA sequencing from laser micro-dissected archival FFPE tissue specimens	Adenocarcinoma in situ (AIS) is considered an intermediate step in the progression of normal lung tissue to invasive adenocarcinoma.  However, the molecular mechanisms underlying this progression remain to be fully elucidated due to difficulties in obtaining and preserving clinical samples for downstream analyses.  Formalin fixation and paraffin embedding (FFPE) is a tissue preservation system that is widely used as a means for long-term storage.  Until now, challenges in working with FFPE have precluded using new RNA sequencing technologies (RNA-seq), which would help clarify some of the key pathways affected in the transition from normal to AIS to invasive adenocarcinoma.  Recent technological advances have made it possible to sequence RNA from archival tissues.  Also, isolation techniques including laser-capture micro-dissection provide the ability to select histopathologically distinct tissues, allowing researchers to study transcriptional variations between tightly juxtaposed cell and tissue types.  Utilizing these technologies and new alignment tools we examined differential expression of long intergenic non-coding RNAs and mRNAs across normal, AIS and invasive adenocarcinoma samples from six patients to identify possible markers of lung cancer progression. RNA extracted and sequenced from these 18 samples generated an average of 198 million reads per sample.  After alignment and filtering, uniquely aligned reads represented an average 35% of the total reads.  We detected differential expression of a number of lincRNAs and mRNAs when comparing normal to AIS, or AIS to invasive adenocarcinoma.  Of these, 5 lincRNAs and 31 mRNAs were consistently up- or down-regulated from normal to AIS and more so to invasive carcinoma.  We validated the up-regulation of two mRNAs and one lincRNA by RT-qPCR as proof of principle. Our findings indicate a potential role of not only mRNAs, but also lincRNAs in invasive adenocarcinoma.  We anticipate that our current findings will lay the groundwork for future experimental studies of candidate RNAs from FFPE samples to identify their functional roles in lung cancer. Overall design: RNA-Seq in 6 patients in norma lung, adenocarcinoma in situ of the lung, and invasive lung carcinoma	Co-expression
SRP032926	Comparative analysis of human and mouse transcriptomes of Th17 cell priming.	Uncontrolled Th17 cell activity is associated with cancer and autoimmune and inflammatory diseases. To validate the potential relevance of mouse models of targeting the Th17 pathway in human diseases we used RNA sequencing to compare the expression of coding and non-coding transcripts during the priming of Th17 cell differentiation in both human and mouse. In addition to already known targets, several transcripts not previously linked to Th17 cell polarization were found in both species. Moreover, a considerable number of human-specific long non-coding RNAs were identified that responded to cytokines stimulating Th17 cell differentiation. We integrated our transcriptomics data with known disease-associated polymorphisms and show that conserved regulation pinpoints genes that are relevant to Th17 cell-mediated human diseases and that can be modelled in mouse. Substantial differences observed in non-coding transcriptomes between the two species as well as increased overlap between Th17 cell-specific gene expression and disease-associated polymorphisms underline the need of parallel analysis of human and mouse models. Comprehensive analysis of genes regulated during Th17 cell priming and their classification to conserved and non-conserved between human and mouse facilitates translational research, pointing out which candidate targets identified in human are worth studying by using in vivo mouse models. Overall design: Altogether 114 (57 human and 57 mouse) samples were analyzed representing 3 biological replicates of timeseries data (0, 0.5, 1, 2, 4, 6, 12, 24, 48 and 72 hours) of Th17 polarized cells and control Th0 cells	Co-expression
SRP032928	Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21 [RNA-seq]	Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. Overall design: mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21	Co-expression
SRP032953	Epigenetic regulation of the MEG3-DLK1 microRNA cluster in human Type 2 diabetic islets	Type 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo. Overall design: There are three experiments in this submission. All are in human islets or islet cell types. The first is a  comparison of miRNA levels in sorted alpha versus beta cells. There is one replicate for this experiment. The second  experiment is to measure the expression of miRNAs in whole islets as a function of glucose levels. There are three  levels and one replicate for each condition. The third exeriment is a comparison of whole islets taken from human  donors that were suspected/confirmed Type 2 diabetic or considered controls. There are 3 controls and 4 T2D samples.	Co-expression
SRP032989	mRNA expression in C-33A cells expressing HPV1 E2	Profile of RNA expression in a C-33A cell line derived from an HPV negative cervical carcinoma in the presence or absence of HPV1 E2 expression. Overall design: mRNA profiles of C-33A cells in presence or absence of HPV1 E2 expression were generated by deep sequencing using Illumina GAIIx. Two samples (no replicates). One control and one experimental.	Co-expression
SRP032999	Next generation sequencing of the transcriptome in MCF-7 cells with/without SRA knockdown	We employed next generation sequencing to examine whether knocking down the steroid receptor RNA activator (SRA) gene significantly affect the expression levels of certain genes in MCF-7 cells. MCF-7 cells were transfected with either a pool of four non-target control siRNAs or a pool of four SRA siRNAs for 32 hrs. 157 million reads were generated from triplicate samples of the control group; 151 million reads were generated from triplicate samples of the SRA knockdown group. Six genes were identified as significantly changed in the expression levels with the cutoff of q value = 0.05, fold change = 0.5 or = 2, and reads per kilobase per million mapped reads (RPKM) = 1. However, except for SRA itself, the other five genes were shown by real-time PCR to be only affected by one siRNA in the SRA siRNA pool. Further analysis of this dataset with different cuttoff setting may reveal true SRA-regulated genes in MCF-7. Overall design: MCF-7 cells were cultured in high glucose DMEM with 10% fetal bovine serum, 2 mM Glutamax-1, 100 units/ml penicillin and 100 µg/ml streptomycin. ON-TARGETplus SMARTpool for human SRA (Thermo Scientific, L-027192-00-0005) was used to knockdown SRA (siSRA) and ON-TARGETplus Non-targeting Pool Thermo Scientific, D-001810-10-05) was used as a negative control (siCtrl). A total of 25 nM siRNA was transfected in 6-well dishes using Lipofectamine™ RNAiMAX Reagent (Life Technologies, Invitrogen) following the manufacturer’s recommendations. Polyadenylated RNA was purified from the cells 32 hrs after transfection. cDNA libraries were prepared and double-stranded cDNA was fragmented using DNase I according to Illumina specifications, prior to adaptor ligation. Sequencing libraries were amplified and sequenced using an Illumina HiSeq 2000 sequencer.	Co-expression
SRP033057	Functional Annotation of Colon Cancer Risk SNPs	To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers'' putatively targeted genes,  we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function Overall design: Two biological replicates of HCT116 were compared to the data of two normal colon samples already deposited in GEO (GSM1010974 and GSM1010942).	Co-expression
SRP033078	Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging	Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) sets their identity back to an embryonic age. This presents a fundamental hurdle for modeling late-onset disorders using iPSC-derived cells. We therefore developed a strategy to induce age-like features in multiple iPSC-derived lineages and tested its impact on modeling Parkinson’s disease (PD). We first describe markers that predict fibroblast donor age and observed the loss of these age-related markers following iPSC induction and re-differentiation into fibroblasts. Remarkably, age-related markers were readily induced in iPSC-derived fibroblasts or neurons following exposure to progerin including dopamine neuron-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes requiring both aging and genetic susceptibility such as frank dendrite degeneration, progressive loss of tyrosine-hydroxylase expression and enlarged mitochondria or Lewy body-precursor inclusions. Our study presents a strategy for inducing age-related cellular properties and enables the modeling of late-onset disease features. Overall design: Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.	Co-expression
SRP033095	Transcriptome analysis reveals differential splicing events in IPF lung tissue	Objectives: Idiopathic pulmonary fibrosis (IPF) is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of genome-wide transcription through RNA sequencing (RNA-Seq) enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. Methods: Messenger RNA extracted from 8 IPF lung samples and 7 healthy controls was sequenced on an Illumina HiSeq. Analysis of differential expression and exon usage was performed using Bioconductor packages. The gene periostin was selected for validation of alternative splicing by quantitative PCR, and pathway analysis was performed to determine enrichment for differentially expressed and spliced genes. Results: There were 873 genes differentially expressed in IPF (FDR 5%), and 440 unique genes had significant differential splicing events (FDR 5%). In particular, cassette exon 21 of the gene periostin was significantly more likely to be spliced out in IPF samples (adj pval = 2.06e-09), and this result was confirmed by qPCR (Wilcoxon pval = 3.11e-4). We also found that genes close to SNPs in the discovery set of a recent IPF GWAS were enriched for genes differentially expressed in our data, including genes like mucin5B and desmoplakin which have been previously associated with IPF. Conclusions: There is significant differential splicing and expression in IPF lung samples as compared with healthy controls. We found a strong signal of differential cassette exon usage in periostin, an extracellular matrix protein whose increased gene-level expression has been associated with IPF and its clinical progression, but for which differential splicing has not been studied in the context of IPF. Our results suggest that alternative splicing of periostin and other genes may be involved in the pathogenesis of IPF. Overall design: mRNA sequencing of 8 IPF and 7 control lung tissue samples.	Co-expression
SRP033098	RNAseq of Mantle Cell Lymphoma (MCL) cell lines	The goal was to catalogue mutations in mantle cell lymphoma cell lines.	Co-expression
SRP033115	SF3B1 mutations in Breast Cancer	No description.	Co-expression
SRP033117	Global Bidirectional Transcription of the Epstein-Barr Virus Genome During Reactivation	Using strand specific RNA-seq to assess the EBV transcriptome during reactivation of Akata cells, we found extensive bidirectional transcription extending across nearly the entire genome. Overall design: Illumina strand-specific RNA-seq of BCR-activated Akata cells at 9 time points	Co-expression
SRP033119	Transcriptome-wide mapping of human Staufen1 binding sites	Purpose: We performed RNA-Immunoprecipitation in Tandem (RIPiT) experiments against human Staufen1 (Stau1) to identify its precise RNA binding sites in a transcriptome-wide manner. To monitor the consequences of Stau1 binding in terms of target mRNA levels and ribosome occupancy, we modified the levels of endogenous Stau1 in cells by siRNA or overexpression and performed RNA-sequencing and ribosome-footprinting experiments. Staufen1 (Stau1) is a double-stranded RNA (dsRNA) binding protein implicated in mRNA transport, regulation of translation, mRNA decay and stress granule homeostasis. Here we combined RNA-Immunoprecipitation in Tandem (RIPiT) with RNase footprinting, formaldehyde crosslinking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1 binding sites transcriptome-wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3''UTRs or in "strongly distal" 3''UTRs extending far beyond the canonical polyadenylation signal. Stau1 also interacts with both actively translating ribosomes and with mRNA coding sequences (CDS) and 3''UTRs in proportion to their GC-content and internal secondary structure-forming propensity.  On mRNAs with high CDS GC-content, higher Stau1 levels lead to greater ribosome densities, suggesting a general role for Stau1 in modulating the ability of ribosomes to elongate through secondary structures located in CDS regions. Overall design: We used HEK293 cells expressing near endogenous levels of wild-type Flag-Stau1 (65KDa isoform with an N-Terminal Flag tag). As a control we used a mutant version of Stau1 that is not functional for dsRNA binding. Formaldehyde crosslinking experiments and RNase footprinting experiments were done in two biological replicates. All RNASeq, Ribosome footprinting and PAS-Seq were done in two biological replicates.	Co-expression
SRP033131	Global analyses of the effect of different cellular contexts on microRNA targeting (RNA-Seq)	RNA-seqs followed by miRNA transfections (miR-124 and miR-155) into four different cell lines( HeLa, HEK293, Huh7, and IMR90). Overall design: There are two biological replicates of RNA-seqs per each miRNA transfection per each sample and there are corresponding mock transfections.	Co-expression
SRP033135	Pseudo-temporal ordering of individual cells reveals regulators of differentiation	Single-cell expression profiling by RNA-Seq promises to exploit cell-to-cell variation in gene expression to reveal regulatory circuitry governing cell differentiation and other biological processes.  Here, we describe Monocle, a novel unsupervised algorithm for ordering cells by progress through differentiation that dramatically increases temporal resolution of expression measurements. This reordering unmasks switch-like changes in expression of key regulatory factors, reveals sequentially organized waves of gene regulation, and exposes regulators of cell differentiation. A functional screen confirms that a number of these regulators dramatically alter the efficiency of myoblast differentiation, demonstrating that single-cell expression analysis with Monocle can uncover new regulators even in well-studied systems. Overall design: We selected primary human myoblasts as a model system of cell differentiation to investigate whether ordering cells by progress revealed new regulators of the process. We sequenced RNA-Seq libraries from each of several hundred cells taken over a time-course of serum-induced differentiation. Please note that this dataset is a single-cell RNA-Seq data set, and each cell comes from a capture plate.  Thus, each well of the plate was scored and flagged with several QC criteria prior to library construction, which are provided as sample characteristics; CONTROL indicates that this library is a off-chip tube control library constructed from RNA of approximately 250 cells and ''DEBRIS'' indicates that the well contained visible debris (and may or may not include a cell). Libraries marked DEBRIS thus cannot be confirmed to come from a single cell.	Co-expression
SRP033239	Epigenetic regulation of the MEG3-DLK1 microRNA cluster in human Type 2 diabetic islets	Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing ß-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human ß-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased ß-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM. Overall design: Identification of miRNA-target interaction in human islets using HITS-CLIP, one mRNA library and one miRNA library	Co-expression
SRP033248	MicroRNA Marker Based Prognostication of Oral Squamous Cell Carcinoma	The aim of our study was to discover a miR marker panel prognostic of 5-year survival in OSCC patients that may be utilized in parallel with the current clinical covariates. We assessed differential expression of miRNAs genome-wide via deep sequencing in 20 tumor tissue samples. We also attempted to identify deregulated miR expression signatures that may serve as the prognostic marker of cancer survival. Selected miR marker-based panel then may serve as a guide for selection of appropriate follow-up chemo/radiation treatment, significantly improving the clinical management of OSCC and the overall survival rate. Overall design: Identify miRs differentially expressed in the poor prognosis group compared to the good prognosis group	Co-expression
SRP033250	Fusion discovery in breast cancer cell line	SnowShoes-FTD, a fusion transcript discovery tool, was used to identify fusions in breast cancer cell lines using the RNA-Seq data Overall design: Total RNA extracted from cell lines. The total RNA was used for construction of RNA-Seq library for RNA-Sequencing.	Co-expression
SRP033266	Leucegene: AML sequencing (part 2)	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.	Co-expression
SRP033276	Distinct gene expression profiles between overt GIST and miniGIST	In contrast to the paucity of clinic GIST (Gastrointestinal stromal tumor; 0.0014 % happening rate), there is a more than twenty thousand times higher rate for miniGISTs, about ~30% of human population could be identified to have miniGISTs. Exploring the molecular differences between miniGISTs and overt GISTs will help us to understand the transformation mechanisms along with GIST progression, but C-kit and PDGFRA mutations analysis failed to identify the differences between these two groups.   Conclusion: miniGISTs have significant distinct gene expression profile with overt GISTs by both unsupervised and supervised analysis. Our finding indicated that c-kit and DOG1 expression are the very early events in the genesis of miniGIST and overt GIST, and miniGIST is a molecular distinct group with overt GIST. Overall design: Within our study, we collected six miniGISTs with diameter less than 1cm from autopsies and seven overt GISTs from clinic, performed the first system-wide gene expression profiling of miniGISTs and overt GISTs by 3’end RNA Sequencing, and further compared the expression profiles between these two groups.	Co-expression
SRP033282	The RON receptor tyrosine kinase promotes metastasis by triggering epigenetic reprogramming through the thymine glycosylase MBD4 (RNA-Seq)	Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo. Overall design: Examination of 3 cell types.	Co-expression
SRP033291	Homo sapiens Transcriptome or Gene expression	Superior frontal gyrus grey and white matter	Co-expression
SRP033335	Genome-wide expression profiling of B Lymphocytes reveals IL4R increase in allergic asthma	In this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy. Overall design: RNA-seq was used to asses expression differences in B CD19 Lymphocytes from house dust mite allergic patients and healthy controls.	Co-expression
SRP033336	The splicing activator DAZAP1 integrates splicing control into MEK/Erk regulated cell proliferation and migration	DAZAP1 was depleted in culterd HEK 293T cells using shRNA and the resulting poly A RNA were isolated  c-DNA library constructed and paired end sequenced on illumina Hi-seq 2000 platform the data was compared to a control shRNA depleted cell Overall design: Gene expression and splicing switches upon DAZAP1 knockdown	Co-expression
SRP033351	Human Airway Smooth Muscle Transcriptome Changes in Response to Asthma Medications	Rationale: Asthma is a chronic inflammatory airway disease. The most common medications used for its treatment are ß2-agonists and glucocorticosteroids, and one of the primary tissues that these drugs target in the treatment of asthma is the airway smooth muscle. We used RNA-Seq to characterize the human airway smooth muscle (HASM) transcriptome at baseline and under three asthma treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for HASM cells from four white male donors under four treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with a glucocorticosteroid (i.e. Dexamethasone (Dex), 1µM for 18h); 4) simultaneous treatment with a ß2-agonist and glucocorticoid, and the libraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for four primary human airway smooth muscle cell lines that were treated with dexamethasone, albuterol, dexamethasone+albuterol or were left untreated.	Co-expression
SRP033369	Poly(A)-tail profiling reveals an embryonic switch in translational control	Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA mediated deadenylation concurrently shifts from translational repression to mRNA destabilization. Overall design: 64 samples from a variety of species	Co-expression
SRP033393	Analysis of pre-mRNA splicing trans-regulation in human lymphoblastoid cell lines	To understand the role of trans factors in the regulation of splicing and alternative splicing, we knocked-down 22 RNA-binding proteins previously shown or suspected to be involved in the regulation of splicing (“splicing factors”). We performed knockdown experiments in triplicate in the Hapmap lymphoblastoid cell line GM19238 using small interfering RNAs (siRNAs). RNA was extracted 72 hours after knockdown for RNA-seq library preparation. The following splicing factors were analyzed: ACIN1, ADAR, HNRPA2B1, HNRPF, HNRPH1, HNRPH2, HNRPK, HNRPL, HNRPR, PCBP2, PTBP1, RBM23, RBM39, RBMX, RNPS1, SRSF1, SRSF3, SRSF4, SRSF8, SRSF9, SRSF10 and SYNCRIP. Seven controls were generated with non-specific siRNA probes transfection. RNA-seq libraries were multiplexed and sequenced on 3 different flow-cells on an Illumina HiSeq 2000 sequencer (single-end 107 bp long reads). Overall design: 73 samples, including 3 replicates for each of the 22 knockdowns and 7 controls	Co-expression
SRP033432	Differential expression of human parthenogenic stem cells, neural stem cells and DA progenitors.	Neural stem cells (NSC) derived from human parthenogenic stem cells (hpSC) have been observed to show stronger positive functional effects than hpSC-derived dopaminergic neuron precursors (DAP) in treatment of induced Parkinson Disease in animal models. RNAseq of the two types of cells were normalized and analyzed to compare gene expression profiles. Overall design: cDNA library of hpsC, NSC and DAP triplicates were sequenced using Illumina HiSeq 2000. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.	Co-expression
SRP033464	miR-155 plays a crucial role in ALS and is an immune therapeutic target [RNA-Seq]	Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155. Overall design: Total RNA was isolated from whole lumbar spinal cord homogenate from healthy control donors without known neurologic diseases and sporadic and familial ALS.	Co-expression
SRP033466	Transcriptome analysis of Jurkat T cells expressing MALT1 or its mutants MALT1-R149A and MALT1-C464A or the MALT1-R149A-C464A double mutant.	Purpose: study the role of MALT1 auto-proteolysis in T cell receptor mediated activation of NF-kB. Methods: Jurkat cells were generated that express wild type MALT1, the auto-cleavage deficient MALT1-R149A mutant, the catalytic inactive MALT1-C464A mutant or the R149A-C464A double mutant (RACA). Expression of endogenous MALT1 was inactivated using TALEN technology for the Jurkat cells expressing MALT1-R149A (JDM-RA) and MALT1-C464A (JDM-CA). Illumina HISeq 2000 deep sequencing was performed to determine the mRNA profiles for MALT1, JDM-RA, JDM-CA and RACA cells in unstimulated conditions or after treatment with 75ng/ml PMA and 150 ng/ml ionomycin for 3 or 18 hrs. Results: PMA ionomycin stimulation of the MALT1 auto-cleavage defective JDM-RA cells fails to activate NF-kB-dependent transcription like for the MALT1 catalytic inactive JDM-CA cells and the double RACA mutant cells. Conclusion: MALT1 autoproteolysis is essential for transcription of NF-kB target genes Overall design: mRNA profiles of Jurkat expressing MALT1, MALT1-R149A, MALT1-C464A and MALT1-R149A-C464A after 0, 3 and 18 hours of stimulation with PMA and Ionomycin were generated by deep sequencing, in duplicate, using  Illumina HISeq 2000	Co-expression
SRP033498	Integrative AUF1 PAR-CLIP analysis uncovers AUF1 roles in translation and genome integrity (RNA-Seq 1)	We report that AUF1 modulates global mRNA stability and translation, in turn promoting the maintenance of DNA integrity. Overall design: Please see individual series. For AUF1 PAR-CLIP, the four isoforms of AUF1 (p37, p40, p42, and p45) tagged with a Flag epitope were expressed in HEK293 cells. For total RNA-Seq HEK293 cells were transfected with Control siRNA, AUF1 siRNA, Empty Vector, Flag-AUF1 p37, p40, p42, or p45 as well as WI-38 cells were collected at PDL 15 and 55 and also transfected with Control siRNA, AUF1 siRNA, HuR siRNA. For Ribo-Seq HeLa cells were transfected with Control siRNA, AUF1 siRNA, or HuR siRNA.	Co-expression
SRP033502	Integrative AUF1 PAR-CLIP analysis uncovers AUF1 roles in translation and genome integrity (RNA-Seq 2)	We report that AUF1 modulates global mRNA stability and translation, in turn promoting the maintenance of DNA integrity. Overall design: Please see individual series. In short, for AUF1 PAR-CLIP, the four isoforms of AUF1 (p37, p40, p42, and p45) tagged with a Flag epitope were expressed in HEK293 cells. For total RNA-Seq HEK293 cells were transfected with Control siRNA, AUF1 siRNA, Empty Vector, Flag-AUF1 p37, p40, p42, or p45 as well as WI-38 cells were collected at PDL 15 and 55 and also transfected with Control siRNA, AUF1 siRNA, HuR siRNA. For Ribo-Seq HeLa cells were transfected with Control siRNA, AUF1 siRNA, or HuR siRNA.	Co-expression
SRP033559	Anaylsis of the effect of down-regulation of the EWS-FLI1 fusion protein in Ewing Sarcoma cells by RNA-seq.	We generated A673 Ewing Sarcoma cell lines which stably express shRNA targeting the EWS-FLI1 fuison protein or Luciferase as a control to study the effect of EWS-FLI1 on the transcriptome. The vectors used to generate the cell lines were a gift from Stephen Lessnick and were first published in PMID 16697960 Overall design: We analysed five A673 cell lines in which the EWS-FLI1 fusion is down-reagulated by shRNA and three control cell lines which express shRNA targeting Luciferase.	Co-expression
SRP033566	Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers [small RNA-seq]	Heart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers. Overall design: Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).	Co-expression
SRP033569	Epigenetic and transcriptional aberrations in human pluripotent stem cells reflect differences in reprogramming mechanisms [RNA-Seq]	Human pluripotent stem cells hold great potential for regenerative medicine, but available cell types have important limitations. While embryonic stem cells derived from fertilized embryos (IVF-ESCs) are considered the "gold standard" of pluripotency, they are allogeneic to potential recipients. Autologous induced pluripotent stem cells (iPSCs) are prone to epigenetic and transcriptional aberrations. To determine whether accumulation of such aberrations is intrinsic to somatic cell reprogramming or secondary to the reprogramming method, we generated a genetically matched collection of human IVF-ESCs, iPSCs, and ESCs derived by somatic cell nuclear transfer (SCNT; NT-ESCs), and subjected them to genome-wide genetic, epigenetic and transcriptional analyses. SCNT-based reprogramming is mediated by the full complement of oocyte cytoplasmic factors, thus closely recapitulating early embryogenesis. NT-ESCs and iPSCs derived from the same somatic donor cells contained comparable numbers of de novo copy number variations (CNVs), suggesting that the two reprogramming methods may not differ significantly in mutagenic or selective pressure. On the other hand, the DNA methylation and transcriptome profiles of NT-ESCs corresponded very closely to those of IVF-ESCs, while iPSCs differed markedly from IVF-ESCs and harbored residual DNA methylation patterns typical of parental fibroblasts, suggesting incomplete reprogramming. We conclude that human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal candidates for cell replacement therapies. Overall design: Duplicate cDNA libraries of two IVF-ESCs, three sendai produced iPSC lines, two retro-virus produced iPSC lines, four NT-ESCs, and the parental fibroblast line were sequenced using Illumina HiSeq 2000. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.	Co-expression
SRP033696	Global gene expression changes in peripheral blood during H7N9 infection	Comparison of gene expression profiles in the peripheral blood samples were collected from patients with H7N9 infection and healthy people	Co-expression
SRP033725	RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms, and GTPase binding in bipolar disorder	See "Akula et al., Molecular Psychiatry in Press". RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality post-mortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls.  Deep sequencing was performed, with over 350 million reads per specimen. At a false-discovery rate of <5%, we detected 5 differentially-expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD.  Among these, PROM1/CD133 and ABCG2 play important roles in neuroplasticity. We also show for the first time differential expression of long non-coding RNAs (lncRNAs) in BD.  DE transcripts include those of SRSF5 and RFX4, which along with lncRNAs play a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology (GO) categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment.  Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies. Overall design: Brain transcriptome in bipolar disorder	Co-expression
SRP034008	Transcriptomic profiling of HeLa cells treated with miR-15a, miR-16, miR-503 and control-miR	To have a global picture of the targets of the miR-15 family, we assessed transcriptome changes, by deep-sequencing, of HeLa cells transfected with 3 members of the miR-15 family (miR-15a, miR-16 or miR-503) or a control miRNA (cel-miR-231). We observed a very extensive overlap between the genes down-regulated by these 3 miRNAs, as expected for miRNAs belonging to the same family. Overall design: transcriptmic profiles of HeLa cells treated miR-15a, miR-16, miR-503 and control-miR  were generated by deep sequencing, using Illumina HiSeq2000.	Co-expression
SRP034009	Transcriptomic profiling of HeLa cells infected with Salmonella Typhimurium	We evaluated the transcriptome changes induced by infection with Salmonella (20 hpi, MOI 100). Overall design: Transcriptmic profiles of HeLa cells infected with Salmonella Typhimurium were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP034011	Transcriptomic analysis of Plasmodium PBANKA, PBSLTRiP-KO, PB268-KO parasite infected and uninfected host cell	Liver stage of malaria parasite exports SLTRiP and PB268 to the cytosol of parasite infected host cell. To know the host genes perturbed by WT-PBANKA, SLTRiP-KO and PB268-KO parasite growth, we did transcriptomic sequencing of infected host cells.  We did mRNA sequencing of four samples for comparative analysis of WT and PB-knockout parasites infected host cells at 22 hours of post sporozoites infection. Overall design: mRNA profiles of Plasmodium PBANKA, PBSLTRiP-KO, PB268-KO parasite infected and uninfected HepG2 cells after  22hrs of sporozoites infections  were generated by deep sequencing using Illumina GAIIx.	Co-expression
SRP034013	Small RNA profiling of KSHV-miRNA-expressing and KSHV-infected B cell lines	Micro (mi)RNAs are small non-coding RNAs with key regulatory functions. Recent advances in the field allowed researchers to identify their targets. However, much less is known regarding the regulation of miRNA themselves. The accumulation of these tiny regulators can be modulated at various levels during their biogenesis from the transcription of the primary transcript (pri-miRNA) to the stability of the mature miRNA. Here, we studied the importance of the pri-miRNA secondary structure for the regulation of mature miRNAs accumulation. To this end, we used the Kaposi’s sarcoma herpesvirus, which encodes a cluster of twelve pre-miRNAs. Using small RNA profiling and quantitative northern blot analysis, we measured the absolute amount of each mature miRNAs in different cellular context. We found that the difference in expression between the least and most expressed viral miRNA could be as high as 60-fold. Using high-throughput selective 2’-hydroxyl acylation analyzed by primer extension (hSHAPE), we then determined the secondary structure of the long primary transcript. We found that highly expressed miRNAs derived from optimally structured regions within the pri-miRNA. Finally, we confirmed the importance of the local structure by swapping stem-loops for highly and lowly expressed miRNAs, which resulted in a perturbed accumulation of the mature miRNA. Overall design: Examination of sRNA profiles in 3 independent B cell lines expressing KSHV miRNAs or infected with KSHV, without replicate	Co-expression
SRP034157	Genome-wide discovery of human splicing branchpoints [BPCapture]	Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: CaptureSeq identification of branchpoint nucleotides	Co-expression
SRP034158	Genome-wide discovery of human splicing branchpoints [RNAse]	Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: RNaseR validation of branchpoint nucleotides	Co-expression
SRP034528	RNA m5C Methylation in breast cancer using MeRIP-Seq	RNA m5C methylation profile of MCF10A and MDA486 by using MeRIP-Seq protocol Overall design: Immunoprecipitation of Methylated mRNA at Cytosine (m5C) residues: Affinity purified of anti-methyl cytosine (m5C) polyclonal antibody 7ug (Zymo Research, Catalog#A3001-50) was conjugated with protein-A magnetic beads for 2 h at 4°C in end to end rotator. After that, conjugated beads were extensively washed with RNA immunoprecipitation (RIP) wash buffer to remove unbound antibody. Fragmented 25 ug polyA RNA (mRNA) was incubated with m5C conjugated beads for overnight at 4°C in in the rotating platform in RIP buffer. RIP was done using Megna RNA Immunoprecipitation kit (Millipore, Catalog#17-700). m5C mRNA-immune bead complex was treated with proteinase K buffer to release m5C mRNA from the conjugated antibody. To isolate m5C, mRNA was treated with phenol:chloroform:isoamyl and mixed with 400 ul of chloroform, which was centrifuged at 14000 rpm for 10 minutes to separate aqueous phase. The aqueous phase was ethanol precipitated at -80°C for overnight, to get m5C mRNA. This precipitated m5C mRNA pellet was washed twice with 70% ethanol and air dried. Finally, m5C mRNA pellet was dissolved in nuclease free Water. The m5C mRNA integrity and conentration was quantified by bioanalyzer (Agilent) and Qubit 2.0 flurometer (Invitrogen). The fragmented mRNA was used by following TruSeq RNA Sample Preparation Guide to develop RNA-Seq library for sequencing.	Co-expression
SRP034541	Expression data from PD32 and PD88 IMR90	IMR90 cells were passaged until replicative senescence and compared with proliferating cells. Overall design: We used RNA-Seq to detail the global programme of gene expression in human IMR90 replicative induced senescence	Co-expression
SRP034543	Single-cell RNA-Seq transcriptome analysis of circular RNAs in mouse embryos	We reported a new method of single-cell universal poly(A)-independent RNA sequencing (SUPeR-seq) to obtain single cell whole transcriptome analysis that covers both poly(A) plus and poly(A) minus RNA species. We built libraries of single mouse ESC , 10pg, 100pg and 1ng diluted mouse ES total RNA, single HEK293T cell and mouse early embryos before 4-cell stage. We analyzed these data using bioinformatics and find a good coverage of non-polyadenylated RNAs, circular RNA for example. to make a comparison,we also used mouse ES cells and HEK293T cells to build libraries using the protocol publish by F.Tang in 2009(sample name Tang2009_*). We also de novo assembled new genes in mouse ESCs and early embryo samples, further validated known and novel zygotic genes with a-Aminatine treated 2-cell embryos(sample name SUPeR-seq_a-AM_treated_2-cell*). Overall design: 3 Single mouse ES cells, 7 single HEK293T cells, 8 diluted mouse ES total RNA samples and 19 mouse embryo samples are performed using SUPeR-seq to evaluate its ability to detect genes in single RNAs and to cover poly(A)- RNA species.	Co-expression
SRP034547	Human CLP1 mutations alter tRNA biogenesis affecting both peripheral and central nervous system function	We elucidate a neurological syndrome affecting both the PNS and CNS defined by CLP1 mutations that impair tRNA splicing Overall design: Identification and biochemical characterization of mutant CLP1 in human patients	Co-expression
SRP034586	Age-related changes in microRNA levels in serum [miRNA]	microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFa and to correlate positively with the anti-inflammatory cytokines TGFb and IL-10.  These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age. Overall design: Examination of microRNAs isolated from human serum from 11 young (mean age 30 yrs) and 11 old (mean age 64 yrs) individuals and from peripheral blood mononuclear cells from one young (30 yr) and one old (64 yr) individual.	Co-expression
SRP034592	eRNA: A graphic user interface-based tool for RNA sequencing data analysis [mRNA-Seq]	we performed RNA sequencing analysis using 10 tissue samples from human prostate and evaluated efficiency and accuracy of eRNA on mRNA-seq data analysis. Overall design: We sequenced mRNAs from the 10 human tissue samples. After that, we identified mRNAs in these samples against known human genes.	Co-expression
SRP034601	ERK signaling regulates opposing functions of JUN family transcription factors in prostate cancer cell migration	Knockdowns of c-JUN and JUND had opposite effects on PC3 prostate cell migration. We predicted that c-JUN and JUND control the same set of cell migration genes, but in opposite directions. To test this hypothesis, mRNA with expression changes in c-JUN and JUND knockdown PC3 cell lines were compared to mRNA levels in control (luciferase knockdown) PC3 cells by RNA-seq. Overall design: mRNA profiles of luciferase knockdown (WT),  c-Jun knockdown, and Jun-D knockdown in PC3 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.	Co-expression
SRP034606	Cell cycle positioning drives heterogeneity within the pluripotent stem cell compartment	Heterogeneity in pluripotent cells marks a metastable state where cells may drift between native and lineage-primed populations.  While the role for these heterogeneities are unclear, they may reflect the dynamic equilibriums of signaling networks and have a direct effect on differentiation potentialities.  Here, we report the role of the cell cycle in establishing heterogeneity of human pluripotent stem cells.  By utilizing the FUCCI cell cycle indicator system coupled to fluorescent activated cell sorting (FACS), we have uncovered that the cell cycle drives heterogeneity at the epigenetic, transcriptional and post-transcriptional levels.  Our data show widespread dynamics in 5-hydroxymethylcytosine (5hmC) during the cell cycle.  Furthermore, transcript profiling by RNA-sequencing identified >500 genes that were cell cycle-regulated, of which the largest cohort of genes were transcriptional regulators. In sum, we demonstrate the role of the cell cycle in coordinating cellular transitions between metastable states in pluripotent stem cells. Overall design: mRNA sequencing of the cell cycle phases; early & late G1, S and G2/S from human ES cells in triplicate.	Co-expression
SRP034634	Multiple waves of transcriptome changes during extended hypoxic induction in human pulmonary microvascular endothelial cells	We profile the expression pattern of human pulmonary microvascular endothelial cells (HPMECs) at different time points of hypoxic stress. Through mRNA-seq, we identify functional waves of minor gene up-regulation at 8 and 24h hypoxia exposure followed by a massive wave of transcriptional activation after 48 hours. By weighted gene co-expression network analysis, we identify hub genes that likely play central roles in hypoxia transcription program. Strikingly, these hub genes included a prominent group of lincRNAs, suggesting non-coding RNAs may also have pivotal roles in the hypoxia regulatory circuit.  HPMECs share a core hypoxia signature profile, but with some notably differences, indicating a portion of HPMECs hypoxia response is cell-specific. Collectively, our study comprehensive surveys the hypoxia transcriptome, and provides insight into the temporal dynamics of hypoxia transcriptional response. Overall design: Time-course expression profiling of HPMECs exposed to hypoxia	Co-expression
SRP034698	Characterization of the Merkel cell carcinoma miRNome	MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, with the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveals that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1.  These data indicate that we have identified a set of MCC-miRs with high implications for MCC research. Overall design: To identify microRNAs specific to Merkel cell carcinoma (MCC) next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin	Co-expression
SRP034711	RNA-seq analysis of differentiating human erythroblasts	Human erythroblasts purified from cord blood were cultured in vitro and FACS-sorted into five highly purified populations representing distinct differentiation stages:  proerythroblasts, early basophilic erythroblasts, late basophilic erythroblasts, polychromatophilic erythroblasts, and orthochromatophilic erythroblasts. The methods for culture and sorting experiments are given in Hu et al. 2013. For each RNA-seq library, RNA was isolated from 1x 106 sorted human erythroblasts using RNeasy Plus Mini kits (Qiagen). Libraries were then prepared using Illumina TruSeqTM RNA kits to obtain 50 nt reads. Collaborators at the New Your Blood Center were responsible for erythroblast culture, FACS purification of erythroblast populations, and acquisition of RNA-seq data. Collaborators at U.C. Berkeley and Lawrence Berkeley National Laboratory performed data analysis and experimental validation of alternative splicing in erythroblasts. Results: Differentiating erythroblasts execute a dynamic alternative splicing program that is enriched in genes affecting cell cycle, organelle organization, chromatin function, and RNA processing. Alternative splicing plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells. Overall design: Erythroid differentiation stage-specific transcriptome analysis was performed by RNA-seq analysis of highly purified erythroblast populations	Co-expression
SRP034712	Characterization of differentiating adipose cells by high-throughput single-cell RNA-Seq	Directed differentiation of cells in vitro is a powerful approach for dissection of developmental pathways, disease modeling and regenerative medicine, but analysis of such systems are complicated by heterogeneous and asynchronous cellular responses to differentiation-inducing stimuli. To enable deep characterization of heterogeneous cell populations, we developed an efficient digital gene expression profiling protocol that enables surveying of mRNA in thousands of single cells at a time. We then applied this protocol to profile 11,116 cells collected during directed differentiation of human adipose-derived stem/stromal cells. The resulting data reveals the major axes of cell-to-cell variation within and between time points and suggests a link between incomplete adipogenesis in vitro and adipocyte dysfunction in vivo. Overall design: High-throughput single cell RNA-seq method applied to human adipose tissue-derived stromal/stem cells during differentiation towards an adipogenic fate	Co-expression
SRP034732	Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion	In this study we aimed to assess technical variability associated with globin depletion in addition to assessing general technical variability in RNA-Seq from whole blood derived samples. We compared technical and biological replicates having undergone globin depletion or not and found that globin depletion removed approximately 80% of globin transcripts, improved the correlation of technical replicates, allowed for reliable detection of thousands of additional transcripts and generally increased transcript abundance measures. Overall design: Peripheral whole blood transcriptome assessed by RNA-Seq on Illumina HiSeq 2000 in 6 healthy individuals and 6 pooled samples, either globin depleted or not.	Co-expression
SRP034736	Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias	High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia. Overall design: RNA sequencing in ERG overexpressing human CD34+ cells	Co-expression
SRP034737	Gene expression profiling in an induced pluripotent stem cell model of the developing human telencephalon: effect of heat shock and its potential impact on the development of neuropsychiatric disorders	Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable neuropsychiatric/neurodevelopmental disorders, although environmental factors, such as maternal immune activation (MIA), play a role as well. Inflammatory cytokines appear to mediate the effects of MIA on neurogenesis and behavior in animal models. However, drugs and cytokines that trigger MIA can also induce a febrile reaction, which could have independent effects on neurogenesis through heat shock (HS)-regulated cellular stress pathways. However, this has not been well-studied. As a first step towards addressing the role of fever in MIA, we used a recently described model of human brain development in which induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal aggregates that resemble a first trimester telencephalon. RNA-seq was carried out on aggregates that were heat shocked at 39oC for 24 hours, along with their control partners maintained at 37oC.  Overall, 186 genes showed significant differences in expression following HS (p<0.05), including known HS-inducible genes, as expected, as well as those coding for NGFR and a number of SZ and ASD candidates, including SMARCA2, DPP10, ARNT2, AHI1 and ZNF804A. The degree to which the expression of these genes decrease or increase during HS is similar to that found in copy loss and copy gain CNVs, although the effects of HS are likely to be more transient. Overall design: RNA-seq was carried out on neuronal aggregates as described by Mariani et al. with slight modification (PMID:22761314). For the heat shock experiment, a group of 49 day old aggregates was placed in an incubator set at 39C for 24 hours, while control sets of aggregates were maintained at 37C. The incubator conditions were otherwise unchanged. After detaching the aggregates, total cellular RNA was isolated using the miRNeasy Kit (Qiagen) according to the manufacturer's protocol. Lastly, RNAseq profiles of HS and Control were compared	Co-expression
SRP034829	nELAVL HITS-CLIP in Alzheimer''s Disease patients	Human brain samples from control and advanced Alzheimer''s Diseased subjects were subjected to HITS-CLIP to monitor nELAVL binding changes during AD progression Overall design: Human brain samples were obtained from the Mount Sinai Brain Bank; samples were UV-irradiated and subjected to nELAVL HITS-CLIP (detailed desription in accompanying paper)	Co-expression
SRP034832	RNAseq in IMR-32 neuroblastoma cells	IMR-32 cells were subjected to lentiviral YRNA infection or nELAVL RNAi and/or UV stress followed by RNAseq analysis to monitor RNA level changes Overall design: RNA from IMR-32 cells was Trizol extracted, Ribominus selected and submitted for high-throughput sequencing.	Co-expression
SRP034929	XSAnno: A framework for building ortholog models in cross-species transcriptome comparisons	The accurate characterization of transcripts and levels across species is critical for understanding transcriptome evolution. As available RNA-seq data accumulate rapidly, there is a great demand for tools that build gene annotations for cross-species RNA-seq analysis. Prevailing methods of ortholog annotation for RNA-seq analysis, do not take inter-species variation in mappability into consideration. Here we developed a computational framework that integrates previous approaches with multiple filters to improve the accuracy of inter-species transcriptome comparisons. The implementation of this approach in comparing RNA-seq data of human, chimpanzee, and rhesus macaque brain transcriptomes has reduced the false discovery of differentially expressed genes, while keeping the false negative rate low.	Co-expression
SRP035252	AML-twins-PT_Leukemia	PT_Leukemia	Co-expression
SRP035268	RNA-sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate	Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)	Co-expression
SRP035312	Global Transcriptome Analyses of Mammalian Terminal Erythroid Differentiation	Purpose:The purpose of this study is to create unbiased, stage-specific transcriptomes by RNA-seq analyses of pure populations of both murine and human erythroblasts at distinct developmental stages. Methods: Recently developed FACS-based methods (Chen et al, PNAS, Liu et al, Blood, Hu et al Blood) were employed to purify morphologically and functionally discrete populations of cells, each representing specific stages of terminal erythroid differentiation. RNA was prepared from these cells and subjected to RNA-seq analyses. Results: There were vast temporal changes in gene expression across the differentiation stages, with each stage exhibiting unique transcriptomes.Clustering and network analyses revealed that differing stage-specific patterns of expression across differentiation were transcriptionally enriched for genes of differing function. Numerous differences were present between human and murine transcriptomes, with significant variation in the global patterns of gene expression. Conclusions: These data provide a significant resource for studies of normal and perturbed erythropoiesis, allowing a deeper understanding of mechanisms of erythroid development, differentiation, and inherited and acquired disease. Overall design: Both murine and human erythroblasts at distinct developmental stage mRNA profiles were generated by deep sequencing, in triplicate, using IlluminaHiSeq 2000.	Co-expression
SRP035316	Comparative total RNA and mRNA sequencing and systems analysis reveals nascent transcriptional response to early HIV-1 infection in a CD4+ T cell line	To systematically investigate early host transcriptional response to HIV-1 infection, including polyadenylated and non-polyadenylated transcripts, we separately sequenced Total RNAs (Total RNA-seq) from HIV-1-infected SupT1 cells, a human CD4+ T cell line. We show many non-polyadenylated RNAs were also differentially expressed upon HIV-1 infection, as expected only detected by Total RNA-seq. Interestingly, we identified 8 times more differentially expressed genes at 12 hour post-infection by Total RNA-seq than by mRNA-seq, mostly protein-coding genes. Overall design: 6 Total RNA sample sets were sequenced. Samples were either Mock infected, HIV-1 infected, or UV-inactivated viron infected for either 12 hours or 24 hours. Each sample set contains replicates. mRNA-seq data was processed previously and is part of a different study. It was referenced in this study. The mRNA-seq data can be found in GSE38006. This data set refers to the Whole Transcriptome data from similar samples.	Co-expression
SRP035387	Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming	We generated induced human hepatocyte by transduction of several lineage specific transcription factors and analyzed the gene expression profile of generated hepatocytes and freshly isolated human hepatocytes through RNA sequencing. Overall design: Global gene expression profile analysis	Co-expression
SRP035391	An atlas of TNF-a-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2	Sequencing of 5''ends of RNA molecules from Caco-2 cells +/- TNFa stimulation Overall design: CAGE library construction from RNA extracted from Caco-2 cells	Co-expression
SRP035417	ZNF804A transcriptome networks in differentiating human neurons derived from induced pluripotent stem cells	The goal of this project is to study transcriptome change by knocking down ZNF804A, a schizophrenia and bipolar disorder candidate gene, in early neurons derived from iPSCs. Overall design: Neural progenitor cells (NPCs) were developed from human induced pluripotent stem cells (iPSCs) and transduced by two independent shRNA vectors targeting ZNF804A, a schizophrenia and bipolar disorder candidate gene. After recovery and selection in puromycin, neuronal differentiation was induced. After 14 days, RNA was recovered and analyzed by RNA-seq. The expression profiles were compared with NPCs that were transduced with scrambled control vectors. This corresponds to controls 1-3 and KD 1-3, which was carried out on a male iPSC line. Scramble 1 and 2 and KD1 and 2 are technical replicates. Scrambled 3 and KD 3 were carried out on an independent NPC culture. For control 4 and KD4, neuronal differentiation was induced, and on day 10 the cells were transduced with the same ZNF804A KD and scrambled control vectors used for scrambled control 3 and KD3. In addition, this last set was carried out on a female iPSC line	Co-expression
SRP035464	Transcriptome profiling of untreated and doxycycline-treated HeLa/TO-SmN	Purpose is to examine the effect of SmN expression to gene expression in HeLa Overall design: Compare the differences between the transcriptome of untreated and doxycycline-treated HeLa/TO-SmN in which expression of SmN is under doxycycline control	Co-expression
SRP035482	MARIS: Method for Analyzing RNA following Intracellular Sorting [RNA-seq]	We''ve developed a new Method to Analyze RNA following Intracellular Sorting (MARIS) allowing us to carry out gene expression studies on cells sorted based on intracellular immunoflourescence. The purpose of this study is to determine the degree of bias that MARIS introduces on gene expression. We report RNA-seq gene expression data from human embryonic stem cells differentiated to a stage in which insulin-expressing cells are present. Gene expression data using RNA isolated from live cells is compared to gene expression data using RNA isolated from MARIS processed cells (fixed, permeabilized, antibody stained and mock sorted) to determine the degree of correlation in gene expression between these two biologically identical samples. Overall design: Human embryonic stem cells are differentiated to a stage in which insulin-expressing cells are present and split into two biologically identical samples. RNA is immediately isolated from one sample using the RNeasy protocol (live sample). RNA is isolated from the second sample following MARIS (processed sample) with all cells collected after the sort in order to keep the cell type composition between the live and processed samples the same.	Co-expression
SRP035503	Small molecule inhibitor of BCL2 in combination with RCHOP is effective in CD20 negative lymphoma	Rituximab alone or in combination with chemotherapeutics is the first-line therapy for variety of lymphoproliferative disorders including low- and high grade non-Hodgkin’s lymphomas (NHL). Although the complete response rate is quite impressive, vast majority of patient presents recurrent disease. The association between CD20 expression and clinical outcome in patients strongly suggests that reduced CD20 expression leads to inferior response to RCHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone). In order to understand how loss of CD20 leads to development of RCHOP resistance, we developed rituximab resistant DOHH2 model in vivo by chronic exposure to rituximab. Characterization of several resistant in vivo xenografts revealed one model that maintained resistance to an acute dose of rituximab and demonstrated loss of CD20. Further characterization of the model demonstrated a loss of CD20 is associated with over expression of BCL2 and BIM. In vivo efficacy studies showed resistant line is insensitive to acute dose of RCHOP and treatment with an inhibitor of BCL2 (ABT199) in combination with chemotherapy resulted in better efficacy than RCHOP alone. We have identified an in vivo model of DLBCL where loss of CD20 and over expression of anti-apoptotic protein BCL2 leads to RCHOP resistance. These data suggest the addition of BCL2 inhibitor to chemotherapy might be effective in treating CD20 negative lymphomas. Overall design: mRNA profiles of parental and rituximab resistant DOHH2 xenograft were generated by deep sequencing using Illumina HiSeq	Co-expression
SRP035599	Transcriptome Sequencing from Diverse Human Populations Reveals Differentiated Regulatory Architecture	To understand the full range of expression variation, alternative splicing, and the genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of 45 individuals in the Human Genome Diversity Panel (HGDP) from seven worldwide populations that span the geographic breadth of human migration history. We find few genes that are systematically differentially expressed among populations. Further, allelic expression analysis indicates that previously mapped common regulatory variants identified in eight HapMap3 populations have similar effects across HGDP populations, suggesting that the cellular effects of common variants are shared even across very diverse populations. In contrast, comparisons of alternative splicing across pairwise populations reveal highly significant differences, with ~20% of alternatively spliced exons varying significantly by population. Greater genomic differences are associated with significantly more splicing variability overall. Together, these results provide a resource and an estimate for the degree of sharing of gene expression, alternative splicing, and regulatory genetics across populations. Overall design: Lymphoblastoid cell line mRNA profiles of 45 human samples from the Human Genome Diversity Panel sequenced on an Illumina HiSeq 2000, each sample library was sequenced in duplicate to produce a merged sample bam.	Co-expression
SRP035638	Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection	MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs. Overall design: Examination of small RNA populations in KMB17 cells infected by human hepatitis A virus genotype IA (isolate H2) (21 days post-infected cells) and mock-infected KMB17 cells (21 days mock-infected control cells).	Co-expression
SRP035641	RNA-seq analysis in Cornea epithelial cells (CECs), skin epithelial cells (SECs), LSCs after knocking down PAX6 (3-D shPAX6 LSCs) and SESCs transduced with PAX6(3-D PAX6+ SESCs) upon 3-D differentiation	Purpose: We find that Wnt7a-PAX6 axis determine corneal epithelial cell fate. To obtain global evidence for successful cell fate conversion, we performed gene expression profiling by RNA-seq on CECs, SECs, and LSCs after knocking down PAX6 and on SESCs transduced with PAX6 upon 3-D differentiation. Methods: Under 3-D culture condition, limbal stem cell (LSCs) can be differentiated to Cornea epithelial cells (CECs), and skin epithelial stem cells (SESCs) can be differentiated to skin epithelial cells (SECs). Total RNA was isolated from CECs, SECs, and LSCs after knocking down PAX6 (3-D shPAX6 LSCs) and on SESCs transduced with PAX6 (3-D PAX6+ SESCs) upon 3-D differentiation. Libraries were prepared following published standard protocol (Fox-Walsh K et al., 2011, genomics, 266-71). mRNA profiles were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000. Results: Following optimized decoding and mapping workfollow, we mapped about 5 million sequence reads to the human genome and identified more than 23659 transcripts per sample. Conclusions: Hierarchical clustering analysis of differentially expressed gene signatures revealed that the gene expression pattern of SESCs with PAX6 transduction was strikingly similar to that of CECs, whereas the profile of LSCs with PAX6 knockdown was highly related to that in SECs upon differentiation. These data therefore provided global evidence for a decisive role of the WNT7A/PAX6 axis in cell fate conversion from SESCs to CECs. Overall design: RNA-seq on CECs, SECs, and LSCs after knocking down PAX6 and on SESCs transduced with PAX6 upon 3-D differentiation, using Illumina HiSeq 2000	Co-expression
SRP035679	Genomic expression analysis of human monocyte-derived DCs and monocytes	To identify the functional non-coding RNAs in human DC development, we explored the gene expression profiles during DC development from peripheral monocytes. Using RNA-seq, we identified many annotated lncRNAs with markedly altered expressions during human DC differentiation and maturation. Overall design: RNA samples from human peripheral blood monocytes and monocyte-derived DCs were collected. RNAs from 3 donors were pooled together to form monocyte sample or DC sample and then these two samples were subjected to RNA-seq and analysis.	Co-expression
SRP035864	Genome-wide Transcriptional Profiling of Skin and Dorsal Root Ganglia after Ultraviolet-B-Induced Inflammation	Ultraviolet-B (UVB) irradiation of the skin was performed on rat (skin and DRG) and human (skin) tissue. The resulting changes in gene expression were then profiled by using RNA-seq to compare gene expression between irradiated and non-irradiated samples Overall design: Poly(A) selected RNA was sequenced for 5 irradiated and 4 non-irradiated humans (skin), and for 6 irradiated and 6 non-irradiated rats (DRG and skin)	Co-expression
SRP035883	Global gene expression differences between blood- and lymphatic-specific endothelial colony forming cells	The identification of circulating endothelial progenitor cells has led to speculation regarding their origin as well as their contribution to neovascular development. Two distinct types of endothelium make up the blood and lymphatic vessel system. However, it has yet to be determined whether there are distinct lymphatic-specific circulating endothelial progenitor cells. We isolated circulating endothelial colony forming cells (ECFCs) from whole peripheral blood. These cells are endothelial in nature, as defined by their expression of endothelial markers and their ability to undergo capillary morphogenesis in three-dimensional culture. A subset of isolated colonies express markers of lymphatic endothelium, including VEGFR-3 and Prox-1, with low levels of VEGFR-1, a blood endothelial marker, while the bulk of the isolated cells express high VEGFR-1 levels with low VEGFR-3 and Prox-1 expression. The different isolates have differential responses to VEGF-C, a lymphatic endothelial specific cytokine, strongly suggesting that there are lymphatic specific and blood specific ECFCs. Global analysis of gene expression revealed key differences in the regulation of pathways involved in cellular differentiation between blood and lymphatic-specific ECFCs. These data indicate that there are two distinguishable circulating ECFC types, blood and lymphatic, which are likely to have discrete functions during neovascularization. Overall design: RNA was isolated from 2 blood-specific ECFC cell lines and 2 lymphatic-specific ECFC cell lines 3 separate times each	Co-expression
SRP035934	Gene expression analysis of human primary lung fibroblast cell line IMR-90 infected by adenovirus type 2	In the present study adenovirus type 2 RNA splicing events were quantitatively mapped by using deep cDNA sequencing. The majority of the previously identified splice sites could be confirmed. The lack of complete consistency between the present and previous results appears to be that some sites have been incorrectly mapped in previous studies, such as the splice sites for pVII, pVIII and E3-11.6K. everal previously predicted splice sites such as that for E3-14.5K and E4ORF3/4 were not detected.	Co-expression
SRP035988	Transcriptome analysis of psoriasis in a large case-control sample:  RNA-seq provides insights into disease mechanisms	To increase our understanding of psoriasis, we utilized RNA-seq to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived cDNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ~38 million single-end 80-bp reads per sample. Comparison of 42 samples* examined by both RNA-seq and microarray [GSE13355] revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes.  Weighted gene co-expression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long non-coding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally-expressed genes were significantly down-regulated in psoriatic biopsies, most likely due to expansion of the epidermal compartment. These results demonstrate the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and co-expression analysis. *The list of 42 samples examined by both RNA-seq and microarray is provided in the 'MAoverlappedsamples.txt'. Overall design: 92 psoriatic and 82 normal skin samples	Co-expression
SRP036035	TWIST1-induced microRNA-424 drives an intermediate epithelial-to-mesenchymal transition that opposes metastasis	Epithelial-to-mesenchymal transition (EMT) is a dynamic process that relies on cellular plasticity; an EMT/MET axis is critical for metastatic colonization of carcinomas. Unlike epithelial programming, regulation of mesenchymal programming is not well understood in EMT. Here we describe the first microRNA that enhances exclusively mesenchymal programming. We demonstrate that microRNA-424 is up-regulated early during a TWIST1/SNAI1-induced EMT, and that it causes cells to express mesenchymal genes without affecting epithelial genes, resulting in a mixed/intermediate EMT. Further, microRNA-424 increases motility, decreases adhesion and induces a growth arrest, changes associated with a complete EMT. Patient microRNA-424 levels positively associate with TWIST1/2 and EMT-like gene signatures and is increased in primary tumors versus matched normal breast. However, microRNA-424 is down-regulated in metastases versus matched primary tumors. Correspondingly, microRNA-424 decreases tumor initiation and is post-transcriptionally down-regulated in macrometastases in mice. RNA-seq identified microRNA-424 regulates numerous genes associated with EMT and breast cancer stemness including the novel miR-424 target, TGFBR3, which regulates mesenchymal phenotypes without influencing miR-424 effects on tumor-initiating phenotypes; instead, we show that ERK signaling is critical for such tumor-initiating effects of miR-424. These findings suggest microRNA-424 plays distinct roles downstream of EMT-inducing factors, facilitating earlier stages, but repressing later stages, of metastasis. Overall design: Examination of mRNA levels in MCF12A human breast cell lines that stably over-expressed miR-424 or an empty vector (EV) control. Each group has three replicates.	Co-expression
SRP036053	Different molecular pathways along with pathogenesis of three subtypes of Leiomyosarcoma	Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma. Overall design: Within this study, we collected four Myometrium, three Leiomyoma, three LMS cell lines and 99 LMSs (GSE45510), performed the system-wide gene expression profiling by 3''end RNA Sequencing, and found that there are significant different molecular pathways along the pathogenesis for those three molecular subtypes.	Co-expression
SRP036133	Developmental transcriptome analysis of human erythropoiesis	We profiled the dynamic, comprehensive transcriptome during human erythroid differentiation in vitro. The erythroid cells at day 4, 8, 11 and 14 differentiation stages were harvested and sequenced by Illumia 72 bp paired-end sequencing format, respectively. Overall design: Expression profiling of erythroid cells on differentiation days 4, 8, 11 and 14 and performed mRNA-seq on two biological replicates at each stage.	Co-expression
SRP036769	Transcriptome profiling of a mouse model of alveolar soft part sarcoma	In order to dtermine how well a mouse genetic model of alveolar soft part sarcoma (ASPS) mimics the human disease, five human ASPS tumor samples and three normal skeletal muscle samples were profiled by RNAseq and compared to samples from five mouse tumors induced by expression of ASPSCR1-TFE3 and three normal mouse skeletal muscle samples, also profiled by RNAseq. Overall design: The reference was really comparing 5 human ASPS tumors to 5 mouse tumors that histologically mimic ASPS, but using skeletal muscle controls (3 from each species) as a sounding board for differential expression.	Co-expression
SRP036790	Comparative gene expression profiling of human PGP1 iPS, lymphocyte, donor fibroblasts	Human iPS cell line, immortalized B-cells, and primary fibroblasts frome Personal Genome Project voluteer 1 Overall design: Each sample per cell type.	Co-expression
SRP036821	Distinct expression profiles of soft tissue sarcomas	Soft tissue sarcomas (STTs) are neoplasms of mesenchymal cells, and are composed of more than 60 subtypes. Although many of these STTs could be distinguished from each other by morphology and limited IHC biomarkers, the precise diagnosis of STTs with similar morphology is still difficult to achieve. Therefore developing novel diagnosis biomarker and molecular signatures will be very helpful to pathologist in clinic. Overall design: Within this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile different subtypes of soft tissue sarcomas.	Co-expression
SRP036843	Orphan nuclear receptor TR4 uses non-equivalent binding sites to regulate gene targets from proximal and distal transcriptional regulatory elements during human definitive erythropoiesis [RNA-seq]	We knocked down TR4 expression by 2 lentiviral mediated vectors at day 11 of erythroid differentiation in order to identify TR4 downstream targets. Overall design: Two lentiviruses and one empty control were used to knockdown TR4 expression. The cells were harvested at day 11 during erythroid differentiation.	Co-expression
SRP036848	RNAseq Analysis of Formalin-Fixed Paraffin-Embedded Prostate Cancer Tissues	In an effort to identify biomarkers of recurrence, we have performed global RNA-sequencing on 106 formalin-fixed, paraffin-embedded (FFPE) prostatectomy samples from 100 patients at three independent sites, and identified a new set of biomarkers of biochemical recurrence composed of a 24-gene panel. We validated this 24-gene panel on an independent publicly available dataset of 140 patients and this new panel outperformed previously published markers based on cell proliferation gene sets in terms of prediction of biochemical recurrence (BCR).  In addition we identified differences in gene expression between Gleason Pattern 4+3 and Gleason Pattern 3+4 tumors. Overall design: 106 samples from 100 patients were sequenced.  Six samples were sequenced from two independent RNA preps and libraries.  All samples were taken from FFPE Radical Prostatectomies.  Samples were obtained from Atlanta VA Medical Center, U. Toronto Sunnybrook Research Centre, and Moffitt Cancer Center.	Co-expression
SRP037550	RNA-seq from control and macroH2A1-depleted IMR90 primary human lung fibroblasts	The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression. Overall design: Three biological replicates of RNA-seq from cells expressing shRNA directed against macroH2A1 or luciferase as a control	Co-expression
SRP037579	RNA-sequencing analysis of NGN3-GFP positive and negative cells purified from differentiating human embryonic stem cells	NGN3-eGFP could be used to mark endocrine progenitor cells and their progeny in differentiating hESCs, suggesting that profiling analysis of NGN3-eGFP+ cells could lead to the discovery of novel gene participation. Six batches of NGN3-eGFP+ and NGN3-eGFP -cells purified by FACS from a reporter hES cell line cell cultures at stage 4 were pooled together, respectively. RNA-seq-based analysis of the two cell fractions identified a total of 3976 differentially expressed genes (P-value<0.05; Fold >2), of which 72% are enriched in NGN3-GFP+ cells. As expected, all the genes expressed in pancreatic progenitor cells are enriched in NGN3-eGFP-cells; while all endocrine-associated genes are enriched in NGN3-eGFP+ cells. Among the 3976 genes, 195 have potential transcriptional factor activity and 453 are potential non-coding RNA genes, most of which have not been well investigated in pancreatic endocrine cells. The gene ontology term ‘integral to membrane’ GO: 0016021 identified 1003 differentially expressed genes that encoded ion channels, adhesion molecules and transporters. Overall design: NGN3-eGFP Postive and negtive cells were purified at stage 4 and subjected to RNA-sequncing	Co-expression
SRP037718	Vascular histone deacetylation by pharmacological HDAC inhibition [SAHA, RNA-seq]	HDAC inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action, however, little is known of the extent of genome-wide changes of the mammalian genome when stimulated by the hydroxamic acids, TSA and SAHA. In primary human vascular endothelial cells we map the chromatin modifications, histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation mediated gene expression is often associated with modification of other lysine residues we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). Genome-wide mRNA sequencing indicates the differential expression of about 30% of genes, with almost equal numbers being up- and down- regulated. We observe deacetylation conferred by TSA and SAHA that are associated with decreased gene expression. Histone deacetylation is associated with the loss of p300/CBP binding at gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation. Overall design: HAEC mRNA profiles of SAHA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP037719	Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]	The human genome shares a remarkable amount of genomic sequence with our closest living primate relatives. Researchers have long sought to understand what regions of the genome are responsible for unique species-specific traits. Previous studies have shown that many genes are differentially expressed between species, but the regulatory elements contributing to these differences are largely unknown. Here we report a genome-wide comparison of active gene regulatory elements in human, chimpanzee, and macaque, and we identify hundreds of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence. These elements contain evidence of natural selection and correlate with species-specific changes in gene expression. Polymorphic DNA bases in transcription factor motifs that we found in these regulatory elements may be responsible for the varied biological functions across species. This study directly links phenotypic and transcriptional differences between species with changes in chromatin structure. Overall design: DGE-seq	Co-expression
SRP037735	The systematic shortening of 3’ UTRs has limited influence on the relative change in protein abundance in proliferating cells	Alternative polyadenylation is an important cellular mechanism that enables generation of  mRNA isoforms that differ in their 3' untranslated regions (3' UTRs) and consequently in their susceptibility to miRNA and RNA binding protein mediated regulation. A dramatic change in polyadenylation site usage, leading to the systematic expression of short 3’ UTR isoforms is known to occur upon induction of proliferation in resting cells. To understand the functional consequences of short 3’ UTR isoform expression we used 3' end sequencing and quantitative mass spectroscopy to determine polyadenylation site use, mRNA and protein levels in murine and human naive and activated T cells. We found that while the process and its impact on the susceptibility to miRNA and RNA binding protein mediated regulation are evolutionarily conserved, the conservation is poor at the level of individual orthologous genes. Contrary to the common belief, we did not find that transcriptome-wide 3' UTR shortening leads to a matched increase in mRNA and protein levels of genes with tandem polyadenylation sites. Overall design: 3' ends of transcripts were profiled by high-throughput sequencing in murine and human naive and activated T cells.	Co-expression
SRP037762	Transcriptomic analysis reveals novel long non-coding RNAs critical for vertebrate development [RNA-Seq]	Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development. Overall design: Time course RNA-Seq analysis H1 ESCs differentiated into endothelial cells	Co-expression
SRP037775	mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer	The intention was to detect genes that are determining trastuzumab efficiency in HER2-positive breast cancer cell lines with different resistance phenotypes. While BT474 should be sensitive to the drug treatment, HCC1954 is expected to be resistant due to a PI3K mutation. The cell line BTR50 has been derived from BT474 and was cultured to be resistant as well. Based on RNA-Seq data, we performed differential expression analyses on these breast cancer cell lines with and without trastuzumab treatment. In detail, five separate tests were performed, namely resistant cells vs. wild type, i.e. HCC1954 and BTR50 vs. BT474, respectively, and untreated vs. drug treated cells. The significant genes of the first two tests should contribute to resistance. The significant genes of the test BT474 vs. its drug treated version should contribute to the trastuzumab effect. To exclude false positives from the combined gene set (#64), we removed ten genes that were also significant in the test BTR50 vs. its drug treated version. This way we ended up with 54 genes that are very likely to determine trastuzumab efficiency in HER2-positive breast cancer cell lines. Overall design: mRNA profiles of human breast cancer cell lines were generated by deep sequencing using Illumina HiSeq 2000. The cell lines BT474 and HCC1954 were analyzed with and without trastuzumab treatment. HCC1954 is known to be trastuzumab resistant. Additionally, the cell line BTR50 was generated as resistant version of BT474, and was analyzed with and without trastuzumab as well.	Co-expression
SRP037778	Transcriptome profiling of omental adipose tissues in human obesity by RNA-Seq	Purpose: To profile the transcriptomes of omental adipose tissues from obese and lean humans. Methods: Omental adipose tissues from obese and lean patients were subjected to RNA-Seq. Results: Differential expression analysis identified 206 dysregulated genes (p-value < 0.05 by moderated t-test and fold change = 2 in obesity) that are known to be involved in a multitude of functions, including response to stress, inflammatory response and leukocyte adhesion. Differential splicing analysis uncovered the possible role of TLR4 RNA splicing in obesity. Our findings suggest that, as a person experiences weight gain/obesity, the adipose splicing pattern of TLR4 transcripts changes in favor of activation of TLR4 signaling, which in turn may contribute to the progression of obesity-related inflammation and complications. Conclusion:  This study provides a look into the transcriptome of disease-state adipose tissue in obesity, and demonstrates the potential importance of aberrant RNA splicing and expression in obesity-associated immune dysregulation. Overall design: Study design is of cross-sectional nature. Seven samples (three obese and four lean) were analyzed.	Co-expression
SRP037982	Transcriptomic characterization of Hepatocellular Carcinoma with CTNNB1 mutation	we report transcritomic characterization of changes in CTNNB1 mutation positive HCCs in comparison to paratumoral tissues Overall design: 4 pair of HCC and paratumoral liver tissues are sequenced and compared	Co-expression
SRP037988	Global gene expression profiling from LeuCAG3''tsRNA depleted- HeLa and HCT-116 cell lines through 50 base pair paired-end RNA-seq	We sequenced mRNA expression from 3 HeLa and 3 HCT-116 cell lines transfected with LNA (Locked nucleic acid) GL2, LNA CAGMM, or LNA CAGPM respectively. In order to dissect the biological role of 3?tsRNAs (type I tsRNAs) in mammals, we reduced the bioavailable abundance of specific tsRNA species using complementary locked nucleic acid/DNA-mixed antisense oligonucleotides (LNA). The LNA forms a highly stable complex with the target RNA in a sequence specific manner, essentially inhibiting its ability to interact with their biological targets. In our tsRNA-knockdown experiments of HeLa and HCT-116 cell lines, we used three different LNA probes. GL2, is the LNA probe complementary to firefly luciferase gene from pGL2 vector (Promega, WI, USA), which serve as negative control. CAGPM, is the LNA probe perfect complementary to LeuCAG3?tsRNA. CAGMM, is the LNA probe complementary to LeuCAG3?tsRNA with 2 nt mismatches. The sequences for LNA probes are as follows. LNA bases are upper-case letter and DNA bases are lower ?case letter. GL2: GtaCgCgGaaTaCTtC CAGPM: tGTcAGgAgTggGaT CAGMM: tCTcACgAgTggGaT Overall design: Examination of mRNA levels in individual HeLa and HCT-116 cell lines 24h after transfection of LNA GL2, LNA CAGMM, LNA CGPM respectively.	Co-expression
SRP038006	Functional studies of NKX2-2 in Ewing sarcoma	Domain analysis of NKX2-2''s role in the regulation of transcription in Ewing sarcoma.	Co-expression
SRP038101	Expression data from untreated and Aza treated AML3 cells	AML3 cells were treated with Azacytidine and compared against untreated cells Overall design: We used RNA-Seq to detail the global programme of gene expression in human untreated and Azacytidine treated AML3 cells	Co-expression
SRP038143	Pancreatic Cancer Cell Lines Transcriptome Sequencing	Whole transcriptome sequencing for three common pancreatic cancer cell lines.	Co-expression
SRP038695	Ribosome profiling data obtained from HEK293T cells 30 minutes after treatment with arsenite to a final concentration of 40 µM	Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions. This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor, eIF2. However, the persistent translation of certain mRNAs is required for deployment of an adequate stress response. We carried out ribosome profiling of cultured human cells under conditions of severe stress induced with sodium arsenite. Although this led to a ~4.5-fold general translational repression, the protein coding ORFs of certain individual mRNAs exhibited resistance to the inhibition. Nearly all resistant transcripts possess at least one efficiently translated uORF that repress translation of the main coding ORF under normal conditions. Site specific mutagenesis of two identified stress resistant mRNAs (PPP1R15B and IFRD1) demonstrated that a single uORF is sufficient for eIF2-mediated translation control in both cases. Phylogenetic analysis suggests that at least two regulatory uORFs (namely in SLC35A4 and MIEF1) encode functional protein products. Overall design: Ribosome profiling of sodium arsenite treated cells for examination of translational response to induction of eIF2 phosphoylation	Co-expression
SRP038702	Genomewide analysis of QKI-dependent alternative splicing	To identify QKI targets, we performed QKI knockdown in BEAS2B cells and analyzed alternative splicing patterns by high-throughput RNA sequencing. Overall design: The mRNA profiles of control- and QKI-knockdown BEAS2B cells were generated by deep sequencing using Illumina GAIIx sequencer.	Co-expression
SRP038761	Major and Minor Group Human Rhinovirus Response in Human Macrophages	Major- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus. Overall design: RNA sequencing of monocyte-derived macrophages after mock infection or infection by HRV16 or HRV1A	Co-expression
SRP038767	Activin A and BMP4 Modulation of Wnt/ß-catenin Signaling Directs Fate Specification of Mesoderm Derivatives from Human Embryonic Stem Cells	We report the derivation of 2 different methods of generating cardiac myocytes from human ESCs. The traditional route is via cardiac progenitor cells and the second, new approach is through re-directing hemogenic endothelium into the cardiac lineage using inhibition of Wnt/b-catenin signaling Overall design: Examination of 2 different cardiac populations using RNA-seq	Co-expression
SRP038863	Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone	We report on explant osteoblast cultures from human patients, demonstrating that there are at least three sub-types of non-syndromic craniosynostosis defined by similarity of gene expression profiles. Overall design: Osteoblast growth in culture, 23 craniosynostosis skull samples (7 metopic; 8 coronal; 3 lambdoid; 5 sagittal) and 8 normal (4 cranial bones and 4 long bones)	Co-expression
SRP038919	Transcriptome wide identification of Dicer binding in human and C. elegans reveals a variety of substrates (HEK PAR-CLIP)	Dicer is a deeply conserved endoribonuclease with key functions in small RNA biogenesis. Here we employed PAR-CLIP/iPAR-CLIP to identify direct Dicer binding sites in the transcriptomes of human cells and human. We found hundreds of novel miRNAs and non-canonical Dicer substrates with high sensitivity. Small RNA production depended on structure of the binding site and is globally biased towards the 5'' arm of hairpins. Unexpectedly, in both species Dicer bound numerous hairpins inside mRNAs without observable small RNA production. Our data revealed ~100 mRNAs of protein coding genes to be targeted in both human and worm. These mRNAs significantly overlapped with the RNAi pathway. We also, unexpectedly, found that mitochondrial transcripts are Dicer targets in both species. We demonstrate functional consequences of Dicer binding by perturbation analysis. Taken together,we provide the first genome-wide catalog of direct Dicer targets. Our results suggest widespread function outside of miRNA biogenesis. Overall design: PAR-CLIP basically as described previously (Hafner et al. 2010).	Co-expression
SRP038921	Transcriptome wide identification of Dicer binding in human and C. elegans reveals a variety of substrates (HEK RNA-Seq)	Dicer is a deeply conserved endoribonuclease with key functions in small RNA biogenesis. Here we employed PAR-CLIP/iPAR-CLIP to identify direct Dicer binding sites in the transcriptomes of human cells and human. We found hundreds of novel miRNAs and non-canonical Dicer substrates with high sensitivity. Small RNA production depended on structure of the binding site and is globally biased towards the 5'' arm of hairpins. Unexpectedly, in both species Dicer bound numerous hairpins inside mRNAs without observable small RNA production. Our data revealed ~100 mRNAs of protein coding genes to be targeted in both human and worm. These mRNAs significantly overlapped with the RNAi pathway. We also, unexpectedly, found that mitochondrial transcripts are Dicer targets in both species. We demonstrate functional consequences of Dicer binding by perturbation analysis. Taken together,we provide the first genome-wide catalog of direct Dicer targets. Our results suggest widespread function outside of miRNA biogenesis. Overall design: Regulatory impact of Dicer binding was assessed by knock down experiments in human HEK293 cells. Drosha knockdown and mock transfections were used as controls. In total 3 samples.	Co-expression
SRP038925	Transcriptome wide identification of Dicer binding in human and C. elegans reveals a variety of substrates (small RNA AGO-IP)	Dicer is a deeply conserved endoribonuclease with key functions in small RNA biogenesis. Here we employed PAR-CLIP/iPAR-CLIP to identify direct Dicer binding sites in the transcriptomes of human cells and human. We found hundreds of novel miRNAs and non-canonical Dicer substrates with high sensitivity. Small RNA production depended on structure of the binding site and is globally biased towards the 5'' arm of hairpins. Unexpectedly, in both species Dicer bound numerous hairpins inside mRNAs without observable small RNA production. Our data revealed ~100 mRNAs of protein coding genes to be targeted in both human and worm. These mRNAs significantly overlapped with the RNAi pathway. We also, unexpectedly, found that mitochondrial transcripts are Dicer targets in both species. We demonstrate functional consequences of Dicer binding by perturbation analysis. Taken together,we provide the first genome-wide catalog of direct Dicer targets. Our results suggest widespread function outside of miRNA biogenesis. Overall design: Argonaute loaded small RNAs were extracted from FLAG:AGO2 and FLAG:AGO3 expressing HEK293 cells. Small RNA was purified and length selected (see supplementary methods).	Co-expression
SRP038963	Systematic Mapping of ADAR1 Binding Reveals its Regulatory Roles in Multiple RNA Processing Pathways [CLIP-seq]	ADARs are the primary factors underlying A-to-I editing in metazoans. We conducted the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. In contrast to the expected predominant binding of ADAR1 to Alu repeats, thousands of CLIP sites were located in non-Alu regions. This unexpectedly frequent non-Alu binding enabled discovery of transcriptome-wide functional and biophysical targets of ADAR1 in the regulation of mRNA processing including alternative 3'' UTR usage and alternative splicing. In addition, a global analysis of ADAR1 binding to non-Alu regions also revealed its primary interaction with microRNA (miRNA) transcripts in the nucleus, which subsequently affected expression levels of mature miRNAs. A complex global picture was revealed regarding the dependence of this function on the double-stranded RNA binding domains or deaminase activity. Our study unfolded a broad landscape of the diverse functional roles of ADAR1. Overall design: To charaterize ADAR1 binding profiles in U87 cells, we performed CLIP-seq using two different ADAR1 monoclonal antibodies.	Co-expression
SRP038964	Systematic Mapping of ADAR1 Binding Reveals its Regulatory Roles in Multiple RNA Processing Pathways [small RNA-seq]	ADARs are the primary factors underlying A-to-I editing in metazoans. We conducted the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. In contrast to the expected predominant binding of ADAR1 to Alu repeats, thousands of CLIP sites were located in non-Alu regions. This unexpectedly frequent non-Alu binding enabled discovery of transcriptome-wide functional and biophysical targets of ADAR1 in the regulation of mRNA processing including alternative 3'' UTR usage and alternative splicing. In addition, a global analysis of ADAR1 binding to non-Alu regions also revealed its primary interaction with microRNA (miRNA) transcripts in the nucleus, which subsequently affected expression levels of mature miRNAs. A complex global picture was revealed regarding the dependence of this function on the double-stranded RNA binding domains or deaminase activity. Our study unfolded a broad landscape of the diverse functional roles of ADAR1. Overall design: To identify ADAR binding dependent miRNA defferential expression profiles, U87MG cells were transfected with ADAR1 overexpression vector, RNA binding mutant (EAA and E912A), siRNA of ADAR1 or controls.	Co-expression
SRP038997	Cell Cycle Reprogramming for PI3K Inhibition Overrides Relapse-Specific C481S BTK Mutation Revealed by Longitudinal Functional Genomics in Mantle Cell Lymphoma	The RNA-seq data presented in this study include libraries from Mantle Cell Lymphoma (MCL) tumor cells sequentially obtained from patients Overall design: RNA-Seq on MCL patient samples	Co-expression
SRP039039	RNA-seq on Human hepatocytes	RNA-seq on cryopreserved human hepatocytes from a 19 year old Caucasian male donor with no history of medications	Co-expression
SRP039077	Gene expression analysis of airway epithelial cells exposed to flagellin via RNA-seq	Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using exon microarrays and RNAsequencing. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. In conclusion, In vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium. Overall design: A total of eight independent RNAseq experiments were conducted. Four RNAseq experiments (n = 2 unstimulated, n = 2 stimulated with flagellin) were performed using AECs grown in monolayer. Four RNAseq experiments (n =2 unstimulated, n = 2 stimulated with flagellin) were conducted using AECs grown in ALI cultures	Co-expression
SRP039085	Homo sapiens strain:HL-60 Transcriptome or Gene expression	Transcriptome of human HL-60 and HEK-293 cells depending on culture cell density	Co-expression
SRP039338	Gene expression profile of calcified and normal tricuspid aortic valves by RNA sequencing.	Purpose: Calcific aortic valve stenosis (AS) is a fatal disease with currently no medical therapy. Some genes were associated with AS, but the genetic architecture of the disease has yet to be discovered. The objective of this study was to combine genome-wide association studies (GWAS) and gene expression in human valve tissues to identify new susceptibility genes of AS. Methods: A meta-analysis was performed combining the results of two independent GWAS in 474 patients that underwent aortic valve replacement from Quebec city and 486 echocardiography cases from France. The controls consisted of 3,151 publically available individuals of European ancestry. Sixty-nine SNPs selected from the meta-analysis (p < 1 x 10-4) were followed-up for replication in a third cohort of 395 cases and 404 controls. Single marker and gene set association analyses were performed. The mRNA expression levels of susceptibility genes were evaluated in 19 human aortic valves with (n=9) and without (n=10) AS by RNA sequencing. Results: Single marker analysis identified 15 SNPs with p values lower than 1 x 10-6 in the meta-analysis near the FAR2 gene on chromosome 12. At the replication stage, none of these SNPs were confirmed and three other SNPs on chromosomes 2 and 5 reached p < 0.05. Gene set analysis revealed more meaningful association with the calcium signaling pathway enriched for genes mapped to disease-associated SNPs. Genes in this pathway including F2R, GNA14, HTR4, P2RX6, and TNNC1 were found differentially expressed in valves with and without AS. Conclusions: This integrative genomic study identified new AS susceptibility genes expressed in human valve tissue. Moderate but coordinated genetic association and expression patterns were observed for genes implicated in the calcium signaling pathway and may provide new therapeutic targets to treat this frequent and rising life-threatening disease. Overall design: Samples of aortic valves were collected from 19 male patients undergoing aortic valve replacement surgery. RNA sequencing was performed using the Illumina Hiseq 2000. Three pairwise comparison among the two kind of valves were made.	Co-expression
SRP039348	Domains of genomewide gene expression dysregulation in Down syndrome [RNA-seq]	Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins’ fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of DS and wild-type, also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome and that GEDDs may therefore contribute to some T21 phenotypes. Overall design: mRNA-Seq profiling in Down syndrome: fibroblasts derived from a pair of monozygotic twins discordant for trisomy 21 (4 replicates), iPS cells from the same pair of discordant twins, fibroblasts from a pair of normal monozygotic twins, fibroblasts from 16 unrelated individuals (8 trisomic and 8 euploid controls), fibroblasts from the Ts65Dn mouse model of Down syndrome (1 trisomic mouse and 1 control wt).	Co-expression
SRP039354	Genome-wide transcriptome analysis of human epidermal melanocytes	This work provides a comprehensive and global perspective of gene expression in human epidermal melanocytes using RNA-Seq. Our focus on cell signalling genes and differential expression between lightly and darkly pigmented melanocytes may help to identify novel pigmentation genes and potential pharmacological targets.	Co-expression
SRP039359	Rate of elongation by RNA polymerase II is influenced by specific gene features and histone modifications	The rate of transcription elongation plays important roles in the timing of expression of full-length transcripts as well as for the regulation of alternative splicing. In this study we coupled Bru-Seq technology with 5,6-dichlorobenzimidazole 1-ß-D-ribofuranoside (DRB) to estimate the elongation rates of over 2,000 individual genes in human cells. This technique, BruDRB-Seq, revealed gene-specific differences in elongation rates with a median rate of around 1.5 kb/min. We found that genes with fast elongation rates showed higher densities of H3K79m2 and H4K20me1 marks compared to slower elongating genes. Furthermore, fast elongation rates had a positive correlation with gene length, low complexity DNA sequence and distance from nearest active transcription unit. Features that negatively correlated with elongation rate included exon density and the number of LINE sequences in the gene. The BruDRB-Seq technique offers new opportunities to interrogate mechanisms of regulation of transcription elongation. Overall design: Measurement of RNA Pol II elogation rate. Normal fibroblasts (HF1 and TM), Cockayne syndrome group B fibroblasts, K562 and MCF-7 cells were exposed to DRB for 60 minutes, after which a washout was performed. Nascent RNA was labeled using bromouridine for 10 minutes immediately after the washout. The genomic region extending from actice Trancription Start Sites was used to determine the gene''s elongation rate. Please note that the nf_0h_3* samples are duplicated sample records of GSM1062445 and GSM1062446, for the convenient retrieval of the complete raw data from SRA.	Co-expression
SRP039361	Functional and Transcriptomic Characterization of iPSC-derived Macrophages and their Application in Modeling Mendelian Disease	Using RNA-Seq, we reported novel findings in the comparison of transcriptome profiles of isogenic HMDM and IPSDM during differentiation and polarization. First, IPSDM lost expression of pluripotency markers, had remarkably distinct gene expression profiles relative to precursor iPSCs, and had largely similar gene expression as HMDM. Second, macrophage polarization to M1 was associated with a dramatic change in the transcriptome; expression profiles of IPSDM- and HMDM-derived M1 lines were highly correlated with each other but much less so with their respective IPSDM and HMDM precursors. Third, M2-HMDM lines had limited difference in gene expression compared to their non-polarized precursors, likely due to the known M2-like phenotype of M-CSF differentiated macrophages and their similarity to the IL-4 derived M2 phenotype Finally, through RNA-Seq we identified many new genes modulated during polarization in both HMDM and IPSDM thus providing novel, and potentially regulatory, candidates that warrant further study. Overall design: iPS, IPSDM (including M1/M2) and HMDM (including M1/M2)cells were sequenced by Illumina HiSeq 2000 with poly-A selection	Co-expression
SRP039397	High-resolution mapping reveals a conserved, widespread, dynamic meiotically regulated mRNA methylation program [Hs]	N6-methyladenosine (m6A) is a common modification of mRNA, with potential roles in fine-tuning the RNA life cycle, but little is known about the pathways regulating this process and its physiological role. Here, we used mass-spectrometry to identify a dense network of proteins physically interacting with METTL3, a core component of the methyltransferase complex, and show that two of them, WTAP and KIAA1429, are required for methylation.  Combining high resolution m6A-Seq with knockdown of WTAP allowed us to define accurate maps, at near single-nucleotide resolution, of sites of mRNA methylation across four dynamic programs in human and mouse, including development, differentiation, reprogramming and immune response. Internal WTAP-dependent methylation sites were largely static across the different surveyed conditions and present in the majority of mRNAs. However, methylations were found at much lower levels within highly expressed mRNAs, and methylation is inversely correlated with mRNA stability, consistent with a role in establishing an overall basal, cell-type invariant, distribution of degradation rates. In addition, we identify thousands of WTAP-independent methylation sites at transcription initiation sites, forming part of the mRNA cap structure. We show that the methylations occur at the first transcribed nucleotide, and find that thousands of transcripts are present in different isoforms differing in the methylation state of the first transcribed nucleotide, a previously unappreciated complexity of the transcriptome. Together, our data sheds new light on the proteomic and transcriptional underpinnings of this epitranscriptomic modification in mammals. Overall design: Examination of m6A methylation in human Hek293 and A549 cell lines, in human embryonic stem cells (ESCs) undergoing differentiation to neural progenitor cells (NPCs),  in OKMS inducible fibroblasts reprogrammed into iPSC, and upon knockdown of factors using siRNAs or shRNAs.	Co-expression
SRP039399	Homo sapiens Transcriptome or Gene expression	Rectal cancer stage II carcinoma and adjacent normal tissue transcriptome	Co-expression
SRP039591	Integrative Genomic and Transcriptomic Analysis Identified Candidate Genes Implicated in the Pathogenesis of Hepatosplenic T-cell Lymphoma	Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q   [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six HSTL cases with i(7)(q10) and three cases with ring 7   [r(7)], a rare variant aberration. Using high resolution array CGH, we prove that HSTL is characterized by the common loss of a 34.88 Mb region at 7p22.1p14.1 (3506316-38406226 bp) and duplication/amplification of a 38.77 Mb region at 7q22.11q31.1 (86259620-124892276 bp). Our data indicate that i(7)(q10)/r(7)-associated loss of 7p22.1p14.1 is a critical event in the development of HSTL, while gain of 7q sequences drives progression of the disease and underlies its intrinsic chemoresistance. Loss of 7p22.1p14.1 does not target a postulated tumor suppressor gene but unexpectedly enhances the expression of CHN2 from the remaining 7p allele, resulting in dysregulation of a pathway involving RAC1 and NFATC2 with a cell proliferation response. Gain of 7q leads to increased expression of critical genes, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any additional recurrent mutations or fusion, suggesting that i(7)(q10) is the only driver event in this tumor. Our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies Overall design: The fastq files of all samples were mapped to the reference human genome (assembly GRCh37.68). The mapping was performed  allowing detection of insertions and deletions (indels). The mapped reads were used to calculate read counts and FPKM (Fragment Per Kilobase of exon model per Million of mapped read) per gene. The DESeq algorithm was applied to identify differentially expressed genes. The mapped reads were used to predict mutations and gene fusions.	Co-expression
SRP039694	Promoter methylome and integrative transcriptome profiling identify key epigenetics-regulated genes in human HCCs [expression]	Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide and has a poor prognosis. Promoters represent an essential regulatory element of gene transcription in human genome. In order to understand the promoter methylation in relation with gene transcription in HCCs, We applied a liquid hybridization capture-based bisulfite sequencing (LHC-BS) approach to examine the promoter methylome of HCCs, for which we customized 150,407 capture probes and enabled coverage of 91.8% of the RefSeq gene promoters within human genome. We found the differential promoter DNA methylation between HCCs and peripheral normal tissues. Then we integrated promoter methylomic and transcriptomic profiling and described gene expression and regulation in HCCs. Lastly, We validated the key genes in larger number of samples and screened candidate genes aberrantly regulated by DNA methylation in human HCCs. Overall design: RNA-seq for 8 pairs of HCC tumor and non-tumor liver (NTL) samples.	Co-expression
SRP040070	Transcriptomic analysis of the Novel Middle East Respiratory Syndrome Coronavirus (MERS-CoV)	No description.	Co-expression
SRP040110	Comparison of Varicella-Zoster Virus RNA sequences in human neurons and fibroblasts	These are RNAseq reads from human cell culture (neurons and fibroblasts) infected with VZV. Thus the reads are a mixture of human and viral. The study was designed to assess whether VZV was in true latency, or whether is was simply an aborted infection.	Co-expression
SRP040117	"Drug-seq": An Approach to Identify the Genomic Targets of Chemicals Identified by Functional Phenotypic Screens [GRO-seq]	Here we report an approach that has permitted us to uncover the sites and mechanisms of action of a drug, referred to as SD70, initially identified by phenotypic screening for inhibitors of ligand and genotoxic stress-induced translocations in prostate cancer cells. Based on synthesis of a derivatized form of SD70 that permits its application for a ChIP-seq-like approach, referred to as Drug-seq, we were next able to efficiently map the genome-wide binding locations of this small molecule, revealing that it largely co-localized with androgen receptor (AR) on regulatory enhancers. Based on these observations, we performed the appropriate global analyses to ascertain that SD70 inhibits the androgen-dependent AR program, and prostate cancer cell growth, acting, at least in part, by functionally inhibiting the jumonji (JMJ) domain-containing demethylase, KDM4C. Drug-seq represents a powerful strategy for new drug development by mapping genome-wide location of small molecules, a powerful adjunct to contemporary drug development strategies. Overall design: Global Run-On (GRO) assay followed by high-throughput sequencing (GRO-seq).	Co-expression
SRP040136	Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [RNA-Seq]	The estrogen receptor-a (ERa) is a transcription factor which plays a critical role in controlling cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to induce or repress gene transcription. A deeper understanding of these transcriptional mechanisms may uncover novel therapeutic targets for ERa-dependent cancers. Here we show for the first time that BRD4 regulates ERa-induced gene expression by affecting elongation-associated phosphorylation of RNA Polymerase II (RNAPII P-Ser2) and histone H2B monoubiquitination (H2Bub1). Consistently, BRD4 activity is required for estrogen-induced proliferation of ER+ breast and endometrial cancer cells and uterine growth in mice. Genome-wide occupancy studies revealed an enrichment of BRD4 on transcriptional start sites as well as EREs enriched for H3K27ac and demonstrate a requirement for BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we further demonstrate that BRD4 occupancy correlates with active mRNA transcription and is required for the production of ERa-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ERa function and potential therapeutic target. Overall design: mRNA expression profiles of MCF7 cells treated with +/- estrogen treatment under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.	Co-expression
SRP040145	Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies	Induced pluripotent stem cells (iPSCs) offer opportunity for insight into the genetic requirements of the X chromosome for somatic and germline development. Turner syndrome is caused by complete or partial loss of the second sex chromosome; while more than 90% of Turner cases result in spontaneous fetal loss, survivors display an array of somatic and germline clinical characteristics. Here, we derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We analyzed gene expression profiles of derived iPSCs and in vitro differentiated cells by single cell qRT-PCR and RNA-seq. We whoed that two X chromosomes are not necessary for reprogramming or pluripotency maintenance. Genes that escape X chromosome inactivation (XCI) between control iPSCs and those with X chromosome aneuploidies revealed minimal expression differences relative to a female hESC line. Moreover, when we induced germ cell differentiation via murine xenotransplantation of iPSC lines into the seminiferous tubules of busulfan-treated mice, we observed that undifferentiated iPSCs, independent of X chromosome composition, when placed within the correct somatic environment, are capable of forming early germ cells in vivo. Results indicate that two intact X chromosomes are not required for germ cell formation; however, clinical data suggest that two sex chromosomes are required for maintenance of human germ cells. Overall design: RNA-seq of  H9 cells, iPSCs from Turner syndrome and control individuals and in vitro differentiated cells	Co-expression
SRP040236	Next generation sequencing identifies discrete classes of box C/D snoRNAs featuring different ends and RNA binding protein dependency	The paired-end next-generation sequencing of all small RNAs of less than 200 nucleotides in length from four different human cell lines (SKOV3ip1, MCF-7, BJ-Tielf, INOF) allowed us to determine the exact sequence(s) and variations of human box C/D snoRNAs (small nucleolar RNAs), revealing processing patterns of this class of molecules.   Two distinct groups of box C/D snoRNAs were identified based on the position of their ends with respect to their characteristic boxes and the terminal base pairing potential. Short box C/D snoRNAs start sharply 4 or 5 nucleotides upstream of their box C and end 2 or 3 nucleotides downstream of their box D. In contrast, long box C/D snoRNAs start 5 or 6 nucleotides upstream of their box C and end 4 or 5 nucleotides downstream of their box D, increasing the likelihood of formation of a k-turn between their boxes C and D. Sequencing of SKOV3ip1 cells following the depletions of NOP58, a core box C/D snoRNA-binding protein and of RBFOX2, a splicing factor, shows that the short box C/D snoRNA forms are significantly more affected by the depletion of RBFOX2 while the long snoRNA forms, which display more canonical box C/D snoRNA features, are significantly more affected by the depletion of NOP58. Together the data suggest that box C/D snoRNAs are divided into at least two groups of RNA with distinct maturation and functional preferences. Overall design: Small RNAs (<200 nucleotides) were isolated from different human cell lines that were either untreated or depleted of NOP58 or RBFOX2 using specific siRNAs. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.	Co-expression
SRP040275	Homo sapiens Transcriptome or Gene expression	Many addictive drugs such as nicotine mediate reward and reinforcing mechanisms within the mesolimbic pathway involving midbrain dopaminergic (mDA) neurons via nicotinic acetylcholine receptors (nAChRs). Previously, genome-wide association analyses (GWAs) identified several nucleotide polymorphism (SNP) associated with increased risk of addictive phenotypes including the nonsynonymous rs16969968 SNP encoding D398->N398 variation in the CHRNA5 gene (Bierut et al., 2008; Saccone et al., 2007) . However, the etiology and the pathophysiology associated with the N398 allele is unknown. Previous animal studies using a knock-in of human CHRNA5 N398 revealed increased nicotine consumption. However, given the evolutionary distance between mice and humans, identifying intrinsic factors that affect addiction may correlate poorly, limiting the conclusiveness of these studies. In this study, induced pluripotent stem cell (iPSC) lines were derived from cryopreserved lymphocytes drawn from patients with homozygous minor alleles (N398) of rs16969968 and demonstrated nicotine addiction as well as age- and gender-matched unaffected controls carrying the major allele (D398). Cultures of primarily mDA neurons were prepared from these iPSC lines. Gene expression analysis using RT-PCR and RNAseq revealed similar expression of mRNAs encoding subunits of nAChR in mDA neurons derived from both D398 and N398 iPSC lines, however, gene ontology (GO) analysis revealed an increased enrichment of genes associated with neuroactive ligand-receptor interactions and Ca2+ signaling pathways in N398 neurons. Moreover, the N398 neuronal population responded more actively to application of nicotine in both electrophysiological analysis and Ca2+-imaging analysis. Together, these results suggest that the N398 variation affects Ca2+-signaling in neurons, which may explain the predisposition of subjects carrying this mutation for addictive behavior in subjects carrying the nonsynonymous rs16969968 SNP (Sherva et al., 2008).	Co-expression
SRP040278	Widespread N6-methyladenosine-dependent RNA Structural Switches Regulate RNA-Protein Interactions	We show that N6-methyladenosine (m6A), the most abundant internal modification in mRNA/lncRNA with still poorly characterized function, alters RNA structure to facilitate the access of RBM for heterogeneous nuclear ribonucleoprotein C (hnRNP C). We term this mechanism m6A-switch. Through combining PAR-CLIP with Me-RIP, we identify 39,060 m6A-switches among hnRNP C binding sites transcriptome-wide. We show that m6A-methyltransferases METTL3 or METTL14 knockdown decreases hnRNP C binding at 16,582 m6A-switches. Taken together, 2,798 m6A-switches of high confidence are identified to mediate RNA-hnRNP C interactions and affect diverse biological processes including cell cycle regulation. These findings reveal the biological importance of m6A and provide insights into the sophisticated regulation of RNA-RBP interactions through m6A-induced RNA structural remodeling. Overall design: Measure the m6A methylated hnRNP C binding sites transcriptome-wide by PARCLIP-MeRIP; measure the differential hnRNP C occupancies upon METTL3/METTL14 knockdown by PAR-CLIP; measure RNA abundance and splicing level changes upon HNRNPC, METTL3 and METTL14 knockdown	Co-expression
SRP040288	Homo sapiens strain:K562 Transcriptome or Gene expression	K562 single cell RNA-seq study	Co-expression
SRP040309	Homo sapiens Transcriptome or Gene expression	Study single cell transcriptional heterogeneity	Co-expression
SRP040327	Epigenetic Repogramming by an Environmental Carcinogen Through Chromatin Domain Disruption [RNA-Seq]	Alterations in chromatin modifications, including DNA methylation and histone modification patterns, have been characterized under exposure of several environmental pollutants, including nickel. As with other carcinogenic metals, the mutagenic potential of nickel compounds is low and is not well correlated with its carcinogenic effects. Nickel exposure, however, is associated with alterations in chromatin modifications and related transcriptional programs, suggesting an alternative pathway whereby nickel exposure can lead to disease. To investigate the extent to which nickel exposure disrupts chromatin patterns, we profiled several histone modifications, including H3K4me3, H3K9ac, H3K27me3 and H3K9me2 as well as the insulator binding protein CTCF and the transcriptomes of control BEAS-2B cells and cells treated with nickel for 72 hours. Our results show significant alterations of the repressive histone modification H3K9me2 in nickel-exposed cells with spreading of H3K9me2 into new domains associated with gene silencing. We furthermore show that local regions of active chromatin can protect genes from nickel-induced H3K9me2 spreading. Interestingly, we show that nickel exposure selectively disrupts weaker CTCF sites, leading to spreading of H3K9me2 at these regions. These results have major implications in the understanding of how environmental carcinogens can affect chromatin dynamics and the consequences of chromatin domain disruption in disease progression. Overall design: Treat BEAS-2B cells with NiCl2 for 72 hours and compare histone modification, CTCF binding to control BEAS-2B cells to see how they regulated gene expression by RNA-seq	Co-expression
SRP040328	Parallel T-cell cloning and deep sequencing of the transcripts of human MAIT cells reveal stable oligoclonal TCRß repertoire	Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize conserved bacterial antigens derived from riboflavin precursors, presented by the non-polymorphic MHC class I-like molecule MR1. Here, we show via transcriptomic analysis that human MAIT cells are remarkably oligoclonal in both blood and liver, display high inter-individual homology, and exhibit a restricted length CDR3ß domain of the TCRVß chain. We extend this analysis to a second sub-population of MAIT cells expressing a semi-invariant TCR conserved between individuals. Overall design: Study of CDR3 regions of TCRalpha and beta sequences	Co-expression
SRP040418	RNA-seq data from MCF-7 cells (breast cancer model) treated with soy extracts	The MCF-7 were infected with either control adenovirus expressing B-galactosidase (Ad) or adenovirus expressing ERB (AdERbeta) for 72 h.  For knockdown of the endogenous ERa in MCF-7 cells, cells were treated with siRNA for 24h (AdERbeta+SiERalpha).  Then cells were treated with Veh (0.1% EtOH), 10 nM E2 or 1 uM BEs (botanical extracts) for 24h. Overall design: Duplicate samples run; treatment after knockdown included a control treatment (V), estradiol (E2) or botanical extracts; genistein (Gen), S-equol, liquiritigenin (Liq)	Co-expression
SRP040421	Next generation sequencing of small RNAs isolated from exosomes in human semen	Preparation of exosomes isolated from semen contain a substantial amount of RNA, mostly from 20 to 100 nucleotides in length. We sequenced separately 20-40 and 40-100 nucleotide fractions of  RNA from exosomes isolated from semenal fluid from six healthy donors. We found various classes of small non-coding RNA, including mature microRNA and piwi-RNA,  as well as abundant Y RNAs and tRNAs present in both full length and fragmented forms. Specific RNAs were consistently present in all donors. For example, fifteen (of ~2,600 known) microRNAs constituted over 80% of mature microRNA in SE. Additionally, tRNA fragments were strongly enriched for 5’-ends of 18-19 or 30-34 nucleotides in length. Overall design: Size-fractionated small RNA profiles from exosomes isolated from the seminal fluid of six healthy donors	Co-expression
SRP040442	Next Generation Sequencing identifying the dosage compensation state in human endometrial carcinoma and adjacent tissues	Mammals have evolved an XY sex chromosome system, resulting in dosage imbalance not only between sexes, but also between X-chromosome and autosome. Overall design: mRNA profiles of 9 pairs of human endometrial carcinoma and adjacent tissues were generated by Illumina 100-nucleotide paired-end sequencing	Co-expression
SRP040454	Rhabdomyosarcoma transcriptome sequencing	No description.	Co-expression
SRP040472	Simultaneous Transcriptional profiling of Obligate Intracellular Pathogens and their Host Cells	Development of heterogeneous RNA-Seq (hRNA-Seq) to simultaneously capture prokaryotic and eukaryotic expression profiles of bacteria-infected cells.	Co-expression
SRP040505	RNA sequencing identifies specific PIWI-interacting small non-coding RNA expression patterns in breast cancer	PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162)  database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERß and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. Overall design: In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.	Co-expression
SRP040525	RNA-seq and small RNA-seq from WT and ADAR1 knockdown H9 lines and their differentiation to specific types of neurons	Adenosine deaminases acting on RNA (ADARs) are involved in adenosine (A) to inosine (I) RNA editing and human ADARs are implicated in neurological diseases. Here we generated human embryonic stem cells (hESCs) lacking ADAR1 to investigate its role in neural development in a human context. We found that ADAR1 deficiency significantly retarded neural induction with widespread mRNA and miRNA expression changes. We have genome widely examined the changes of  A-to-I editing and miRNA expression after ADAR1 knockdown. Such aberrant mRNA and miRNA expression was not due to reduced A-to-I editing after ADAR1 knockdown. We further revealed that ADAR1 regulates miRNA biogenesis independent of its editing activity. Overall design: In order to study the function role of ADAR1 in neural induction, we used shRNA to stably knocked down ADAR1 in human embryonic stem cell (hESC) h9 line and then differentiated ADAR1 deficiency hESC h9 cells to specific types of neurons. We then collect total RNAs at different time points at undifferentiated stage (day 0, d0 for short), day 10 (d10), day 17 (d17) and day 35 (d35), and obtained RNA-seq and small RNA-seq datasets for further analyses.	Co-expression
SRP040547	Human and Toxoplasma gondii genetics and cellular/molecular interactions	The goal of this project is to infect relevant human host cells (MonoMac6, adult human neural progenitor (AHNP) cells, AHNP-derived neurons and human fibroblasts) with Toxoplasma gondii parasites of differing lineages to generate transcriptional mRNA and miRNA profiles. These datasets will allow the characterization of how genetically different parasites that cause distinct types of human toxoplasmosis alter the expression of protein-encoding and miRNA-encoding genes in both the human host and the parasite.	Co-expression
SRP040577	Effect of PRDM11 depletion in U2932 cells	The PR-domain family e(PRDMs) encodes transcriptional regulators, several of which are deregulated in cancer. We found that loss of Prdm11 accelerates MYC-driven lymphomagenesis in the Eµ-Myc mouse model. Moreover, we show that patients with PRDM11-deficient diffuse large B cell lymphomas (DLBCLs) have poorer overall survival and belong to the non-Germinal Center B cell (GCB)-like subtype. Mechanistically, genome-wide mapping of PRDM11 binding sites coupled with transcriptome sequencing in human DLBCL cells evidenced that PRDM11 associates with transcriptional start sites of target genes and regulates important oncogenes such as FOS and JUN.  Hence, we characterize PRDM11 as a novel tumor suppressor controlling the expression of key oncogenes and add new mechanistic insight into B-cell lymphomagenesis. Overall design: RNA-seq performed after knockdown of Prdm11	Co-expression
SRP040622	The age and genomic integrity of neurons after cortical stroke in humans	It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA-rearrangements in the human neocortex. We show here that neither is the case, using immunohistochemistry, transcriptome-, genome- and ploidy-analyses, and determination of nuclear bomb test-derived 14C-concentration in neuronal DNA. A large proportion of cortical neurons display DNA-fragmentation and DNA-repair short time after stroke, whereas neurons at chronic stages after stroke show DNA-integrity, demonstrating the relevance of an intact genome for survival. Overall design: Analyze of potential fusion transcripts in 13 samples, seven cortical ischemic stroke tissue and six control cortex, by deep sequencing using Illumina HiSeq 2000	Co-expression
SRP040647	RNA-seq of Human microvascular lung endothelial cells	Patients receiving mechanical ventilation for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are at risk for ventilator-associated lung injury (VILI). Our RNA-Seq data provides a comprehensive survey of the transcriptome of HMVLECs under pathological and physiological CS conditions, either with TNF-alpha or not. It provides a useful resource for our in-depth understanding of genes and pathways contributing the pathogenesis of ALI and VILI.	Co-expression
SRP040692	Next-generation sequencing facilitates quantitative analysis of AcKLF5 and unAcKLF5 transcriptomes in xenografts of DU-145 cell line	KLF5 possesses both tumor-suppressing and tumor-promoting activities, though the mechanism controlling these opposing functions is unknown. In cultured non-cancerous epithelial cells, KLF5 converts from pro-proliferative to anti-proliferative activity upon TGFß-induced acetylation, which sequentially alters the KLF5 transcriptional complex and the expression of genes such as p15 and MYC. In nude mice, KLF5 also suppressed tumor growth in an acetylation-dependent manner. Furthermore, deacetylation switched KLF5 to tumor-promoting activity, and blocking TGFß signaling attenuated the tumor suppressor activity of KLF5. The results from RNA-Seq indicated the different downstream genes of AcKLF5 and unAcKLF5 and the mechanisms that determine the opposing functions of AcKLF5 and unAcKLF5. These results provide novel insights into the mechanism by which KLF5 switches from anti-tumorigenic to pro-tumorigenic function, and also suggest the roles of AcKLF5 and unAcKLF5, respectively, in the tumor-suppressing and tumor-promoting functions of TGFß. Overall design: Xenografts of DU-145 cell lines expressing KLF5, KLF5 mutant K369R or the empty vector PLHCX were surgically isolated from mice at day 38 after injection. RNA-Seq was performed using these three groups of xenografts.	Co-expression
SRP040727	Effect of TTF-1/NKX2-1 expression on TGF-beta induced gene expression in A549 lung cancer cell line.	TTF-1/NKX2-1 was expressed by adenoviral vector and changes in gene expression were determined by RNA-sequencing. Overall design: A549 cells were infected with Ad-TTF-1 or Ad-LacZ vectors and stimulated with TGF-beta for 24 hours or left untreated. Expression of polyA RNA was determined.	Co-expression
SRP040745	Genome-wide expression analysis of young, senescent and p38MAPK-inhibitited senescent human fibroblasts.	We utilized whole genome sequencing of mRNA (RNA-seq) to understand the extent to which the senescence-associated secretory phenotype is regulated by p38MAPK Overall design: Examination of replicates of young, senescent or p38MAPK-inhibited senescent BJ human foreskin fibroblasts.	Co-expression
SRP040772	miRNome of endometriotic lesion	miRNA high-throughput sequencing was used to investigate endometriosis lesion-specific miRNA expression profiles by comparing a set of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissue together with eutopic endometrium of the same patients. We found that miRNAs of surrounding peritoneal tissue mask most of the miRNA expression differences that could originate from endometriotic tissue and thus only miRNAs with significantly different levels in the endometriotic lesions compared to peritoneal tissue were detected. According to the results of this study, two miRNAs – miR-34c and miR-449a showed remarkably higher expression in lesions compared to healthy tissue. Overall design: Eleven tissue samples (two endometria, five peritoneal lesions and four matched adjacent normal-appearing tissues) were analysed from two patients with a histologically confirmed diagnosis of moderate-severe endometriosis (III-IV stage)	Co-expression
SRP040806	Hypoxia and the transcriptome of human monocyte-enriched peripheral blood mononuclear cells	Monocytes, a type of mononuclear white blood cells, leave the circulation and enter into tissues in response to tissue damage or infection. These cells can encounter a hypoxic environment in the tissue that they extravasate to. The goal of this study was to identify changes in the transcriptome of such cells following exposure to hypoxia.	Co-expression
SRP040966	InFusion: advancing discovery of fusion genes and chimeric transcripts from RNA-seq data	Gene fusions and chimeric transcripts occur frequently in cancers and in some cases drive the development of the disease. An accurate detection of these events is crucial for cancer research and in a long-term perspective could be applied for personalized therapy. RNA-seq technology has been established as an efficient approach to investigate transcriptomes and search for gene fusions and chimeric transcripts on a genome-wide scale. A number of computational methods for the detection of gene fusions from RNA-seq data have been developed. However, recent studies demonstrate differences between commonly used approaches in terms of specificity and sensitivity. Moreover their ability to detect gene fusions on the isoform level has not been studied carefully so far. Here we propose a novel computational approach called InFusion for fusion gene detection from deep RNA sequencing data. Validation of InFusion on simulated and on several public RNA-seq datasets demonstrated better detection accuracy compared to other tools. We also performed deep RNA sequencing of two well-established prostate cancer cell lines. Using these data we showed that InFusion is capable of discovering alternatively spliced gene fusion isoforms as well as chimeric transcripts that include non-exonic regions. In addition our method can detect anti-sense transcription in the fusions by incorporating strand specificity of the sequencing library. Overall design: Detection of fusion genes and chimeric transcripts from deep RNA-seq data	Co-expression
SRP041008	Critical role of transient activation of human endogenous retroviruses during reprogramming toward pluripotency (RNA-Seq)	We recently showed that some human induced pluripotent stem cell (iPSC) clones were defective in neural differentiation and were marked with the activation of long term repeats (LTRs) of human endogenous retroviruses (HERVs). We herein demonstrated that these LTRs were transiently overexpressed during the generation of iPSCs and contributed to reprogramming. When the generation of iPSCs was completed, LTRs were re-suppressed to levels similar to those in human ES cells. However, differentiation-defective iPSC clones maintained high LTR expression levels, which indicated that these clones failed to complete reprogramming. lincRNA-RoR, a long intergenic non-coding RNA (lincRNA) that was previously shown to support the induction and maintenance of pluripotency, was detected among the LTR-driven transcripts. Short hairpin RNAs against the conserved sequence in LTRs or lincRNA-RoR markedly reduced the efficiency of iPSC generation. Reprogramming factors including OCT3/4, SOX2, and KLF4 bound to most LTRs. The expression of KLF4 was low in normal iPSC clones, but remained high in differentiation-defective clones. The forced expression of KLF4 in human embryonic stem cells led to the activation of LTRs and defects in neural differentiation. These results demonstrated that the transient overexpression of KLF4/LTR/lincRNA-RoR played crucial roles in reprogramming toward pluripotency in humans, whereas a failure in its re-silence resulted in differentiation defects. Overall design: Nine samples were prepared as intermediate state of cells between human dermal fibroblast and iPSC. One iPSC clone and 4 subclones derived from defective iPSC exhibit normal differentiation ability.	Co-expression
SRP041036	RNAseq to investigate transcriptional changes in human MM cell lines due to panobinostat, 5-Azacytidine, panobinostat+5-Azacytidine or n-methyl-2-pyrroldine (NMP) treatments.	Purpose: We applied RNA sequencing technology for high-throughput analysis of transcriptional changes within human MM cell lines JJN3 and U266 due to individual and combination drug treatment. Methods: JJN3 and U266 cells were treated with pan-HDACi panbobinostat, DNMTi 5-Azacytidine, panobinostat+5-Azacytidine or NMP for 4h or 24h in triplicate and transcriptional changes assessed by RNAseq using Illumina HiSeq platform. Specifically, JJN3 cells were treated with 10nM panobinostat, 2.5µM 5-Azacytidine, panobinostat+5-Azacytidine (at given doses), or 10mM NMP. U266 cells were treated with 10nM panobinostat, 10µM 5-Azacytidine, panobinostat+5-Azacytidine (at given doses), or 10mM NMP. Results: We report unique and overlapping transcriptional signatures that lead to the induction of apoptosis in human MM cell lines in a cell-specific manner due to individual or combination treatments. Conclusions: A detailed analysis of differential transcriptional events in human MM cell lines due to HDACi, DNMTi, HDACi+DNMTi and NMP appear to define the molecular events leading to apoptosis and drug mechanism of action. Overall design: We tested triplicate experiments at 4h and 24hr time points in JJN3 and U266 cell lines against vehicle control treated cells.	Co-expression
SRP041044	Integrative analyses reveal complexity of human brain transcriptome by deep RNA-sequencing	Research human brain function and evolution by using high depth transcriptome sequencing data from different human brain region.	Co-expression
SRP041063	Establishment of Highly Tumorigenic Human Colorectal Cancer Cell Line (CR4) with Properties of Putative Cancer Stem Cells	Colorectal cancer (CRC) has the third highest incidence and mortality rates among the US population. According to the most recent concept of carcinogenesis, human tumors are organized hierarchically, and the top of this hierarchy is occupied by malignant stem cells, or cancer stem cells (CSCs), which possess unlimited self-renewal and tumor-initiating capacities and high resistance to conventional anticancer therapies. To reflect the complexity and diversity of human tumors and to provide clinically and physiologically relevant in vivo and in vitro models, a large banks of well characterized patient-derived low-passage cell lines, and especially CSC-enriched cell lines are urgently needed. Overall design: Using RNA-Seq, we have performed a functional genomic analysis in tumor-initiating fractions of CR4 (small) cells grown adherent to type I collagen versus grown as 3D spheroids, in comparison to the bulk tumor cells (long and dychotomized cells) grown under standard culture conditions.	Co-expression
SRP041094	RNA-Seq analysis of prostate tumors with or without androgen receptor splice variant	Background.  Androgen receptor splice variant-7 (AR-V7) is a truncated form of the androgen receptor protein which lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of AR-V7 in circulating tumor cells (CTCs) from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. Methods.  We used quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with metastatic castration-resistant prostate cancer initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status and PSA response rates, PSA-progression-free-survival (PSA-PFS), clinical/radiographic-progression-free-survival (PFS), and overall survival (OS). Multivariable Cox regression analyses were performed to determine the independent effect of AR-V7 status on clinical outcomes. Results.  Thirty-one enzalutamide-treated patients and thirty-one abiraterone-treated patients were enrolled, of which 38.7% and 19.4% had detectable AR-V7 from CTCs, respectively. Among men receiving enzalutamide, AR-V7–positive patients had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median: 1.4 vs 6.0 months, P<0.001), PFS (median: 2.1 vs 6.1 months, P<0.001), and OS (median: 5.5 months vs not reached, P=0.002) compared to AR-V7–negative patients. Similarly, among men receiving abiraterone, AR-V7–positive patients had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median: 1.3 months vs not reached, P<0.001), PFS (median: 2.3 months vs not reached, P<0.001), and OS (median: 10.6 months vs not reached, P=0.006). The negative prognostic impact of AR-V7 was maintained after adjusting for full-length-AR expression. Conclusions.  Detection of AR-V7 in CTCs from patients with castration-resistant prostate cancer is associated with resistance to enzalutamide and abiraterone. Overall design: A total of four metastatic castration-resistant prostate tumor samples from four patients were subjected to RNA-seq. Two samples were positive for androgen receptor splice variant 7 and the other two were negative for this variant.	Co-expression
SRP041100	Characterizing the contrasting roles of JMJD3 and UTX histone demethylases in T cell acute lymphoblastic leukemia [short_hairpins_RNA-seq]	T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we abrogated the expression of JMJD3 (KDM6B) and UTX (KDM6A) H3K27me3 demethylases in human T-ALL lines and assayed for genome-wide expression changes using RNA sequencing. This piece of data was further integrated to ChIP-Sequencing analysis of H3K27me3 from the same treatment as well as H3K27me3 and JMJD3 genome-wide analysis from treatment of T-ALL lines with the GSKJ4 inhibitor. These results, coupled to genomic analysis of primary samples for the genomic status of the UTX gene in T-ALL, helped us to identify a hitherto unknown role of JMJD3as an oncogenice facilitator in leukemia whereas UTX seems to play a tumor suppressor role. Overall design: Whole RNA was extracted from 1-5 million T-ALL (lines) cells or primary cells using the RNAeasy kit (Qiagen) according to the manufacturer’s protocol. Poly-A+ (magnetic oligodT-containing beads (Invitrogen)) or Ribominus RNA was used for library preparation. cDNA preparation and strand-specific library construction was performed using the dUTP method. Libraries were sequenced on the Illumina HiSeq 2000 using 50bp single-read method. Differential gene expression analysis was performed for each matched knockdown vs control pairs, separately in each biological or technical replicate in each of two cell lines (CUTLL1, CEM). Three types of comparisons were tested: (a) JMJD3 knockdown vs Renilla, (b) JMJD3 knockdown vs UTX knockdown, and (c) UTX knockdown vs Renilla. Analysis was performed using both DEGseq and Cufflinks packages leading to very similar conclusions.	Co-expression
SRP041102	Characterizing the contrasting roles of JMJD3 and UTX histone demethylases in T cell acute lymphoblastic leukemia [GSKJ4_RNA-seq]	T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we chemically inhibited the H3K27me3 demethylase JMJD3 using the GSKJ4 inhibitor and assayed for genome-wide changes in H3K27me3 and JMJD3 enrichment. This piece of data was further integrated to expression changes using RNA sequencing as well as ChIP-Sequencing analysis of H3K27me3 upon genomic knock-down of JMJD3 and UTX. These results, coupled to genomic analysis of primary samples for the genomic status of the UTX gene in T-ALL, helped us to identify a hitherto unknown role of JMJD3 as an oncogenice facilitator in leukemia whereas UTX seems to play a tumor suppressor role. Overall design: Whole RNA was extracted from 1-5 million primary cells from CUTLL1 human T cell leukemia cells untreated or treated with 2micromolar GSKJ4 using the RNAeasy kit (Qiagen) according to the manufacturer’s protocol. Poly-A+ (magnetic oligodT-containing beads (Invitrogen)) or Ribominus RNA was used for library preparation. cDNA preparation and strand-specific library construction was performed using the dUTP method. Libraries were sequenced on the Illumina HiSeq 2000 using 50bp single-read method. Differential gene expression analysis was performed between knockout vs wild-type background samples. Analysis was performed using DEGseq package leading to very similar conclusions.	Co-expression
SRP041126	Abraxane, the Nanoparticle Formulation of Paclitaxel can Induce Drug Resistance by Up-regulation of P-gp	Abraxane, a nanoparticle (NP) formulation of paclitaxel (PTX), has been demonstrated to be more effective than Taxol, the small molecule formulation, for the treatment of breast cancer and non-small cell lung cancer (NSCLC). It was reported that Abraxane existed in plasma as particles with the size of ~10 nm. NPs get in and out of the cells by endocytosis and exocytosis, whereas small molecules by diffusion and efflux. It is intriguing to know whether the improved pharmaceutical performance is related to the “too-big-to-be-pumped-out” phenomenon. Here we established an Abraxane-resistant NSCLC cell line A549/Abr and compared its transcriptomes with that of the Abraxane-sensitive parental cell line by RNA-Seq technology. To our surprise, the most significantly up-regulated genes were ABC transporters, the common efflux pump for small molecules. We further found that the ABCB1 inhibitor Verapamil reversed the drug resistance and confirmed the important role of ABCB1 in Abraxane resistance. Overall design: mRNA profiles of A549 and A549/Abr cells were generated using Illumina Hiseq 2000 and compared.	Co-expression
SRP041130	MOV10 Is a 5'' to 3'' RNA Helicase Contributing to UPF1 mRNA Target Degradation by Translocation along 3''UTRs (expression)	RNA helicases are important regulators of gene expression that act by remodeling RNA secondary structures and as RNA-protein interactions. Here, we demonstrate that MOV10 has an ATP-dependent 5'' to 3'' in vitro RNA unwinding activity and determine the RNA-binding sites of MOV10 and its helicase mutants using PAR-CLIP. We find that MOV10 predominantly binds to 3'' UTRs upstream of regions predicted to form local secondary structures and provide evidence that MOV10 helicase mutants are impaired in their ability to translocate 5'' to 3'' on their mRNA targets. MOV10 interacts with UPF1, the key component of the nonsense-mediated mRNA decay pathway. PAR-CLIP of UPF1 reveals that MOV10 and UPF1 bind to RNA in close proximity. Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10-bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in UPF1-mediated mRNA degradation as an RNA clearance factor to resolve structures and displace proteins from 3'' UTRs. Overall design: Flp-In T-REx HEK293 cells expressing FLAG/HA-tagged MOV10 WT, MOV10 K530A, MOV10 D645N and UPF1 were used to determine the protein-RNA interaction sites of RNA helicases MOV10 and UPF1 as well as MOV10 inactive variants using PAR-CLIP in combination with next generation sequencing. mRNA half-life changes of MOV10-targeted mRNA were determined by measuring mRNA half-lives by mRNA sequencing of mock and MOV10-depleted HEK293 cells.	Co-expression
SRP041159	RNA-Seq characterization of human H1-derived NPC differentiation timecourse	High resolution transcriptional profiling of H1-derived human neuronal precursor cells over a timecourse of differentiation in vitro. Overall design: Human NPC differentiation timecourse covers Days 0,1,2,4,5,11, and 18 after induction of neuronal differentiation as described in manuscript. Each time point was assayed in triplicate cultures with the exception of Day 5, in which one outlier culture has been removed.	Co-expression
SRP041162	RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of potential vorinostat-resistance candidate genes	Potential vorinostat-resistance candidate genes were identified using RNA interference screening in vorinostat-resistant HCT116 cells (HCT116-VR) using a synthetic lethal approach.  In order to understand the mechanisms by which these genes contributed to vorinostat response, transcriptomic analysis was conducted on HCT116-VR cells and those with siRNA-mediated knockdown of each of the vorinostat resistance candidate genes. Overall design: There are 45 samples in total, from triplicate independent biological experiments of 15 samples each.  The negative control to which all gene knockdowns are compared is the mock transfection control (mock).	Co-expression
SRP041179	CORTECON: A Temporal Transcriptome Analysis of In Vitro Human Cerebral Cortex Development From Human Embryonic Stem Cells	Many neurological and psychiatric disorders affect the cerebral cortex, and a clearer understanding of the molecular processes underlying human corticogenesis will provide greater insight into such pathologies. To date, knowledge of gene expression changes accompanying corticogenesis is largely based on murine data. Here we present a searchable, comprehensive, temporal gene expression dataset encompassing cerebral cortical development from human embryonic stem cells (hESCs). Using a modified differentiation protocol and RNA-Seq technology with computational analysis, we identified sets of genes and long non-coding RNAs that significantly change during corticogenesis, and those enriched for disease-associations. Numerous alternatively-spliced genes with varying temporal patterns of expression are revealed, including TGIF1, involved in holoprosencephaly and MARK1, involved in autism. We have created a database (http://cortecon.neuralsci.org) that provides online, query-based access to changes in RNA expression and alternatively spliced transcripts during human cortical development. Overall design: Nine timepoints (days 0,7,12,19,26,33,49,63,77) covering human corticogenesis from embyronic stem cells.	Co-expression
SRP041252	Effects of LKB1/STK11 expression on MDA-MB-231 triple-negative breast cancer cells	MDA-MB-231 cells transfected with pcDNA-vector or pcDNA-LKB1 were analyzed for changes in gene expression. Results provide insight into genes regulated by LKB1 signaling with implications in tumor and metastasis suppression in breast cancer. Overall design: 4 samples, duplicates of -vector and -LKB1 stable cell lines	Co-expression
SRP041255	RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer	The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A/DDX2 RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of Silvestrol and related compounds. For example, eIF4A promotes T-ALL development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with Silvestrol has powerful therapeutic effects in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5'UTR sequences such as the 12-mer guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and Silvestrol-sensitive transcripts are a number of oncogenes, super-enhancer associated transcription factors, and epigenetic regulators. Hence, the 5'UTRs of selected cancer genes harbour a targetable requirement for the eIF4A RNA helicase. Overall design: Comparison of ribosome-protected RNA for drug treated and DMSO treated KOPT-K1 cell, two replicates of ribosome-protected RNA sequencing and three replicates of RNA-seq.	Co-expression
SRP041298	Ribosome profiling reveals an important role for translational control in circadian gene expression	Physiological and behavioral circadian rhythms are driven by a conserved transcriptional/translational negative feedback loop in mammals. Although most core clock factors are transcription factors, post-transcriptional control introduces delays that are critical for circadian oscillations. Little work has been done on circadian regulation of translation, so to address this deficit we conducted ribosome profiling experiments in a human cell model for an autonomous clock. We found that most rhythmic gene expression occurs with little delay between transcription and translation, suggesting that the lag in the accumulation of some clock proteins relative to their mRNAs does not arise from regulated translation. Nevertheless, we found that translation occurs in a circadian fashion for many genes, sometimes imposing an additional level of control on rhythmically expressed mRNAs and, in other cases, conferring rhythms on non-cycling mRNAs.  Most cyclically transcribed RNAs are translated at one of two major times in a 24h day, while rhythmic translation of most non-cyclic RNAs is phased to a single time of day. Unexpectedly, we found that the clock also regulates the formation of cytoplasmic processing (P) bodies, which control the fate of mRNAs, suggesting circadian coordination of mRNA metabolism and translation. Overall design: U2-OS cell time course over one day of 12 wildtype total RNA-seq samples, 12 wildtype ribosome profiling samples, 12 Bmal1 knockdown total RNA-seq samples and 12 Bmal1 knockdown ribosome profiling samples. All samples have duplicates.	Co-expression
SRP041338	Transcriptome sequencing of a large human family identifies the impact of rare non-coding variants	We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants. Overall design: RNA-Sequencing of CEPH/UTAH family 1463	Co-expression
SRP041367	JAGuaR: Junction Alignments to Genome for RNA-seq Reads	JAGuaR is an alignment protocol for RNA-seq reads that uses an extended reference to increase alignment sensitivity. It uses BWA to align reads to the genome and reference transcript models (including annotated exon-exon junctions) specifically allowing for the possibility of a single read spanning multiple exons. Reads aligned to the transcript models are then re-mapped on to genomic coordinates, transforming alignmentsthat span multiple exonsinto large-gapped alignments on the genome. While JAGuaR does not detect novel junctions, we demonstrate how JAGuaR generates fast and accurate transcriptome alignments, which allows for both sensitive and specific SNV calling.	Co-expression
SRP041377	Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells	Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many of the potential applications are still limited by the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. These challenges could be overcome by the use of adult tissue stem cells derived from hPSCs, as their restricted potential could limit the differentiation towards other undesired linages, and allow in vitro expansion and long- term propagation of fully differentiated tissue. To isolate adult stem cells from hPSCs, we applied genome-editing to generate an LGR5-GFP reporter system and subsequently developed a differentiation protocol for human intestinal tissue comprising an adult stem cell niche and all major cell types of the adult intestine. This novel derivation protocol is highly robust and even permits the isolation of intestinal organoids without the LGR5 reporter. Transcriptional profiling, electron microscopy and functional analysis revealed that such human organoid cultures could be derived with high purity, and a composition and morphology similar to that of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. With our ability to genetically engineer hPSCs using site-specific nucleases, this adult stem cell system provides a novel platform by which to study human intestinal disease in vitro. Overall design: RNA from primary organoid samples was isolated from organoid lines that were both cultured for 1-6 months and derived from duodenum, ileum, or rectum biopsies of human subjects as described previously (Sato et al., Gastroenterology 2011) grown in media called WENR+inhibitors. RNA was also isolated from various steps in the culturing and differentiation protocol.	Co-expression
SRP041396	Controlling for gene expression changes in transcription factor protein networks.	The development of affinity purification technologies together with mass spectrometric analyses of the purified protein mixtures (AP-MS) has been used both to identify new protein-protein interactions and to define the subunit composition of protein complexes. Transcription factor protein interactions, however, have not been systematically analyzed using these approaches. Here, we have investigated whether ectopic expression of an affinity tagged transcription factor as bait in AP-MS experiments perturbs gene expression in cells resulting in false positive identification of bait associated proteins when typical experimental controls are used. Using quantitative proteomics and RNA-Seq, we determined that the increase in the abundance of a set of proteins caused by overexpression of the transcription factor RelA is not sufficient for these proteins to then copurify non-specifically and be misidentified as bait associated proteins. Therefore typical controls should be sufficient and a number of different baits can be compared with a common set of controls. This is of practical interest when identifying bait interactors from a large number of different baits. As expected, we found several known RelA interactors enriched in our RelA purifications (NFêB1, NFêB2, Rel, RelB, IêBá, IêBâ and IêBå). We also found several proteins not previously described in association with RelA, including the small mitochondrial chaperone Tim13. Using a variety of biochemical approaches, we further investigated the nature of the association between Tim13 and NFêB family transcription factors. The work here therefore provides a conceptual and experimental framework for analyzing transcription faction protein interactions. Overall design: Gene expression profiles were assayed in triplicate from HEK293 cells expressing either Halo-RelA, Halo-NFkB1, or Halo tag alone.	Co-expression
SRP041471	4sUDRB-seq: measuring transcription elongation and initiation genomewide	A new method to measure elongation and intitiation rates Overall design: Reversal inhibition of transcription with DRB and tagging newly transcribed RNA with 4-thiouridine (4sU)	Co-expression
SRP041494	GSE57096: Analysis of the Epigenomic and Transcriptional Landscapes during mammalian spermatogenesis [sperm; RNA-seq]	Summary: Adult germline stem cells (AGSCs) are multifunctional - they must self renew, maintain genome pluripotency, and prepare for gametogenesis – which involves meiotic and chromatin repackaging phases. To better understand AGSCs and gametogenesis, we derived high-resolution profiles of transcription, DNA methylation, 5hmC, and multiple histone modifications at key stages. First, AGSCs display chromatin ‘poising’ of enhancers and promoters of genes utilized in embryo development. Second, the pluripotency network in AGSCs is remarkably distinct from ESCs - lacking Nanog, Sox2, or Prdm14 expression.  Third, spermatogenesis involves stage-specific transcription and distinctive chromatin dynamics, but virtually no changes in DNAme.  Surprisingly, we observe co-incidence of RNA polymerase II, high H3K4me3, and DNA methylation at 20-35% of genes transcribed during gametogenesis - including piRNA clusters - but often observe attendant promoter 5hmC.  Our work reveals key differences between AGSCs and other germ/stem cells, and reveals both logical and unexpected chromatin-transcription relationships accompanying germline developmental transitions. Overall Design: mRNA and small RNA profiles of human sperm generated by deep sequencing using Illumina HiSeq 2000 and Illumina Genome Analyzer II.	Co-expression
SRP041531	Homo sapiens Transcriptome or Gene expression	Given that many soft tissue tumors is driven by genomic translocations, we performed whole transcriptome sequencing in 9 gastrointestinal stromal tumors to identify global expression patterns and fusion genes.	Co-expression
SRP041538	Characterizing gene expression in lung tissue of COPD subjects using RNA-seq	We analyzed gene expression profiling of lung tissue to define molecular pathway of COPD using recent RNA sequencing technology.Lung tissue was obtained from 98 COPD subjects and 91 subjects with normal spirometry. RNA isolated from these samples was processed with RNA-seq using HiSeq 2000. Gene expression measurements were calculated using Cufflinks software. Differentially expressed genes and isoforms were chosen using t-test. Some of differentially expressed genes were validated by quantitative real-time PCR. Overall design: Examination of lung tissue in COPD patients versus normal control	Co-expression
SRP041573	DECIDUALIZATION INDUCES A SECRETOME SWITCH IN THE PERIVASCULAR NICHE CELLS OF THE HUMAN ENDOMETRIUM	The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and non-perivascular (W5C5-) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+ to W5C5- cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared to their W5C5- counterparts. This divergence in secretomes became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of trophic and immunomodulatory cytokines, including leukemia inhibitory factor (LIF). Our findings indicate that the decidual response is spatially organized with differentiating perivascular cells establishing distinct cytokine and chemokine gradients that could direct trophoblast towards maternal vessels and govern local immune responses in pregnancy. Overall design: Analysis of paired human endometrial stromal cultures, originating from either W5C5+ or W5C5- cells, from four biological replicates - a total of 8 samples - by Illumina RNAseq.	Co-expression
SRP041620	An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome	Inflammasomes are intracellular innate immune sensors that respond to pathogen and damage-associated signals with the proteolytic cleavage of caspase-1, resulting in IL-1_ and IL-18 secretion and macrophage pyroptosis. The discovery that heterozygous gain-of-function mutations in NLRP3 lead to oversecretion of IL-1_ and cause the autoinflammatory disease spectrum Cryopyrin Associated Periodic Syndrome (CAPS), led to the successful use of IL-1 blocking therapies1. We found that a de novo missense mutation in the regulatory domain of the NLRC4 (IPAF, CARD12) inflammasome causes early-onset recurrent fever flares and Macrophage Activation Syndrome (MAS). Functional analyses demonstrated spontaneous production of the inflammasome-dependent cytokines IL-1² and IL-18 exceeding levels in CAPS patients. The NLRC4 mutation led to constitutive caspase-1 cleavage in transduced cells and enhanced spontaneous production of IL-18 by both patient and NLRC4 mutant macrophages. Thus, we describe a novel monoallelic inflammasome defect that expands the autoinflammatory paradigm to include MAS and suggests novel targets for therapy. Overall design: Whole blood RNA-seq from seven timepoints of one patient with NLRC4-MAS as compared to five healthy pediatric controls, 7 NOMID patients with active disease prior to anakinra treatment and the same 7 NOMID patients with inactive disease after anakinra treatment. Please note that seven time points are chronologic time point. They are ordinal, in that "1" was drawn before "2", but the distance in time between points is not constant. Thus, time points 4 through 7 correspond to samples drawn while the patient was well AND on treatment. However there may be differences between 4 and 7 pertaining to the length of treatment, and for that reason any of these samples were not considered replicates.	Co-expression
SRP041675	Transcriptome data of CD34+ human cord blood-derived cell treated with UM171, SR1 or both	mRNA profiling of CD34+ human cord blood-derived cell treated with UM171, SR1 or both Overall design: mRNA profiles of CD34+ human cord blood-derived cell treated with DMSO (control), SR1 [500nM], UM171  [35nM] or combination SR1 [500nM]+ UM171  [35nM] for 30min, 3hr, 12hr, 24hr, 48hr, 72hr were generated by deep sequencing	Co-expression
SRP041694	BCLAF1 and its pre-mRNA splicing regulator SRSF10 both regulate tumorigenic capacity of human colon cancer cells	Bcl-2-accociated transcription factor 1(BCLAF1) has been shown to be involved in multiple biological processes. Transcript variants encoding different isoforms that are generated by alternative splicing have been found for this gene, but little is known about the mechanisms governing its splicing regulation and whether the misregulation is associated with cancer development. Mechanistic analysis revealed that splicing factor SRSF10 specifically interacts with exon5a and activates its inclusion, as RNAi-mediated knockdown of SRSF10 induced a dramatic skipping of exon5a. To define a comprehensive programm of alternative splicing that is regulated by SRSF10 in RKO cells, we used RNA-seq coupled with a bioinformatic analysis to identify the extensive splicing network regulated by SRSF10 in RKO cells. Overall design: RNA-seq for control (si-NC) and SRSF10-knockdown (si-SRSF10) human RKO cells	Co-expression
SRP041706	RNA-Seq Identifies Novel Myocardial Gene Expression Signatures of Heart Failure [RNA-seq]	We have utilized the RNA-Seq technology to identify genes with distinct expression patterns between failing and non-failing hearts. In an era of next-generation sequencing studies, our study demonstrates how knowledge gained from a small set of samples with accurately measured gene expressions using RNA-Seq can be leveraged as a complementary strategy to discern the genetics of complex disorders. Overall design: Identify the signature genes based on RNA-seq come from six Heart Failure and healthy individuals. Validation is based on Affymetrix microarray of a total of 313 individuals with/without Heart Failure.	Co-expression
SRP041736	Transcriptome Proflings of 347 Single cells from 10 Distinct Populations	Analyze the transcriptomes of 347 cells from 10 distinct populations in both of low-coverage (~0.27 million reads per cell) and high-coverage (~5 million reads per cell) to identify cell-type-specific biomarkers, and to compare gene expression across samples specifically for cells of a given type as well as to reconstruct developmental lineages of related cell types.	Co-expression
SRP041751	Direct Induction of Hematoendothelial Program in Human Pluripotent Stem Cells by Transcriptional Regulators	Advancing pluripotent stem cell technologies for modeling hematopoietic stem cell development and therapies requires identifying key regulators of hematopoietic commitment from human pluripotent stem cells (hPSCs). Here, by screening the effect of 27 candidate factors, we identified two groups of transcriptional regulators capable of inducing distinct hematopoietic programs from hPSCs: pan-myeloid (GATA2 and ETV2) and erythro-megakaryocytic (GATA2 and TAL1). In both cases, these transcription factors directly converted hPSCs to endothelium, which subsequently transformed into blood cells with pan-myeloid or eryhtro-megakaryocytic potential. These data demonstrate that two distinct genetic programs regulate the hematopoietic development from hPSCs and that both of these programs specify hPSCs directly to hemogenic endothelial cells. Additionally, this study provides a novel method for efficient induction of blood and endothelial cells from hPSCs via overexpression of modified mRNA for selected transcription factors. Overall design: mRNA profiles of 54 samples, including 4 samples in duplicate and 6 control samples were generated by deep sequencing, using Illumina HiSeq 2500.	Co-expression
SRP041753	Transriptional profiling upon heat shock and recovery in cells deficient for FBXW7 and their wild type counterpart.	FBXW7 modulates stress response by post-translational modification of HSF1 HSF1 orchestrates the heat-shock response upon exposure to heat stress and activates a transcriptional program vital for cancer cells. Genes positively regulated by HSF1 show increeased expression during heat shock while their expression is reduced during recovery. Genes negatively regulated by HSF1 show the opposite pattern. In this study we utilized the HCT116 FBXW7 KO colon cell line and its wild type counterpart to monitor gene expression changes during heat shock (42oC, 1 hour) and recovery (37oC for 2 hours post heat shock) using RNA sequencing. These results revealed that the heat-shock response pathway is prolonged in cells deficient for FBXW7. Overall design: Whole RNA was extracted from 1 million HCT116 WT or FBXW7KO  cells using the RNAeasy kit (Qiagen) according to the manufacturer’s protocol. Poly-A+ (magnetic oligodT-containing beads (Invitrogen)) or Ribominus RNA was used for library preparation. cDNA preparation and strand-specific library construction was performed using the dUTP method. Libraries were sequenced on the Illumina HiSeq 2000 using 50bp single-read method. Differential gene expression analysis was performed for each matched recovery versus heat-shock pairs, separately in each biological replicate and cell line (WT or KO). Two types of comparisons were tested: (a) WT recovery vs WT heat shock, (b) FBXW7 KO recovery vs heat shock.	Co-expression
SRP041755	Transcriptome analysis of human reninomas as an approach to understanding juxtaglomerular cell biology	Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. Although these cells line the media of the glomerular afferent arterioles and share some characteristics with contractile cells, they are filled with lysosome-like organelles where renin is activated and stored for regulated secretion in response to physiological and pathophysiological stimuli. Chronic stimulation of renin release results in a recruitment of new JG cells by the seeming conversion of adjacent smooth muscle cells along the afferent arterioles. Because JG cells rapidly de-differentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain largely unclear. In an effort to overcome this limitation, we have performed RNA expression analysis on four human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in mouse kidney. Our results add 40 new genes to the list that characterize renin-producing cells and reveal a significant variation in the expression patterns of developing, mature and recruited JG cells. Overall design: RNA-Seq was performed with a HiSeq 2000 on three biopsies of a first reninoma from Paris (Par1B1-B3), one biopsy from a reninoma from Montreal (Mon), two biopsies from a reninoma from Rotterdam (RotB1, B2), and a second reninoma from Paris (Par2) along with a biopsy from adjacent supposedly normal tissue from the same patient (Par2N).	Co-expression
SRP041788	Human Nonsense-Mediated RNA Decay Initiates Widely by Endonucleolysis and Targets snoRNA Host Genes	Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we unambiguously establish that SMG6-catalyzed endonucleolysis is the primary initiating step in human nonsense RNA decay. We also show that both protein-coding and 'non-coding' genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, suggesting that these RNAs are merely by-products of a primary snoRNA production process. Finally, genes encoding multiple snoRNAs generally yield elevated numbers of alternative transcript isoforms, enabling the differential expression of individual snoRNAs. These findings demonstrate a hitherto unappreciated potential for decoupling of the individual expression levels of functional exon- and intron-encoded species from such composite genes. ------------------------------------------------------------------------------------- This article was corrected in http://genesdev.cshlp.org/content/30/9/1128.short Completely mapped 5'p-end sequencing data from the corrigendum have been updated in corresponding samples. Overall design: HEK293 Flp-In T-Rex cells were subjected to siRNA-mediated depletion of XRN1 and co-depletion of XRN1 with either SMG6 or UPF1. All the treated samples together with the controls were subjected to both RNA-seq and 5'-end-seq. RNA-seq was used for detecting NMD isoforms and their expression levels. 5'-end-seq was used for finding NMD decay intermediates (decapped and endocleaved molecules). CAGE was used to distinguish decapped from endocleaved RNA fragments.	Co-expression
SRP041819	Treatment of multiple myeloma cells with EZH2 small molecule inhibitor	We investigated differential gene expression in response to treatment of multiple myeloma cells with EZH2 inhibitor Overall design: RNA-seq in two cell lines	Co-expression
SRP041825	RNA-sequencing analysis of glucose and acetate regulated transcripts in glioblastoma cells	Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. Overall design: The experiments were performed in quadruplicates for each condition with a total of 12 samples	Co-expression
SRP041826	GPBAR1 agonism has a broad impact on blocking macrophage activation	Human D14+ / CD16+  monocytes were treated with GPBAR1 agonists or controls, and were stimulated with interferon gamma and LPS.  At 6 and 24 hours, the cells were profiled by RNAseq Overall design: 40 total samples, 5 per group with eight groups.  Individual donors used for multiple comparisons, so paired analysis is possible.  Control samples include unstimulated cells, and stimulated cells treated with vehicle control (DMSO).	Co-expression
SRP041831	The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway [RNA-Seq]	The aim of this study is to identify the SPIN1 target genes in liposarcoma cells Overall design: Liposarcoma is one of the most common histological subtypes of soft tissue sarcoma and causes high incidence of morbidity and mortality. Since therapeutic options for liposarcoma treatment are insufficient, there is an urgent need to identify novel therapeutic targets. Here, we show that knockdown of SPIN1, a reader of H3K4me3 and H3R8me2a chromatin marks, strongly reduces proliferation and survival of liposarcoma cells in vitro and in xenograft mouse models. Combining genome-wide chromatin binding and transcriptome analyses, we found that SPIN1 in cooperation with the transcription factor MAZ directly enhances expression of GDNF, an activator of the RET signaling pathway. Accordingly, knockdown of SPIN1 results in reduced levels of GDNF and activated RET explaining diminished liposarcoma cell proliferation and survival. In line with these observations, levels of SPIN1, GDNF, and activated RET are highly increased in human liposarcoma compared to lipoma or normal adipose tissue. Importantly, SPIN1-mediated transcriptional control depends on binding to H3K4me3 suggesting that targeting of this interaction with small molecule inhibitors is a novel strategy to treat liposarcoma.	Co-expression
SRP041833	Evaluation of RNA amplification and RNA-Seq library preparation protocols for spermatozoa RNA profiling	RNA-Seq technique was applied to investigate the effects of four cDNA amplification kits and two RNA-Seq library preparation kits to the deep sequencing results at different perspectives. Overall design: The same set of semen samples were applied to investigate the qualitative and quantitative effect of four cDNA amplification methods and two RNA-Seq library preparation methods on sperm transcript profiling.	Co-expression
SRP041840	ERG augments YAP1 transcriptional output and induces the development of age-related prostate tumors	Half of human prostate cancers overexpress the transcription factor ERG. The in vivo consequences of ERG expression and the mechanisms by which ERG activity modulates prostate carcinogenesis remain poorly defined. We show that prostate-specific overexpression of ERG, at levels comparable to human prostate cancer, results in upregulation of the Hippo pathway target genes and age-dependent development of prostate tumors. We show that ERG binds to chromatin sites occupied by TEAD4, increases histone H3K9/14 acetylation at these sites and transactivates Hippo target genes. In human prostate cancer cells, ERG binds to the promoter of YAP1 and is required for promoter histone H3K9/14 acetylation and YAP1 expression. We found that while in normal mouse prostate YAP1 is prominantly nuclear in both basal and luminal epithelial cells, in normal human prostate YAP1 is present in basal but absent in luminal cells. In contrast, in human prostate cancer, YAP1 is upregulated in luminal cancer cells in a subset of the tumors. Expression of ERG in human prostate tumors correlates with the appearance of nuclear YAP1, which, in turn, strongly correlates with tumor recurrence. Futhermore, we demonstrate that genetic activation of YAP1 in mouse prostate epithelium is sufficient for the appearance of age-dependent prostate tumors with histological phenotypes that are similar to tumors caused by ERG upregulation. These results provide direct genetic evidence of a causal role for ERG in prostate cancer and reveal a previously unrecognized connection between ERG and the Hippo signaling pathway.	Co-expression
SRP041846	c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas [RNA-Seq]	We assayed the effect of c-Jun overexpression on gene expression in the three DDLPS cell lines using RNA-Seq (Illumina). Overall design: 141, LPS12 and 510 has been overexpressed with c-Jun or control c-DNA and results were analyzed in high-througput sequencing metadata.	Co-expression
SRP041885	RNA expression profiling of human mPB or CB-derived CD34+ cells treated with UM171 at different doses	RNASeq data for mPB or CB-derived CD34+ exposed to UM171 Overall design: human mobilized peripheral blood or cord blood-derived CD34(+) cells were cultured for 16 hours with vehicle (DMSO),  dose response of UM171 [11.9nM, 19nM, 30.5nM, 48.8nM, 78.1nM and 125nM], SR1 [500nM] and combination of( UM171  [48.8nM]+SR1 [500nM])	Co-expression
SRP041955	Homo sapiens Transcriptome or Gene expression	The use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be normalized, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples are at times the sole means of addressing specific questions – e.g., samples collected in the course of fieldwork.	Co-expression
SRP041988	Reprogramming of Endothelium Into Hematopoietic Progenitors by Defined Factors and Vascular Induction	Generation of abundant engraftable hematopoietic cells from autologous tissues promises new therapies for hematologic diseases. Differentiation of pluripotent stem cells into hematopoietic cells results in emergence of cells that have poor engraftment potential.  To circumvent this hurdle, we have devised a vascular niche model to phenocopy the developmental microenvironment of hemogenic cells thereby enabling direct transcriptional reprogramming of human endothelial cells (ECs) into hematopoietic cells. In this approach, transduction of human umbilical vein ECs (HUVECs) or adult human dermal microvascular ECs (hDMECs) with transcription factors (TFs), FOSB, GFI1, RUNX1, and SPI1 (FGRS) and induction with a instructive vascular niche feeder layer in a xenobiotic- and serum-free microenvironment results in generation of long-term engraftable hematopoietic multilineage progenitors (rEC-HMLPs).  The rEC-HMLPs had robust proliferative and multilineage colony forming units (CFU) potential, including granulocytic/monocytic, megakaryocytic, erythroid and lymphoid lineages. When transplanted, hDMEC-derived rEC-HMLPs were capable of long-term multilineage primary and secondary hematopoietic engraftment. A subset of engrafted rEC-HMLPs phenotypically and functionally resembled cord blood cells. By conditionally expressing the FGRS TFs, we further optimized reprogramming of ECs into rEC-HMLPs manifesting features of self-renewing multi-potent progenitor populations (MPPs).  Our approach replicates critical aspects of hematopoietic development and essential role of vascular niche induction in orchestrating hematopoietic specification and may prove useful for engineering autologous engraftable hematopoietic cells for treatment of inherited and acquired blood disorders. . Overall design: Transcriptome sequencing of rEC-HMLPs, hDMECs, HUVECs and other cell types	Co-expression
SRP042027	Noninvasive in vivo monitoring of tissue-specific global gene expression in humans	Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape of circulating RNA in human subjects. By focusing on tissue-specific genes, we were able to identify the relative contributions of these tissues to circulating RNA and monitor changes during tissue development and neurodegenerative disease states.	Co-expression
SRP042043	Genomic-scale identification of host genes regulated by EBV during lytic cycle [RNA-Seq]	Infection of resting primary B-lymphocytes by Epstein Barr virus (EBV) generates a population of cells that are effectively immortal. This represents the first step in the establishment of life-long viral latency in vivo and generates precursors that can develop into the lymphoid malignancies. However, virus spread requires a switch from latency to the lytic replication cycle, a process orchestrated by the virally encoded protein Zta, an AP1-like transcription factor that interacts with a 7 base-pair DNA sequence element.  As Zta has the potential to reprogram the patterns of gene expression in the host cell, we undertook global transcriptome analyses (RNA sequencing) in a Burkitt''s lymphoma derived cell line in which the Zta is expressed from an inducible promoter, mimicking the switch from latency to lytic cycle. We identified 2,263 host genes whose expression levels were altered. In parallel, we performed chromatin precipitation and next-generation DNA sequencing (ChIP-Seq) to identify genes that are direct targets of Zta. Integrating these data sets revealed 277 host genes that appear to be directly regulated by Zta. Surprisingly, the frequency and distribution of the Zta binding peaks suggests that Zta regulates host genes through long-range enhancers, with a median distance of 25.8kb from the transcriptional start site, rather than equivalents of the promoter elements through which Zta regulates viral genes. Overall design: Akata cells transduced with a plasmid encoding Zta, NGFR and GFP from a doxycycline regulated promoter, and control cells in which the Zta sequences were in the opposite orientation, were treated with 500 ng/ml doxycycline for 24h.  The NGFR-expressing cells were isolated with anti-NGFR antibodies coupled to paramagnetic beads.  RNA was prepared from two independent populations of control and Zta-expressing cells and the poly A-selected transcripts were analyzed by direct sequencing. ZTA: also referred to as BZLF1.	Co-expression
SRP042086	Gene Expression Signature in Adipose Tissue of Acromegaly Patients	OBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.	Co-expression
SRP042112	Transcriptional dysregulation of synaptic genes in a human iPSC model of major mental disorders	Schizophrenia and other psychiatric disorders are postulated to be developmental disorders resulting from synapse dysfunction. How susceptibility genes for major mental disorders could lead to synaptic deficits in humans is not well-understood. Here we generated induced pluripotent stem cells (iPSCs) from four members of a family in which a frame-shift mutation of Disrupted-in-schizophrenia-1 (DISC1) co-segregated with psychiatric disorders and further produced different isogenic iPSC lines via genetic editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPSC-derived forebrain neurons. Mechanistically, mutant DISC1 dysregulates the expression of many genes related to synapses and psychiatric disorders and depletes wild-type DISC1 and the NCoR1 transcription co-repressor complex. Furthermore, mechanism-guided pharmacological inhibition of phosphodiesterases rescues synaptic defects in mutant neurons. Our study uncovers a novel gain-of-function mechanism through which the psychiatric disorder-relevant mutation affects synaptic functions via transcriptional dysregulation and provides insight into the molecular and synaptic etiopathology of psychiatric disorders. Overall design: Two patient derived iPSC lines carrying heterozygous 4bp deletion in DISC1 gene and 1 related control were analyzed in biological triplicate	Co-expression
SRP042153	RNAseq transcriptome data from reprogramming human CD34+ cells to iPS	We reprogrammed human CD34+ cells from cord blood using a lentiviral vector encoding OCT4, SOX2 and KLF4.We collected RNA from parental CD34+ cells (3samples), reprogramming timepoints (9 timepoints), iPS clones derived from this experiment (6 clones), and human ES cell lines (9 samples). All samples were sequenced at 100bp reads. Overall design: Endogenous retroelement expression during reprogramming	Co-expression
SRP042158	RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of GLI1 or PSMD13 with or without vorinostat treatment	Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat.  Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen.  To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control.  Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). Overall design: There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.	Co-expression
SRP042161	Single cell RNA-seq of primary human glioblastomas	We report transcriptomes from 430 single glioblastoma cells isolated from 5 individual tumors and 102 single cells from gliomasphere cells lines generated using SMART-seq. In addition, we report population RNA-seq from the five tumors as well as RNA-seq from cell lines derived from 3 tumors (MGH26, MGH28, MGH31) cultured under serum free (GSC) and differentiated (DGC) conditions. This dataset highlights intratumoral heterogeneity with regards to the expression of de novo derived transcriptional modules and established subtype classifiers. Overall design: Operative specimens from five glioblastoma patients (MGH26, MGH28, MGH29, MGH30, MGH31) were acutely dissociated, depleted for CD45+ inflammatory cells and then sorted as single cells (576 samples). Population controls for each tumor were isolated by sorting 2000-10000 cells and processed in parallel (5 population control samples). Single cells from two established cell lines, GBM6 and GBM8, were also sorted as single cells (192 samples). SMART-seq protocol was implemented to generate single cell full length transcriptomes (modified from Shalek, et al Nature 2013) and sequenced using 25 bp paired end reads. Single cell cDNA libraries for MGH30 were resequenced using 100 bp paired end reads to allow for isoform and splice junction reconstruction (96 samples, annotated MGH30L). Cells were also cultured in serum free conditions to generate gliomasphere cell lines for MGH26, MGH28, and MGH31 (GSC) which were then differentiated using 10% serum (DGC). Population RNA-seq was performed on these samples (3 GSC, 3 DGC, 6 total). The initial dataset included 875 RNA-seq libraries (576 single glioblastoma cells, 96 resequenced MGH30L, 192 single gliomasphere cells, 5 tumor population controls, 6 population libraries from GSC and DGC samples). Data was processed as described below using RSEM for quantification of gene expression. 5,948 genes with the highest composite expression either across all single cells combined (average log2(TPM)>4.5) or within a single tumor (average log2(TPM)>6 in at least one tumor) were included. Cells expressing less than 2,000 of these 5,948 genes were excluded. The final processed dataset then included 430 primary single cell glioblastoma transcriptomes, 102 single cell transcriptomes from cell lines(GBM6,GBM8), 5 population controls (1 for each tumor), and 6 population libraries from cell lines derived from the tumors (GSC and DGC for MGH26, MGH28 and MGH31). The final matrix (GBM_data_matrix.txt) therefore contains 5948 rows (genes) quantified in 543 samples (columns). Please note that the samples which are not included in the data processing are indicated in the sample description field.	Co-expression
SRP042184	A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors	Next generation sequencing of 28 thymic epithelial tumors (TETs) revealed a high frequency of GTF2I missense mutation (chr7:74146970T/A) in A thymomas, a  relatively indolent subtype. The GTF2I mutation was confirmed in 82% of A and 74% of AB thymomas in a series of 274 TETs but was rare in aggressive subtypes, where recurrent mutations of known cancer genes were identified. Therefore, GTF2I mutation correlated with a better survival. GTF2I Beta and Delta isoforms were expressed in TETs and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas presented a higher number of mutations than thymomas (average 43.5 and 18.4, respectively). Recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1 were identified in thymic carcinomas. These findings will complement the diagnostic work up of these rare tumors, and also help the development of a molecular classification, and assessment of prognosis and treatment strategies. Overall design: Tumor samples of 286 patients were collected from 4 different institutions: National Cancer Institute (Bethesda MD), Pisa University Hospital (Pisa, Italy), Padua University Hospital (Padua, Italy) and IRCCS Istituto Clinico Humanitas (Rozzano, Italy).	Co-expression
SRP042186	White-to-brown metabolic conversion of human adipocytes by JAK inhibition	The rising incidence of obesity and related disorders such as diabetes and heart disease has  focused considerable attention on the discovery of novel therapeutics. One promising  approach has been to increase the number or activity of brown-like adipocytes in white  adipose depots, as this has been shown to prevent diet-induced obesity and reduce the  incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into  metabolically active thermogenic cells has become an appealing therapeutic strategy to  combat obesity. Here, we report a screening platform for the identification of small molecules  capable of promoting a white-to-brown metabolic conversion in human adipocytes. We  identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue  biology that permanently confer brown-like metabolic activity to white adipocytes.  Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and  increased mitochondrial activity. We further found that repression of interferon signalling and  activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic  conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT  pathway in the control of adipocyte function and establish a platform to identify compounds  for the treatment of obesity. Overall design: Human pluripotent stem-cell derived mesenchymal progenitor cells (PSC-MPCs), white adipose cells (PSC-WA), and brown adipose cells (PSC-BA) were treated with DMSO (as control), a JAK3-inhibitor compound, and a SYK-inhibitor compound respectively. Transcriptomic expression profiling was performed at 24 hours and 7 days respectively. Three biological replicates are available for each condition defined by cell type, compound, and time.	Co-expression
SRP042212	Transcriptome Sequencing (RNA-seq) of Normal Human Osteoblasts	Three normal human osteoblast samples, acquired from PromoCell, were used as controls to compare to RNA-seq data from prepublished osteosarcoma samples (submitted to the European Bioinformatics Institute; EGAS00001000263) for the purpose of evaluating expression levels of genes identified as common insertions sites in a Sleeping Beauty screen of osteosarcomas in mice. Overall design: Three normal human osteoblast samples (pellet form in RNAlater) were acquired from PromoCell (Heidelberg, Germany), and RNA was isolated from them immediately upon receipt.	Co-expression
SRP042228	Core Ileal Transcriptome in Pediatric Crohn Disease	We report the global pattern of ileal gene expression in a cohort of 359 treatment-naïve pediatric Crohn Disease, Ulcerative Colitis patients and controls. We focus on genes with consistent altered expression in inflamed and unaffected ileum of CD [ileal-involved CD (iCD) and non-invloved ileal CD (cCD)], but not in the ileum of ulcerative colitis or control. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents aged less than 17 years, who presented with IBD-like symptoms. All patients underwent baseline colonoscopy and histological characterization; non-IBD controls were those with suspected IBD, but with no microscopic or macroscopic inflammation and normal radiographic, endoscopic, and histologic findings. Biopsies were stored at -80 degrees.	Co-expression
SRP042249	Bioreactor-engineered cancer tissues mimic phenotypes, gene expression profiles and drug resistance mechanisms detectable in xenografts and clinical specimens.	Cancer tissue-like structures were developed by using established human tumor cell lines in perfusion-based bioreactor systems. In colorectal cancer (CRC) cell lines, perfusion allowed more homogeneous scaffold seeding than tri-dimensional (3D) static cultures and significantly (13.7 fold, p<0.0001) higher proliferation. Resulting tissues exhibited morphology and phenotypes similar to xenografts generated in immunodeficient mice. Whole transcriptome analysis of 2D, 3D static and 3D perfusion cultures revealed the highest correlation between xenografts and 3D perfusion cultures (r=0.985). Clinically relevant concentrations of 5-FU, used in neo- and adjuvant CRC treatment, had no effect on numbers of HT-29 CRC cells cultured in 3D perfusion or xenografts, as compared with a 55.8% reduction in 2D cultures. Treatment induced apoptosis in 2D cultures, but only “nucleolar stress” in perfused cells and xenografts, consistent with partial responsiveness.  In 3D perfusion cultures BCL-2, TRAF1, and FLIP gene expression was marginally affected, as compared with significant down-regulation in 2D cell cultures. Accordingly, ABT-199 BCL-2 inhibitor, induced cytostatic effects in 3D perfusion but not in 2D cell cultures (p=0.003). Tumor cells from partially responsive (Dworak 2) patients undergoing neo-adjuvant treatment, typically (10/11) expressed BCL-2, as compared with 0/3 highly (Dworak 3-4) responsive and 4/15 fully resistant CRC (Dworak 0/1, p=0.03), closely matching 3D perfusion cultures data. These results indicate that 3D perfusion cultures efficiently mimic phenotypic and functional features observed in xenografts and clinical specimens. These models may be of critical translational relevance to address fundamental human tumor cell biology issues and to develop predictive pre-clinical tests of novel compounds. Overall design: Expression profiles of colorectal cancer cell lines cultured in 2D, 3D static, 3D perfusion or growing as xenografts were generated by deep sequencing, in triplicates, using Illumina HiSeq2000.	Co-expression
SRP042282	Age-dependent gene expression changes in human islets	We report the transcriptomic profiling of islet cell subtypes obtained from young and old human donors. We report the transcriptomic profiling of Endo-ßH1C cells expressing SIX3, SIX2 or GFP. Overall design: Profiling FACS-purified human pancreatic islet cells by RNA-Seq. We analyzed the gene expression changes in Endo-ßH1C cells expressing SIX3, SIX2 or GFP using RNA-Seq.	Co-expression
SRP042286	Transcriptome profiling in human T-ALL	Genome-wide mapping and characterization of novel Notch-regulated long non-coding RNAs in acute leukemia Overall design: Total RNA was extracted from samples using the RNeasy Plus mini kit (Life Technologies, Carlsbad, CA). Samples were then subject to PolyA  selection (Figures 1E, 5F and 5G only) using oligo-dT beads (Life Technologies, Carlsbad, CA) or rRNA removal (all other samples) using the Ribo-Zero kit (Epicentre, Madison, WI)  according to the manufacturers instructions. The resulting RNA samples were then used as input for library construction using the dUTP method as described by Parkhomchuck et al, 2009. RNA libraries were then sequenced on the Illumina HiSeq 2000 or 2500 using 50bp paired-end reads.	Co-expression
SRP042303	Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer	Inhibition of SET by siRNA or SET antagonist and CIP2A by siRNA can downregulate c-MYC and c-MYC target genes. Overall design: Cells were treated with a SET antagonist (1µMOP449) for 12 hours, or siRNA for 48 hours.	Co-expression
SRP042402	Characterization of human CDK12 and CDK13 in the regulation of RNA processing	We report the total RNA-seq results after CDK9, CDK12 and CDK13 depletion in human HCT116 cells for three days. RNA-seq was performed in cells using two non-targeting replicates and two different shRNAs for each CDK knockdown.  For each CDK knockdown, most of the differentially expressed genes were down-regulated with a very small subset of genes upregulated. Different CDK proteins control distinct subsets of genes in vivo, with CDK12 and CDK13 sharing more overlap in function compared to CDK9. Besides, CDK12 and CDK13 loss preferentially affects DNA damage response and snRNA gene expression, respectively. Overall design: Examine the changes of mRNA expression levels after CDK9, CDK12 and CDK13 depletion.	Co-expression
SRP042579	Gene expression profiles of blood vascular endothelial cells (BECs) in response to larminar shear flow [RNA-Seq]	RNA sequencing (RNA-seq) analysis of a genome-wide gene expression change in primary human neonatal dermal BECs when subjected to laminar flow-induced shear stress Overall design: Primary human neonatal dermal BECs were subjected to low level laminar flow (2 Dyne/cm2) -induced shear stress for 12 hours. Total RNA were isolated from these cells as well as from the equivalent cells cultured under the static condition as a control.	Co-expression
SRP042596	Serial RNA-seq of a single human	Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of human brain function over this timescale in healthy individuals are unknown.  Over a period of 18 months, we performed intensive phenome-wide assessment of a single human, including brain connectivity using resting fMRI, measurements of psychological and physical health, and transcriptomic and metabolomic profiling. Brain connectivity varied across sessions in relation to behavioral variables including mood, fatigue, and food/caffeine intake, as well as variables related to inflammation and gut health.   Pathway-based analysis of gene expression in peripheral lymphocytes identified associations with physical health and brain connectivity, including associations between specific brain networks and a broad set of immune-related pathways. Metabolomic measures were strongly associated with dietary variance. This study integrates dense neuroimaging and -omics profiling to provide a detailed picture of the joint dynamics of human brain and metabolic function over time, an approach that is critical for the understanding of brain disorders characterized by increased variability of brain function. Overall design: Repeated measures on a single individual; RNA was extracted from PBMCs from a single human repeatedly over the course of 18 months, under fasted conditions at a consistent time of day.  This was collected along side a large number of other variables including brain imaging. More information is available at http://www.myconnectome.org	Co-expression
SRP042597	Modeling Familial Cancer with iPSC Approaches	In vitro modeling of human disease has recently become feasible with the adoption of induced pluripotent stem cell (iPSC) technology. Here, we established patient-derived iPSCs from an Li-Fraumeni Syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS). Several members of this family carried a heterozygous p53(G245D) mutation and presented with a broad spectrum of tumors including OS. Osteoblasts (OBs) differentiated from iPSC-derived mesenchymal stem cells (MSCs) recapitulated OS features including defective osteoblastic differentiation (OB differentiation) as well as tumorigenic ability. Systematic analyses revealed that the expression of genes enriched in LFS-derived OBs strongly correlated with decreased time to tumor recurrence and poor patient survival. In silico cytogenetic region enrichment analysis (CREA) demonstrated that LFS-derived OBs do not have genomic rearrangements and hence are a particularly valuable tool for elucidating early oncogenic events prior to the accumulation of secondary alterations. LFS OBs exhibited impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration of H19 expression in LFS OBs facilitated osteogenic differentiation and repressed tumorigenic potential. By integrating human imprinted gene network (IGN) and functional genomic analyses, we found that H19-mediates suppression of LFS-associated OS through the IGN component DECORIN (DCN). Downregulation of DCN impairs H19-mediated osteogenic differentiation and tumor suppression. In summary, these findings demonstrate the feasibility of studying inherited human cancer syndromes with iPSCs and also provide molecular insights into the role of the IGN in p53 mutation-mediated tumorigenesis. Overall design: mRNAseq profiling during mesenchymal stem cell differentiation to osteoblasts.	Co-expression
SRP042616	Genome-wide analysis of transcriptome and translatome following eIF4A1 knockdown in MCF7 cells [RNA-Seq]	To identify which genes were regulated by mRNA helicase activity, the effect of eIF4A1 knockdown on the MCF7 cell transcriptome and translatome was determined. eIF4A1-dependent mRNAs were highly enriched for several classes of genes with oncogenic potential, which leads to a model whereby dysregulation of mRNA unwinding contribues to the malignant phenotype in breast cancer cells via preferential translation of a subset of genes. Overall design: Total, subpolysomal and polysomal RNA was isolated from MCF7 cells treated with either control siRNAs or siRNAs directed against eIF4A1 (48h post-transfection).	Co-expression
SRP042620	Breast Cancer RNA-seq	RNA-seq was performed on breast cancer cell lines and primary tumors Overall design: RNA-seq was performed on 28 breast cancer cell lines, 42 Triple Negative Breast Cancer (TNBC) primary tumors, and 42 Estrogen Receptor Positive (ER+) and HER2 Negative Breast Cancer primary tumors, 30 uninovlved breast tissue samples that were adjacent to ER+ primary tumors, 5 breast tissue samples from reduction mammoplasty procedures performed on patients with no known cancer, and 21 uninvolved breast tissue samples that were adjacent to TNBC primary tumors.	Co-expression
SRP042623	Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification	Peripheral blood RNA-Seq from human coronary artery calcification cases and controls; Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. Overall design: Eight cases and eight controls (matched for gender, age and ancestry); RNA sequencing of peripheral blood from a discovery set of eight CAC cases and eight matched controls was used to identify dysregulated genes, which were validated using the NanoString® and Affymetrix GeneChip® Human Exon ST Array platforms.  The median CAC scores for cases in the screening and validation sets were 1531.5 and 668.5, respectively, while all controls had a score of zero.	Co-expression
SRP042630	P493-6 treated with KJ-Pyr-9 and/or Doxycycline	In a fluorescence polarization screen for MYC-MAX interaction, we have identified a novel small molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 ± 1.0 nM as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC-MAX complex formation in the cell as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-overexpressing  human cancer cells. Overall design: 4 treatment groups analyzed in triplicate: no treatment(control), 20uM KJ-Pyr-9, 0.1ug/mL doxycycline and KJ-Pyr-9 in combination with doxycycline	Co-expression
SRP042647	Transcriptome of UV treated XPD mutant cells (Homo sapiens)	Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we investigate the transcriptional dysregulation that follows UV irradiation in XP-D/CS compared with “pure” XP-D cells or WT cells. We also study how this process is affected by the inhibition of the histone deacetylase Sirt1.	Co-expression
SRP043008	Human Foreskin Fibroblasts-Trypanosoma cruzi infectome	The goal of this study is to simultaneously interrogate the gene expression programs in human host cells (human foreskin fibroblasts) infected with the intracellular parasite Trypanosoma cruzi. We conducted high-resolution sequencing of the transcriptomes of T. cruzi and infected human foreskin fibroblasts (HFFs) using an RNA-seq approach. An array of computational tools was applied to map reads to the T. cruzi and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for T. cruzi genes at at various time points post-infection enabling us to identify co-expression patterns that correlate with the biology of the parasite. We also conducted a time course of infection in host cells to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. These data provide the first glimpse of T. cruzi gene expression programs that are uniquely activated in the context of intracellular infection along with the transcriptional response of the human host cell. The study provides a solid framework for future functional and genomic studies of Chagas disease as well as intracellular pathogenesis in general.	Co-expression
SRP043027	Homo sapiens strain:U2OS Transcriptome or Gene expression	To adapt a non-strandaed library preparation protocol into a strand specific one in an automated fashion. Use the data to emphasize the advantages of strand specific data.	Co-expression
SRP043043	Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with Eralpha	Background: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance Overall design: Differential RNA-seq profiling from triplicate biological replicates of MCF7 cells treated with scrambled siRNA or siZNF217.	Co-expression
SRP043078	The BCL6 RD2 domain governs commitment of activated B-cells to form germinal centers	Our data demonstrated that Bcl6 directly binds and represses trafficking receptors S1pr1 and Grp183 by recruiting Hdac2 through the RD2 domain.  Deregulation of these genes impairs B-cell migration and may contribute to the Germinal Center failure in Bcl6RD2MUT mice. Overall design: RNAseq was performed in endogenous BCL6-depleted OCI-LY1 cells rescued with either WT or RD mutant BCL6 (N=3 for each group).	Co-expression
SRP043080	Transcriptomic profiling of peripheral blood mononuclear cells from healthy individuals	Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.	Co-expression
SRP043081	Human	We have generated nine synthetic poly-adenylated RNA transcripts that correspond to previously reported oncogenic gene fusions. These synthetic RNAs were spiked at known concentrations over a wide range into total RNA prior to construction of next-generation sequencing mRNA libraries to generate RNA-seq data.	Co-expression
SRP043085	SMO variants explain the majority of drug resistance in basal cell carcinoma [RNA-Seq]	Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms, providing a unique opportunity to study human tumor evolution. Here, we identify SMO mutations in 50% (22/44) of resistant BCCs compared with 5.6% (2/36) of untreated BCCs (p<0.0001), and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket (LBP) mutations that define sites of inhibitor binding and four variants that confer constitutive activity and inhibitor resistance, thus defining pivotal residues of SMO that ensure receptor autoinhibition. Finally, we show that both classes of SMO variants respond to the aPKC-?/? inhibitor PSI and GLI2 antagonist ATO that operate downstream of SMO Overall design: Genome-wide gene expression profiling of 8 normal skin biopsies, 9 resistant basal cell cancers and 4 sensitive basal cell cancers.	Co-expression
SRP043090	Identification of alternatively spliced transcripts in brain metastatic derivatives of MDA-MB-231 breast cancer cells in response to RBM47 expression	Changes in alternative splicing in breast cancer cells expressing control, empty vector or Flag-tagged wild type RBM47 were analyzed using paired-end, 100bp RNAseq. Related data published together with these data are found in GSE53779 Overall design: Triplicate RNAseq libraries were prepared from non-clonal brain metastatic breast cancer cells stably expressing empty-vector, and a clonal cell line (wt#10) expressing Flag-tagged, wild-type RBM47 under a doxycline-inducible promoter, both treated for three days with doxycycline to induce transgene expression	Co-expression
SRP043108	The human skeletal muscle transcriptome – sex differences, alternative splicing and tissue homogeneity assessed with RNA sequencing	The amount of RNA sequencing data on skeletal muscle is very limited. We have analyzed a large set of human muscle biopsy samples and provide extensive information on the baseline skeletal muscle transcriptome, including completely novel protein-coding transcripts. Overall design: Analyze of transcriptome in 23 skeletal muscle biopsy samples from six individuals. Four biopsies from each subject, two biopsies from each leg (except subject 6 which has only three biopsies in total).	Co-expression
SRP043144	The ribonuclease activity of SAMHD1 is required for HIV-1 restriction	SAMHD1  restricts  HIV-1  replication  in  dendritic  and  other  myeloid  cells. SAMHD1 has been shown to possess a dGTP-dependent dNTP triphosphatase (dNTPase) activity and is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. Arguing against a role for SAMHD1 dNTPase in HIV-1 restriction, the phosphorylation of SAMHD1 regulates the restriction activity toward HIV-1 without affecting its ability to decrease cellular dNTP levels. Here, we show that SAMHD1 is a phospho-regulated RNase and that the RNase function is required for HIV-1 restriction. Mutation of the SAMHD1 D137 residue in the allosteric site (SAMHD1D137N) abolishes dNTPase activity but has no effect on RNase activity. This dNTPase-defective SAMHD1D137N mutant is able to restrict HIV-1 infection to nearly the same extent as wild-type SAMHD1. SAMHD1 associates with and degrades the HIV-1 genomic RNA during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, thus rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at position T592 abolishes the RNase activity toward HIV-1 RNA, and consequently the ability of SAMHD1 to restrict HIV-1 infection, uncovering the phosphorylation of SAMHD1 T592 as a negative regulatory mechanism of RNase activity. Together, our results demonstrate that SAMHD1 is an essential RNase that prevents HIV-1 infection by directly degrading HIV-1 genomic RNA in a phosphorylation-regulated manner. The unique property of SAMHD1 that cleaves HIV-1 genomic RNA with no sequence preferences could be exploited to develop a new class of intervention for error-prone retroviruses. Overall design: Ribosomal RNA-depleted total RNA profiles of mock, SAMHD1 wild type and mutants infected with HIV-1 were examined at the time of 0, 1, 3 h by Illumina Hiseq2500.	Co-expression
SRP043162	Fatal Asthma vs. Control Human Airway Smooth Muscle Transcriptome Changes in Response to Vitamin D or Albuterol	Rationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for primary human airway smooth muscle cell lines from fatal asthma or control donors that were treated with vitamin D, albuterol, or were left untreated.	Co-expression
SRP043166	Molecular Effects of Doxycycline Treatment on Pterygium from Caucasian Patients as Revealed by Massive Transcriptome Sequencing	Genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in three human pterygium samples.	Co-expression
SRP043204	Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins	Background: Exosomes and extracellular vesicles (EVs) are increasingly recognized as important sources of biomarkers for disease study and diagnosis. Results: A synthetic peptide, Vn96, allows for capture of EVs from biological fluids using basic laboratory equipment. Conclusion: The Vn96-captured EVs are qualitatively equivalent or superior to exosomes isolated by ultracentrifugation. Significance: The Vn96 peptide provides an effective affinity-capture method for the isolation of EVs from biological fluids. Overall design: In order to compare different methods of exosome purification, we compared RNA content of exosomes purified with each method. We used two different breast cancer cell lines MCF7 and MDA-MB-231. We processed data in order to identify large RNAs as well as small RNA by using different methods for the alignment	Co-expression
SRP043217	Transcriptomic analysis of LSD1	Determination of the genes regulated by LSD1 in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for LSD1 using siRNA. Two different siRNAs were used (siL1, siL2). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq	Co-expression
SRP043221	DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle	Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression of the D4Z4 macrosatellite array and recent studies have shown that this results in the expression of low levels of the DUX4 mRNA in skeletal muscle. Several other mechanisms have been suggested for FSHD pathophysiology and it remains unknown whether DUX4 expression can account for most of the molecular changes seen in FSHD. Since DUX4 is a transcription factor, we used RNA-seq to measure gene expression in muscle cells transduced with DUX4, and in muscle cells and biopsies from control and FSHD individuals. We show that DUX4 target gene expression is the major molecular signature in FSHD muscle together with a gene expression signature consistent with an immune cell infiltration. In addition, one unaffected individual without a known FSHD-causing mutation showed expression of DUX4 target genes. This individual has a sibling with FSHD and also without a known FSHD-causing mutation, suggesting the presence of yet unidentified modifier locus for DUX4 expression and FSHD. These findings demonstrate that expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration. Overall design: RNA-seq for muscle cells and biopsies from control and FSHD individuals.	Co-expression
SRP043273	Genomewide analysis of the human p53 transcriptional network unveils a lncRNA tumor suppressor signature (RNA-seq)	We report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are non coding and are differentially expressed by the DNA damage drug. Overall design: Description of the p53 transcriptome in HCT116 colon cancer cell line. The RNA-seq libraries were prepared from purified poly-A+ RNA from untreated and 5-Fluorouracil treated p53 +/+ HCT116 cells for 4 and 12h, including two independent samples for the time 12h. Paired-end and strand specific RNA sequencing libraries were prepared according to Illumina instructions and sequenced on HiSeq 2000 (Ilumina) with sequence length of 150 bp. Raw sequencing data were alignment to the human genome (hg19) using Tophat mapper.	Co-expression
SRP043320	Characterizing the Chemoresistant Ovarian Cancer Population using the Heterogeneous PDX	The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer Overall design: 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing	Co-expression
SRP043336	The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression	Gene expression and splicing switches upon RBM4 overexpression Overall design: 2 Samples	Co-expression
SRP043339	Global Transcriptome Analysis and Enhancer Landscape of Human Primary T Follicular Helper and T Effector Lymphocytes (RNA-Seq)	T follicular helper (Tfh) cells are a subset of CD4+ T helper (Th) cells that migrate into germinal centers and promote B cell maturation into memory B and plasma cells. Tfh cells are necessary for promotion of protective humoral immunity following pathogen challenge, but when aberrantly regulated, drive pathogenic antibody formation in autoimmunity and undergo neoplastic transformation in angioimmunoblastic T-cell lymphoma and other primary cutaneous T-cell lymphomas. Limited information is available on the expression and regulation of genes in human Tfh cells. Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq. Tfh cell enhancers were enriched near genes highly expressed in lymphoid cells or involved in lymphoid cell function, with many mapping to sites previously associated with autoimmune disease in genome-wide association studies. A group of active enhancers unique to Tfh cells associated with differentially expressed genes was identified. Fragments from these regions directed expression in reporter gene assays. These data provide a significant resource for studies of T lymphocyte development and differentiation and normal and perturbed Tfh cell function. Overall design: Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq.	Co-expression
SRP043364	Human cortical transcriptome informs brain imaging	We carried out RNA-sequencing (RNA-seq) of adult human postmortem neocortical brain tissue, and then correlated those expression values with the fMRI signal in each brain region Overall design: Ten cortical regions were included in the analysis: pre-motor cortex - PMV (BA6), dorsolateral prefrontal cortex – DLPFC (BA9), middle temporal gyrus – pMTG (BA21), superior temporal gyrus – pSTG (BA22), angular gyrus  - AG (BA39), supramarginal gyrus  - SMG (BA40), pars opercularis  - POP (BA44), pars triangularis  - PTr (BA45), middle frontal gyrus – MFG (BA46) and pars orbitalis  - POrB (BA47). For each brain region, three or more samples from left adult brain hemispheres were collected (ages range from 33 to 49) and only males were included to avoid the effect of sex	Co-expression
SRP043368	The human skeletal muscle transcriptome assessed with RNA sequencing	The amount of RNA sequencing data on skeletal muscle is very limited. We have analyzed a large set of human muscle biopsy samples and provide extensive information on the baseline skeletal muscle transcriptome, including completely novel protein-coding transcripts. Overall design: Analyze of transcriptome in 24 skeletal muscle biopsy samples, 12 individuals and one biopsy per leg per individual	Co-expression
SRP043388	Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing	We utilized RNA sequencing to expand and better define the molecular entities involved in the transcriptional programming within the eosphagus in eosinophilic esophagitis (EoE) Overall design: Examination of differentially expressed genes from RNA sequencing data performed on esophageal biopsy specimen from 6 healthy controls and 10 patients with active EoE	Co-expression
SRP043391	Fecal Microbiome Transplantation Transiently Supports Immunotherapy Withdrawal in Pediatric Ulcerative Colitis	Complex bacteriotherapy, such fecal microbiome transplantation (FMT) is an emerging therapeutic modality. Recent trials showed variable efficacy of FMT for treating ulcerative colitis (UC). However, only one case report utilized more than 5 FMTs when treating UC, thus far. We studied the clinical, metagenomic, and mucosal gene expression changes induced by serial FMTs in 3 pediatric UC patients during withdrawal of their immunosuppression. FMTs were safe and transiently supported immunotherapy withdrawal. This therapeutic effect associated with host gene expression changes relevant for enterocyte replication suppression. Our findings indicate the safety and therapeutic potential of serial FMTs in pediatric UC.	Co-expression
SRP043426	Molecular Mechanisms of Endothelial Hyperpermeability	Vascular permeability reflects changes in the function of the endothelium,  its interendothelial junctions and transcellular delivery. Here, we show that common molecular mechanisms exist between VEGF and histamine in regulating  vascular hyperpermeability. Crosstalk between downstream signaling of VEGF and histamine receptors are involved in calcium signaling and cell proliferation. Understanding the molecular mechanisms of vascular permeability is crucial in order to reduce vascular hyperpermeability and oedema in various pathological conditions and in VEGF therapy. Overall design: In despite of the substantial knowledge of VEGF and histamine signal transduction and their physiological responses, molecular mechanisms inducing endothelial cell permeability and proliferation have remained inconclusive. To monitor the transcriptional alteration of proteins known to regulate the endothelial permeability, next-generation RNA sequencing was used. Fold changes of several genes known to regulate calcium signaling, cell adhesion, cell proliferation, ion flux and immune response were compared between the permeabilizing agents.	Co-expression
SRP043434	Human hepatocyte metaplasia in injured humanized mouse livers	The goal of this experiment was to test whether human hepatocytes could give rise to biliary-like progenitor cells in an in vivo context.  Here Fah-/- Il2ry-/- Rag2-/-NOD mouse livers were humanized with human hepatocytes. Only hepatocytes engraft in the Fah-/- mouse at detectable levels in this model.  Then animals were given chronic liver injury with 0.1% ddc.  After injury we measured human-specific transcripts to determine whether the phenotype of the human cells had changed.  Specifically, we evaluated the relative levels of human biliary duct markers such as Spp1, Sox9, Krt7, etc.  and hepatocyte markers such as Alb, Ttr, Fah, etc. Overall design: 3 DDC treated chimeras and 6 untreated chimeras are included.  Additional controls include a normal human liver biopsy, FACS sorted primary intrahepatic human bile duct cells, mouse hepatocytes, and mouse intrahepatic biliary cells in ddc treated animal.	Co-expression
SRP043470	Transcriptomic profiling of sequential tumours from breast cancer patients provides a global view of metastatic expression changes following endocrine therapy	We profiled primary breast cancer, nodal and liver metastatic tumours from three patients. At the time of initial diagnosis, all three patients presented with luminal breast cancer with adjacent nodal metastasis. They all received 5 years of enodrine therapy and all subsequently developed liver metastasis. Overall design: Examination of mRNA differences between primary, nodal and metastatic tumour samples.	Co-expression
SRP043593	Microprocessor mediates transcription termination in long noncoding microRNA genes	MicroRNA (miRNA) play a major role in the post-transcriptional regulation of gene expression. In mammals most miRNA derive from the introns of protein coding genes where they exist as hairpin structures in the primary gene transcript, synthesized by RNA polymerase II (Pol II). These are cleaved co-transcriptionally by the Microprocessor complex, comprising DGCR8 and the RNase III endonuclease Drosha, to release the precursor (pre-)miRNA hairpin, so generating both miRNA and spliced messenger RNA1-4. However, a substantial minority of miRNA originate from Pol II-synthesized long non coding (lnc) RNA where transcript processing is largely uncharacterized5. Here, we show that most lnc-pri-miRNA do not use the canonical cleavage and polyadenylation (CPA) transcription termination pathway6, but instead use Microprocessor cleavage both to release pre-miRNA and terminate transcription. We present a detailed characterization of one such lnc-pri-miRNA that generates the highly expressed liver-specific miR-1227. Genome-wide analysis then reveals that Microprocessor-mediated transcription termination is commonly used by lnc-pri-miRNA but not by protein coding miRNA genes. This identifies a fundamental difference between lncRNA and pre-mRNA processing. Remarkably, inactivation of the Microprocessor can lead to extensive transcriptional readthrough of lnc-pri-miRNA, resulting in inhibition of downstream genes by transcriptional interference. Consequently we define a novel RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells. Overall design: Chromatin associated RNA-seq from sicntrl,siDrosha,siDGCR8 treated Hela cells. Same for sicntrl and siDGCR8 from Huh7 cells. Nuclear polyA + and polyA- RNA-seq from sicntrl and siDGCR8 in HeLa cells. Chromatin associated RNA-seq from siDicer treated Hela cells.	Co-expression
SRP043621	U2AF1 mutations alter splice site recognition in hematological malignancies	Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3'' splice site recognition factor U2AF1 altered its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways implicated in myeloid disease such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3'' splice site motif in vivo, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1’s zinc finger domains. Overall design: mRNA profiles of K562 cells expressing U2AF1 WT, mutants and knockdown of U2AF1 generated by deep sequencing.	Co-expression
SRP043644	Transcriptome analysis of oxdative-stress induced senescence in human astrocytes	Purpose:  Cellular senescence is a cell stress response resulting in permanent growth arrest and the production of an altered pro-inflammatory secretory profile known as the senescecnce-associated secretory phenotype (SASP). The induction of senescence in astrocytes, a cell type responsible for maintaining homeostasis within the central nervous system (CNS) and responding to CNS insults, has been implicated in neurodegenerative disease. However, little is known about the senescent transcriptome in CNS-derived cell types including astrocytes. Methods: To better understand senescence-associated gene expression changes in astrocytes, we investigated global changes in the astrocyte transcriptome using RNA-seq following the induction of oxidative stress-induced senescence with hydrogen peroxide. Results:  During senescence, we find evidence of a loss of brain expressed transcripts involved in diverse CNS processes including neuronal differentiation and development, gliogenesis, axonogenesis, and learning and memory as well as a loss of transcripts involved in MHC class II antigen processing and presentation. In addition, we find evidence for induction of the senescent phenotype including a loss of transcripts involved in cell division and an increase in the mRNA level of inflammatory mediators suggestive of a SASP. Conclusions: Overall, our findings suggest a loss of differentiated function in senescent astrocytes and a gain in neuroinflammatory function as part of the SASP as a potential mechanisms for dysfunction in the aging brain. Overall design: Examination of transcriptome changes by RNAseq in pre-senescent and senescent astrocytes using 2 biological replicates per condition	Co-expression
SRP043684	Hyper-excitability of Neurons generated from Patients with Bipolar Disorder	Bipolar Disorder (BD) is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression and, without treatment, 15% of patients commit suicide1. Hence, among all diseases, BD has been ranked by the WHO as a top disorder of morbidity and lost productivity2. Previous neuropathological studies have revealed a series of alterations in the brains of BD patients or animal models3, such as reduced glial cell number in the patient prefrontal cortex4, up-regulated activities of the PKA/PKC pathways5-7, and changes in dopamine/5-HT/glutamate neurotransmission systems8-11. However, the roles and causation of these changes in BD are too complex to exactly determine the pathology of the disease; none of the current BD animal models can recapitulate both the manic and depressive phenotypes or spontaneous cycling of BD simultaneously12,13. Furthermore, while some patients show remarkable improvement with lithium treatment, for yet unknown reasons, other patients are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model has been a challenge for research into BD. The development of induced pluripotent stem cell (iPSC) technology has provided such a new approach. Here, we developed a human BD iPSC model and investigated the cellular phenotypes of hippocampal dentate gyrus neurons derived from the patient iPSCs. Using patch clamp recording, somatic Ca2+ imaging and RNA-seq techniques, we found that the neurons derived from BD patients exhibited hyperactive action potential (AP) firing, up-regulated expression of PKA/PKC/AP and mitochondria-related genes. Moreover, lithium selectively reversed these alterations in the neurons of patients who responded to lithium treatment. Therefore, hyper-excitability is one endophenotype of BD that is probably achieved through enhancement in the PKA/PKC and Na+ channel signaling systems, and our BD iPSC model can be used to develop new therapies and drugs aimed at clinical treatment of this disease. Overall design: total RNAseq from neurons generated from BD patient-specific iPS cells	Co-expression
SRP043686	Comprehensive transcriptome analysis of nasopharyngeal carcinoma cell lines	To explore infectious agents associated with nasopharyngeal carcinomas (NPCs), we have sequenced human NPC cell lines using Illumina RNA-sequencing.	Co-expression
SRP043688	Homo sapiens strain:Cell line Transcriptome or Gene expression	The study goal was to develop a new and robust protocol for blood preservation. It also involved a proof-of-concept study to preserve rare cell samples.	Co-expression
SRP043694	IL-1ß and SERPINA3 are markers of an aggressive Barrett’s Oesophagus phenotype identified using mRNA sequencing	Introduction: The identification of biomarkers in Barrett’s oesophagus (BO) that stratify groups at risk of progressing to oesophageal adenocarcinoma (OAC) would allow tailored surveillance strategies. We have applied a novel high throughput RNA sequencing analysis characterizing the BO mRNA transcriptome across the metaplasia-dysplasia sequence to identify potential markers of progression in an unbiased fashion and functionally validated these at the protein level. Methods: Matched biopsy samples for histology and RNA extraction were taken from BO patients of known histological grade. RNA was extracted from matched samples and sequenced to 60bp length (paired-end).21 samples were sequenced (HGD,7; LGD, 7 and SIM, 7). Reads obtained were mapped to NCBI build37.2 using TopHat. Read count generation, normalisation and differential expression (DE) analysis was performed using the HTSeq-DESeq pipeline. Significantly DE genes (>2 fold change in expression with B-H adjusted p-value <0.1) were further assessed for network and biological relevance using Ingenuity Pathway analysis. Candidate genes were selected and validated in a larger cohort (n=64) using RT-PCR.  Targets were further validated (by ELISA and immunohistochemistry) in independent cohorts of patients using serum and tissue microarrays. Results: DE analysis was performed in 3 groups with 2 conditions at a time using the lower grade cohort as control and the higher grade as comparator: SIM vs. LGD (demonstrated 218 DE genes, 131 up-regulated in LGD, 87 down-regulated compared to SIM), SIM vs. HGD (49 DE, 27 up, 22 down) and LGD vs. HGD (317 DE, 81 up, 216 down). Six network-central candidate genes (FOSB, IL-1B, SERPINA3, KLK7, GSTM5 &SCUBE2) were selected for RT-PCR validation following network and functional analysis. Circulating IL-1ß and SERPINA-3 demonstrated progressive significant increases in expression across the dysplasia sequence to OAC (p<0.005)). This was confirmed at the tissue level showing significant differences between SIM and dysplastic BO (p<0.05). Conclusion: The use of RNA-sequencing as a detailed and unbiased analysis method identifies IL-1ß and SERPINA-3 as novel candidates differentially expressed along the metaplasia-dysplasia-cancer sequence in BO. Overall design: RNA sequencing was performed on mRNA extracted from oesophgeal biopsies from patients with non dysplstic Barrett''s esophagus, low grade dysplasia and high grade dysplasia using Illumina GAIIx	Co-expression
SRP043960	GATA2 shRNA Expression in Castration Resistant Prostate Cancer Cell Lines	The transcription factor GATA2 regulates chemotherapy resistance in prostate cancer. We report a novel GATA2 transcriptional program that has implications for chemotherapy resistance disease and aggressiveness in castration resistant prostate cancer. Overall design: Examination of the transcriptional network changes induced in human Ch-CRPC cell lines by two shRNA mediated knock down of GATA2 versus random shRNA control	Co-expression
SRP043962	Nuclear stability and transcriptional directionality separate functionally distinct RNA species	Sequencing of 5' ends of RNA molecules from control and exosome-depleted HeLa-S3 cells. Overall design: CAGE library construction from RNA extracted from control and exosome-depleted cells.	Co-expression
SRP044013	ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells (RNA-Seq)	ETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.	Co-expression
SRP044042	RNA-seq transcriptomic analysis of sarcomatoid (E/S), rhabdoid (E/R) and non-sarcomatoid (E*) clear cell renal cell carcinoma	The biphasic epithelioid (E-) and sarcomatoid(S-) components of sarcomatoid RCC and epithelioid (E-) and rhabdoid (R-) components of rhabdoid RCC shared a similar transcriptomic signature, despite morphologic differences; by contrast, the transcriptome of sarcomatoid and rhabdoid RCC was sharply distinct from non-sarcomatoid RCC. Overall design: Total RNA was processed for RNA-seq from the following patient samples:  7 sarcomatoid RCC (E- and S- pairs), 4 rhabdoid RCC (E- and R- pairs) and 15 non-sarcomatoid RCC.	Co-expression
SRP044056	RNA-seq transcriptional profiling in primary human erythroid progenitor cells upon shRNA-mediated knockdown of PRC2 core subunits	Polycomb Repressive Complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during hematopoiesis. We examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 sub-complex lacking EED. We provide evidence that EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin domains in the absence of H3K27me3, and positively regulate gene expression. Loss of EZH2 expression leads to global repositioning of EZH1 chromatin occupancy to EZH2 targets. Moreover, we demonstrate that an erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers during erythropoiesis. Thus, the lineage- and developmental stage-specific regulation of PRC2 expression and subunit composition leads to a switch from canonical silencing to non-canonical PRC2 functions during blood stem cell specification. Overall design: Transcriptional profiling in primary human fetal liver proerythroblasts upon lentiviral shRNA-mediated knockdown of EZH1, EZH2, EED, or SUZ12 by RNA-seq analysis.	Co-expression
SRP044062	DDX3X regulation of global translation is impaired by medulloblastoma-associated mutations [RNA-Seq]	Whole-genome sequencing recently identified recurrent missense mutations in the RNA helicase DDX3X in pediatric medulloblastoma (MB) and other tumors. The normal function of DDX3X is poorly understood, and the consequences of its cancer-associated mutations have not been explored. Here we used genomic, biochemical, cell biological, and animal modeling approaches to investigate normal DDX3X function and the impact of cancer-associated DDX3X mutations. Cross-linking immunoprecipitation–high-throughput sequencing (CLIPseq) analyses revealed that DDX3X binds primarily to ~1000 mature mRNA targets at binding sites spanning the full mRNA length; their enrichment in the coding regions suggests that DDX3X plays a role in translational elongation. The association of wild-type DDX3X with polysomes is consistent with this observation. Cancer-associated mutations result in loss of DDX3X from polysomes and accumulation of mutant DDX3X in stress granules (cytoplasmic accumulations of translationally arrested mRNAs). Mutation-dependent redistribution of DDX3X to stress granules is also observed in a Drosophila model system and in MB tumor cells from patients carrying DDX3X mutations. Importantly, mRNAs targeted by DDX3X are enriched in translation factors, suggesting that DDX3X regulates translation both directly and indirectly. Indeed, depletion of DDX3X by RNAi or over-expression of mutant DDX3X significantly impairs global protein synthesis. Ribosome profiling confirmed this observation and showed a 5’ bias in ribosomal occupancy, further confirming the role of DDX3X in translational elongation. Together, our data show that DDX3X is a key regulator of translation and that this function is impaired by cancer-associated mutations. Finally, we found that medulloblastoma-related mutant DDX3X can efficiently bind the wild-type form suggesting that mutant DDX3X could exert a dominant negative effect in vivo. Overall design: Examination of the whole tarnscriptome under conditions of DDX3X knockdown or overexpression of WT DDX3X or cancer-associated DDX3X mutants	Co-expression
SRP044084	Molecular mechanism underlying increased ischemic damage in the ALDH2*2 genetic polymorphism using a human iPSC model system	We investigated the ALDH2*2 genetic polymorphism and its underlying mechanisms for the first time in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation confers elevated levels of reactive oxygen species (ROS) and toxic aldehydes such as 4HNE, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. ALDH2 exerts control of cell survival decisions via modulation of oxidative stress levels. This regulatory circuitry was found to be dysfunctional in the loss-of-function ALDH2*2 genotype, causing upregulation of apoptosis in cardiomyocytes following ischemic insult. These results reveal a novel function of the metabolic enzyme ALDH2 in modulation of cell survival decisions. Overall design: Molecular mechanism of increased ischemic damage in cardiomyocytes of ALDH2*2 genotype.	Co-expression
SRP044171	Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase	Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARFBP1,  MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high throughput screening, we identify small  molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells. Overall design: MIZ1 and MYC ChIPseq experiments in HUWE1 inhibitor-treated Ls174T cells as well as RNAseq experiments in HUWE1- or MIZ1-depleted Ls174T cells after HUWE1 inhibitor treatment. Sequencing was performed on an Illumina Genome Analyzer IIx.	Co-expression
SRP044174	Functional conservation of both CDS and 3’UTR -located miRNAs binding sites between species	Combining the knock-down of miR-15a, miR-16 and miR-92a in human and macaque cells transiently, we performed RNA-seq to quantify the regulatory effect of miRNAs on their 3’UTR and CDS targets	Co-expression
SRP044181	Impaired DNA damage metabolism promotes autoimmunity in TREX1 deficiencyÂ	Constitutive low level DNA damage is linked to innate immune activation. Hierarchical clustering of over 9000 transcripts revealed remarkably similar profiles in a patient with lupus erythematosus and a patient with AGS with up-regulation of genes involved in DNA damage signaling, p53-inducible genes, senescence-associated genes as well as  up-regulation of interferon-stimulated genes. Transcriptional profiling of fibroblasts exposed to oxidative stress showed a marked up-regulation of genes involved in DNA replication/repair and replication licensing in TREX1-deficient cells compared to wild type cells suggesting massive replication stress. Overall design: Comparison of transcriptional profiles of unstressed patient fibroblasts with wild type cells as well as fibroblasts exposed to oxidative stress	Co-expression
SRP044187	RNA-sequencing experiment: Treatment of MCF-7 breast cancer cells with the novel small molecule ZNA	MCF-7 cells were treated with either ZNA (30 uM) or a vehice control for 3 or 12 hours.  Following RNA sequencing, the control-normalized data was used to analyze genes altered by ZNA treatment. Following RNA sequencing, the control-normalized data was used to analyze genes altered by ZNA treatment. Overall design: MCF-7 cells were treated with either ZNA (30 uM) or a vehice control for 3 or 12 hours.	Co-expression
SRP044206	RNA-seq of IL-4 stimulated human keratinocytes	In this study we aim to determine the role of IL-4/STAT6 in gene expression in human keratinocytes using RNA-sequencing approach. Human keratinocytes were cultured for 2 or 5 days with calcium chloride to induce terminal differentiation as determined by the expression of epidermal differentiation complex genes. The cells were then stimulated with IL-4 for 3 and 24 hours, or along the 5 days culture period.  We observed that IL-4 inhibits fully differentiation of keratinocytes, induces genes involved with production of inflammatory mediators, and reduces the healing capacity of human keratinocytes. Moreover, STAT6 controlled important genes involved with calcium binding, inflammation and epidermis development. Overall design: Human keratinocytes were differentiated with calcium chloride for 2 days and incubated with media alone or 20ng/ml of recombinant human IL-4 for 3 and 24 hours. Human keratinocytes were differentiated with calcium chloride for 5 days with or wihout recombinant human IL-4 (20ng/ml). Keratinocytes transfected with control or STAT6 siRNA were differentiated with calcium chloride for 2 days and then stimulated with recombinant huma IL-4 for 24 hours.	Co-expression
SRP044228	Disruption of human-specific synaptogenesis program in autism [RNA-seq]	To test the connection between the molecular mechanisms underlying autistic disorder and human cognitive evolution, we analyzed the gene expression changes taking place during prefrontal cortex development in autism patients and healthy controls, as well as non-human primates. We found the genes with expression changes in autism are significantly overlapped with genes showing human-specific developmental profile. A major pattern of the overlapped genes reflects the aberrant acceleration of synaptogenesis and synaptic maturation followed by premature synaptic pruning in the prefrontal cortex of autism patients. This pattern involves the same developmental program that controls human-specific extension of cortical synaptogenesis in healthy individuals. Taken together, these findings shed light on the molecular mechanisms underlying autistic phenotype and provide potential targets for clinical intervention. Overall design: Compare the gene expression change in autism and the gene expression specificly changed in human.	Co-expression
SRP044229	MiRNA23B REGULATES SELF-RENEWAL AND CHEMORESISTANCE PROPERTIES OF COLON CANCER STEM CELLS	MiRNAs have been identfied to play an important role in cancer stem cells. MiR23b is differentially expressed in various forms of cancer including colorectal cancer as compared to their normal counterparts. MiR23b regulates various aspects of cell behaviour such as differentiation, apoptosis and motility. The goal of the study was to identify the novel role of miR23b in self-renewal property of colon cancer stem cells via regulation of its candidate target mRNAs. To address this aim, HT29 colon cancer cells were transfected with miR23b Precursor, Antimir and their respective controls. RNA SEQ analysis of the cells with altered levels of miR23b assisted in the identification of interesting mRNA targets influenced by miR23b expression and involved self-renewal pathways. Overall design: HT29 cells with altered levels of miR23b was subjected to RNA SEQ analysis to identify differential expresssion of mRNA targets of mIR23b	Co-expression
SRP044241	Gene expression changes as a result of E-cadherin loss in an isogenic non-malignant MCF10A and MCF10A CDH1-/- breast cells	Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Overall design: Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.	Co-expression
SRP044286	Extensive remodeling of DC function by rapid maturation-induced epigenetic gene silencing [RNA-Seq]	Dendritic-cell (DC) maturation involves substantial remodeling of their gene-expression program. Most research has focused on inducible gene-expression networks promoting the acquisition of new functions, such as cytokine production and enhanced T-cell-stimulatory capacity. In contrast, mechanisms that modulate DC-function by inducing gene silencing remain poorly understood. Here we describe a novel primary epigenetic-silencing response that makes major contributions to the DC-maturation process. The repressed genes function in pivotal processes - including antigen-presentation, extracellular-signal detection, signal-transduction and lipid-mediator biosynthesis - underscoring the central contribution of the silencing mechanism to rapid reshaping of DC-function. Interestingly, promoters of the repressed genes exhibit a surprisingly high frequency of PU.1-occupied sites, suggesting a novel role for this transcription factor in marking genes poised for inducible repression Overall design: Transcriptional changes induced by one hour LPS treatment in monocyte derived dendritic cells.	Co-expression
SRP044296	Homo sapiens Transcriptome or Gene expression	We generated HeLa cell lines stably expressing either empty vector or MYC-UPF1-FLAG TEV and transfected each with either empty vector or TEV-protease encoding vector. The goal is to see what mRNAs are upregulated upon UPF1 cleavage.	Co-expression
SRP044303	Homo sapiens Transcriptome or Gene expression	LPMC MNP subsets	Co-expression
SRP044373	Transcriptomic analysis of an archived bladder cancer cohort	Establishment and application of RNAseq based transcriptome analayis on an archivaed bladder cancer cohort. Overall design: Total RNA profilling 61 archived bladder cancer samples and comparison of 4 pairs of fresh frozen and FFPE bladder cancer samples.	Co-expression
SRP044593	Genome-wide DNA methylation map reveals widespread epigenetic variation in healthy individuals (RNA-Seq)	Using neutrophils from a cohort of normal individuals, we generated transcriptomic profile of 4 individuals. Overall design: Here we generated gene expression profile of neutrophil cells of 4 normal individuals.This data was integreated with DNA methylation profiles of same individuals.	Co-expression
SRP044608	TNFa Signaling Exposes Latent Estrogen Receptor Binding Sites in Breast Cancer Cells [GRO-seq]	The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers.  We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNFa, or both.  In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ERa), the pioneer factor FoxA1 and the p65 subunit of the NF-?B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes.  In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes.  The synergistic and antagonistic interplay between estrogen and TNFa signaling at the gene level is also evident in the patterns of ERa and NF-?B binding, which relocalize to new binding sites that are not occupied by either treatment alone.  Interestingly, the chromatin accessibility of classical ERa binding sites is predetermined prior to estrogen treatment, whereas ERa binding sites gained upon co-treatment with TNFa require NF-?B and FoxA1 to promote chromatin accessibility de novo.  Our data suggest that TNFa signaling recruits FoxA1 and NF-?B to latent ERa enhancer locations and directly impact ERa enhancer accessibility. Binding of ERa to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response.  This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer. Overall design: Using GRO-seq and ChIP-seq (ER, FoxA1 and p65) to assay the molecular crosstalk of MCF-7 cells treated with E2, TNFa or both E2+TNFa.	Co-expression
SRP044610	c-Src Modulates Estrogen-Induced Stress and Apoptosis in Estrogen-Deprived Breast Cancer Cells [MCF-7:5C]	The emergence of anti-estrogen resistance in breast cancer is an important clinical phenomenon affecting long-term survival in this disease. Identifying factors that convey cell survival in this setting may guide improvements in treatment. Estrogen (E2) can induce apoptosis in breast cancer cells that have been selected for survival after E2 deprivation for long periods (MCF-7:5C cells), but the mechanisms underlying E2-induced stress in this setting have not been elucidated. Here, we report that the c-Src kinase functions as a key adapter protein for the estrogen receptor (ER, ESR1) in its activation of stress responses induced by E2 in MCF-7:5C cells. E2 elevated phosphorylation of c-Src, which was blocked by 4-hydroxytamoxifen (4-OHT), suggesting that E2 activated c-Src through the ER. We found that E2 activated the sensors of the unfolded protein response (UPR), IRE1a (ERN1) and PERK kinase (EIF2AK3), the latter of which phosphorylates eukaryotic translation initiation factor-2a (eIF2a). E2 also dramatically increased reactive oxygen species production and upregulated expression of heme oxygenase HO-1 (HMOX1), an indicator of oxidative stress, along with the central energy sensor kinase AMPK (PRKAA2). Pharmacologic or RNA interference-mediated inhibition of c-Src abolished the phosphorylation of eIF2a and AMPK, blocked E2-induced ROS production, and inhibited E2-induced apoptosis. Together, our results establish that c-Src kinase mediates stresses generated by E2 in long-term E2-deprived cells that trigger apoptosis. This work offers a mechanistic rationale for a new approach in the treatment of endocrine-resistant breast cancer. Overall design: MCF-7:5C cells were treated with vehicle (0.1% EtOH) as control, E2 (10-9mol/L), 4-OHT (10-6mol/L), E2 (10-9mol/L) plus 4-OHT (10-6mol/L), PP2 (5x10-6mol/L), and E2 (10-9mol/L) plus PP2 (5x10-6mol/L) respectively for 72 hours.	Co-expression
SRP044611	Identification of gene regulation patterns underlying both E2- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells [MCF-7]	A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rß). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients. Overall design: Wild-type MCF-7 cells were treated with vehicle control (0.1% ethanol), E2 (10-9 mol/L) and 4-OHT (10-6 mol/L) respectively for 24 hours.	Co-expression
SRP044651	mRNA expression in human DAOY cells	We generate ZNF423 knockdown and control DAOY cells with lentivirus that co-expressed the fluorescent protein mCherry. We performed whole genome RNA sequencing (RNA-seq) of three batched of cultured ZNF423 KD or control KD cells. The sequence reads were analyzed by Homer followed by edgeR. The analyzed RNA-seq results showed  differential expression profile including 12 known cilia genes, and 3 of these were validated with qRT-PCR on mouse granule cell precursors. This study proved data how ZNF423 linked to cilia complexes. Overall design: RNA-seq in three batched of control and ZNF423 KD cells(generated by lentivirus delivered shRNA targeting ZNF423 sequence).	Co-expression
SRP044668	MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma	We obtained radiographically-localized biopsies during glioma resection surgeries to sample the tumor core and margins from multiple glioma patients. We also procured fresh, non-neoplastic brain tissue specimens from multiple patients having procedures to relieve epilespy symptoms or to place shunts to treat normal pressure hydrocephalus.  We then used RNA-Seq to compare expression patterns between geographically distinct regions of gliomas and computational deconvolution to estimate cell type-specific expression patterns in different disease subtypes. Overall design: RNA-Seq analysis in 39 contrast-enhancing glioma core samples, 36 non-enhancing FLAIR glioma margin samples, and 17 non-neoplastic brain tissue samples.	Co-expression
SRP044673	A Non-Canonical Nuclear Activity Triggered by Small RNAs and Argonaute Proteins in Human Cells	In this study we report the discovery of an unexpected nuclear activity of small RNAs that target an ~8.6 megabase chromosomal domain located on the telomeric q-arm of chromosome 5 from an unbiased genome-wide RNAi screen. Short-hairpin RNAs that target genes within this large domain induce trans-activation of CREB signaling transcriptional reporters and induce an endogenous gene expression signature that includes CREB-target and neuronal-fate genes. Furthermore, CRISPR-guided deletion of AGO-1 and -2 demonstrate their mutually redundant roles in this mechanism, which we named Chromosomally Induced Trans Activation by RNAi (CITAR). Overall design: We sequenced the transcriptome of HEK293 cells undergoing Chromosomally-Induced Trans Activation by RNAi (CITAR), as measured by transcriptional activation of a CRE-Luciferase reporter (pGL4.29), by shRNAs targeting Chr5q35 loci (TSPAN17 at Chr5:176,074,388, TMED9 at  Chr5:177,019,213 and N4BP3 at Chr5:177,540,556), as well as two negative control shRNAs to account for infection (non-hairpin) and for engagement of the RNAi pathway (ASNA1 encoded on Chr19).	Co-expression
SRP044679	Uridylation by TUT4 and TUT7 marks mRNA for degradation [RNA-Seq]	Uridylation occurs pervasively on mRNAs in mammals, yet its mechanism and significance remain unknown. Here we identify TUT4 and TUT7 (also known as ZCCHC11 and ZCCHC6, respectively) as the enzymes that uridylate mRNAs. Uridylation readily occurs on deadenylated mRNAs that are not associated with poly(A) binding protein (PABPC1) in cells. Consistently, purified TUT4 and TUT7 (TUT4/7) selectively uridylate RNAs with short A tails (< ~25 nt) while PABPC1 antagonizes uridylation of polyadenylated mRNAs in vitro. In cells depleted of TUT4/7, the vast majority of mRNAs lose the U tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 is required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs, and demonstrates a fundamental role of the U tail as a molecular mark for global mRNA decay. Overall design: HeLa cells were knocked down of control or TUT4/7, then total RNAs were prepared for RNA-seq on 0, 1, 2, 4h after actinomycin D treatment. The whole processes of experiments were repeated two times.	Co-expression
SRP044763	Adenovirus Small E1A Employs the Lysine Acetylases p300/CBP and Tumor Suppressor Rb to Repress Select Host Genes and Promote Productive Virus Infection [RNA-seq]	Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF?-, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Overall design: Examination of transcriptome by mRNA sequencing before and after infection by adenoviral e1a expressing vectors in growth arrested IMR90	Co-expression
SRP044766	Wide-spread disruption of transcription termination in HSV-1 infection:  Next generation sequencing of total and newly transcribed (4sU-RNA) RNA	Primary human foreskin fibroblasts (HFF) were infected with wild-type simplex virus 1 (HSV-1) strain 17 at a multiplicity of infection (MOI) of 10. Newly transcribed RNA was labelled by adding 500µM 4-thiouridine (4sU) to the cell culture media for 1h. Total cellular RNA was isolated using Trizol. Newly transcribed RNA was purified following the protocol described in Raedle et al. JoVE 2013. Overall design: Newly transcribed RNA was labelled in one hour intervals during the first eight hours of HSV-1 infection. All nine 4sU-RNA samples as well as total cellular RNA of every second hour of infection were sent for sequencing. Two independent biological replicates were analysed.	Co-expression
SRP044809	Proteomic informed by transcriptomic analysis of host response to Hendra virus	Compare the response of human (HEK293T) and bat (PakiT03) kidney cells infected with Hendra virus using proteomics informed by transcriptomics	Co-expression
SRP044854	EGFR and MEK pathway signature RNA-Seq datasets	EGFR and MEK pathways were activated alone or in combination in human mammary epithelial cells. We profiled the pathway gene expression signatures using RNA-Seq. Overall design: mRNA was extracted from human mammary epithelial cells overexpressing EGFR gene, MEK gene, or EGFR and MEK genes in combination (or GFP control) for RNA-Seq analysis. Experiment was performed in six replicates per condition.	Co-expression
SRP044867	Open chromatin mapping identifies transcriptional networks regulating human epididymis epithelial function [Rnase-Seq]	The epithelium lining the epididymis in the male reproductive tract maintains a luminal environment that promotes sperm cell maturation. This process is dependent on the coordinated expression of many genes that encode proteins with a role in epithelial transport. We previously generated genome-wide maps of open chromatin in primary human fetal epididymis epithelial cells to identify potential regulatory elements controlling coordinated gene expression in the epididymis epithelium. Subsequent in silico analysis identified transcription factor binding sites (TFBS) that were over-represented in the HEE open chromatin, include the motif for paired box 2 (PAX2). PAX2 is a critical transcriptional regulator of urogenital tract development, which is well studied in the kidney but is unexplored in the epididymis. Due to the limited lifespan of primary HEE cells in culture we investigated the role of PAX2 in an immortalized HEE cell line (REP). First, REP cells were evaluated by DNase-seq and their open chromatin map overlapped that of primary HEE cells at ~ 65% of sites. Moreover, the PAX2-binding motif was again identified as an overrepresented TFBS within intergenic open chromatin, though on fewer chromosomes than in the primary HEE cells. To identify PAX2-target genes in REP cells, RNA-seq analysis was performed after siRNA-mediated depletion of PAX2 in comparison to a non-targeting siRNA. In response to PAX2-represssion, 3142 transcripts were differentially expressed (1334 up-regulated and 1808 down-regulated). Novel PAX2 targets included multiple genes encoding proteins with a predicted function in the epididymis epithelium. Overall design: mRNA profile of control and PAX2 knockdown REP cells	Co-expression
SRP044917	Discovery of biomarkers predictive of GSI response in triple negative breast cancer and adenoid cystic carcinoma	Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Overall design: Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates	Co-expression
SRP044925	Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (RNA-Seq)	Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Overall design: Comparison of gene expression at different stages of keratinocyte differentiation	Co-expression
SRP044956	GIST cell cycle dysregulation is required for progression to high-risk disease but not for resistance to kinase inhibitors	Background: To understand the transcriptional consequences of a TP53 modulation in the GIST cell context, we treated GIST430 with increasing doses of the MDM2-inhibitor nutlin-3 (racemate). Overall design: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile GIST430 cell lines treated with DMSO and Nutlin-3, 2.5µM or 10µM for 18h. Then the gene expression profiles between these concentrations were compared.	Co-expression
SRP045048	Gene expression profiling associated with knockdown of LKB1 in human intrahepatic cholangiocarcinoma	The experiment was designed to display differential gene expression profiling in three human intrahepatic cholangiocarcinoma (ICC) cells upon knockdow of LKB1 tumor suppressor, by using RNAseq technology. Overall design: LKB1 was first attenuated in three ICC cells: HuH-28, RBE, and SSP-25 by siRNA-mediated knockdown. Total RNA was extracted from duplicated cancers cells transfected with control siRNA and LKB1 specific siRNA at 48h posttransfection for RNAseq analysis. Differentially expressed genes in LKB1-attenuated ICC cells were identified in comparison to that in ICC cells transfected with control siRNA.	Co-expression
SRP045052	Defining CD4 T Cell Memory by the Epigenetic Landscape of CpG DNA Methylation [RNA-Seq]	Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. Overall design: RNA sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.	Co-expression
SRP045065	PTBP1 excludes UPF1 to protect long 3''UTRs from nonsense-mediated mRNA decay	RNA-seq analysis of human 293 Tet-off cells depleted of PTBP1 and UPF1 alone and in tandem with specific siRNAs. Overall design: siRNA-based depletion of PTBP1, UPF1, and PTBP1/UPF1 together, with a validated non-silencing siRNA as a control.	Co-expression
SRP045118	RNAseq and ChIPseq analysis of NKX2-1 dependent NSCLC cell lines	Single-end 36bp RNAseq in control and NKX2-1 knockdown samples to uncover genes regulated by NKX2-1. Single-end 36bp ChIPseq using NKX2-1 antibody (Santa Cruz, sc-13040) to indentify direct NKX2-1 binding sites across the NSCLC genome.	Co-expression
SRP045126	Homo sapiens Transcriptome or Gene expression	RNA-seq Identification of a Novel Fusion Gene in a Mesenchymal Tumor	Co-expression
SRP045154	Replicative senescence is associated with nuclear reorganization and DNA methylation at specific transcription factor binding sites (RNA-seq)	Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [RNA-seq] Overall design: RNA was isolated from 1,000,000 cells of three MSC donors (59, 64, and 73 years old) at passage 4 and passage 13 using the miRNeasy Mini Kit (Qiagen). Gene expression profiles were analzyed by  deep sequencing with IlluminaHiSeq 2000 technology with a read length of 50 bases at EMBL gene core facility (Heidelberg, Germany).	Co-expression
SRP045156	TET1 regulates hypoxia-induced epithelial-mesenchymal transition through DNA demethylation (RNA-Seq)	In order to explore the status of DNA methylation in hypoxia response, we show that TET1, a DNA dioxygenase converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates hypoxia-responsive gene expression. Hypoxia/HIF-2a regulates the expression of TET1. Knockdown of TET1 mitigated hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes. Overall design: Four samples (Four samples, Hypoxia (scrambled control), Hypoxia (TET1-si), Normoxia (scrambled control) and Normoxia (TET1-si), are performed by RNA-Seq and hMeDIP-Seq  RNA-Seq and hMeDIP-Seq	Co-expression
SRP045204	Human MDA-MB-231 Cell HITS-CLIP RNA sequencing	HITS-CLIP of control and transfected cells to find direct targetting of miR-200 family to mRNA	Co-expression
SRP045207	Homo sapiens Transcriptome or Gene expression	The goal of this study is to identify deferentially expressed genes among three groups of individuals of the same family. These groups are : affected, unaffected wild, unaffected carrier.	Co-expression
SRP045214	Wide-spread disruption of transcription termination in HSV-1 infection: Next-generation sequencing of translational activityd by ribosome profiling	Primary human foreskin fibroblasts (HFF) were infected with wild-type simplex virus 1 (HSV-1) strain 17 at a multiplicity of infection (MOI) of 10. Ribosome profiling was performed at various times during infection with minor modification to the protocol described in Stern-Ginossar N et al., Science 2012 Overall design: Ribosome profiling was performed a 0, 1, 2, 4, 6 and 8 h post infection. Two biological replicates were analysed.	Co-expression
SRP045222	Transcriptome-wide mapping reveals widespread dynamic regulated pseudouridylation of mRNA	Pseudouridine is the most abundant modification occurring on RNA, yet with the exception of a few well-studied RNA molecules little is known about the modified positions and their function(s). Here, we develop ?-seq, a method for transcriptome-wide quantitative mapping of pseudouridine. We validate ?-seq with synthetic spike-ins and de novo identification of the vast majority of previously reported pseudouridylated positions. ?-seq permits discovery of hundreds of novel pseudouridine modifications in human and yeast mRNAs and snoRNAs. Knockdown and knockout of pseudouridine synthases uncovers the cognate PUSs mediating pseudouridine catalysis at these individual novel sites and their target sequence features. In both human and yeast pseudouridine formation on mRNA depends on both site-specific PUSs – often guided by a specific sequence motif - and snoRNA-guided PUSs. Importantly, upon heat shock in yeast, Pus7-mediated pseudouridylation is induced at >200 sites in diverse mRNAs. Pus7 deletion in yeast leads to decreased recovery from heat shock and decreased RNA levels at otherwise pseudouridylated messages, suggesting a role for pseudouridine in enhancing transcript stability. Pseudouridine stoichiometries in rRNA are highly conserved from yeast to mammals, but are reduced in cells derived from dyskeratosis congenita patients, where the pseudouridine synthase DKC1 is mutated, compared to age matched controls. Our results establish pseudouridine as a ubiquitous and dynamic modification in mRNA, and provide a sensitive, quantitative and transcriptome-wide methodology to address its underlying mechanisms and function. Overall design: Examination of m6A methylation in human Hek293 and A549 cell lines, in human embryonic stem cells (ESCs) undergoing differentiation to neural progenitor cells (NPCs),  in OKMS inducible fibroblasts reprogrammed into iPSC, and upon knockdown of factors using siRNAs or shRNAs.	Co-expression
SRP045225	The RNAseq of 79 small cell lung cancer (sclc) and 7 normal control	Even though small cell lung cancer (SCLC) has entered the age of broad genomic analysis, platinum-based chemotherapy remains the standard care for SCLC. Topotecan is the only approved agent for recurrent or progressive SCLC (1).  In the absence of well-defined genomic biomarkers, clinical efficacy signals in genomically distinct subsets of SCLC could have been missed. Serine/Arginine Splicing Factor 1 (SRSF1) is a member of SR protein family. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation (2). Whole exome and transcriptome sequencing of primary tumor SCLC from 99 Chinese patients has identified SRSF1 DNA amplification and mRNA over-expression which predicts poor survival in Chinese SCLC patients. In vitro and in vivo studies have demonstrated that SRSF1 is essential for tumorigenecity of SCLC and plays a key role in DNA repair and chemo-sensitivity. Overall design: We did RNAseq on 79 small cell lung cancer patients'' tumor sample and 7 normal lung tissue. We normalized the RNAseq data and did differential expression analysis.  The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation.	Co-expression
SRP045234	Chronic Myeloid Leukemia (CML), induced pluripotent stem cell (iPSC)-derived lin-CD34+CD45+ (iCD34) cell population	Analysis of lin-CD34+CD45+ (iCD34+) cell population from two normal bone marrow-derived (BM1K and BM9) iPSCs  and two CML (CML15 and CML17) iPSCs . CML iCD34+ cells have characteristics similar to primary CML leukemia stem cell in patients. Results provide insight into molecular profile characterized CML iCD34 and mechanism of its maintenance and drug resistance. Overall design: iCD34+ cell samples obtained from two control BM1K and BM9 iPSCs (both for the same normal donor) and CML15 and CML17 iPSCs (both from the same patient in chronic phase of CML). Each group was treated with DMSO (control) or 5 µM imatinib. The complete phenotype for iCD34+ cells: lin-CD34+CD45+CD90+CD117+CD45RA-. This population also inclyde Rhodaminelow and ALDKhigh cells.	Co-expression
SRP045257	Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes	Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be non-coding, including 5' UTRs and lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs). Here we show hallmarks of translation in these footprints: co-purification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including induction of immune responses following human cytomegalovirus (HCMV) infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts to understand how cells manage and exploit its consequences. Overall design: Ribosome profiling to verify that true ribosome footprints shift in response to different elongation inhibitors (CHX vs Emetine) and co-purify with an affinity-tagged large ribosomal subunit (bound vs input)	Co-expression
SRP045294	SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate	Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information. Overall design: RNA-Seq analysis to investigate transcriptomes of hPGC-like cells (hPGCLCs), fetal hPGCs, TCam-2 and hESCs	Co-expression
SRP045308	Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer associated pluripotency genes	BET-regulated transcriptome and BRD4, BRD2, BRD3 and Pol II ChIP-seq datasets in human ESCs before and after BET inhibition. Transcription factors and chromatin remodeling complexes are key determinants of embryonic stem cell (ESC) identity. In this study, we investigate the role of BRD4, a member of the bromodomain and extra-terminal domain (BET) family of epigenetic reader proteins, in control of ESC identity. We performed RNA-seq analyiss in the presense of small molecule inhibitors of BET proteins to show that BRD4 positively regulates the ESC transcriptome. We also integrated RNA-seq analysis with ChIP-sequencing datasets s for BRD4 (and for other BRD2 and BRD3) to demonstrate that BRD4 binds SEs and regulates the expression of SE-associated pluripotency genes. We have also conducted ChIP-seq analysis for Pol II binding to demonstrate that SE-associated genes depend on BRD4-dependent Pol II binding at TSS and gene body for their productive transcriptional elongation. Overall design: Total RNA was extracted from samples using the RNeasy Qiagen kit according to the manufacturer’s instructions. Deep sequencing of RNA (1ug) from hESCs FGF- or MS436-treated at day 1 and day 5 was performed as described in (Higgin et al., 2010c). Samples were subjected to PolyA  selection using magnetic oligo-dT beads. The resulting RNA samples were then used as input for library construction  as described by the manufacturer (Illumina, CA, USA). RNA libraries were then sequenced on the GAIIx system using 50bp single reads. Chromatin for ChIP-sequencing was obtained from FGF-maintained hESCs, vehicle or MS417-treated (at 250nM concentration for 6h) (10 to 20x106 cells/IP). ChIP-Seq libraries were generated using standard Illumina kit and protocol as described in (Ntziachristos et al., 2012). We performed cluster amplification and single read 50 sequencing-method using the Illumina HiSeq 2000, following manufacturer’s protocols.	Co-expression
SRP045318	Human embryonic stem cell, rhesus embryonic stem cell and mouse transchromosomic (hsa11) embryonic stem cell (with and without ectopic ZNF91 expression) RNA-seq	We compared the expression in embryonic stem cells of KRAB ZNF proteins and retrotransposon elements in the human genome under several conditions. Native human stem cells. Mouse stem cells containing a transchromosomic copy of human chromosome 11, with and without the introduction of plasmids containing KRAB Zinc Finger sequences. We show that certain KZNFs are responsible for the repression of certain retrotransposons in embryonic stem cells, preventing their spread across the genome. Overall design: RNA-seq of hESCs, rhESCs and mouse TC11 ESCs with ZNF91 plasmids (2 replicates), with empty vector plasmids (2 replicates), or no plasmids.	Co-expression
SRP045322	Integrative transcriptome-wide analyses reveal critical HER2-regulated mRNAs and lincRNAs in HER2+ breast cancer	Breast cancer is a major health problem affecting millions of women worldwide. Over 200,000 new cases are diagnosed annually in the USA, with approximately 40,000 of these cases resulting in death. HER2-positive (HER2+) breast tumors, representing 20–30 % of early-stage breast cancer diagnoses, are characterized by the amplification of the HER2 gene. However, the critical genes and pathways that become affected by HER2 amplification in humans are yet to be specifically identified. Furthermore, it is yet to be determined if HER2 amplification also affects the expression of long intervening non-coding (linc)RNAs, which are involved in the epigenetic regulation of gene expression. We examined changes in gene expression by next generation RNA sequencing in human tumors pre- and post- HER2 inhibition by trastuzumab in vivo, and changes in gene expression in response to HER2 knock down in cell culture models. We integrated our results with gene expression analysis of HER2+ tumors vs matched normal tissue from The Cancer Genome Atlas. The integrative analyses of these datasets led to the identification of a small set of mRNAs, and the associated biological pathways that become deregulated by HER2 amplification. Furthermore, our analyses identified three lincRNAs that become deregulated in response to HER2 amplification both in vitro and in vivo. Our results should provide the foundation for functional studies of these candidate mRNAs and lincRNAs to further our understanding of how HER2 amplification results in tumorigenesis. Also, the identified lincRNAs could potentially open the door for future RNA-based biomarkers and therapeutics in HER2+ breast cancer. Overall design: We compared changes in gene expression of both mRNAs and lincRNAs in BT474 cells that are treated with HER2 siRNAs vs cells treated with negative control siRNAs by RNA-seq.	Co-expression
SRP045326	Acetylation-Dependent Control of Global Poly(A) RNA Degradation by CBP/p300 and HDAC1/2	Acetyltransferases and histone deacetylases regulate gene expression at the level of chromatin, mainly by affecting transcription. In this study, we report that hyperacetylation induced by inhibition of histone deacetylases (HDACs) causes massive degradation of mRNA. The effect is promoter-independent and affects poly-A mRNA globally. HDAC inhibition leads to the removal of poly-A tails from mRNAs through activation of the deadenylase CAF1a, which we find to be acetylated together with its activator BTG2 by the histone acetyl transferases (HATs) p300 and CBP. By mutation of critical lysine residues, we provide evidence that acetylation of CAF1a and BTG2 induces enhanced poly-A mRNA degradation. Our study reveals a fundamental mechanism by which cells coordinate epigenetic and transcriptional control of gene expression with posttranscriptional control of poly-A mRNA stability. In this experiment, HeLa cells were exposed to the HDAC inhibitor trichostatin A (TSA) for 16 hours, followed by treatment with actinomycin D. Total RNA was isolated after 0, 2, 4 and 6 hours, and analysed by RNA sequencing. The half-lives of 7431 RNAs were calculated after normalization to rRNA (18S + 28S) levels. The experiment shows that TSA treatment causes a general reduction of poly-A RNA stability, while replication-dependent histone mRNA stability is not affected. Overall design: RNA half-lives were measured in TSA-treated or untreated HeLa cells by RNA-Seq using Illumina HiSeq 2000.	Co-expression
SRP045330	Global 3' RACE in yeast and humans	Mpn1 proteins are evolutionarily conserved exonucleases that modify spliceosomal U6 small nuclear RNAs (snRNAs) post-transcriptionally. Mutations in the human MPN1 gene are associated to the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Mpn1 deficiency leads to aberrant U6 3’ end processing and accelerated U6 decay through unknown molecular mechanisms. Here we show that in mpn1? fission yeast cells U6 is barely bound by the protective Lsm2-8 complex, undergoes extensive oligoadenylation and is degraded by the nuclear RNA exonuclease Rrp6 independently of the poly(A) polymerase Cid14/Trf4. Mpn1 processes U6 in a spliceosome-dependent manner, as mutant U6 molecules that fail to join the spliceosome are not substrates for Mpn1. Moreover, human U6atac, the U6-like snRNA of the minor spliceosome, is a novel substrate for hMpn1. We unveil mechanistic details of a new U6 degradation pathway and further corroborate the notion that inefficient canonical and minor pre-mRNA splicing promotes PN. Overall design: The 3' termini of total RNA containing  2'3' cyclic phosphate from Mpn1-proficient and deficient human and yeast cells was sequenced	Co-expression
SRP045352	Comparative Analysis of Transcriptional Responses in Monocytes from Human Neonates, Adults, and Older Adults	Human neonates and older adults frequently exhibit a reduced capacity to control microbial infections. A variety of mechanisms involving both the innate and adaptive immune systems have been proposed to contribute to these deficiencies. The emergence of RNA sequencing (RNA-seq) as an accurate and quantitative method for examining mRNA levels provides an opportunity to compare transcriptional responses to a stimulus at a global scale in neonates, adults, and older adults. An examination of ex vivo monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection (with cord blood monocytes representing neonatal monocytes) revealed extensive similarities between all three age groups, with only a small number of genes exhibiting statistically significant differences. Using transcription factor motif analyses and RNA-seq data sets from a variety of mouse mutants, the most significant neonatal deficiencies corresponded to genes that require interferon response factor-3 or type 1 interferon signaling for their activation. In older adults, the most striking difference was broad, low-level activation of inflammatory genes prior to stimulation, consistent with prior evidence of a chronic inflammatory state in older adults. These results demonstrate the value of quantitative RNA-seq analyses and the feasibility of cross-species comparisons between well-defined mouse networks and human data sets. Overall design: RNA-seq of primary cells from three independent donors in three different age-groups across 3 time-points stimulated with either LPS or Listeria monocytogenes.	Co-expression
SRP045355	Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation	Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx+ regions, which form a long stem–loop structure that is recognized by ADAR1 as a substrate for editing. RNA editing enables the recruitment of the stabilizing RNA-binding protein human antigen R (HuR; encoded by ELAVL1) to the 3' UTR of the CTSS transcript, thereby controlling CTSS mRNA stability and expression. In endothelial cells, ADAR1 overexpression or treatment of cells with hypoxia or with the inflammatory cytokines interferon-? and tumor-necrosis-factor-a induces CTSS RNA editing and consequently increases cathepsin S expression. ADAR1 levels and the extent of CTSS RNA editing are associated with changes in cathepsin S levels in patients with atherosclerotic vascular diseases, including subclinical atherosclerosis, coronary artery disease, aortic aneurysms and advanced carotid atherosclerotic disease. These results reveal a previously unrecognized role of RNA editing in gene expression in human atherosclerotic vascular diseases. Overall design: 1) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in poly(A) RNA-seq data derived from endothelial cell transcriptome after ADAR1 or ADAR2 knockdown (n=2 biological replicates per condition, total n=8 biological samples). 2) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total-RNA-seq data derived from peripheral blood mononuclear cells (n=12 total biological samples; n=4 replicates per condition). 3) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total-RNA-seq data derived from endothelial cell transcriptome under basal and hypoxic conditions (n=2 biological replicates per condition, total n=4 biological samples). 4) Evaluation of RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total RNA-seq data derived from endothelial cell transcriptome under basal and hypoxic conditions after ADAR1 knockdown (n=3 replicates per condition, total n=12 biological samples). 5) HuR iCLIP RNA-sequencing data derived from HUVEC HuR iCLIP after ADAR1 knockdown (scrambled control and siADAR1, n=1 per condition, total n=2 biological samples).	Co-expression
SRP045364	A hyper-dynamic nature of bivalent promoter states underlies coordinated developmental gene expression modules	Adipose stem cells (ASCs) and adipocytes play a crucial role in maintaining energy balance. We aim to examine the temporal relationship between gene expression and histone modification transitions during in vitro differentiation of human ASCs into adipocytes. Here, we examine by RNAseq proliferating ASCs (Day -2 prior to adipogenic induction), confluent ASCs (Day 0, adipogenic induction), pre-adipocytes (Day 3) and maturing adipocytes (Day 9). We find 1060, 5452 and 2216 genes differentially expressed between D-2/D0, D0/D3 and D3/D9 respectively. We identify gene clusters with distinct and dynamic expression patterns. In particular, adipogenic induction is marked by temporal waves of gene induction and downregulation. We report two types of transcriptional waves: (i) those showing transient induction or inactivation at D0, D3 or D9, and involved in sensory perception and immune response functions; and (ii) those showing long-lived induction or repression at these time points. Our data reveal a dynamic network of gene regulation during adipogenesis, involving signaling, immune and developmental processes. We identify 15 unique epigenetic states using Hidden Markov Modeling which reflects an epigenetically highly organised genome showing enhancer states are commonly consecutive. A heatmap for the abundance of epigenetic states for the expression clusters reveals a link between expression and epigenetic marking of the state suggesting an increase in the number of number of chromatin states with increase in expression. Our data point to a model of increased epigenetic complexity associated with gene expression. Overall design: Examination of expression of profiles of ASCs across differentiation	Co-expression
SRP045391	Enhancer Activation Requires Trans-Recruitment of a Mega Transcription Factor Complex (Gro-seq)	Enhancers provide critical information directing cell-type specific transcriptional programs, regulated by binding of signal-dependent transcription factors and their associated cofactors. Here we report that the most strongly activated estrogen (E2)-responsive enhancers are characterized by trans-recruitment and in situ assembly of a large 1-2MDa complex of diverse DNA-binding transcription factors by ERa at ERE-containing enhancers. We refer to enhancers recruiting these factors as mega transcription factor-bound in trans (MegaTrans) enhancers. The MegaTrans complex is a signature of the most potent functional enhancers and is required for activation of enhancer RNA transcription and recruitment of coactivators, including p300 and Med1. The MegaTrans complex functions, in part, by recruiting specific enzymatic machinery, exemplified by DNA-dependent protein kinase. Thus, MegaTrans-containing enhancers represent a cohort of functional enhancers that mediate a broad and important transcriptional program and provide a molecular explanation for transcription factor clustering and hotspots noted in the genome. Overall design: Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq)	Co-expression
SRP045406	Analysis of the interferon-induced changes in transcriptome of primary human hepatocytes at three time points by RNA-seq	This study aims to determine, in detail, the changes in gene expression that occur in response to interferon alpha stimulation in human primary hepatocytes. Using a transcriptome sequencing approach, the study aimed to identify novel transcripts that were induced in response to interferons and may play a role in innate immunity.	Co-expression
SRP045421	Comparison of total and cytoplasmic mRNA reveals global regulation by nuclear retention and miRNAs	We extracted RNA from whole cells and RNA from the cytoplasm and performed RNA sequening to compare differences in gene expression level and investigate what is the most appropriate estimate of the amount of mRNA present in a given cell population. The study was based on three human cell lines. Overall design: Analyze of transcriptome in 3 human cell lines (U-2 OS, A-431, U-251MG). Each cell line was prepared with four biological replicates for total RNA and four for cytoplasmic RNA.	Co-expression
SRP045425	Selective reactivation of human X-linked genes in female fibroblasts reprogrammed by cell fusion	In female mammals, one of the two X chromosomes is silenced as pluripotent cells differentiate. This process, termed X-inactivation, is random and results in mosaic expression of many X-linked genes in female tissues. Although X-inactivation can be reversed in vitro by reprogramming, the extent varies according to species, operator and conditions. Here, we have reprogrammed cloned female human fibroblasts by fusing them with mouse ESCs and examined the kinetics of X-linked gene re-expression. Allele-specific RNA sequencing analysis was used to determine the expression from the inactive X chromosome. This study revealed that a subset of loci within domains prone to escape X-inactivation, or that showed variable expression between somatic clones, were consistently reactivated upon pluripotent reprogramming. This suggests that stochastic events may be stabilised by reprogramming, and conversely, that variable expression is predictive for Xi genes susceptible to re-activation. Overall design: We performed RNA-sequencing of two human fibroblast clones derived from TERT-immortalised NHDF17914 (Lonza) and expressing reciprocal X chromosomes  (i.e. clone 12 and 34) before and at 0, 4 and 6 days  after fusion with mouse ESC (E14Tg2a:puroR). Two biological replicates were sequenced for each clone.	Co-expression
SRP045441	Pathway Profiling of Replicative and Induced Senescence	RNA-seq was performed on LFS MDAH041 cells that were young (PD10-12), aging (PD17-19) and replicatively senescent (PD28-30), as well as spontaneously immortal cells and cells that were induced into senescence or quiescence,  in order to profile the pathways common in all 4 types of sensecence and the pathways affected as a cell approaches senescence. Overall design: RNA was sequenced in biological triplicates of each sample using the Illumina HiSeq2000	Co-expression
SRP045481	Global Regulation of Alternative Internal Exon Usage by mRNA 3'' End Formation Factors [RNA-Seq]	RNA-seq analysis of samples from Non-silencing, RBFOX2 and CPSF2 knockdown cells Overall design: We analyzed 6 samples using the Illumina HiSeq 2000. Sequence data was processed by DexSeq. Two biological replicates were performed for Non-silencing, RBFOX2 and CPSF2 knockdown cells	Co-expression
SRP045500	Next generation sequencing of human immune cell subsets across diseases	This study compared whole transcriptome signatures of 6 immune cell subsets and whole blood from patients with an array of immune-associated diseases. Fresh blood samples were collected from healthy subjects and subjects diagnosed type 1 diabetes, amyotrophic lateral sclerosis, and sepsis, as well as multiple sclerosis patients before and 24 hours after the first treatment with IFN-beta. At the time of blood draw, an aliquot of whole blood was collected into a Tempus tube (Invitrogen), while the remainder of the primary fresh blood sample was processed to highly pure populations of neutrophils, monocytes, B cells, CD4 T cells, CD8 T cells, and natural killer cells. RNA was extracted from each of these cell subsets, as well as the whole blood samples, and processed into RNA sequencing (RNAseq) libraries (Illumina TruSeq). Sequencing libraries were analyzed on an Illumina HiScan, with a target read depth of ~20M reads. Reads were demultiplexed, mapped to human gene models (ENSEMBL), and tabulated using HTSeq. Read count data were normalized by the TMM procedure (edgeR package). Overall design: We performed whole genome RNAseq profiling of immune cell subsets and whole blood from subjects with an array of immune-associated diseases.	Co-expression
SRP045501	mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (sequencing)	MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%–>90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects. Overall design: 85 samples from a variety of cell types and species	Co-expression
SRP045569	Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum	Background:  A subset of patients with atopic dermatitis (AD) is prone to disseminated herpes simplex virus (HSV) infection, i.e. eczema herpeticum (ADEH+). Biomarkers that identify ADEH+ are lacking. Objective: To search for novel ADEH+ gene signatures in peripheral blood mononuclear cells (PBMCs). Methods: A RNA-sequencing (RNA-seq) approach was applied to evaluate global transcriptional changes using PBMCs from ADEH+ and AD without a history of EH (ADEH-). Candidate genes were confirmed by qPCR or ELISA. Results:  ADEH+ PBMCs had distinct changes to the transcriptome when compared to ADEH- PBMCs following HSV-1 stimulation: 792 genes were differentially expressed at a false discovery rate (FDR) < 0.05 (ANOVA), and 15 type I and type III interferon (IFN) genes were among the top 20 most down-regulated genes in ADEH+.  We further validated that IFN-a and IL-29 mRNA and protein levels were significantly decreased in HSV-1 stimulated PBMCs from ADEH+ compared to ADEH- and normal. Ingenuity pathway analysis (IPA) demonstrated that the up-stream regulators of type I and type III IFNs, IRF3 and IRF7 was significantly inhibited in ADEH+ based on the down-regulation of their target genes. Furthermore, we found that gene expression of IRF3 and IRF7 were significantly decreased in HSV-1 stimulated PBMC from ADEH+ subjects. Conclusions: PBMCs from ADEH+ have a distinct immune response following HSV-1 exposure compared to ADEH- .  Inhibition of the IRF3 and IRF7 innate immune pathways in ADEH+ may be the important mechanisms for increased susceptibility to disseminated viral infection. Overall design: Expression profiles of PBMCs were taken from 5 AD patients with a history of disseminated herpes simplex virus (HSV) infection, i.e. eczema herpeticum (ADEH+) and 6 AD patients who don’t have a history of disseminated HSV infection (ADEH-).  PBMC samples from each subject were divided in two and were treated with and without HSV-1 virus for 21 hours before processing for total RNA.	Co-expression
SRP045573	Loss of MBNL Leads to Disruption of Developmentally Regulated Alternative Polyadenylation in RNA-Mediated Disease	Mapping MBNL-regulated genome-wide alternative polyadenylation: We report that depletion of Mbnl proteins in mouse embryo fibroblasts (MEFs), DM mouse model quadriceps muscle, and DM-autopsy muscle tissue leads to mis-regulation of alternative polyadenylation Overall design: We compared WT, Mbnl1/2KO, Mbnl1/2KO/3siRNA, and Mbnl1/2KO/scrambled siRNA MEFs (n=2 for each group) to evaluate alternative polyadenylation shifts that occur due to progressive loss of Mbnl proteins. We also compared WT (1 day old, and 4 months old, n=2 each) and HSALR mouse model (4 months old, n=2) of myotonic dystrophy for developmental alternative polyadenylation defects in myotonic dystrophy. Finally, we compared control and DM1 autopsy muscle tissues (n=3) for changes in alternative polyadenylation. We performed HITS-CLIP analysis of binding sites of Mbnl1, Mbnl2 and Mbnl3 in MEFs (n=3 each). We also performed HITS-CLIP analysis for major skeletal muscle Mbnl protein, Mbnl1 in FVB WT adult muscle (4 months, n=3). Finally we performed HITS-CLIP analysis for CPSF6 in WT and Mbnl1/2 KO MEFs (n=3 each) Please note that the 'readme_Table.txt' describes the contents of 'Table S*.xlsx' files, and the readme_method.txt include additional details about experiemenal procedures.	Co-expression
SRP045592	Homo sapiens strain:MCF Cells Transcriptome or Gene expression	Examination of polyA+ long RNA population from MCF-7 and MCF-10 cells in cytoplasm, nucleus & total sample to study the changes in alternative splicing in breast cancer.	Co-expression
SRP045611	Profile of gene expression in U87-MG xenografts expressing control vector (V0), the ubiquitin ligase KPC1 or the p50 subunit of the NF-kB transcription factor, using RNASeq analysis of transcripts mapped independently to the human and murine genomes	Purpose: We identified KPC1 as the ubiquitin ligase that binds to the p105 precursor of NF-kB, ubiquitinates it and mediates its proteasomal processing to generate the p50 active subunit of the transcription factor. Using U87-MG human glioblastoma xenografts, we observed that overexpression of KPC1 results in strong inhibition of tumor growth mediated via excessive generation of p50.The goal of this RNASeq study was to analyze the profile of gene expression in xenografts overexpressing control (V0), KPC1 or p50 vectors, and to further understand how the altered gene expression patterns can explain the tumor suppressive effect we observed. Results:Transcript analysis of U87-MG xenografts overexpressing control (V0), KPC1 or p50 vector mapped  to the human genome  revealed: • A strong similarity between overexpression of p50 and KPC1 (correlation of 0.51, p-value<10-300 ) • A specific signature of NF-kB targets [21 of the consistently changed genes are known to be regulated by NF-kB (p-value<3.4×10-9 )] • A significant (p-value<1.4×10-18) increase in the expression of 40 tumor suppressor genes, with no significant change in other classes. • A significant down regulation of a cluster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB. Overall design: Exponentially growing U87-MG cells were stably transfected with an empty vector (V0) or vectors coding for Myc-KPC1 or Flag-p50. Cells were dissociated with trypsin, washed with PBS, and brought to a concentration of 50×10^6 cells/ml. Cell suspension (5×10^6/0.1 ml) was inoculated subcutaneously at the right flank of 7-weeks old male Balb/C nude mice (n=7). Following 21 days, mRNA from U87-MG xenografts was isolated using an RNA purification kit, and analyzed using the Illumina HiSeq 2500 sequencer. The RNASeq analysis experiment was repeated twice independently. Run1 included a total of 7 samples. Samples 1-3 were isolated from V0 – control tumors (3 different tumors), samples 4-5 were isolated from KPC1-expressing  tumors (2 different pools of 3 tumors each due to small tumor size), and samples 6-7 were isolated from p50-expressing tumors for (2 different pools of 2-3 tumors each, due to very small tumor size). Run2 included a total of 5 samples. Samples 8-10 were isolated from V0 (control) tumors (3 different tumors), samples 11-12 were isolated from KPC1 tumors (2 different pools of 3 tumors each due to small tumor size). Several repeated attempts to extract RNA from the p50-expressing tumors did not yield any results, as the tumors were miniscule.	Co-expression
SRP045624	VHL reintroduction in RCC4 cells	VHL inactivation is a major component of renal cancer. In this study we re-engineered RCC4 cells to re-express VHL and performed mRNA-sequencing on triplicates to analyse gene and transcript expression changes specific to VHL inactivation.	Co-expression
SRP045632	Rapid neurogenesis through transcriptional activation in human stem cell (RNA-Seq)	Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two murine Neurogenin transcription factors in human induced pluripotent stem cells, and obtained neurons with bipolar morphology in four days at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the transition from stem cell to neuron. These profiles were then analyzed to identify the regulatory networks underlying the differentiation of the neurons. Overall design: Paired end RNA sequencing of iPS cells (PGP1) at 0, 1, 3, and 4 days post- doxycycline induction of murine NGN1 and NGN2. This was done using an Illumina HiSeq, and reads were aligned to hg19	Co-expression
SRP045635	RNA-sequencing in HEK293T cells under the knockdown of Arkadia or ESRP2	We evaluated the role of Arkadia and ESRP2 in HEK293T cells Overall design: Expression of mRNA in HEK293T cells under the knockdown of Arkadia or ESRP2	Co-expression
SRP045638	LIBD Human DLPFC Development	RNAseq data of 36 samples across human brain development by age group from LIBD	Co-expression
SRP045639	Aneuploidy-induced cellular stresses limit autophagic degradation.	An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Determining how aneuploidy affects cells is thus critical to understanding tumorigenesis. Here we show that aneuploidy interferes with the degradation of autophagosomes within lysosomes. Mis-folded proteins that accumulate in aneuploid cells due to aneuploidy-induced proteomic changes overwhelm the lysosome with cargo, leading to the observed lysosomal degradation defects. Importantly, aneuploid cells respond to lysosomal saturation. They activate a lysosomal stress pathway that specifically increases the expression of genes needed for autophagy-mediated protein degradation. Our results reveal lysosomal saturation as a universal feature of the aneuploid state that must be overcome during tumorigenesis. Overall design: RPE-1 cells either untreated or treated with one of Reversine, Bafilomycin A1 or MG132, each condition was done in triplicate. D14-*_Control: untreated control D14-*_Rev: cells treated with 0.5uM Reversine for 24hrs and harvested 48hrs later D14-*_Baf: cells treated with 0.1uM BafA1 for 6hrs D14-*_Mg: cells treated with 1uM MG132 for 24 hrs	Co-expression
SRP045663	Integrator complex regulates NELF-mediated RNA Polymerase II pause/release and processivity at coding genes [RNA-seq]	RNAPII pausing/termination shortly after initiation is a hallmark of gene regulation. However, the molecular mechanisms involved are still to be uncovered. Here, we show that NELF interacts with Integrator complex subunits (INTScom) forming a stable complex with RNPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both HIV-1 promoter and genome wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated complex. Interestingly, in addition to controlling RNAPII pause release INTS11 catalytic subunit of the INTScom is required for the synthesis of full length mRNA. Finally, INTScom-target genes are enriched in HIV-1 TAR/ NELF-binding element and in a 3'box sequence required for snRNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pausing/release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle. Overall design: Genome-wide expression in HeLa cells in the absence of Integrator 11, or NELF or mock (control) depleted by strand-specific RNASeq (Illumina)	Co-expression
SRP045666	Dynamics of the human skeletal muscle transcriptome in response to exercise training - part 1	A total of 23 participants (data available in present submission and in GSE58608) completed three months of supervised aerobic exercise training of one leg. Skeletal muscle biopsies have been collected before and after the training period. We have investigated differences between trained and untrained leg and before and after training by studying the gene and isoform expression. Additional samples present in this study has been previously published (GEO accession number GSE58608). Overall design: Analysis of transcriptome in skeletal muscle biopsy samples in response to exercise training in 22 participants (of the total 23 participants). One biopsy is collected from each leg before and after training period.	Co-expression
SRP045673	An alternative pluripotent state confers interspecies chimaeric competency [RNA-Seq]	Here we show that by simple modulation of extrinsic signaling pathways, a new class of pluripotent stem cells, referred to as region selective epiblast stem cells (rsEpiSCs), could be efficiently derived from different stages of the early embryo. rsEpiSCs share features of primed pluripotency yet are distinct from EpiSCs in their molecular characteristics and ability to colonize post-implantation embryos. We performed RNA-sequencing experiments and examined the global gene expression profiles of EpiSCs, rsEpiSCs, in vivo isolated four regions of E6.5 mouse epiblasts: AP (anterior-proximal), AD (anterior-distal), PP (posterior-proximal) and PD (posterior-distal), human H1 ESCs, H1 rsESCs, H9 ESCs, H9 rsESCs, rhesus monkey ORMES23 rsESCs, and chimpanzee rsiPSCs. Overall design: Examination of global gene expression profiles in 2 pluripotent stem cell types across multiple species.	Co-expression
SRP045695	RNA-Seq to assess the transcriptional effects of G quadruplex stabilization by the G4 ligand PhenDC3 in HT-1080 cells	G-quadruplex motifs are frequently located near TSS and in the first introns of transcribed genes. We investigated the role that G4 structures play in transcription by stabilizing G4 DNA with the selective G4 ligand PhenDC3 in the HT-1080 human fibrosarcoma cell line. After treatment of triplicate samples with PhenDC3 or a negative control (DMSO carrier only), we performed RNA-Seq after poly-dT selection to assess changes in gene expression. Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidly in vitro, raising the possibility that they may sequester heme in vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound heme in vitro and alters transcription in cultured human cells, up-regulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. This identifies a new function for G-quadruplexes and a new mechanism for protection of cells from heme. Overall design: 6 samples total; 2 gene expression conditions (treated and untreated) in triplicate; 4 raw sequencing files per sample	Co-expression
SRP045711	Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state.	Understanding the molecular processes underlying intra-tumor heterogeneity is of critical importance to improve the efficiency of therapy and overcome drug resistance. In malignant melanoma, heterogeneity is though to arise -at least partly- through epigenetic rather than genetic reprogramming of proliferating cells, leading to the appearance within the primary tumors of a phenotypically distinct invasive cell subpopulation. The invasive melanoma cells are at the origin of metastatic spread and are thought to provide a reservoir of therapeutically resistant cells. To decipher the gene regulatory networks that underlie the proliferative and invasive cellular states we integrated publicly available gene expression and DNA methylation data from tumor biopsies with a newly generated compendium of open chromatin and histone modification profiling of melanoma cultures that are dominant in either of the two subpopulations. Extensive in silico analyses identified SOX10 and MITF, and AP-1 and TEADs as key upstream regulators of the proliferative and invasive transcriptomes, respectively. Knock-down experiments confirmed the implication of TEADs in the invasive gene network and, more importantly, established a causative link between activation of these transcription factors and melanoma cell invasion and sensitivity to MAPK inhibitors. Overall design: Investigation of the transcriptomes of 11 different melanoma cultures & Investigation of the effects of the Knock down of all 4 TEADs in an invasive melanoma culture (MM047).	Co-expression
SRP045785	RNA sequencing of polymorphous low-grade adenocarcinoma of the salivary gland	No description.	Co-expression
SRP045823	Dynamics of the human skeletal muscle transcriptome in response to exercise training - part 2	In the present study 23 participants completed three months of supervised aerobic exercise training of one leg (training period 1) followed by 9 months of rest before 12 of the participants completed a second exercise training period (training period 2) of three months of both legs. Skeletal muscle biopsies have been collected before and after the training periods. We have compared trained leg with untrained leg and studied gene and isoform expression. Additional samples included in this study has been previously submitted (GEO accession number GSE58387 and GSE60590). Overall design: Analyze of transcriptome in skeletal muscle biopsy samples in response to exercise training in 23 participants in total (in addition to data previously submitted GEO accession number GSE58387 and GSE60590). Biopsy is collected from skeletal muscle before and after training period.	Co-expression
SRP045859	Transcriptome of EBV-infected gastric cancer cell lines	To understand epigenic dysregulation of host and viral genes upon EBV infection in human gastric cancer, genome wide transcripts by RNAseq were undertaken for total RNAs of 3 EBVnGC, their isogenic cell lines converted by in vitro EBV-infection and 3 EBV-naturally infected GC cell lines. Overall design: Three independent gastric cancer (GC) cell lines (NUGC3, SNU-484, SNU-638) were experimentally infected with AKATA strain of EBV to derive EBV-infected isogenic GC cell lines (NUGC3EBV, SNU-484EBV, SNU-638EBV). Three indepedent GC cell lines with natural EBV-infection (SNU-719, NCC24, YCCEL1)) were also included in this study.	Co-expression
SRP045867	RNA-seq of young and quiescent MRC-5 human fibroblasts	Quiescent MRC-5 fibroblasts were compared to young fibroblasts Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 6 samples: 3 biological replicates for each age group: young and quiescent MRC-5 cells. 50bp, single-end reads, no strand-specific reads	Co-expression
SRP045869	pMPC EF vs control 3seq	Ewing sarcoma is a highly aggressive tumor characterized by a translocation between members of the FET family of RNA binding proteins and one of several ETS transcription factors, with the most common translocation being EWS-FLI1. EWS-FLI1 leads to changes in gene expression through mechanisms that are not completely understood. We performed RNA sequencing analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify novel target genes. This analysis identified lnc277 as a previously uncharacterized long non-coding RNA upregulated by EWS-FLI1 in pMPCs. Inhibiting the expression of lnc277 diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar whereas inhibiting lnc277 had no effect on other cell types tested. By analyzing gene expression after shRNA knockdown, we found that both EWS-FLI1 and lnc277 repressed many more genes that they induced and that a significant fraction of EWS-FLI1 repressed targets were also repressed by lnc277. Analysis of primary human Ewing sarcoma RNA sequencing data further supports a role for lnc277 in mediating gene repression. We identified hnRNPK as an RNA binding protein that interacts directly with lnc277. We found a significant overlap in the genes repressed by hnRNPK and those repressed by both EWS-FLI1 and lnc277, suggesting that hnRNPK participates in lnc277 mediated gene repression. Thus, lnc277 is a previously uncharacterized long non-coding RNA downstream of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes. Our studies identify a novel mechanism of oncogenesis downstream of a chromosomal translocation and underscore the importance of lncRNA-mediated gene repression as a mechanism of EWS-FLI1 transcriptional regulation. Overall design: RNA from primary human bone marrow derived mesenchymal cells either control or with inducible expression of  EWS-FLI1 for 13 days was used to prepare PolyA selected cDNA libraries.	Co-expression
SRP045870	hnRNPK knock down in Ewing cell line	Ewing sarcoma is a highly aggressive tumor characterized by a translocation between members of the FET family of RNA binding proteins and one of several ETS transcription factors, with the most common translocation being EWS-FLI1. EWS-FLI1 leads to changes in gene expression through mechanisms that are not completely understood. We performed RNA sequencing analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify novel target genes. This analysis identified lnc277 as a previously uncharacterized long non-coding RNA upregulated by EWS-FLI1 in pMPCs. Inhibiting the expression of lnc277 diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar whereas inhibiting lnc277 had no effect on other cell types tested. By analyzing gene expression after shRNA knockdown, we found that both EWS-FLI1 and lnc277 repressed many more genes that they induced and that a significant fraction of EWS-FLI1 repressed targets were also repressed by lnc277. Analysis of primary human Ewing sarcoma RNA sequencing data further supports a role for lnc277 in mediating gene repression. We identified hnRNPK as an RNA binding protein that interacts directly with lnc277. We found a significant overlap in the genes repressed by hnRNPK and those repressed by both EWS-FLI1 and lnc277, suggesting that hnRNPK participates in lnc277 mediated gene repression. Thus, lnc277 is a previously uncharacterized long non-coding RNA downstream of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes. Our studies identify a novel mechanism of oncogenesis downstream of a chromosomal translocation and underscore the importance of lncRNA-mediated gene repression as a mechanism of EWS-FLI1 transcriptional regulation. Overall design: A673 Ewing cells expressing an shRNA targeting hnRNPK or control were subjected to paired end RNA sequencing and compared to shGFP control.	Co-expression
SRP045876	Restoration of Progranulin Expression Rescues Cortical Neuron Generation in Induced Pluripotent Stem Cell Model of Frontotemporal Dementia	To understand how haploinsufficiency of progranulin (PGRN) protein causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSC) from patients carrying the GRNIVS1+5G>C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD and known to express PGRN. Although generation of neuroprogenitors was unaffected, their further differentiation into neurons, especially CTIP2-, FOXP2- or TBR1-TUJ1 double positive cortical neurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of PGRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNAseq analysis confirmed reversal of altered gene expression profile following genetic correction. Wnt signaling pathway, one of the top defective pathways in FTD-iPSC-derived neurons coupled with its reversal following genetic correction, makes it an important candidate. Therefore, we demonstrate for the first time that PGRN haploinsufficiency hampers corticogenesis in vitro. Overall design: We profiled 6 samples: two biological replicates for 3 conditions. Condition 1 consists of neuronal progeny derived from human Embryonic Stem Cells. Condition 2 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation. Condition 3 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation, genetically modified to correct the PGRN defect.	Co-expression
SRP045898	Potent antitumor activity of Cabozantinib, a c-MET and VEGFR2 Inhibitor, in a Colorectal Cancer Patient-derived Tumor Explant Model	Anti-angiogenic therapy is commonly used for the treatment of CRC. Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to anti-angiogenic therapy. MET is upregulated in response to VEGF pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study we set out to determine the efficacy of cabozantinib in a preclinical CRC PDTX model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. Overall design: CRC PDTX Model treated with cabozantinib	Co-expression
SRP045900	Next Generation Sequencing of Pattern II Demyelinating Brain Lesions from a Multiple Sclerosis Patient	Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Overall design: Examination of 3 different demyelinating lesions identified by Immunohistopathology.	Co-expression
SRP045905	EWS-Fli and LNC regulated genes in comparison to GFP samples	RNA from A673 cells with shRNA-mediated knockdown of GFP (4 libraries),  EWS-FLI1 (4 libraries), or lnc277 (7 libraries) was isolated with TRIzol (Invitrogen).  Each sample was DNase treated and further purified on an RNeasy  Mini column (Qiagen) before quality analysis on an Agilent 2100 Bioanalyzer.  For each sample, 100-150ng of RNA was synthesized into cDNA, sheared on  a Covaris ultrasonicator, and amplified using the NuGen Encore Complete kit  (NuGen) to produce strand-specific and rRNA-depleted libraries. Samples were  multiplexed (4/lane) for 2x100bp paired-end sequencing on an Illumina HiSeq  2000 Overall design: RNA from A673 cells with shRNA-mediated knockdown of GFP (4 libraries), EWS-FLI1 (4 libraries), or lnc277 (7 libraries) was isolated with TRIzol (Invitrogen).	Co-expression
SRP045983	Tracking distinct RNA populations using efficient and reversible covalent chemistry	We describe a chemical method to label and purify 4-thiouridine (s4U) -containing RNA. We demonstrate that methanethiolsulfonate (MTS) reagents form disulfide bonds with s4U more efficiently than the commonly used HPDP-biotin, leading to higher yields and less biased enrichment. This increase in efficiency allowed us to use s4U-labeling to study global microRNA (miRNA) turnover in proliferating cultured human cells without perturbing global miRNA levels or the miRNA processing machinery. This improved chemistry will enhance methods that depend on tracking different populations of RNA such as 4-thiouridine-tagging to study tissue-specific transcription and dynamic transcriptome analysis (DTA) to study RNA turnover. Overall design: s4U metabolic labeling of RNA in 293T cells, followed by biochemical enrichment of labeled RNA with two biotinylation reagents, RNAs >200nt and miRNAs in separate experiments	Co-expression
SRP045985	POU2AF1 Functions in the Human Airway Epithelium to Regulate Expression of Host Defense Genes [RNA-Seq]	In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU2AF1, a known transcription co-factor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of up-regulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation and analysis of differentiating single basal cell clones. Lentivirus-mediated up-regulation of POU2AF1 in airway basal cells induced up-regulation of host defense genes, including MX1, IFIT3, IFITM and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a "host defense tone" even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of lentivirus mediated POU2AF1 or RFP (control) gene expression in human primary airway epithelial cells (3 samples per group). Uninfected basal cell was used as a further control. Conclusions: The genes up-regulated by POU2AF1 in human airway epithelial cells are mainly related to the intracellular or extracellular anti-pathogen response, suggesting POU2AF1 plays a role in airway epithelial host defense. Overall design: By genome-wide-based screening, POU2AF1, a known lymphocyte transcription co-factor, was found to be expressed in human airway epithelium and regulate host defense genes. It might be a drug target as smoking-compromised host defense is associated with down-regulation of POU2AF1. In this Series, human airway epithelial cell transcriptomes (3 uninfected without treatment, 3 infected with lenti-RFP virus and 3 infected with lenti-POU2AF1 virus) were compared using massive parallel RNA sequencing (Illumina HiSeq 2000).	Co-expression
SRP045986	Homo sapiens strain:THP1 Transcriptome or Gene expression	Coxiella and Leishmania both inhabit the lysozome. Not much is currently known about the differences in host response to these microbial pathogens inhabiting the same niche. Understanding differences in host response may elucidate new treatments to these difficult to treat pathogens.	Co-expression
SRP045999	Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics (RNA-Seq)	Comparative studies in primates are extremely restricted because we only have access to a few types of cell lines from non-human apes and to a limited collection of frozen tissues. In order to gain better insight into regulatory processes that underlie variation in complex phenotypes, we must have access to faithful model systems for a wide range of tissues and cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee (Pan troglodytes) induced pluripotent stem cell (iPSC) lines derived from fibroblasts of healthy donors. All lines are free of integration from exogenous reprogramming vectors, can be maintained using standard iPSC culture techniques, and have proliferative and differentiation potential similar to human and mouse lines. To begin demonstrating the utility of comparative iPSC panels, we collected RNA-seq data and methylation profiles from the chimpanzee iPSCs and their corresponding fibroblast precursors, as well as from 7 human iPSCs and their precursors, which were of multiple cell type and population origins. Overall, we observed much less regulatory variation within species in the iPSCs than in the somatic precursors, indicating that the reprogramming process has erased many of the differences observed between somatic cells of different origins. We identified 4,918 differentially expressed genes and 1,986 differentially methylated regions between iPSCs of the two species, many of which are novel inter-species differences and not observed between the somatic cells of the two species. Our panel will help realize the potential of iPSCs, and in combination with genomic technologies, transform studies of comparative evolution in primates. Overall design: We obtained RNA sequencing and methylation profiles from 7 chimpanzee iPSCs and the fibroblasts used to generate them, as well as 7 human iPSCs and the LCLs and fibroblasts used to generate them.	Co-expression
SRP046066	Use of chimpanzee RNA as a spike-in standard for human transcriptome analysis	We devised a novel normalization approach employing chimpanzee RNA as a spike-in standard in NGS-based human gene expression analysis. In this approach, human transcripts were normalized read-by-read by spiked-in chimpanzee transcripts that were readily discriminated by natural single nucleotide variations (SNVs) between the two species. The SNV-normalized analysis enabled more accurate measurement of differential gene expression than an ordinary read-based approach.	Co-expression
SRP046226	Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus	We report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors.  RNA-seq analysis identified sets of genes associated with asthma specific viral responses.  These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3).   We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets.  Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation. Overall design: Differentiated air-liquid interface cultured human airway epithelial cell mRNA profiles from 6 asthmatic and 6 non-asthmatic donors after 24 hour treatment with either HRV or vehicle control were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP046233	Specific molecular signatures underlie response to decitabine in CMML [RNA-seq]	Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. Overall design: mRNA profiling in bone marrow mononuclear cells (BM MNC) from 14 CMML patients (8 decitabine responders vs. 6 non-responders).	Co-expression
SRP046254	Analysis of the senescent transcriptome upon expression of a ZFP36L1 phosphomutant	We expressed either a wt or a phosphomutant version of ZFP36L1 in IMR90 ER:RAS cells. 7 days upon RAS induction (when the cells reach a fully senescent phenotype) we collected the RNA. ZFP36L1 is a RNA binding protein that binds to AU-rich elements in the 3’UTR of mRNAs and triggers their degradation. Our previous experiments showed that the activity of ZFP36L1 was key in the regulation of the senescent phenotype.By performing RNAseq we have uncovered the effect of expressing a constitutively active mutant of ZFP36L1 within the senescent transcriptome. Overall design: 4 samples examined: Non-senescent cells (EV - 4OHT), Senescent cells (EV + 4OHT), Senescent cells expressing ZFP36L1wt and Senescent cells expressing ZFP36L1mut	Co-expression
SRP046271	Transcriptome wide identification of retained introns upon depletion of the splicing factors SNW1 or PRPF8	We identified which mRNAs are dependent on the splicing factors SNW1 or PRPF8. These factors were depleted in HeLa cells by RNAi, and the levels of intronic reads in mRNAs was compared to control RNAi. Overall design: Intronic reads from polyA containing RNAs from HeLa cells and mSnw1-LAP ''rescued'' cells, both depleted for endogenous SNW1, were compared. Furthermore, intronic reads from polyA containing RNAs from HeLa cells depleted for SNW1 or PRPF8 were compared to control depleted HeLa cells.	Co-expression
SRP046376	Analysis Of The TGFb-Induced Program In Primary Airway Epithelial Cells Shows Essential Role Of NF-kB/RelA Signaling Network In Type II Epithelial Mesenchymal Transition	The airway epithelial cell plays a central role in coordinating pulmonary response to injury and inflammation.  Here, transforming growth factor-b (TGFb) activates gene expression programs to induce stem cell-like properties, inhibit expression of differentiated epithelial adhesion proteins and express mesenchymal contractile proteins.  This process is known as epithelial mesenchymal transition (EMT); although much is known about the role of EMT in cellular metastasis in an oncogene-transformed cell, less is known about Type II EMT, that occurring in normal epithelial cells.  In this study, we applied next generation sequencing (RNA-seq) in primary human airway epithelial cells to understand the gene program controlling Type II EMT and how cytokine-induced inflammation modifies it. Generalized linear modeling was performed on a two-factor RNA-seq experiment of 6 treatments of telomerase immortalized human small airway epithelial cells (3 replicates).  Using a stringent cut-off, we identified 3,478 differentially expressed genes (DEGs) in response to EMT.  Unbiased transcription factor enrichment analysis identified three clusters of EMT regulators, one including SMADs/TP63 and another NF-kB/RelA.  Surprisingly, we also observed 527 of the EMT DEGs were also regulated by the TNF-NF-kB/RelA pathway.  This Type II EMT program was compared to Type III EMT in TGFb stimulated A549 alveolar lung cancer cells, revealing significant functional differences. Moreover, we observe that Type II EMT modifies the outcome of the TNF program, reducing IFN signaling and enhancing integrin signaling.  We confirmed experimentally that TGFb-induced the NF-kB/RelA pathway by observing a 2-fold change in NF-kB/RelA nuclear translocation.  A small molecule IKK inhibitor blocked TGFb-induced core transcription factor (SNAIL1, ZEB1 and Twist1) and mesenchymal gene (FN1 and VIM) expression.  These data indicate that NF-kB/RelA controls a SMAD-independent gene network whose regulation is required for initiation of Type II EMT.  Type II EMT dramatically affects the induction and kinetics of TNF-dependent gene networks. Overall design: A human small airway epithelial cell line was treated with TGF-Beta to induce the epithelial to mesenchymal transition. TGF-Beta treated and untreated cells were further treated with TNF-alpha for 1 and 12 hours. Three replicates for each treatment and untreated controls were performed for a total of 18 samples.	Co-expression
SRP046741	SMYD2 specificly regulate BIX-01294 induced TP53 target genes revealed by RNA-Seq	We characterized expression profilings of SMYD2 knockdown and control cells treated by BIX-01294 and Rapamycin. Overall design: We used siRNAs to knockdown SMYD2 in HCT116 cells, and NC as control. We treated those cell lines with BIX-01294 and Rapamycin, and the expression profilings were perfomed by Illumina high throughput sequencing.	Co-expression
SRP047065	Ribosome profiling upon inhibition of eIF4A	Ribosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency Overall design: Translation efficiency (TE) of mRNAs dervied from ribosome footprints was monitored in the presence or absence of 25 nM Silvestrol, an inhibitor of eukaryotic translation initiation factor 4A (eIF4A).  Transcripts with reduced TE in the presence of Silvestrol were compare to transcripts with reduced TE in the presence of INK128, a catalytic mTOR inhbitor.	Co-expression
SRP047082	Genetic Correction and Metabolic Rescue of Pluripotent Cells from Patients with mtDNA	Mitochondria are vital due to their principal role in energy production via oxidative phosphorylation (OXPHOS)1. Mitochondria carry their own genome (mtDNA) encoding  critical genes involved in OXPHOS, therefore, mtDNA mutations cause fatal or severely debilitating disorders with limited treatment options. 2. Clinical manifestations of mtDNA disease vary based on mutation type and heteroplasmy levels i.e. presence of mutant and normal mtDNA within each cell. 3,4. We evaluated therapeutic concepts of generating genetically corrected pluripotent stem cells for patients with mtDNA mutations. We initially generated multiple iPS cell lines from a patient with mitochondrial encephalomyopathy and stroke-like episodes (MELAS) caused by a heteroplasmic 3243A>G mutation and a patient with Leigh disease carrying a homoplasmic 8993T>G mutation (Leigh-iPS). Due to spontaneous mtDNA segregation in proliferating fibroblasts, isogenic MELAS iPS cell lines were recovered containing exclusively wild type (wt) mtDNA with normal metabolic function. As expected, all iPS cells from the patient with Leigh disease were affected. Using somatic cell nuclear transfer (SCNT; Leigh-NT1), we then simultaneously replaced mutated mtDNA and generated pluripotent stem cells from the Leigh patient fibroblasts. In addition to reversing to a normal 8993G>T, oocyte derived donor mtDNA (human haplotype D4a) in Leigh-NT1 differed from the original haplotype (F1a) at a additional 47 nucleotide sites. Leigh-NT1 cells displayed normal metabolic function compared to impaired oxygen consumption and ATP production in Leigh-iPS cells or parental fibroblasts (Leigh-fib). We conclude that natural segregation of heteroplasmic mtDNA allows the generation of iPS cells with exclusively wild type mtDNA. Moreover, SCNT offers mitochondrial gene replacement strategy for patients with homoplasmic mtDNA disease. Overall design: Duplicate cDNA libraries of fibroblasts from a Leigh patient and a MELAS patient, two sendai produced iPSC lines from the Leigh patient and three sendai produced iPSC lines from the MELAS patient, three fibroblasts lines produced by differentiating three iPS Leigh patient iPSC lines to fibroblasts, two somatic cell nuclear transfer produced NT-ESC lines from the Leigh patient, two fibroblast lines produced by differentiating two Leigh patient NT-ESC lines, four fibroblasts lines produced by differentiating four MELAS patient iPSC lines with the mutation to fibroblasts, four fibroblast lines produced by differentiating two IVF-ESC lines without mutated mtDNA genomes, four fibroblast lines produced by differentiating two somatic cell nuclear transfer NT-ESC lines without mutated mtDNA genomes, and four fibroblasts lines produced by differentiating two MELAS patient iPSC lines without the mutation to fibroblasts. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.	Co-expression
SRP047122	Upregulation of inflammation-related genes in the blood of Huntington’s patients	Blood is a very accessible tissue and as such constitutes a useful source of clinical markers. While it is obvious that metabolic disorders leave a clear mark in blood, it is not so clear whether this is the case for neurodegenerative diseases of the brain. Markers for neurodegenerative diseases are potentially useful to advance our understanding of the mechanisms involved in these diseases but are nearly impossible to obtain from living patients. To find whether altered gene expression could be found in blood of patients with a neurodegenerative disease, we collected blood samples from patients of Huntington’s disease (HD) and analysed their differences versus controls in terms of gene expression by RNA-seq analysis. We observed significant differential expression of a set of genes, with genes upregulated in patients enriched in immune response related functions and inflammatory response. We conclude that it is possible to detect changes in the expression of RNAs in blood from patients of HD and that this reflects the inflammatory pathology associated to the disease. Overall design: RNA-seq profiles of blood taken from normal controls and Huntington''s disease patients Please note that the ''readme'' spreadsheet in the ''HTT.fpkm_v2.xls'' contains data processing and column header details.	Co-expression
SRP047126	Transcriptomic profiling of bone marrow cells from healthy individuals	We performed whole-genome transcriptomic profiling of RNA from mononuclear cells from bone marrow aspirates taken from healthy individuals. This study complements GSE58335: transcriptomic profiling of peripheral blood mononuclear cells from healthy individuals. Overall design: High-throughput sequencing was done using the Illumina GA IIx. The RNA is from previously published samples (Stirewalt et al., Genes Chromosomes Cancer, 2008, PMID:17910043)	Co-expression
SRP047192	Quantitative profiling of long noncoding RNAs with targeted RNA sequencing.	We compared the performance of conventional RNAseq with RNA Capture Sequencing (CaptureSeq) to assemble and quantify known RNA spike-Ins and human transcripts. We find CaptureSeq to be superior for the detection and quantification of the 37% lowest expressed genes, and comparable for the next 45% of moderately expressed genes. CaptureSeq contributes only minor technical variation and measures differential gene expression accurately. We demonstrate these advantages by the targeted sequencing of long noncoding RNAs across 20 human tissues, expanding previous annotations two-fold and simultaneously generating a quantitative atlas of expression. This analysis confirms the use of CaptureSeq as an important method for transcriptional profiling. Overall design: Long noncoding RNA assembly and expression is analysed by targeted RNA sequencing for 20 human tissues and 4 human cell lines	Co-expression
SRP047194	FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders	Autism spectrum disorder (ASD) is a disorder of brain development believed, in most cases, to be of genetic origin. We use induced pluripotent stem cells (iPSCs)-derived 3-dimensional neural cultures (organoids) in patients with ASD and macrocephaly to investigate neurodevelopmental alterations that cause this form of ASD. By using transcriptome analyses, we identified modules of co-expressed genes significantly upregulated in ASD patients compared to non-ASD first-degree family members. Overall design: Total RNA was prepared from terminal differentiation day 0, 11 and 31 of iPSCs-derived neural cultures from ASD patients and non-ASD first-degree family members. A total of 4 patients and 8 controls (unaffected family members) were analyzed in replicates (two to three iPSC clones per person).	Co-expression
SRP047232	RNA-sequencing study of peripheral blood monocytes for chronic periodontitis	We confirmed immune response as the key mechanism and provided solid evidence for novel genes (e.g., FCAR and CUX1) and distinct biological processes (e.g., endocytosis, cytokine production and apoptosis) as potentially new important factors/mechanisms contributing to chronic periodontitis pathogenesis. Overall design: We performed an RNA-sequencing (RNA-seq) study of peripheral blood monocytes (PBMs) in 5 non-smoking moderate to severe CP (case) subjects vs. 5 controls. We replicated the DEx transcripts/isoforms using an independent microarray dataset. We also pathway-based analysis on the identified/replicated DEx transcripts/isoforms using DAVID performed (Database for Annotation, Visualization and Integrated Discovery).	Co-expression
SRP047233	CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors [RNA-Seq]	Truncating mutations of CHD8, encoding a chromodomain helicase, and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA-seq) with genome-wide CHD8 binding (ChIP-seq). Suppressing CHD8 to levels comparable with loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated.  CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8 binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (p = 1.01x10-9) and CHD8-bound genes (p = 4.34x10-3), which align with previously identified co-expression modules during fetal development. We also find an intriguing enrichment of cancer related gene-sets among CHD8-bound genes (p < 1.9x10-11). In vivo suppression of chd8 in zebrafish produced macrocephaly comparable to that of humans with inactivating mutations. These data indicate that heterozygous disruption of CHD8 precipitates a network of gene expression changes involved in neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis. Overall design: RNA-seq in NPCs treated with shRNAs targeting CHD8. For controls, NPCs were treated with shRNAs targeting GFP and LacZ. Infection and sequencing was carried out in two separate batches, with one GFP and one LacZ sample in each batch. All samples were sequenced in two technical replicates.	Co-expression
SRP047251	AXL mediates resistance to PI3Ka inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas.	Phosphoinositide-3-kinase (PI3K)-a inhibitors are clinically active in squamous carcinoma (SCC) of the head and neck (H&N) bearing mutations or amplification of PIK3CA. We aimed to identify potential mechanism of resistance and have observed that SCCs cells overcome the antitumor effects of the PI3Ka inhibitor BYL719 by maintaining PI3K-independent activation of the mammalian target of rapamycin (mTOR).  The persistent mTOR activation is mediated by the tyrosine kinase receptor AXL.  We found that AXL is overexpressed in resistant tumors, dimerizes with the epidermal growth factor receptor (EGFR), phosphorylates EGFR tyrosine 1173, resulting in activation of phospholipase C? (PLC?)- protein kinase C (PKC) that, in turn, activates mTOR. Finally, simultaneous treatment with PI3Ka and either EGFR, AXL or PKC inhibitors reverts this resistance. Overall design: RNAseq from acquired resistant cells CAL33B, K180B were compared to their parental counterpart CAL33 and K180, respectively. K180 is a shortcut of KYSE180, and B stands for BYL719.  Duplicate of parental sensitive cells and K180B, and triplicate for CAL33B.	Co-expression
SRP047252	Strand-specific Dual RNA-seq of Bronchial Epithelial cells Infected with Influenza A/H3N2 Viruses Reveals Splicing of Gene Segment 6 and Novel Host-Virus Interactions	Host-influenza virus interplay at the transcript level has been extensively characterized in epithelial cells. Yet, there are no studies that simultaneously characterize human host and influenza A virus (IAV) genomes. We infected human bronchial epithelial BEAS-2B cells with two seasonal IAV/H3N2 strains, Brisbane/10/07 and Perth/16/09 (reference strains for past vaccine seasons) and the well-characterized laboratory strain Udorn/307/72. Strand-specific RNA-seq of the infected BEAS-2B cells allowed for simultaneous analysis of host and viral transcriptomes, in addition to pathogen genomes, to reveal changes in mRNA expression and alternative splicing (AS). In general, patterns of global and immune gene expression induced by the three IAVs were mostly shared. However, AS of host transcripts and small nuclear RNAs differed between the seasonal and laboratory strains. Analysis of viral transcriptomes showed deletions of the polymerase components (defective interfering (DI)-like RNAs) within the genome. Surprisingly, we found that the neuraminidase gene undergoes AS, and that the splicing event differs between seasonal and laboratory strains. Our findings reveal novel elements of the host-virus interaction and highlight the importance of RNA-seq in identifying molecular changes at the genome level that may contribute to shaping RNA-based innate immunity. Overall design: Examination of RNA from three different H3N2 viruses (and mock infection) at three timepoints with 3 biological replicates each.	Co-expression
SRP047271	TNFa and INCA-6 effect on HRMEC transcriptome	Diabetes is one of the leading causes of blindness in the western world. TNFa is a known regulator of diabetic retinopathy pathology. This study was performed to determine the effect of TNFa on retinal microvascular endothelial cells and whether NFAT signaling has a role in mediating this effect.	Co-expression
SRP047299	Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma	Increased MITF expression contributes to melanoma progression and resistance to BRAF pathway inhibition. We show that, unexpectedly, lack of MITF is associated with more severe resistance to a range of inhibitors. Indeed, the presence of endogenous MITF was essential for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlated with expression of several activated receptor tyrosine kinases, most commonly AXL. The MITF-low/AXL-high/drug resistance phenotype was seen in roughly half of BRAF mutant and the majority of NRAS mutant melanoma cell lines. The dichotomous behavior of MITF in drug response was corroborated in vemurafenib-resistant biopsies, including MITF high and low clones in a relapsed patient. Drug cocktails containing AXL inhibitor enhanced melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas. Overall design: Experssion analysis by RNAseq of 14 melanoma cell lines.	Co-expression
SRP047307	Homo sapiens Transcriptome or Gene expression	RNA-Seq study from Caco2 cells following transduction with control shRNA and shRNA against CHD6	Co-expression
SRP047323	Isolation and Transcriptome Analyses of Human Erythroid Progenitors: BFU-E and CFU-E	Burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) cells are erythroid progenitors traditionally defined by colony assays. We developed a flow cytometry-based strategy for isolating human BFU-E and CFU-E cells based on the changes in expression of cell surface markers during in vitro erythroid cell culture. BFU-E and CFU-E are characterized by CD45+GPA-IL-3R-CD34+CD36-CD71low and CD45+GPA-IL-3R-CD34-CD36+CD71high phenotypes, respectively. Colony assays validated phenotypic assignment giving rise to BFU-E and CFU-E colonies, both at a purity ~90%. The BFU-E colony forming ability of CD45+GPA-IL-3R-CD34+CD36-CD71low cells required SCF and erythropoietin, while the CFU-E colony forming ability of CD45+GPA-IL-3R-CD34-CD36+CD71high cells required only erythropoietin. Bioinformatic analysis of the RNA-seq data revealed unique transcriptomes in each differentiation stage. The sorting strategy was validated in uncultured primary cells isolated from bone marrow and peripheral blood, indicating that marker expression is not an artifact of in vitro cell culture, but represents an in vivo characteristic of erythroid progenitor populations. The ability to isolate highly pure human BFU-E and CFU-E progenitors will enable detailed cellular and molecular characterization of these distinct progenitor populations and define their contribution to disordered erythropoiesis in inherited and acquired hematological disease. Our data provide important resource for future studies. Overall design: Transcription profiles of Human erythroid progenitors at distinct developmental stages were generated by deep sequencing, in triplicate, using IlluminaHiSeq 2000. The complete dataset comprises 4 sample types: CD34, BFU, CFU, and Pro (reanalysis of GSM1304777-GSM1304779).	Co-expression
SRP047358	Homo sapiens Transcriptome or Gene expression	Whole transcriptome study on lung cancer	Co-expression
SRP047363	Comparison of human PRDM12 mutants D31Y and E172D with wildtype fibroblasts	Fibroblasts from PRDM12 patients and unaffected wildtype relatives were cultured until near confluency. The transcriptional profile of those cells was determined by mRNA sequencing and uncovered differential expression in several known pain and neurodevelopmental genes. Overall design: Transcriptome comparison of human PRDM12 mutant and wildtype fibroblasts	Co-expression
SRP047395	Whole transcriptome sequencing of transient HEK 293T transfectants of human APOBEC 3A, 3G or 2 cDNAs	To examine the effect of APOBEC 3A, 3G or 2 on gene expression, human HEK 293T cells were transiently transfected for two days with empty (vector alone) plasmids or mammalian expression plasmids bearing ORFs of the genes. Cells were transfected in triplicates. RNA was extracted and analyzed using the Illumina HiSeq 2000 platform and TruSeq Stranded Total RNA with Ribo-Zero sequencing library preparation method	Co-expression
SRP047399	Homo sapiens Transcriptome or Gene expression	Whole transcriptome sequencing of lung cancer specimens	Co-expression
SRP047407	Coding mutations and loss-of-imprinting in human pluripotent cells derived by nuclear transfer and defined factors [RNA-Seq]	Human pluripotent stem cells can be derived from somatic cells by forced expression of defined factors, and more recently by nuclear-transfer into human oocytes, revitalizing a debate on whether one reprogramming approach might be advantageous over the other. Here we compared the genetic and epigenetic stability of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal and adult origin. Both cell types shared similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs have comparable numbers of de novo coding mutations but significantly higher than parthenogenetic ESCs. Similar to iPSCs NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes, similarly to iPSCs. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of the underlying technique. Overall design: RNA sequencing analysis was performed on a total of 12 human cell lines, including: an isogenic set of 3 nuclear-transfer embryonic stem cell (NT-ESC) lines, 2 RNA-reprogrammed induced pluripotent stem cell (iPSC) lines and their parental neonatal fibroblast cell line; an isogenic set of 1 NT-ESC line, 3 iPSC lines and their parental adult fibroblast cell line (derived from a type 1 diabetic subject); as well as 1 control embryonic stem cell (ESC) line.	Co-expression
SRP047429	Small RNA sequencing of formalin-fixed and paraffin-embedded lung adenocarcinoma tissue	The suitability of small RNA sequencing on the Illumina® HiSeq™ platform for quantification of small RNAs in formalin-fixed and paraffin embedded tissue was assessed in this project.	Co-expression
SRP047459	NOTCH1 activation in breast cancer confers sensitivity to inhibition of SUMOylation	Breast cancer is genetically heterogeneous, and recent studies have underlined a prominent contribution of epigenetics to the   development of this disease. To uncover new synthetic lethalities with known breast cancer oncogenes, we screened an  epigenome-focused short hairpin RNA library on a panel of engineered breast epithelial cell lines. Here we report a selective  interaction between the NOTCH1 signaling pathway and the SUMOylation cascade. Knockdown of the E2-conjugating enzyme  UBC9 (UBE2I) as well as inhibition of the E1-activating complex SAE1/UBA2 using ginkgolic acid impairs the growth of NOTCH1-activated breast epithelial cells. We show that upon inhibition of SUMOylation NOTCH1-activated cells proceed slower through the  cell cycle and ultimately enter apoptosis. Mechanistically, activation of NOTCH1 signaling depletes the pool of unconjugated small  ubiquitin-like modifier 1 (SUMO1) and SUMO2/3 leading to increased sensitivity to perturbation of the SUMOylation cascade.  Depletion of unconjugated SUMO correlates with sensitivity to inhibition of SUMOylation also in patient-derived breast cancer cell  lines with constitutive NOTCH pathway activation. Our investigation suggests that SUMOylation cascade inhibitors should be  further explored as targeted treatment for NOTCH-driven breast cancer. Overall design: We treated MCF10A and NOTCH1 cells with either DMSO or ginkgolic acid 30 uM for 3 days. Two replicates have been analysed for each condition.	Co-expression
SRP047476	Impact of regulatory variation from RNA to protein	Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation. Overall design: We measured level of translation transcriptome-wide in lymphoblastoid cell lines derived from 72 HapMap Yoruba individuals using ribosome profiling assay, for which we have transcript level, protein level (62 out of 72) and genotype information collected.	Co-expression
SRP048484	Lung cancer RNASeq transcriptome	RNA sequencing of lung adenocarcinoma, lung squamous carcinoma and lung large cell cancer samples	Co-expression
SRP048556	Human fetal pancreas transcriptome analysis	To characterize the transcriptional programs that underlie pancreas differentiation and identity, we have generated genome-scale expression profiles by RNA-seq from human embryonic stem cell derived liver progenitors and human fetal pancreatic tissue (days 54-57 post conception).  These samples were compared to those already published transcriptomes (Xie et al., 2013).  Together, these samples were used to perform principles compotent analysis.  Once this was performed, we were able to identify transcription factors that were important in the identity of each cell type. Overall design: To generate genome-scale expression profiles by RNA-seq from human embryonic stem cell derived liver progenitors and human fetal pancreatic tissue (days 54-57 post conception), total RNA was isolated from human embryonic stem cell derived liver progenitors and frozen human fetal pancreas.  Libraries were sequenced and mapped to the hg19 version of the human genome.  Gene expression was determined using Sailfish. These samples were compared to those already published transcriptomes (Xie et al., 2013).  Together, these samples were used to perform principles compotent analysis.	Co-expression
SRP048557	hESC-derived liver transcriptome analysis	To characterize the transcriptional programs that underlie pancreas differentiation and identity, we have generated genome-scale expression profiles by RNA-seq from human embryonic stem cell derived liver progenitors and human fetal pancreatic tissue (days 54-57 post conception).  These samples were compared to those already published transcriptomes (Xie et al., 2013).  Together, these samples were used to perform principles compotent analysis.  Once this was performed, we were able to identify transcription factors that were important in the identity of each cell type. Overall design: To generate genome-scale expression profiles by RNA-seq from human embryonic stem cell derived liver progenitors, total RNA was isolated from human embryonic stem cell derived liver progenitors.  Libraries were sequenced and mapped to the hg19 version of the human genome.   Gene expression was determined using Sailfish. These samples were compared to those already published transcriptomes (Xie et al., 2013).  Together, these samples were used to perform principles compotent analysis.	Co-expression
SRP048562	Genome-wide chromatin analysis of Ewing sarcoma (RNA-seq)	We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. Overall design: Ewing sarcoma cell lines (A673 and SKNMC) were analyzed by RNA-seq. EWS-FLI1 was depleted by infection with lentiviral shRNAs (shFLI1 and shGFP control).	Co-expression
SRP048565	Host transcriptome analysis of Aspergillus fumigatus infection in Airway Epithelial Cells	The goal of this study is to determine the transcriptional response of primary normal human bronchial epithelial (NHBE) cells following interaction with A. fumigatus conidia at 2, 6, and 12 hours in order to examine the infection of airway epithelial cells at multiple time points of co-incubation. After total RNA isolation, the Illumina® HiSeq 2000 next generation sequencing system was used to characterize the transcriptional response, in untreated and A. fumigatus exposed cells. Overall design: 12 samples were analyzed for this study. Triplicates of each sample were pooled together to form a sample. 2 samples generated in this fashion was used for each time point and condition. Since we have 2 samples, 2 conditions (control vs. infected with A. fumigatus), and 3 time points (2, 6, and 12 hrs), this produces our 12 samples.	Co-expression
SRP048577	BRG1 recruitment by transcription factors MITF and SOX10 defines a specific configuration of regulatory elements in the melanocyte lineage (RNA-seq)	Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. Overall design: 19 samples corresponding to mRNA profiles of 501Mel and Hermes3A after MITF, BRG1 or control shRNA-mediated knockdown were generated by deep sequencing in triplicate (in duplicate for 501_shMITF and corresponding control 501_shSCR2), using HiSeq2500.	Co-expression
SRP048603	RNA-sequencing of the GSI treatment of the CUTLL1 cell line	Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Overall design: CUTLL1 cell lines were treated with Compound E (GSI) or DMSO (solvent control). Cells were collected 12 h and 48 h after treatment. This was performed for 3 replicates. RNA-sequencing was performed on these samples.	Co-expression
SRP048604	RNA-sequencing of CD34+ thymocytes that were cultured on an OP9-GFP or OP9-DLL1 feeder layer.	Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Overall design: CD34+ cells of 2 healthy donors are cultured on a OP9-GFP or OP9-DLL1 feeder layer.	Co-expression
SRP048605	Human induced pluripotent stem cells Transcriptome or Gene expression	We show that ERR? overexpression in ß-like-cells differentiated from human iPSCs enhances genes involved in mitochondrial metabolism, resulting in transformation of these cells into metabolically functional ß-cells that can ameliorate STZ-induced hyperglycemia in NOD-SCID mice. These results suggest that ERR? signaling is essential for the metabolic maturation of ß-like-cells and thus represents a novel therapeutic target in the treatment of diabetes.	Co-expression
SRP048640	EZH2 inhibitor efficacy in non-Hodgkin lymphoma does not require suppression of H3K27 mono-methylation [RNA-Seq]	Here we report the discovery of highly potent and selective EZH2 small molecule inhibitors, their validation by a cellular thermal shift assay, their application across a large lymphoma cell panel and their efficacy in GCBDLBCL xenograft models. Overall design: RNA-seq of KARPAS-422 cell line RNA, in duplicate, treated with DMSO as control, and EZH2 inhibitors CPI360, EPZ-6438 and GSK126. Eight samples in total.	Co-expression
SRP048647	Global study of APA events in human gastric cancer cells	To characterize the genome-wide APA sites in human gastric cancer cells and explore the functional implication of APA modulation in tumorgenesis.	Co-expression
SRP048664	Mutation independent activation of the Notch pathway is associated with Lapatinib resistance in Her2+ breast cancer cell lines	We compared untreated HCC1419 cells with Lapatinib resistant HCC1419 cells that were either treated with Lapatinib for only 9 days before harvesting (drug tolerant persisters, DTPs) or were growing in the presence of Lapatinib (>70 days) (drug tolerant expanded persisters, DTEPs). We show that the Notch pathway is significantly over-expressed in DTEPs when compared to untreated cells. Overall design: RNA-Seq of HCC1419 cells either untreated, treated with 1µM Lapatinib for 9 days or treated with 1µM Lapatinib for greater than 70 days	Co-expression
SRP048669	RNA-Seq Samples of siTFE3 in 8988T PDA Cell Line to Investigate Transcriptional Control of the Autophagy-Lysosome System	The activation of cellular quality control pathways to maintain metabolic homeostasis and mitigate diverse cellular stresses is emerging as a critical growth and survival mechanism in many cancers. Autophagy, a highly conserved cellular self-degradative process, is a key player in the initiation and maintenance of pancreatic ductal adenocarcinoma (PDA). However, the regulatory circuits that activate autophagy, and how they enable reprogramming of PDA cell metabolism are unknown. We now show that autophagy regulation in PDA occurs as part of a broader program that coordinates activation of lysosome biogenesis, function and nutrient scavenging, through constitutive activation of the MiT/TFE family of bHLH transcription factors. In PDA cells, the MiT/TFE proteins - MITF, TFE3 and TFEB - override a regulatory mechanism that controls their nuclear translocation, resulting in their constitutive activation. By orchestrating the expression of a coherent network of genes that induce high levels of lysosomal catabolic function, the MiT/TFE factors are required for proliferation and tumorigenicity of PDA cells. Importantly, unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular AA pools in PDA.  This AA flux is part of a program that is essential for metabolic homeostasis and bioenergetics of PDA but not for their non-transformed counterparts. These results identify the MiT/TFE transcription factors as master regulators of the autophagy-lysosomal system in PDA and demonstrate a central role of the autophagosome-lysosome compartment in maintaining tumor cell metabolism through alternative amino acid acquisition and utilization. Overall design: Examination of mRNA levels in pancreatic ductal adenocarcinoma (PDA) cell line 8988T after treatment with siRNA for control or TFE3	Co-expression
SRP048674	Human ovarian granulosa cell transcriptome	We used mRNA-seq to profile transcriptomes of purified human ovarian granulosa cells Overall design: 12 female individuals	Co-expression
SRP048685	WI-38 histone variant H2AJ function	No description.	Co-expression
SRP048700	Charaterization of genetic alterations and gene expression signatures found in erlotinib-resistant and erlotinib/crizotinib dual-resistant HCC827 subpopulations	The non-small cell lung cancer (NSCLC) cell line HCC827 harbors an activating EGFR mutation (exon 19 deletion) that confers sensitivity to the FDA-approved EGFR inhibitor erlotinib. By applying the ClonTracer barcoding system, we were able to show the presence of pre-existing sub-populations in HCC827 that contribute to erlotinib resistance. Prior studies implicated that MET amplification confers resistance to erlotinib in this cell line. Therefore we examined the effects of the c-Met inhibitor crizotinib on the barcoded HCC827 population when treated either sequentially or simultaneously with both inhibitors. Despite the significant reduction in barcode complexity, the erlotinib/crizotinib combination treatment failed to eradicate all of the resistant clones implying the presence of an erlotinib/crizotinib dual resistant subpopulation. We performed transcriptome profiling (RNA-seq) to elucidate the potential resistance mechanisms of the dual resistant subpopulation in comparison to vehicle-treated or single agent erlotinib-resistant HCC827 cell populations as controls. Overall design: mRNA profiling of the subpopulations of human NSCLC cell line HCC827 that contribute to EGFR inhibitor erlotinib and MET inhibitor crizotinib resistance	Co-expression
SRP048701	Charaterization of genetic alterations and gene expression signatures found in BCR-ABL inhibitor-resistant KCL-22 subpopulations and single clones	KCL-22 is a chronic myeloid leukemia (CML) cell line derived from a patient in blast crisis phase and harbors the BCR-ABL translocation. The catalytic (ATP-competitive) BCR-ABL inhibitors imatinib and nilotinib have dramatically improved CML patient outcome, but the development of resistance remains a clinical challenge. The recent identification of allosteric BCR-ABL inhibitors, such as GNF-2, which target the enzyme by binding to the myristoyl pocket rather than catalytic site of ABL1, may provide a strategy to broadly overcome resistance to the class of ABL1 ATP competitive inhibitors. We therefore wanted to use the ClonTracer barcoding system to compare the clonal responses of KCL-22 to imatinib, nilotinib and GNF-2. RNA-seq was employed to characterize genetic alterations and gene expression signatures in the pooled cell populations resistant to BCR-ABL inhibitors as well as single clones showing differential response to the three inhibitors. Overall design: mRNA profiling of the subpopulations and single clones of human CML cell line KCL-22 that contribute to BCR-ABL inhibitor resistance	Co-expression
SRP048735	Homo sapiens Transcriptome or Gene expression	To study the transcriptomic changes in progression of cervical pre-cancer (from normal cells to LGSIL to HGSIL) from co-existing tissues in a single FFPE block	Co-expression
SRP048759	Leucegene: AML sequencing (part 3)	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.	Co-expression
SRP048801	Ileal immune maturation in Pediatric Crohn''s Disease	We report the global pattern of ileal gene expression in a cohort of 310 treatment-naïve pediatric Crohn Disease patients and controls.  We focus on genes with consistent altered expression in the ileum of younger (Paris age A1a) vs older (Paris age A1b) patients. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents aged less than 17 years, who presented with IBD-like symptoms.  All patients underwent baseline colonoscopy and histological characterization; non-IBD controls were those with suspected IBD, but with normal radiographic, endoscopic, and histologic findings.  Biopsies were stored at -80 degrees.	Co-expression
SRP048804	Identifying genes regulated by Kruppel-like factor-9 by RNA-seq in human glioblastoma stem cells.	Kruppel-like factor-9 (KLF9), a member of the large KLF transcription factor family, has emerged as a regulator of oncogenesis, cell differentiation and neural development; however, the molecular basis for KLF9’s diverse contextual functions remains unclear. This study focuses on the functions of KLF9 in human glioblastoma stem-like cells. We establish for the first time a genome-wide map of KLF9-regulated targets in human glioblastoma stem-like cells, and show that KLF9 functions as a transcriptional repressor and thereby regulates multiple signaling pathways involved in oncogenesis and stem cell regulation. A detailed analysis of one such pathway, integrin signaling, shows that the capacity of KLF9 to inhibit glioblastoma cell stemness and tumorigenicity requires ITGA6 repression. These findings enhance our understanding of the transcriptional networks underlying cancer cell stemness and differentiation, and identify KLF9-regulated molecular targets applicable to cancer therapeutics. Overall design: Two cell lines were used as biological replicates. Each cell line has one KLF9 induction sample and one control sample.	Co-expression
SRP048811	Interphase condensins regulate ligand-depedent enhancer activation (GRO-seq)	An emerging theme of gene regulation is the involvement of architectural chromosomal molecules in transcription control. Condensins are critical regulators of mitotic chromosomes, but their interphase chromatin localization and functions remain poorly understood. Here we report that both the condensin I and condensin II complexes exhibit an unexpected, dramatic 17-?-estradiol-induced preferential recruitment to oestrogen receptor ? (ER-?)-bound active enhancers in interphase breast cancer cells, exhibiting non-canonical interaction with ER-? distinct from classic cofactors. Condensins prove to positively regulate ligand-dependent gene and eRNA transcription by modulating a binding equilibrium of enhancer-associated coactivators/corepressors, including p300 and RIP140. This activity was achieved by the condensin-dependent recruitment of an E3 ubiquitin ligase, HECTD1, to active enhancers, where it polyubiquitinates and dismisses corepressor RIP140 to stimulate eRNA transcription. Collectively, our results reveal an important, unanticipated transcriptional role of interphase condensins in modulating enhancer activation, providing new insights into enhancer function in the regulated transcriptional programs Overall design: The GRO-seq measures the trancription of nascent RNAs in the genome. From MCF7 cells treated with veichle or estrodial, we could identify estrogen-regulated eRNAs and subsequently could study their functions.	Co-expression
SRP048820	Enhancer Sequence Variants and Transcription Factor Deregulation Synergize to Construct Pathogenic Regulatory Circuits in B Cell Lymphoma (RNA-Seq)	Most B cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC-B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions transcriptional circuits from normal GC-B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression is deregulated in FL, target commandeered versus decommissioned REs. Our approach reveals two distinct subtypes of low-grade FL, whose pathogenic circuitries resemble GC-B or activated B cells. Remarkably, FL-altered enhancers also are enriched for sequence variants, including somatic mutations, which disrupt transcription factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC-B transformation. Overall design: Expression profiles of follicular lymphoma, centrocyte and peripheral blood B cells were generated by deep sequencing, using Illumina Hi-Seq 2000.	Co-expression
SRP048842	Genome-wide profiling of DNA methylation at single-base resolution based on MeDIP-bisulfite high-throughput sequencing and ridge regression (RNA)	Unraveling complexity of DNA methylome is essential to decipher DNA methylation mechanism in life. However, this has been subjected to technological constraints to balance between cost and accurate measurement of the DNA methylation level. In this study, by innovatively introducing C-hydroxylmethylated adapters, we have developed MeDIP-Bisulfite sequencing (MB-seq), which could obtain DNA methylome of repertoire CpGs at single-base resolution. We found MB-seq only costs 10% of MethylC-seq, but covers 85% of total CpGs in human genome. Unlike absolute methylation levels determined by MethylC-seq and RRBS, MB-seq presented relative methylation levels that are linearly inflated. This has enlightened us to develop a MB-seq corresponding correction method for methylation level based on ridge regression, which integrates the data of MB-seq and RRBS to predict the methylation level of total 28.2 million CpGs on human genome with high accuracy (Pearson correlation coefficient, PCC=0.90). Moreover, by employing MB-seq, we generated the DNA methylome of an ovarian epithelial cell line (T29) and its oncogenic counterpart (T29H), respectively. After ridge regression, we identified 131,790 differential methylation regions (DMRs) with high accuracy between T29 and T29H, far more than 7,567 obtained from RRBS. Taken together, our result demonstrated that the MB-seq combined with ridge regression is a wide applicable approach for profiling of DNA methylome. Overall design: Total RNAs were extracted from T29 and T29H with RNeasy Mini Kit (QIAGEN, Germany). RNA quality was quality-controlled by Bioanalyser 2100 (RNA nano kits, Agilent). mRNA-Seq libraries were generated from total RNA with polyA+ selection of mRNA using the TruSeq RNA Sample Prep Kit v2 (Illumina, San Diego, CA), and then subjected to transcriptome sequencing on the Illumina Hiseq 2000	Co-expression
SRP048858	Homo sapiens Transcriptome or Gene expression	To identify transcripts that are aberrantly spliced in the CD34+ CMML cells with SRSF2(P95) mutation.	Co-expression
SRP048889	A Novel Population of Human Cardiac Resident Mesenchymal Stem Cells	We describe a novel population of human adult cardiac resident stem cells (CRSCs), which are positive for W8B2 antigen, originating from human adult atrial appendages. W8B2+ CRSCs exhibit a spindle-shaped morphology, are clonogenic and able to self-renew. W8B2+ CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2+ CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1 or Wilm’s tumor gene-1 (WT1). W8B2+ CRSCs can differentiate into the cardiovascular lineages and secrete various cytokines. Overall design: Comparative RNA sequencing was performed using W8B2+ cell from human atrial appendages (passage 2 from 3 different patients), c-Kit+ cell from human atrial appendages (passage 2 from 3 different patients) and W8B2+ cell from bone marrow (passage 3 from 2 different patients, from PromoCell, Heidelberg, Germany).	Co-expression
SRP048957	K-562 Transcriptome or Gene expression	Whole transcriptome sequencing of K-562 cells expressing WT or mutant species of ETV6.	Co-expression
SRP048971	Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell type specificity	Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with risk of autoimmune and immune-related disorders (AID), our understanding of the diseases mechanisms is limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). LncRNAs are known to show more cell-type specificity than protein-coding genes. Methods: In this study, we aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AID which have been well-defined by Immunochip analysis, by transcriptome analysis across seven peripheral blood leukocyte populations (granulocytes, monocytes, NK cells, B-cells, memory-T cells, naive CD4+ and naive CD8+ T-cells) and four cord blood derived T-helper cell populations (precursor, primary, polarized (Th1, Th2) T-helper cells). Results: We show that lncRNAs mapping to loci shared between AIDs are significantly enriched in immune cell types when compared to lncRNAs from the whole genome (a<0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five cell types enriched (a<0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis; memory-T and CD8+ T-cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis). Furthermore we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. Conclusions: The observed enrichment of lncRNA transcripts in AID loci implies an important role for lncRNAs in AID etiology and suggests that lncRNA genes should be studied in more detail to correctly interpret GWAS findings. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways. Overall design: 7 immune cell types	Co-expression
SRP048993	Homo sapiens Transcriptome or Gene expression	Stem cell differentiation timecourse, six time points through induction from induced pluripotency (day0) towards beating cardiomyocytes, mature at day14. Accompanying study investigates careful differentiation protocols.	Co-expression
SRP049004	Enhanced MyoD-Induced Transdifferentiation to a Myogenic Lineage by Fusion to a Potent Transactivation Domain	Synthetic transcription factors can be applied to many areas of biotechnology, medicine, and basic research.  Currently, the most common method for engineering synthetic transcription factors has been based on programmable DNA-binding domains of zinc finger proteins, Transcription Activator-Like Effectors (TALEs), and most recently the CRISPR/Cas9 system. These transcription factor platforms consist of the DNA-binding domain fused to potent transcriptional activation domains, most commonly the tetramer of the minimal transactivation domain of the VP16 protein from herpes simplex virus, referred to as VP64. Although many applications are well-suited for the targeted activation of a single gene, genetic reprogramming requires the coordinated regulation of many nodes of natural gene networks as is typically performed by naturally occurring reprogramming factors. Thus we sought to combine principles from each of these approaches by attaching potent transcriptional activation domains to a natural reprogramming factor to increase the efficiency and/or rate of cell fate conversion. In this study, we evaluated the effects of fusing potent activation domains to the transcription factor MyoD, the master regulator of the skeletal myoblast lineage. In certain non-myogenic lineages, MyoD overexpression causes upregulation of the myogenic gene network and conversion to a myoblast phenotype including cell fusion into multinucleated myotubes. Compared to wild-type MyoD, the VP64-MyoD fusion protein induced greater overall reprogramming of global gene expression. This simple approach for increasing the potency of natural reprogramming factors circumvents the need for screening engineered proteins and leads to a more robust cellular reprogramming compared to treatment with the wild type transcription factor. Overall design: Human dermal fibroblasts were transduced with a single tet inducible lentivirus that expresses either WT-MyoD or VP64-MyoD in response to treatment with doxycycline. Untreated human dermal fibroblast served as the negative control. Gene expression was measured using mRNA-seq, and differential expression was calculated using DESeq. All experiments were performed in biological duplicates.	Co-expression
SRP049021	T-bet recruits P-TEFb to super-enhancers to regulate T helper cell differentiation (RNA-Seq)	The transcription factor T-bet induces differentiation of CD4+ T cells into the Th1 lineage and also allows for a degree of functional plasticity. Here, we show that T-bet acts through super-enhancers to recruit the elongation factor P-TEFb. Th1-specific genes are poised for activation in Th2 cells and P-TEFb recruitment activates transcriptional elongation. T-bet also induces extensive P-TEFb binding at super-enhancers, where it acts to stimulate enhancer RNA transcription. P-TEFb inhibition selectively blocks activation of lineage-specific genes and reverses Th1-associated retinitis pathology. T-bet-mediated recruitment of P-TEFb to super-enhancers at otherwise poised genes provides a model for how lineage-specifying factors promote differentiation towards specific cell fates whilst maintaining a degree of functional plasticity. Overall design: Strand-specific total and poly-A+ RNA-Seq in Th1 and Th2 cells from two independent donors	Co-expression
SRP049028	Human serotonergic neurons	Generating human serotonergic neurons from fibroblasts	Co-expression
SRP049061	IL-33 activates tumor stroma to promote intestinal polyposis	Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by non-epithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin (IL)-33 as an epithelial cell-derived regulator of stromal cell activation and mediator of intestinal polyposis. IL-33 expression was elevated in the tumors and serum of colorectal cancer patients and induced in the adenomatous polyps of ApcMin/+ mutant mice. Genetic and antibody suppression of IL-33 signaling in ApcMin/+ mice inhibited proliferation, induced apoptosis, and suppressed angiogenesis in polyps, which reduced both tumor number and size. In ApcMin/+ polyps, IL-33 expression localized to tumor epithelial cells and expression of the IL-33 receptor, IL1RL1, associated with two stromal cell types, namely subepithelial myofibroblasts (SEMFs) and mast cells, whose activation was previously associated with polyposis. In vitro IL-33 stimulation of human SEMFs induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and expression of mast cell-derived proteases and cytokines known to promote polyposis. Together, our results suggest that IL-33 is a tumor epithelial cell-derived paracrine signal that promotes polyposis through the coordinated activation of stromal cells and the formation of a reactive stroma microenvironment. Overall design: Six T-75 flasks of CCD-18Co cells were grown to 80% confluency; three were treated with rhIL-33, three were given vehicle control; cells were trypsinized and split in two--half of each flask used for sequencing and half for qPCR validation post-sequencing	Co-expression
SRP049063	RNA-sequencing of mRNAs from control and CAP-D3 deficient Salmonella infected HT-29 cells	BACKGROUND & AIMS- More frequent interaction of bacteria with the colonic epithelium is associated with ulcerative colitis (UC).  The identities of all proteins which promote bacterial clearance in colonic epithelial cells are unknown.  Previously, we discovered that dCAP-D3 (Chromosome Associated Protein-D3), regulates responses to bacterial infection.  We examined whether CAP-D3 promotes bacterial clearance in human colonic epithelium. METHODS- Clearance of Salmonella or adherent-invasive Escherichia coli LF82 was assessed by gentamycin protection assays in HT-29 and Caco-2 cells expressing CAP-D3 shRNA.  CAP-D3 levels in colonic epithelial cells from healthy and UC patient tissues were analyzed by immunoblot.  RNA-sequencing identified bacterially-induced CAP-D3 target genes.  The role of CAP-D3 target genes in bacterial clearance was analyzed by gentamycin protection assays, immunofluorescent staining, and by using pharmacologic inhibitors. RESULTS- CAP-D3 expression was reduced in colonic epithelial cells from UC patients with active disease. Reduction of CAP-D3 expression inhibited autophagy and decreased intracellular bacterial clearance.  The components of the heterodimeric SLC7A5/SLC3A2 amino acid transporter were identified as CAP-D3 target genes; their levels increased in infected, CAP-D3 deficient cell lines and in cells from UC patients.  In HT-29 cells, this resulted in earlier SLC7A5 recruitment to Salmonella-containing vacuoles, increased mTOR activity, and enhanced bacterial survival.  Inhibition of SLC7A5/SLC3A2 or mTOR activity rescued the bacterial clearance defect in CAP-D3 deficient cells. CONCLUSIONS- CAP-D3 attenuates amino acid transporter transcription to promote bacterial autophagy in colon epithelial cells.  CAP-D3 protein levels are decreased in patients with active UC, suggesting that CAP-D3 is a potential therapeutic target to restore mucosal homeostasis in UC patients. Overall design: Three RNA samples from 3 independent experiments including timepoints taken at 0, 0.5 and 7 hours post-infection were analyzed on a bioanalyzer for quality; one of the 0.5 hour post-infection samples was excluded at this time due to poor RNA purity.  Directional, cDNA libraries made from cellular mRNAs were generated from the other 8 samples and sequenced (paired-end sequencing of 100 bp reads) in the Genomics Core at the University of Chicago on an Illumina HiSeq2000.	Co-expression
SRP049068	Gene expression profiling of melanoma cell lines by high throughput sequencing	A panel of 29 melanoma cell lines were gene expression profiled by RNA-Seq. Overall design: mRNA profiles of 29 melanoma cell lines	Co-expression
SRP049090	SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy	Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq Overall design: In total 12 samples were analyzed, divided into four distinct groups (treated with SMN-C3 @ 500 nM; controls for SMN-C3; treated with SMN-C1 @ 100 nM; controls for SMN-C1) containing 3 replicates each.	Co-expression
SRP049097	Profiling of three leiomyosarcoma molecular subtypes with RNA-sequencing	Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation, and there are three molecular subtypes of LMS which have been defined previously by our lab. To further validate these subtypes and identify potential therapeutic targets in each subtype, we profiled the LMS cases from each subtype with RNA-Seq technology. Overall design: 8 LMS cases from subtype I, 6 cases from subtype II, 3 cases from subtype III and 7 cases of normal tissues, were selected for RNA-Seq. Then the expression levels and potential mutations were analyzed on these cases.	Co-expression
SRP049171	Nuclear TIGAR mediates an epigenetic-metabolic loop via Nrf2 for cancer therapeutics resistance	Epigenetic and metabolic reprogrammings are implicated in cancer progression with unclear mechanisms. We report here that the histone methyltransferase NSD2 drives cancer cell and tumor resistance to therapeutics such as tamoxifen, doxorubicin, and radiation by reprogramming of glucose metabolism. NSD2 coordinately up-regulates expression of TIGAR, HK2 and G6PD and stimulates pentose phosphate pathway (PPP) production of NADPH for ROS reduction. We discover that elevated expression of TIGAR, previously characterized as a fructose-2,6-bisphosphatase, is localized in the nuclei of resistant tumor cells where it stimulates NSD2 expression and global H3K36me2 mark. Mechanistically, TIGAR interacts with the antioxidant regulator Nrf2 and facilitates chromatin assembly of Nrf2-H3K4me3 methylase MLL1 and elongating Pol-II, independent of its metabolic enzymatic activity. In human tumors, high levels of NSD2 correlate strongly with early recurrence and poor survival and are associated with nuclear-localized TIGAR. This study defines a nuclear TIGAR-mediated, epigenetic autoregulatory loop functioning in redox rebalance for resistance to tumor therapeutics. Overall design: A total of 4 samples were analyzed in this study.  The study included two cell lines, MCF7 and the tamoxifen-resistant subline TMR. Both were were cultured in medium containing vehicle control and/or 4-hydroxytamoxifen (Tam). The untreated MCF7 and TMR cell lines served as controls for the study.	Co-expression
SRP049203	RNA-Seq Analysis in purified iPS cell-derived neuronal samples	We characterized the gene expression differences in mDA neurons from all PD (Parkinson''s disease) cases (6 independent samples) and controls (8 independent samples), identifying 1,028 differentially expressed genes making up the PD expression signature. Strikingly, MAOB gene was identified as significantly differentially expressed (p = 0.046). The heat map clearly differentiates cases from controls, where interestingly most differentially expressed genes had lower expression in PD cases compared to controls. In the clustering, the RNA expression pattern of the control (C2) with a family history of PD located close to the PD expression signature suggested a susceptibility to PD. Overall design: RNA was isolated from FAC-sorted cells of 14 samples (biological duplicates for each cell line, 7 cell lines in total) using RNeasy Micro Kit (QIAGEN). Quality control of the RNA was carried out with the Agilent Bio-analyzer, Qubit 2.0 at the MPSR of Columbia University. 100 ng of RNA with RIN = 9 were used for generating mRNA-focused libraries using TruSeq RNA Sample Preparation Kit v2 and sequencing on an Illumina 2000/2500 V3 Instrument offered by the Columbia Genome Center.	Co-expression
SRP049237	MiR-CLIP capture of a miRNA targetome uncovers a lincRNA H19-miR-106a interaction [III]	Identifying the interaction partners of non-coding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA-cross-linking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-cross-linking and Argonaute 2-immunopurification followed by streptavidin affinity-purification of probe-linked RNAs provided selectivity in the capture of targets, identified by deep-sequencing. MiR-CLIP with pre-miR-106a, a miR-17-5p family member, identified hundreds of putative targets in HeLa cells, many carrying conserved sequences complementary to the miRNA seed but also many that were not predicted computationally. MiR-106a overexpression experiments confirmed that miR-CLIP captured functional targets, including H19, a long-non-coding RNA that is expressed during skeletal muscle cell differentiation. We showed that miR-17-5p family members bind H19 in HeLa cells and myoblasts. During myoblast differentiation levels of H19, miR-17-5p family members and mRNA targets changed in a manner suggesting that H19 acts as a sponge for these miRNAs. Overall design: Two replicates of three cDNA libraries were submitted to deep sequencing: a sample from RNA-7-transfected cells; a sample from pre-miR-106a transfected cells; and a control sample.	Co-expression
SRP049264	FOXP1 orchestration of ASD-relevant signaling pathways.	Mutations in the gene encoding the transcription factor forkhead box P1 or FOXP1 occur in patients with neurodevelopmental disorders, including autism. However, the function of FOXP1 in the brain remains mostly unknown. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and mouse brain and demonstrate a conserved role for FOXP1 transcriptional regulation of autism and Fragile X Mental Retardation Protein (FMRP) mediated pathways. Coexpression networks support a role for Foxp1 in neuronal activity, and we show that Foxp1 is necessary for neuronal excitability. Using a Foxp1 mouse model, we observe defects in ultrasonic vocalizations. This behavioral phenotype is reflected at the genomic level as striatal Foxp1-regulated overlap with genes known to be important in rodent vocalizations. These data support an integral role for FOXP1 in regulating signaling pathways vulnerable in developmental disorders and the specific regulation of pathways important for vocal communication. Overall design: We carried out RNA-sequencing (RNA-seq) and ChIP-sequencing of human neural progenitors cells. We carried out RNA-sequencing (RNA-seq) of mouse striatal tissue, mouse hippocampal tissue and mouse cortical tissue. For the RNA-seq, four indipendent replicates were used for the neural progenitor cells and mouse tissues. For the Chip-seq, a single neural progenitor cell line was used.	Co-expression
SRP049333	Identifying Glioblastoma Gene Networks Based on Hypergeometric Test Analysis	Patient specific therapy is emerging as an important possibility for many cancer patients.  However, to identify such therapies it is essential to determine the genomic and transcriptional alterations present in one tumor relative to control samples. This presents a challenge since use of a single sample precludes many standard statistical analysis techniques.  We reasoned that one means of addressing this issue is by comparing transcriptional changes in one tumor with those observed in a large cohort of patients analyzed by The Cancer Genome Atlas (TCGA).  To test this directly, we devised a bioinformatics pipeline to identify differentially expressed genes in tumors resected from patients suffering from the most common malignant adult brain tumor, glioblastoma (GBM).  We performed RNA sequencing on tumors from individual GBM patients and filtered the results through the TCGA database in order to identify possible gene networks that are overrepresented in GBM samples relative to controls.  Importantly, we demonstrate that hypergeometric-based analysis of gene pairs identifies gene networks that validate experimentally.  These studies identify a putative workflow for uncovering differentially expressed patient specific genes and gene networks for GBM and other cancers. Overall design: RNAseq on 2 gliosblastoma samples and 2 epileptic samples	Co-expression
SRP049340	Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [mRNA-Seq]	Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: mRNA sequencing of primary and secondary fibroblasts with reference BJ (supplementary file fibroblasts), reprogramming intermendiates from untreated hiF-T reprogramming (supplementary file reprogramming), or selective time points upon LSD1 inhibitor treatment (supplementary file LSD1i). RNA samples used for mRNA sequencing are the same used for smallRNA sequencing.	Co-expression
SRP049376	Transcriptome profiling of Normal and Cancerous Prostate Cells [RNA-Seq]	To identify differentially expressed transcripts (both annotated and unannotated) in Cancer and Normal Prostate cells global transcript abundance was assayed by RNA-Sequencing. Overall design: RNA profiles of LNCaP and PrEC cell lines were generated by deep sequencing. Libraries were generated by Illumina TruSeq kits with PolyA+ selection (without maintaining strand information). The resultant cDNA libraries were sequenced at the Next Generation Genome Sequencing Facility (University of Western Sydney, Hawkesbury, NSW, Australia) using the Illumina HiSeq 1500 platform.	Co-expression
SRP049377	RNA-Seq data for five HER2 over-expressed samples with twelve green fluorescent protein control samples using human mammary epithelial cells	Purpose: The goal was to capture the transcriptional activity due to over-expression of HER2 protein. We profiled this transcriptional activity using two different RNA-Seq alignment and quantification pipelines. We also used these samples to generate a gene expression signature of HER2 pathway activity. Over-expression was validated using Western blots. Illumina RNA-Seq technology was used to capture the downstream transcriptional activity. Reads were 101 base pairs long and single ended. An R open source package “Rsubread” was used to align and quantify the read using UCSC hg19 annotation. The integer-based gene counts were later normalized in FPKM and TPM . Overall design: A profile of gene expression, downstream of ERBB2/HER2 over-expression, was generated in cells derived from breast and used to generate a gene-expression signature reflective of HER2 pathway activation status.	Co-expression
SRP049391	Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of miRNA-mRNA Target Pairs in KSHV-Infected Cells [mRNA-Seq]	This SuperSeries is composed of the SubSeries listed below. Purpose: Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) causes several lymphoproliferative disorders, including KS, a common AIDS-associated malignancy. Cellular and viral microRNAs (miRNAs) have been shown to play important roles in regulating the expression of genes in oncogenesis. Herpesviruses, including KSHV, encode for miRNAs that are involved in angiogenesis, inflammation and apoptosis. A better knowledge of the miRNA-mediated pathways that regulate KSHV infection is therefore essential for an improved understanding of viral infection and pathogenesis. Methods: In this study, we used deep sequencing to analyze miRNA, both viral and human, and mRNA expression in KS tumor-derived human cells. Results: This approach revealed 153 differentially expressed human miRNAs between KSHV-positive and -negative cells. Differential expression of eight miRNAs was independently confirmed by qRT-PCR. We additionally showed that a majority (~73%) of KSHV-regulated miRNAs are down-regulated, including most members of the 14q32 miRNA cluster. Specifically, human miR-409-3p, which is known to target the pro-angiogenic growth factor angiogenin and the inflammation marker fibrinogen-beta, was significantly down-regulated in KSHV-infected cells based on deep sequencing and qRT-PCR. Despite this substantial down-regulation of cellular miRNAs, hsa-miR-708-5p was significantly up-regulated by KSHV and has been shown to directly inhibit pro-apoptotic protease Caspase-2. Finally, we evaluated to what extent there was an inverse correlation between miRNA and mRNA expression levels. Using filtered datasets, we identified relevant canonical pathways that were significantly enriched. Conclusion: Taken together, our data demonstrate that most human miRNAs affected by KSHV are repressed and our findings highlight the relevance of studying the post-transcriptional gene regulation of miRNAs for KSHV-associated malignancies. Overall design: Refer to individual Series. 6 samples analyzed (one cell type). Two experimental conditions: uninfected vs. chronically KSHV-infected cells (n=3). Two sequencing platforms: microRNA-Seq and mRNA-Seq.	Co-expression
SRP049408	LncRNAs specific signature in acute myeloid leukemia with intermediate risk	The aim of this study was to investigate the role of lncRNAs in acute myeloid leukemia with normal cytogenetics (NC-AML). To this end, we used RNA-sequencing approach on forty NC-AML to evaluate the lncRNAs expression profile. Overall design: lncRNAs expression profile of 40 AML patients were generated by RNAsequencing using Illumina HiSeq 2000	Co-expression
SRP049409	PER2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells	Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Overall design: Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina	Co-expression
SRP049426	Homo sapiens Transcriptome or Gene expression	RNA seq experiment	Co-expression
SRP049436	Genome-wide expression profile of the Tet-On HCT116 inducible cell line that express either the human HNF4a2 or HNF4a8 under control of Doxycycline (DOX) [RNAseq]	Purpose: Aim of the study is to identify functional differences between the P1 and P2-HNF4a isoforms. To do this, we generated Tet-On inducible lines that express either the human (P1) HNF4a2 or (P2) HNF4a8 under control of DOX in the HCT116 human colon cancer cells. Methods: HNF4a2 and Parental lines were induced with 0.3 µg/mL DOX, while HNF4a8 line was induced with either 0.1 or 0.3 µg/mL DOX for 24 hours. Samples were generated by deep sequencing, using the Illumina TruSeq RNA. Result: There were common and unique dysregulated genes identified in the HNF4a2 and HNF4a8 lines (+DOX); more upregulated genes than downregulated genes in both the lines. Conclusion: The functional difference between HNF4a2 and HNF4a8 is that the latter tends to upregulate genes involved in proliferation and anti-apoptosis while HNF4a2 upregulates genes involved in growth suppression and cell death. Overall design: Tet-On inducible HCT116 cell (Parental, HNF4a2, and HNF4a8) lines, treated with (0.0, 0.1, or 0.3 µg/mL) DOX for 24 hours, were 50bp pair-ended sequenced in triplicate using Illumina TruSeq RNA Sample Prep v2 Kit.	Co-expression
SRP049443	Quantitative analysis of CD133+ liver cancer stem cells vs CD133- non cancer stem cell by RNA-Seq profiling	Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goal of this study is to compare the differentially expressed transcriptomes between CD133+ liver cancer stem cells versus CD133- non cancer stem cells by RNA-Seq profiling Overall design: mRNA profiles of sorted CD133+ and CD133- subsets isolated from HCC cell lines Huh7 and PLC8024 were generated by deep sequencing using Illumina GAIIx	Co-expression
SRP049453	Homo sapiens Transcriptome or Gene expression	Sequence data of HeLa cells were generated based on ribominus RNA sequencing with or without RNase R treatment (RNaseR+/-), respectively. These data sets were used for prediction of circRNAs.	Co-expression
SRP049462	The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells [RNA-seq]	Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation. Overall design: RNAseq of total RNA from a primary CD4 T cell culture at rest and 48 hours after anti-CD3/CD28 bead activation	Co-expression
SRP049465	SOX15 governs a transcriptional program in human esophageal stratified epithelium and in a subset of esophageal adenocarcinomas	We identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett''s esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts Overall design: [RNA-Seq] Total RNA isolated from CPA control cells and CPA cells following SOX15 depletion, samples were prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75 base pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype. [ChIP-Seq] Examine SOX15-chromatin binding in CPA cells.	Co-expression
SRP049475	RNA-Seq Analysis in hES/ iPS cell-derived neuronal samples	We characterized the gene expression by Hierarchical Clustering and one-matrix clustering in hESC, day 12 progenitors, day 25-day 27, day82 differentiated hypothalamic neurons from hESCs and day 45 neurons derived from iPSCs generated from controls (2 independent) and BBS (Bardet-Biedl Syndrome, 3 independent) subjects. Overall design: RNA was isolated from cells of 13 samples (1 hESC, triplicate for day 12 progenitors, 1 day 25 neuron sample, duplicate for day 27 neuron samples, 1 day 82 neuron sample, five day 45 neuron samples made from 5 independent iPSC lines ) using RNeasy Micro Kit (QIAGEN). Quality control of the RNA was carried out with the Agilent Bio-analyzer, Qubit 2.0 at the MPSR of Columbia University. 100 ng of RNA with RIN = 9 were used for generating mRNA-focused libraries using TruSeq RNA Sample Preparation Kit v2 and sequencing on an Illumina 2000/2500 V3 Instrument offered by the Columbia Genome Center.	Co-expression
SRP049479	Human cells contain natural double-stranded RNAs with potential regulatory capacity	Although recent evidence suggests that overlapping sense/antisense transcription is a common feature in higher eukaryotes, the possibility that overlapping transcripts could interact to each other and bear a specific biological function has not been explored. Here we show that a plethora of sense/antisense transcript pairs are co-expressed from 8q24.21 within the same cell and acquire a stable double-stranded RNA conformation. Interestingly, these molecules display predominantly nuclear localization and establish specific interactions with nuclear components. A detailed characterization of a particular sense/antisense pair (ndsRNA-2a) revealed that this molecule displays differential localization throughout the cell cycle, interacts with RCC1 and RAN and through the latter with the mitotic RANGAP1-SUMO1/RANBP2 complex. Notably, an increased number of bi/multi-nucleated cells and chromatin bridges were observed upon ndsRNA-2a overexpression, whereas strand-specific ndsRNA-2a knockdown leads to mitotic catastrophe and cell death. This suggests a functional role of ndsRNA-2a in cell cycle progression that critically requires its double stranded nature. Finally, the identification of hundreds of sense/antisense transcripts pairs harboring ndsRNA profile signatures and their regulation by cellular cues suggests that ndsRNAs constitute a novel class of regulatory molecules that are likely to be involved in a plethora of biological processes. Overall design: PLB985 long (3x datasets) and small (3x datasets) strand specific RNA-Seq for captured RNAs. Global PLB985 for long (2x datasets) and small RNAs (2x datasets). Global libraries for EtOH (vehicle) treated (1x dataset) or retinoic acid induced differentiated PLB985 cells (1x dataset).	Co-expression
SRP049484	Homo sapiens Transcriptome or Gene expression	Investigation of bile acid signaling and liver size in a mouse model wherein the mouse liver is repopulated with human liver cells	Co-expression
SRP049510	Optimized siRNAs with a minimal off-target effect facilitate the screening of essential genes in cancer cells	siRNAs with dN are a promising and easy approach to characterize essential genes by minimizing the off-target effect in cancer cells. Overall design: mRNA profiles of HCT 116 cells after the transfection of siRNAs or blank control by deep sequencing, using HiSeq 2000	Co-expression
SRP049514	RNA sequencing (RNA-SEQ) of EPAS1 knockdown by siRNA in endothelial cells	Purpose: By integrating DNA methylation and gene expression of COPD lung tissues, we identified EPAS1 as a key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profiles and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system developement. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human and mouse endothelial cells HUVEC and C166. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes. Methods: The cell lines of HUVEC (Lonza, MD, USA) and C166 (American Type Culture Collection, VA, USA) were cultured in the appropriate media at 37°C with 5% CO2. The cells were transfected with EPAS1 siRNA and non-targeting negative control siRNA (Life Technologies, CA, USA) using Lipofectamine RNAiMAX as recommended transfection protocols by the manufacturer. After the treatments with 5nM Silencer® Select siRNA (s4700 for EPAS1, s65525 for Epas1; Life Technologies, USA) for 48 hours, the total RNA was purified with RNeasy Mini Kit (QIAGEN, Germany). The efficiencies of knocked down the EPAS1 expression were assessed by qPCR with 1.4% for HUVEC, 3.2% for C166. Approximately 250 ng of total RNA per sample were used for library construction by the TruSeq RNA Sample Prep Kit (Illumina) and sequenced using the Illumina HiSeq 2500 instrument with 100nt single read setting according to the manufacturer's instructions. Sequence reads were aligned to human genome assembly hg19 and mouse genome assembly mm10, respectively, using Tophat [96]. Total 23,228 human and 22,609 mouse genes were quantified using Cufflinks [96]. siRNA signatures were derived by comparing expression profiles of EPAS1 or Epas1 siRNAs with non-targeting siRNAs at paired t-test p-value cutoff 0.05 with resulting signature sizes of 2,796 and 3,730, and corresponding q-values [97] 0.11 and 0.07 for HUVEC and C166, respectively. Results: When comparing endothelial cells treated with EPAS1 siRNAs and scrambled siRNAs, we identified an EPAS1 siRNA signature consisting of 2796 and 3730 genes in human and mouse endothelial cell lines, respectively, whose expression levels significantly changed (t-test p-value<0.05), including EPAS1 itself (p-value = 0.002 and 0.02) and the EPAS1 downstream target gene VEGFA (p-value = 0.03 and 0.01). The EPAS1 siRNA signatures derived from human and mouse cell lines were highly consistent, with 695 genes in common to both signatures (p-value = 7.2x10-65). Both signatures not only significantly overlapped with EPAS1 downstream genes (p-value = 7.3x10-7 and 1.5x10-12), but also with hypoxia response genes in endothelial cells (Fisher’s Exact Test p-value = 5.8x10-8 and 1.2x10-12 in the human and mouse signatures, respectively). Moreover, the EPAS1 siRNA signatures consistently overlapped genes associated with the COPD severity phenotypes. These results together validate that EPAS1 causally regulates the downstream target genes we predicted, and that these genes in turn affect COPD development and progression. Overall design: For each of human and mouse cell lines,  3 siRNA control cells, and 3 siRNA EPAS1 knockdown cells were used and analyzed. To identify EPAS1 signatures, paired t-test was performed between control siRNA and EPAS1 siRNA samples.	Co-expression
SRP049523	Peroxisome Proliferator-activated Receptor gamma- Deficiency in Endothelial Cells Impairs Angiogenic Capacity by Loss-of E2F1 Mediated Wnt Effector Genes	Some of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.	Co-expression
SRP049553	Self-organization of polarized cerebellar plate neuroepithelium in three-dimensional culture of human pluripotent stem cells	During cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Overall design: Examination of mRNA profile in two different treated human ES cells .	Co-expression
SRP049593	7q11.23 dosage-dependent dysregulation in the human pluripotent state primes aberrant transcriptional programs in disease-relevant lineages (RNAseq)	We apply the cellular reprogramming experimental paradigm to two disorders caused by symmetrical copy number variations (CNV) of 7q11.23 and displaying a striking combination of shared as well as symmetrically opposite phenotypes: Williams Beuren syndrome (WBS) and 7q microduplication syndrome (7dupASD). Through a uniquely large and informative cohort of transgene-free patient-derived induced pluripotent stem cells (iPSC), along with their differentiated derivatives, we find that 7q11.23 CNV disrupt transcriptional circuits in disease-relevant pathways already at the pluripotent state. These alterations are then selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. In addition, we functionally define the quota of transcriptional dysregulation specifically caused by dosage imbalances in GTF2I (also known as TFII-I), a transcription factor in 7q11.23 thought to play a critical role in the two conditions, which we found associated to key repressive chromatin modifiers. Finally, we created an open-access web-based platform (accessible at http://bio.ieo.eu/wbs/ ) to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes. Overall design: We reprogrammed skin fibroblasts from patients harbouring a 7q11.23 hemi-deletion (WBS, 4 patients; +1 atypical deletion, AtWBS) or microduplication (7dupASD; 2 patients), as well as from one unaffected relative and two unrelated controls, using integration-free mRNA-reprogramming, leading to the establishment of a total of 27 characterized iPSC clones. We profiled these by RNAseq (either polyA or ribo-zero). To isolate the contribution of GTF2I to the transcriptional dysregulation, we created stable lines expressing a short hairpin against GTF2I from a representative subset of these iPSC clones, and profiled by RNAseq 7 such lines along with their respective scramble controls. Finally, we also profiled by RNAseq mesenchymal stem cells (MSC) derived from a representative subset of the lines.	Co-expression
SRP049599	JunB control of keratinocyte-mediated inflammation [RNA-seq]	To determne JunB target gene in human keratincoytes Mice with epidermal deletion of JunB transcription factor displayed a psoriasis-like inflammation. The relevance of these findings to humans and the mechanisms mediating JunB function are not fully understood. Here, we demonstrate that impaired JunB function via gene silencing or overexpression of a dominant negative mutant increased human keratinocyte cell proliferation but decreased cell barrier function. RNA-seq revealed over 500 genes affected by JunB loss-of-function which included an upregulation of an array of proinflammatory molecules relevant to psoriasis. Among these were TNFa, CCL2, CXCL10, IL6R and SQSTM1, an adaptor protein involved in NF-kB activation. ChIP-Seq and gene reporter analyses showed that JunB directly suppressed SQSTM1 through binding to a consensus AP-1 cis-element located around 2 Kb upstream of SQSTM1-trasncription start site. Similar to JunB loss-of-function, SQSTM1-overexpression induced TNFa, CCL2 and CXCL10. Conversely, NF-kB-inhibition genetically with a mutant IkBa or pharmacologically with PDTC prevented cytokine, but not IL6R, induction by JunB-deficiency.  Taken together, our findings indicate that JunB controls epidermal growth, barrier formation and proinflammatory responses through direct and indirect mechanisms, pinpointing SQSTM1 as a key mediator of JunB-suppression of NF-kB-dependent inflammation. Overall design: 3 indepdent set of priamry human keratinocytes isolated from foreskin skin samples were transfected with nonsilencing control or siRNA oligonucleotides targeting JunB. mRNA was then isolated and used for cDNA library construction followed by RNA-sequencing.	Co-expression
SRP049605	Identification of a Molecular Signature for Acute Lyme Disease by Human Transcriptome Profiling	Lyme disease is challenging to diagnose, as clinical manifestations are variable and current tools to detect nucleic acid or antibody responses from Borrelia burgdorferi infection have low sensitivity.  Here we conducted the first study of the global transcriptome of patients with Lyme disease to identify potential diagnostic biomarkers.  Twenty-nine patients were enrolled and compared to 13 healthy controls at three time points after infection.  Fifteen publicly available transcriptome datasets from patients in vivo or infection models in vitro were used to assess specificity of differentially expressed genes (DEGs).  We found that Lyme disease results in profound and sustained changes in the patient transcriptomes, with a specific signature that shares =44% DEGs with other infections. Overall design: Gene expression profile from peripheral mononuclear blood cells (PBMC) of Lyme disease patients against healthy controls was undertaken. A total of 29 Lyme disease patients were sampled at 3 time points: acute Lyme pre-treatment (V1), 3 weeks later, immediately following completion of a standard course of antibiotics (V2), and 6 months following treatment completion (V5). 13 healthy controls were also sampled at one time point. Total RNA was extracted from 10e7 PBMC, followed by mRNA purification, paired-end barcode library preparation and sequencing on an Illumina Hiseq 2000.	Co-expression
SRP049607	Heterogeneous nuclear ribonucleoprotein C1/C2 links transcriptional and splicing actions of 1,25-dihydroxyvitamin D	Heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) functions as an RNA splicing regulator through co-transcriptional association with nascent mRNA. HnRNPC1/C2 can also bind to double-stranded DNA as a vitamin D response element-binding protein (VDRE-BP), thereby regulating transcriptional activity of the vitamin D receptor (VDR) bound to 1,25-dihydroxyvitamin D (1,25(OH)2D). In this way hnRNPC1/C2 may act as a coupling factor for 1,25(OH)2D-directed transcription and RNA splicing. Studies using MG63 osteoblastic cells confirmed that 1,25(OH)2D-VDR mediated induction of the gene for the enzyme 24-hydroxylase (CYP24A1), involved CYP24A1-specific chromatin and RNA immunoprecipitation of hnRNPC1/C2. Furthermore, small interfering (siRNA) knockdown of hnRNPC1/C2 in MG63 cells and was associated with dysregulated expression of CYP24A1 and an alternatively spliced form of CYP24A1 (CYP24A1-variant 2). Genome-wide analysis of RNA expression and alternative splicing indicated that dual role of hnRNPC1/C2 in directing 1,25(OH)2D-mediated gene expression is not restricted to the classical VDR-target CYP24A1. Knockdown of hnRNPC1/C2 resulted in 3500 differentially expressed genes (DEG), and treatment with 1,25(OH)2D 324 DEG. A further 87 DEG were only observed in 1,25(OH)2D-treated cells in hnRNPC1/C2 knockdown cells. HnRNPC1/C2 knockdown or 1,25(OH)2D treatment also induced alternative splicing (AS) (5039 and 310 AS events respectively). Combined hnRNPC1/C2 knockdown and 1,25(OH)2D treatment resulted in significant overlap between DEG and AS genes, but this was not observed for 1,25(OH)2D treatment alone. These data indicate that hnRNPC1/C2 can act to couple transcriptional and splicing responses to 1,25(OH)2D by binding to both DNA and RNA.  Similar mechanisms may also exist for other members of the hnRNP and steroid receptor family. Overall design: Human MG63 osteosarcoma cells (American Type Culture Collection, CRL-1427) were cultured in Dulbecco’s modified Eagle medium (DMEM, high glucose, Gibco, 11995-065) supplemented with 10% Fetal Bovine Serum (FBS) cultured at 37oC with 5% CO2. Crystalline 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, Enzo Life Sciences, BML-DM200-0050) was reconstituted in ethanol. Ethanol (0.1%) was used as vehicle treatment. RNA-seq analysis was carried out using total RNA extracted from MG63 cells using RNAeasy mini kit (Qiagen, 74104), with on-column DNase treatment to remove contaminating genomic DNA. cDNA libraries were prepared using the Illumina TruSeq RNA Sample Preparation Kit (illumina). High-throughput sequencing was performed using an Illumina HiSeq2500 (paired-end, non-strand-specific 107-bp read length). Knockdown and control samples were sequenced together in two flowcells on four lanes.	Co-expression
SRP049611	Transcriptome-wide modulation of splicing by the exon junction complex	We report that knockdown of EJC core proteins, eIF4A3, Y14, Magoh, causes a transcript-wide changes in alternative splicing, as well as some transcriptional changes. These changes are specific to EJC core proteins, and KD of UPF1 protein caused different sets of alterantive splicing changes. These changes are linked to the rate of transcription. Overall design: Examination of 4 different knockdown, as well as GFP knockdown in HeLa cells, 2 replicates each condition.	Co-expression
SRP049648	Integrin avß3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells	We have found that thyroid hormones (THs), acting as soluble integrin avß3 ligands, activate growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated avß3 integrin signaling promotes TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF. Overall design: CUTLL1 cells were treated with T3- and T4-bound agarose or agarose alone for 24hrs. Total RNA was harvested from cells and used for expression profiling via RNA-seq.	Co-expression
SRP049669	CX3CR1/Fractalkine receptor expression separates memory CD8+ T cells with distinct functional profiles (RNA-seq)	Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory. Overall design: CD8+ T cells were isolated and directly assessed. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.	Co-expression
SRP049676	hiPSCs unravel aberrant TGFß signaling as an etiology of left ventricular non-compaction	Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and has a unique phenotype with characteristically extensive hypertrabeculation of the left ventricle, similar to the embryonic left ventricle, suggesting a developmental defect of the embryonic myocardium. However, studying this disease has been challenging due to the lack of an animal model that can faithfully recapitulate the clinical phenotype of LVNC. To address this, we show that patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) generated from a family with LVNC recapitulated a developmental defect consistent with the LVNC phenotype at the single-cell level. We then utilized hiPSC-CMs to show that increased transforming growth factor beta (TGFß) signaling is one of the central mechanisms underlying the pathogenesis of LVNC. LVNC hiPSC-CMs demonstrated decreased proliferative capacity due to abnormal activation of TGFß signaling. Exome sequencing demonstrated a mutation in TBX20, which regulates TGFß signaling, contributing to the LVNC phenotype. Our results demonstrate that hiPSC-CMs are a useful tool for the exploration of novel mechanisms underlying poorly understood cardiomyopathies such as LVNC. Here we provide the first evidence of activation of TGF? signaling as playing a role in the pathogenesis of LVNC. Overall design: mRNA expression profiles in human iPSC derived cardiomyocytes obtained from 2 independent unrelated control, 1 asymptomatic mild DCM (2 iPSC lines) and 3 LVNC patients (2 proband lines and 1 lines from 2 siblings) 2 weeks after starting cardiac differentiation.	Co-expression
SRP049713	Identification and functional characterization of long noncoding RNAs in breast cancer	In this study, we have integrated RNA-seq data from subcellular fractionated RNA (i.e., cytoplasm, nucleoplasm, and chromatin-associated) with GRO-seq data using a novel bioinformatics pipeline. This has yielded a comprehensive catalog of polyadenylated lncRNAs in MCF-7 cells, about half of which have not been annotated previously and about a quarter of which are estrogen-regulated. Knockdown of selected lncRNAs, such as lncRNA152 and lncRNA67 followed by RNA-seq suggest that these lncRNAs regulate the expression of cell cycle genes. Overall design: characterization of long noncoding RNAs	Co-expression
SRP049714	High throughput analysis of three human adipose cell lines PAZ6, SGBS and SW872	We report molecular characterization of human brown and white adipocytes. We showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, SGBS cells presented a versatile phenotype of adipocyte Overall design: Sequencing of three human adipocytes cell lines (SGBS, SW872 and PAZ6) in undifferentiated and differentiated stages.	Co-expression
SRP049756	Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells (2)	DNA methylation is thought to induce a transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators that do not recognize their binding sites when methylated, and the recruitment of transcriptional repressors that specifically bind methylated DNA. Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. However, the exact contribution of each protein in the DNA methylation dependent transcriptional repression occurring during development and diseases remains elusive. Here we present MBD2 ChIPseq data generated from the endogenous protein in an isogenic cellular model of human mammary oncogenic transformation. In immortalized or transformed cells, MBD2 was found in one fourth of methylated regions and associated with transcriptional silencing. Depletion of MBD2 induces upregulations of genes bound by MBD2 and methylated in their transcriptional start site regions. MBD2 was partially redistributed on methylated DNA during oncogenic transformation, independently of DNA methylation changes. Genes downregulated during this transformation preferentially gained MBD2 binding sites on their promoter. Depletion of MBD2 in transformed cells induced the upregulation of some of these repressed genes, independently of the strategy used for the abrogation of oncosuppressive barriers. Our data confirm that MBD2 is a major interpret of DNA methylation, and show an unreported dynamic in this interpretation during oncogenic transformation. Overall design: RNAseq of untreated HMEC-hTERT cells, siCtrl, siMBD2 or DAC treated HMLER cells, siCtrl or siMBD2 treated HME-ZEB1-RAS and HME-shP53-RAS cells, in duplicates.	Co-expression
SRP049769	Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphoma	Aggressive double and triple hit (DH/TH) DLBCL feature activation of Hsp90 stress pathways.  Herein, we show that Hsp90 controls post-transcriptional dynamics of key mRNA species including those encoding BCL6, MYC and BCL2. Using a proteomics approach, we found that Hsp90 binds to and maintains activity of eIF4E (eukaryotic translation initiation factor 4E). EIF4E drives nuclear export and translation of BCL6, MYC and BCL2 mRNA. eIF4E RIP-sequencing in DLBCL suggests that nuclear eIF4E controls an extended program that includes BCR signaling, cellular metabolism and epigenetic regulation. Accordingly, eIF4E was required for survival of DLBCL including the most aggressive subtypes DH/TH lymphomas. Indeed, eIF4E inhibition induces tumor regression in cell line and patient-derived tumorgrafts of TH-DLBCL, even in the presence of elevated Hsp90 activity. Targeting Hsp90 is typically limited by counter-regulatory elevation of Hsp70B, which induces resistance to Hsp90 inhibitors. Surprisingly, we identify Hsp70 mRNA as an eIF4E target. In this way, eIF4E inhibition can overcome drug resistance to Hsp90 inhibitors. Accordingly, rational combinatorial inhibition of eIF4E and Hsp90 inhibitors resulted in cooperative anti-lymphoma activity in DH/TH DLBCL in vitro and in vivo. Overall design: We found that eIF4E activity regulates the nuclear export of BCL6, MYC, and BCL2 in DH/TH DLBCLs. To determine the extent of nuclear eIF4E activity in DH/TH DLBCLs and how these programs can support the oncogenic activity of BCL6, MYC and/or BCL2 transcripts, we conducted eIF4E-RIP of nuclear RNA followed by RNA-sequencing in OCI-Ly1 cells in triplicates. To understand the changes in gene expression after ribavarin in a clinically relevant sample, we generated a patient-derived xenograft (PDX) in NSG mice from a de-identified specimen isolated from a patient prior to treatment harboring a triple-hit ABC-type DLBCL. PDX cells from passage four (PDX-4) were implanted into NSG mice. When tumors were palpable, mice were randomized to receive vehicle or 80 mg/kg/b.i.d. ribavarin intraperitoneally for 10 days.  We isolated RNA from tumors treated with vehicle (n=2) or ribavarin (n=2) and performed mRNA-seq.	Co-expression
SRP049805	Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle by inducing capillary sprouting and decreasing vascular permeability via reduced eNOS activity	Rationale: Slit2 is a possible modulator of vascular endothelial growth factor (VEGF) - induced angiogenesis, but its effects have not been tested in large animal models. Objective: We studied the effect of Slit2 on therapeutic angiogenesis induced by VEGF receptor 2 (VEGFR2) ligands Vammin and VEGF-D?N?C in vivo in rabbit skeletal muscles. The Slit2 target genes were also studied by RNA sequencing (RNA-Seq) in endothelial cells. Methods and Results: Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Signaling experiments and gene expression analyses were performed to study mechanisms of Slit2 action. Slit2 decreased VEGFR2-mediated vascular permeability. It also reduced VEGFR2-mediated increase in blood perfusion and capillary enlargement, whereas sprouting of the capillaries was increased. Slit2 gene transfer alone did not have any effects on vascular functions or morphology. VEGFR2 activation was not affected by Slit2, but eNOS phosphorylation was diminished. The transcriptome profiling showed Slit2 downregulating angiogenesis-related genes such as nuclear receptor subfamily 4 group A member 1 (NR4A1) and Stanniocalcin-1 (STC-1) as well as genes related to endothelial cell migration and vascular permeability. Conclusions: Combining Slit2 with VEGFs adjusts VEGFR2-mediated angiogenic effects into a more physiological direction. This possibly allows the use of higher VEGF vector doses to achieve a more widespread vector and VEGF distribution in the target tissues leading to a better therapeutic outcome while reducing excess vascular permeability. Overall design: HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.	Co-expression
SRP049820	An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation	Background: Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also induce a suppressive effect known as endotoxin tolerance or cellular reprogramming. It has been proposed that endotoxin tolerance might be associated with the immunosuppressive state that was primarily observed during late-stage sepsis. However, this relationship remains poorly characterised. Here we clarify the underlying mechanisms and timing of immune dysfunction in sepsis. Methods: We defined a gene expression signature characteristic of endotoxin tolerance. Gene-set test approaches were used to correlate this signature with early sepsis, both newly and retrospectively analysing microarrays from 593 patients in 11 cohorts. Then we recruited a unique cohort of possible sepsis patients at first clinical presentation in an independent blinded controlled observational study to determine whether this signature was associated with the development of confirmed sepsis and organ dysfunction. Findings: All sepsis patients presented an expression profile strongly associated with the endotoxin tolerance signature (p < 0.01; AUC 96.1%). Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming) is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis. Overall design: For the RNA-Seq study reported here, 73 patients were recruited with deferred consent at the time of first examination in an emergency ward based on the opinion of physicians that there was a potential for the patient''s condition to develop into sepsis. These were retrospectively divided into groups based on clinical features and compared to 11 non-urgent surgical controls.	Co-expression
SRP049947	Gene expression profile of wt-, S473A- and S473D-KAP1-re-expression in KAP1-depleted MDA-MB-231 cell	We study the gene regulation function of serine 473 phosphorylation of KAP1 (pS473-KAP1) in MDA-MB-231 cells. Wild type KAP1, S473A-KAP1 (phospho-acceptor site mutant) and S473D-KAP1 (phospho-mimetic mutant) are re-expressed in KAP1 knockdown cells. We analyze the gene expression profile in these three cells and find that many mitochondrial complex genes are up-regulated in S473D-KAP1 re-expressing cells. This study provides information about pS473-KAP1-regulated gene expression. Overall design: mRNA profile of wt-, S473A- and S473D-KAP1-expressing MDA-MB-231 cells were generated by deep sequencing	Co-expression
SRP049967	The genomic landscape of nasopharyngeal carcinoma	Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC Overall design: Examination of mRNA expression levels in 4 individuals dignosed for Nasopharyngeal Carcinoma using RNA sequencing.	Co-expression
SRP049981	RNA-Seq of cKIT+ sorted cells from 53-137 day old fetal testes and ovaries and RNA-Seq of TRA-1-81+ H1 and UCLA1 hESCs.	We performed RNA-Seq analyses on 15 human fetal samples at 53-137 days of development, 9 female and 5 male, and identified the transcriptional changes during the transition of human cKIT+ primordial germ cells (PGCs), the precursors of gametes, to the generation of Advanced Germline Cells. Comparing the transcriptional profile of PGCs to that of H1 and UCLA1 hESCs identifies differences between the two cell types and pinpoints molecules that can be used in the development of in vitro germ cell differentiation protocols starting from human pluripotent stem cells. Overall design: RNA-Seq of cKIT+ cells analyzed from 6 biological samples for testes and 9 samples for ovaries from 53-137 days. 2 biological replicates of TRA-1-81+ cells sorted from H1 and UCLA1 hESCs. WGBS of cKIT+ cells analyzed from 4 biological samples of ovaries and 1 biological sample of testes at 57-137 days of development.	Co-expression
SRP049988	Ets homologous factor regulates pathways controlling response to injury in Calu-3 airway epithelial cells [RNA-seq]	Ets homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor, though its targets in lung epithelial cells are largely uncharacterized. RNA-seq after EHF depletion or overexpression showed significant alterations in the expression of genes involved in response to wounding. EHF knockdown also targeted genes in pathways of epithelial development and differentiation and locomotory behavior. Overall design: mRNA profiles from Calu-3 cells treated with negative control (NC) or EHF siRNA, in quintuplicate. mRNA profiles from 3 pcDNA (empty vector control) clones and 3 pcDNA-EHF overexpression A549 clones, 3-4 replicates each.	Co-expression
SRP050036	Knock-in of PIK3CA-H1047R into MCF-10A	We have compared the proteome, transcriptome and metabolome of two isogenic cell lines: MCF-10A, derived from human breast epithelium, and the mutant MCF-10A-H1047R. These cell lines differ by a single amino acid substitution (H1047R) caused by single nucleotide change in one allele of the PIK3CA gene which encodes the catalytic subunit p110a of phosphatidylinositol 3-kinase (PI3K). The H1047R mutation of PIK3CA is one of the most frequently encountered somatic cancer-specific mutations. In MCF-10A, this mutation induces an extensive cellular reorganization that far exceeds the known signaling activities of PI3K. The changes are highly diverse; with examples in structural protein levels, the DNA repair machinery and sterol synthesis. Gene set enrichment analysis reveals a highly significant concordance of the genes differentially expressed in MCF-10A-H1047R cells and the established protein and RNA signatures of basal breast cancer. No such concordance was found with the specific gene signatures of other histological types of breast cancer. Our data document the power of a single base mutation, inducing an extensive remodeling of the cell toward the phenotype of a specific cancer. Overall design: 2 cell lines (H1047R and WT), 4 time points (0, 6, 12, 24 hours), 3 replicates	Co-expression
SRP050055	A variety of Dicer substrates in human and C. elegans (HEK RNA-seq)	The endoribonuclease Dicer is known for its central role in the biogenesis of eukaryotic small RNAs/microRNAs. Despite its importance, Dicer target transcripts have not been directly mapped. Here, we apply biochemical methods to human cells and C. elegans and identify thousands of Dicer binding sites. We find known and hundreds of novel miRNAs with high sensitivity and specificity. We also report structural RNAs, promoter RNAs, and mitochondrial transcripts as Dicer targets. Interestingly, most Dicer binding sites reside on mRNAs/lncRNAs and are not significantly processed into small RNAs. These passive sites typically harbor small, Dicer-bound hairpins within intact transcripts and generally stabilize target expression. We show that passive sites can sequester Dicer and reduce microRNA expression. mRNAs with passive sites were in human and worm significantly associated with processing-body/granule function. Together, we provide the first transcriptome-wide map of Dicer targets and suggest conserved binding modes and functions outside the miRNA pathway. Overall design: Regulatory impact of Dicer binding was assessed by knock down experiments in human HEK293 cells. Drosha knockdown and mock transfections were used as controls. Knockdown was performed with two independent siRNAs each. In total 5 samples.	Co-expression
SRP050058	RNA expression analysis upon JMJD1C depletion	The AML1-ETO fusion protein, a transcription factor generated by the t(8;21) translocation in acute myeloid leukaemia (AML), dictates a leukemic program by increasing self-renewal and inhibiting differentiation.  Here we demonstrate that the histone demethylase JMJD1C functions as a co-activator for AML1-ETO and is required for its transcriptional program. JMJD1C is directly recruited by AML1-ETO to its target genes and regulates their expression by maintaining low H3K9me2 levels. Analyses in JMJD1C knockout mice also establish a JMJD1C requirement for AML1-ETO’s ability to increase proliferation. We also show a critical role for JMJD1C in the survival of multiple human AML cell lines, suggesting that it is required for leukemic programs in different AML cell types through its association with key transcription factors. Overall design: Examination of RNA expression when Kasumi-1 cells are treated with control shRNA or two different JMJD1C shRNAs; in duplicate. Please note that the ''shAML1_ETO_vs_shControl.all_gene_exp.tb.txtl'' was generated comparing control and shRNA treated RNA abundance-using previously published data [GSE43834; GSM1071857 and GSM1071852].	Co-expression
SRP050061	Discovery of cis-spliced chimeric RNAs between adjacent genes in human prostate cells	Total RNA extracted from prostate cancer LNCaP cells transfected with siRNA against CTCF(siCTCF), or negative control siRNA (si-)were processed, and sequenced by two different companies using Illumina Hi-seq 2000 platform to generate RNA sequencing with two output sequences: paired-end 50bp and 101bp in read length. Nearly 100 million and 50 million raw reads were yielded from each sample respectively. We used FastQC to confirm the quality of raw fastq sequencing data, and SOAPfuse software to detect fusion transcripts. Overall design: Discovering fusion genes from siCTCF and si- in LNCaP cells.	Co-expression
SRP050134	The circadian transcriptional landscape in primary human mammary epithelial cells	Cells in peripheral tissue maintain a cell-autonomous molecular clock which is regulated through transcription-translation feedback mechanisms initiated by a core set of circadian proteins. Among these clock proteins are transcription factors and histone modifying enzymes which act in trans to influence the expression of a broad array of clock-controlled genes (CCGs). The CCG set, defined as transcripts with cyclic expression approximating a 24h period, is tissue-specific, such that the circadian transcriptome can only be assembled through experiments conducted in the cell type of interest. Here, we describe for the first time the circadian transcriptome in primary human mammary epithelial cells using time-series massively parallel sequencing. We also show that clinical instruments relying on gene expression, such as molecular subtyping and RNA-based predictive or prognostic biomarkers, provide measurements that are variable across circadian time. This data represents a valuable resource for advancing our understanding of the molecular underpinnings of circadian rhythm. Overall design: mRNA profiles of temperature synchronized (non-immortalized) human breast epithelial cells isolated from a 28 year-old woman undergoing breast reduction mammoplasty.  The experiment was carried out over a 24-hour time period in duplicate and the samples were analyzed using the Illumina HiSeq 2000.	Co-expression
SRP050146	RNA sequencing of bone marrow CD34+ cells from myelodysplastic syndrome patients with and without SF3B1 mutation and from healthy controls	The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA-sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared to wildtype cases include genes involved in MDS pathogenesis (ASXL1, CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7, SLC25A37) and RNA splicing/processing (PRPF8, HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. Our data indicate that SF3B1 plays a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link. Overall design: RNA-Seq was performed to compare the transcriptome of bone marrow CD34+ cells from eight MDS patients with SF3B1 mutation, four MDS patients with no known splicing mutation and five healthy controls.	Co-expression
SRP050179	RNA-seq of human fibroblasts during replicative senescence	Senescent human fibroblasts were compared to young proliferating fibroblasts. Five different cell lines were compared. Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 48 samples: 3 biological replicates for each group: young proliferating and senescent BJ cells;  young proliferating and senescent Wi-38 cells;  young proliferating and senescent IMR-90 cells; 5 population doubling from young proliferating to senescent cell for HFF and MRC-5 cells	Co-expression
SRP050193	Response and resistance to BET bromodomain inhibitors in triple negative breast cancer [RNA-Seq]	Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. After engendering acquired resistance to BET inhibition in previously sensitive TNBCs, we utilized integrative approaches to identify a unique mechanism of epigenomic resistance to this epigenetic therapy. Resistant cells remain dependent on BRD4, confirmed by RNA interference. However, TNBC cells adapt to BET bromodomain inhibition by re-recruitment of unmutated BRD4 to super-enhancers, now in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify hyper-phosphorylation of BRD4 and strong association with MED1. Together, these studies provide a rationale for BET inhibition in TNBC and argue for combination strategies to anticipate clinical drug resistance. Overall design: RNA-Seq in parental and JQ1 resistant triple negative breast cancer (TNBC) in response to DMSO or JQ1 treatment over time	Co-expression
SRP050223	Characterization of a network of tumor suppressor microRNA''s in T Cell acute lymphoblastic leukemia	Purpose: The purpose of this study is to identify functionally inter-connected group of miRNAs whose reduced expression promotes leukemia development in vivo. We searched for relevant target genes of these miRNAs that are upregulated in T-ALL relative to controls. Methods: In order to examine the global gene expression, we generated 9 T-ALL patients and 4 normal controls by deep sequencing using Illumina Hi-Seq sequencer. The sequence reads that passed quality filters were analyzed using Spliced Transcripts Alignment to a Reference aligner (STAR) followed by differential gene expression analysis using DESeq. Results: Using an optimized data analysis workflow, we mapped reads per sample to the human genome (build hg19) and identified transcripts in both patient and controls with STAR workflow. We applied a machine learning approach to eliminate targets with redundant miRNA-mediated control. This strategy finds a convergence on the Myb oncogene and less prominent effects on the Hpb1 transcription factor. The abundance of both genes is increased in T-ALL and each can promote T-ALL in vivo. Conclusion: Our study reveals a Myc regulated network of tumor suppressor miRNAs in T-ALL. We identified a small number of functionally validated tumor suppressor miRNAs.  These miRNAs are repressed upon Myc activation and this links their expression directly to Myb a key oncogenic driver in T-ALL. Overall design: Examination of global gene expression in 9 T-ALL patients and 4 normal controls using total RNA sequencing. BaseMeanA in DESeq_results.xlsx is the control.	Co-expression
SRP050230	Protein coding and noncoding gene signatures in two subtypes of exosomes released by LIM1863 human colon cancer cell line	Exosomes are 40~120 nm diameter vesicles of endocytic origin released by most cells and important in mediating cell-cell communication. As mRNA and noncoding RNA are two main functional RNA molecules in post transcription level and involves in many bio-activities including cancer progression and metastasis, it is important to understand the coding and noncoding genes contained within exosomes released by tumour cells. This study focused on the protein coding and noncoding genes enriched in two subtypes of exosomes (A33-enriched exosomes, A33-Exos and EpCAM-enriched exosomes, EpCAM-Exos) released by human colon cancer LIM1863 cell line. With high throughput sequencing technology and bioinformatics analyses, we demonstrate 350 protein coding genes (PCGs) and 222 noncoding genes (NCGs) are commonly enriched; 56 PCGs and 202 NCGs were specifically enriched in A33-Exos and 276 PCGs and 253 NCGs were enriched unique to EpCAM-Exos. A salient finding was the significant enrichment of TPT1, ribosomal protein genes and GAS5, a tumour noncoding gene, in exosomes. We further demonstrate differentially seven expressed genes (SCARB1, SCD, TPT1, EETF1G, BCL7C, RPS3, and RAB13) by qRT-PCR. Importantly, we correlated these findings with several matched tissue-derived tumour-normal samples showed TPT1 and ribosomal protein genes were up regulated in human tumour samples. Our findings provide a new insight of functional RNA molecules in exosomes and new select non-invasive biomarker candidates for colon cancer diagnosis and prognosis.	Co-expression
SRP050242	The reversed evolution from multicellularity to unicellularity during carcinogenesis	Using xenograft-based experimental evolution, we characterize the full life history from initiation to metastasis of a tumor at the genomic and transcriptomic levels.	Co-expression
SRP050245	Effect of REST on cancer invasiveness in MCF-7 and MDA-MB-231 cells using RNA-sequencing (RNA-seq) analysis .	We report a negative correlation of invasiveness with REST expression. In addition, one alternatively spliced product (ASP) of REST, REST-003, shows a positive correlation with invasiveness. REST has a well-established role in regulating transcription of genes important for neuronal development.  Its role in cancer, though significant, is less well understood.  We would like to investigate the effect of REST on invasive phenotype.  In order to do so, we downregulate REST by siRNA treatment in weakly invasive MCF-7 breast cancer cells in which REST is expressed highly: 1) si-GAPDH (control), two si-RESTs (2)si-REST_1 and 3) si-REST_2).  Conversely, we  overexpress REST by transfection of wt-REST cDNA in highly invasive MDA-MB-231 cells in which REST is expressed at the low level:  4) EGFP (control), 5) mt-REST (another control) and 6) wt-REST. REST (repressor element-1 (RE-1) silencing transcription factor) contains a DNA-binding domain that is localized within eight zinc fingers and two repressor domains located at the N-terminal and C-terminal, respectively.   REST suppresses expression of neural-specific genes.  mt-REST lacks two repressor domains, so it can be used as a control for wt-REST.  In contrast, REST-003 is one of alternatively spliced products (ASPs) of REST. Overall design: Downregulation of REST using two siRNAs in MCF-7 cells or overexpression of REST with wt- or mt-REST cDNA in MDA-MB-231 cells REST_ISOFORM_FIG1.pdf was provided to explain *rawRestIsoformCnts.txt files described in the README1.txt file.	Co-expression
SRP050249	Effects of NAMI-A on MDA-MB-231 and in HBL-100 cell lines	Gene expression study of MDA-MB-231 and in HBL-100 cell lines exposed to the antimetastatic drug NAMI-A	Co-expression
SRP050260	Epigenomic landscape during organ formation in human early embryos	Here we present the whole genome ChIP-Seq analyses of a wide variety of histone marks, H3K27ac, H3K4me1, H3K4me3, and H3K27me3 in the brain, heart, and liver, along with the RNA-seq data of these organs of early human embryos 12 weeks after gestation. Overall design: In total, brain, heart, and liver of early human post-implantation embryos were used, and four histone modifications were detected, including H3K27ac, H3K4me1, H3K4me3 and H3K27me3. Also, the transcriptomes of these three organs were analyzed.	Co-expression
SRP050272	Expression and Prognostic impact of LncRNAs in Acute Myeloid Leukemia	Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis and cell-cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged =60 years) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. Overall design: In this study, we analyzed a large set of older CN-AML patients using custom lncRNA microarrays to investigate whether lncRNA expression is associated with clinical features, molecular abnormalities and outcome and to build a prognostic lncRNA signature that was subsequently validated using RNA sequencing. This submission represents RNA-Seq component of study.	Co-expression
SRP050331	Effect of CHKA knockdown on C4-2 cell transcriptome	Analysis of C4-2 Prostate cancer cell line after 72 hours of knockdown. CHKA is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of CHKA in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptome by Choline kinase alpha (CHKA) which is an important enzyme in Kennedy pathway. In order to achieve this, the endogenous protein was knocked down using siRNA pool that targets the CHKA mRNA.	Co-expression
SRP050332	Effect of PBK knockdown on C4-2 cell transcriptome	Analysis of C4-2 Prostate cancer cell line after 72 hours of knockdown. PBK is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of PBK in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptiome by PDZ domain binding kinase (PBK), which is an important kinase with role in cell cycle. In order to achieve this, the endogenous protein was knocked down using siRNA pool that targets the PBK mRNA.	Co-expression
SRP050365	A common cell state in Triple Negative Breast Cancers represents a druggable vulnerability	A basal (MDAMB468) and luminal (ZR75-1) cell line were treated with DMSO or PKC412 for 6h Overall design: 2 DMSO and 3 PKC412 treated samples for each cell line	Co-expression
SRP050374	RNA-seq data from six cell types for cell type phylogenetics	We sequenced mRNA from a total of 12 samples (6 different cell types, each with two biological replicates) to infer the relationship among those cell types Overall design: Examination of mRNA levels in six different human cell types grown in culture with two biological replicates for each cell type	Co-expression
SRP050376	Next Generation Sequencing Facilitates Comparisons of Control and Schizophrenia-Patient derived hiPSC-derived neurons	Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported.  While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved.  Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue.  Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus. We directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into forebrain neurons.  SZ hiPSC differentiated into forebrain neurons have altered expression of a number of synaptic genes. Methods: We compared global transcription of forebrain neurons from six control and four SZ patients by RNAseq. Results:  Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC neuron samples; 107 genes were significantly differentially expressed (FDR<0.01) Overall design: 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.	Co-expression
SRP050377	Next Generation Sequencing Facilitates Comparisons of Control and Schizophrenia-Patient derived hiPSC-derived NPCs	Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported.  While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved.  Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue.  Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results:  Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). Overall design: 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.	Co-expression
SRP050390	Large-scale profiling of intracellular signalling pathway activation reveals major distinctions between airway smooth muscle cells of asthmatics and non-asthmatics.	Signalling pathways regulate all major cellular events in health and disease, including asthma development and progression. Complexity of human intracellular signalization can be explored using novel systemic approaches that exploit whole-transcriptome analysis. Cap-analysis-of-gene-expression (CAGE) is a method of choice for generating transcriptome libraries, as it interrogates only terminally capped mRNAs that have the highest probability to be translated into protein. In this study we for the first time systematically profiled differentially activated Intracellular Signalling Pathways (ISPs) in cultured primary human airway smooth muscle (ASM) cells from asthmatic (n=8) and non-asthmatic (n=6) subjects in a high-throughput assay, highlighting asthma-specific co-regulatory patterns. CAGE-libraries from primary human ASM cells were subject to massive parallel next generation sequencing, and a comprehensive analysis of ISP activation was performed using a recently developed technique OncoFinder. Analysis of 270 ISPs led to discovery of multiple pathways clearly distinguishing asthmatic from normal cells. In particular, we found 146 (p<0.05) and 103 (p<0.01) signalling pathways differentially active in asthmatic vs non-asthmatic samples. We identified seven clusters of coherently acting pathways functionally related to the disease. Pathways down-regulated in asthma mostly represented cell death-promoting pathways, whereas the up-regulated ones were mainly involved in cell growth and proliferation, inflammatory response and some specific reactions, including smooth muscle contraction and hypoxia - related signalization. Most of interactions uncovered in this study were not previously associated with asthma, suggesting that these results may be pivotal to development of novel therapeutic strategies that specifically address the ISP signature linked with asthma pathophysiology. Overall design: Capped mRNA profiles of primary bronchial smooth muscle cells from 8 asthmatic and 6 healthy donors were generated by deep sequencing using Illumina HiSeq1500.	Co-expression
SRP050397	Defective removal of ribonucleotides from DNA promotes systemic autoimmunity	Constitutive low level DNA damage in RNASEH2 deficiency is linked to innate immune activation. Hierarchical clustering of over 16000 transcripts revealed remarkably similar profiles in patients with lupus erythematosus and patients with AGS with up-regulation of genes involved in DNA damage signaling and type I-IFN signaling. Overall design: Comparison of transcriptional profiles of native RNASEH2-deficient patient fibroblasts with wild type cells.	Co-expression
SRP050422	A novel lncRNA GAS1 promotes gastric carcinogenesis and acts as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern [RNA-seq]	To elucidate whether GAS1 plays a role in gastric cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of GAS1 shRNA and control shRNA transfectants. Overall design: RNA-seq was performed in BGC 823 gastric cancer cells after GAS1 shRNA and control shRNA virus infection	Co-expression
SRP050490	Transcriptome of Stabilin-1 siRNA transfected human monocytes	Stabilin-1/CLEVER-1 is a multidomain protein present in lymphatic and vascular endothelial cells and in M2 immunosuppressive macrophages. Stabilin-1 functions in scavenging, endocytosis and leukocyte adhesion to and transmigration through the endothelial cells. We have analyzed the putative functions of Stabilin-1 in blood monocytes and found that in healthy individuals 60-80% of both CD14+CD16- and CD14+C16+ monocytes, but not CD14dimCD16+ monocytes, expressed Stabilin-1 on the surface. Microarray and RNAseq analysis was performed to get more insight into the effect of Stabilin-1 expression on human monocytes transcriptome. Overall design: The transcriptome of human monocytes transfected with Stabilin-1 siRNA was compared to that of control siRNA transfected monocytes	Co-expression
SRP050493	Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome	Somatic mutations in the spliceosome gene ZRSR2— located on the X chromosome — are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the recognition of 3? splice site during the early stages of spliceosome assembly; however, its precise role in RNA splicing has remained unclear. Here, we characterize ZRSR2 as an essential component of the minor spliceosome (U12-dependent) assembly. shRNA mediated knockdown of ZRSR2 leads to impaired splicing of the U12-type introns, and RNA-Sequencing of MDS bone marrow reveals that loss of ZRSR2 activity causes increased mis-splicing. These splicing defects involve retention of the U12-type introns while splicing of the U2-type introns remain mostly unaffected. ZRSR2 deficient cells also exhibit reduced proliferation potential and distinct alterations in myeloid and erythroid differentiation in vitro. These data identify a specific role for ZRSR2 in RNA splicing and highlight dysregulated splicing of U12-type introns as a characteristic feature of ZRSR2 mutations in MDS. Overall design: RNA sequencing was performed on 16 bone marrow samples (MDS and normal)  and six samples of control or ZRSR2 shRNA transduced TF-1 cells and data was analysed for aberrant splicing caused by ZRSR2 mutations/deficiency.	Co-expression
SRP050497	Altering cancer transcriptomes using epigenomic inhibitors [RNA-Seq]	We have compared the genome-wide effects on the transcriptome after treatment with ICG-001 (the specific CBP inhibitor) versus C646, a compound that competes with acetyl-coA for the Lys-coA binding pocket of both CBP and p300. We found that both drugs cause large-scale changes in the transcriptome of HCT116 colon cancer cells and PANC1 pancreatic cancer cells, and reverse some tumor-specific changes in gene expression. Interestingly, although the epigenetic inhibitors affect cell cycle pathways in both the colon and pancreatic cancer cell lines, the WNT signaling pathway was affected only in the colon cancer cells. Notably, WNT target genes were similarly down-regulated after treatment of HCT116 with C646 as with ICG-001. Overall design: To identify genes affected by direct targeting of a component of the transcriptional complex implicated in WNT regulation, we used siRNAs to knockdown TCF7L2 in PANC1 cells. Cells were treated with control siRNAs or siRNAs specific for TCF7L2 and RNA was analyzed by RNA-seq.	Co-expression
SRP050499	The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells	Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10-11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation; with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes. Overall design: In total, we analyzed the transcriptomes of 233 individual male and female human PGCs from 15 embryos at between 4 and 19 weeks of gestation as well as 86 neighboring somatic cells from 13 of these embryos using a single-cell RNA-Seq method that we developed. Furthermore, we analyzed the DNA methylomes of both male and female human gonadal PGCs as well as the neighboring somatic cells of eleven of these embryos at between 7 and 19 weeks of gestation using whole-genome bisulfite sequencing (WGBS). In total, we generated 1.3 billion 100 bp paired-end reads for transcriptome analyses and 4.1 billion 100 bp or 150 bp paired-end reads for DNA methylome analyses.	Co-expression
SRP050533	RNA profiling of PDX1+ pancreatic progenitors before or after co-culture with different types of cells	Analysis of gene expression of Pdx-EGFP1+ pancreatic progenitors before or after co-culture at mRNA level. The hypothesis tested in the study was that the overall gene expression in Pdx1-EGFP+ does not alter after co-culture with endothelial cells. The result supported our hypothesis. Overall design: Total RNA isolated from Pdx1-EGFP+ progenitors from the Pdx1-EGFP HUES8 cell-derived pancreatic progenitor population before (none) and after co-culture (AKT-HUVEC, MPEC, or BJ) Fig 2d in publication.	Co-expression
SRP050534	RNA profiling of two endothelial cells (MPEC and AKT-HUVEC) and one human fibroblast line (BJ)	Analysis of overall gene expression in endothelial cells, MPEC and AKT-HUVEC, comparing to a human fibroblast line, BJ. We are looking for the highly abundant genes in endothelial cells comparing to fibroblasts. Overall design: Total RNA isolated from MPEC, AKT-HUVEC and BJ Fig 3b in publication.	Co-expression
SRP050596	RNA-sequencing of healthy human skeletal myocytes	Skeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D. Overall design: Isolated skeletal muscle precursor cells from six normal glucose tolerant and non-obese males and females were differentiated in vitro. RNA from fully differentiated myotubes was sequenced using RNA-seq.	Co-expression
SRP050892	Human pluripotent stem cell-derived neural constructs for predictive neurotoxicity screening	Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety.  Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain.  The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearman's correlation coefficients, ? = 0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes.  Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds. Overall design: Note that all cell types were derived from the H1 human embryonic stem cell line. 11 samples for initial quality control (triplicate day 13 neural progenitor cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells and migroglia/macrophage precursor cells), quadruplicate samples of H1 ES cells as a control for comparing to untreated toxicity study samples, and 288 samples associated with toxicity screening (all samples formed using neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors).	Co-expression
SRP050900	RNA sequencing of CACO-2 cells incubated with bifidobacteria grown on human milk oligosaccharides.	Background: Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO).  The two most predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increase adhesion to intestinal cells and increase the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. Results: HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source.  Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both down-regulated genes in Caco-2 cells associated with chemokine activity. Conclusion: The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics. Overall design: CACO-2 cells incubated with Bifidobacterium longum subsp. infantis grown on (1) glucose, (2) lactose, or (3) human milk oligosaccharides. All experiments were run in triplicate.	Co-expression
SRP050954	Differential susceptibility of human pleural and peritoneal mesothelial cells to asbestos exposure	We hypothesize that the observed differences in incidences of pleural and peritoneal malignant mesothelioma (MM) are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis, we characterized cellular responses to asbestos in a controlled environment using high-throughput RNA sequence and other assays. Overall design: Examination of asbestos-treated versus untreated mesothelial cells from four cell lines representing two tissue types in culture.	Co-expression
SRP050971	Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin	Together with the GSE54456 data, we used in total RNA-seq data from 99 lesional psoriatic, 27 uninvolved psoriatic, and 90 normal skin biopsies and applied computational approaches to identify and characterize expressed lncRNAs. Overall design: 7 psoriatic, 27 uninvolved, and 8 normal skin samples	Co-expression
SRP050990	RNA sequencing of CACO-2 cells incubated with Bifidobacteria breve grown on human milk oligosaccharides.	Background: Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO).  The two most predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increase adhesion to intestinal cells and increase the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. Results: HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source.  Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both down-regulated genes in Caco-2 cells associated with chemokine activity.  Conclusion: The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics. Overall design: CACO-2 cells incubated with Bifidobacterium breve grown on (1) glucose, (2) lactose, or (3) human milk oligosaccharides. All experiments were run in triplicate.	Co-expression
SRP050992	Single cell RNA-seq data of human hESCs to evaluate Oscope - a statistical pipeline for identifying oscillatory genes in unsynchronized single cell RNA-Seq	Oscillatory gene expression is fundamental to mammalian development, but technologies to monitor expression oscillations are limited. We have developed a statistical approach called Oscope to identify and characterize the transcriptional dynamics of oscillating genes in single-cell RNA-seq data from an unsynchronized cell population. Applications to a number of data sets, include a single-cell RNA-seq data set of human embroyonic stem cells (hESCs), demonstrate advantages of the approach and also identify a potential artifact in the Fluidigm C1 platform. Overall design: Total 213 H1 single cells and 247 H1-Fucci single cells were sequenced. The 213 H1 cells were used to evaluate Oscope in identifying oscillatory genes. The H1-Fucci cells were used to confirm the cell cycle gene cluster identified by Oscope in the H1 hESCs. Normalized expected counts are provided in GSE64016_H1andFUCCI_normalized_EC.csv.gz	Co-expression
SRP051023	Chimeric RNA profiling demonstrates an association of alveolar rhabdomyosarcoma with specific stages of normal myogenesis	Total RNA extracted from differentiated mesenchymal stem cells at four time points (T1,T2,T3,T4) and sequenced using Illumina Hi-seq 2000 platform to generate RNA sequencing with 101bp in read length. Nearly 50 million raw reads were yielded from each sample respectively. We used FastQC to confirm the quality of raw fastq sequencing data, and SOAPfuse software to detect fusion transcripts. Overall design: Discovering fusion genes from muscle differentiated mesenchymal stem cells	Co-expression
SRP051073	PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells	The aim of this study is to describe expression changes related to the metastatic behavior of PCa cells after siRNA-mediated knockdown of PRK1. Overall design: siRNA-mediated knockdown of PRK1 in androgen-independent prostate cancer cell line PC3-M_luc2	Co-expression
SRP051083	Transcriptome profiling of human lung cancer cell lines.	Purpose: The aim of this study is to compare different RNA extraction methods using a mixture design that allows the relative changes of the majority of genes profiled to be estimated. A number of samples were degraded to allow us to compare methods for dealing with more variable samples. Methods - Cell Culture: Lung adenocarcinoma cell lines NCI-H1975 and HCC827 from a range of passages (2-4) were grown on 3 separate occasions in RPMI media (Gibco) supplemented with Glutamax and 10% fetal calf serum to a 70% confluence. To replicate common experimental conditions cell lines were treated with 0.01% Dimethyl sulfoxide (Sigma), which is commonly used as a vehicle in drug treatment experiments. After 6 hours of treatment, cells were collected, snap-frozen on dry ice and stored at -80 degrees C until required. Methods - RNA preparation: Total RNA was extracted from between half a million and million cells using Total RNA Purification Kit (Norgen Biotek) with on-column DNAse treatment accorting to the kit instructions. RNA concentration for each pair of samples to be mixed was equalised to ~100 ng/µl using Qubit RNA BR Assay Kit (Life Technologies). Replicates were pooled in known proportions to obtain mixtures ranging from pure NCI-H1975 (100:0) to pure HCC827 (0:100) and intermediate mixtures ranging from 75:25 to 50:50 to 25:75  NCI-H1975:HCC827. All mixtures corresponding to the second replicate were split into two equal aliquots. One aliquot was left intact (we refer to this as the ''good'' replicate), while the second aliquot was degraded to produce known outlier samples by incubation at 37 degrees C for 7 days in a thermal cycler with a heated lid. 10 µl from each replicated mixture (both good and degraded) were used for Next Generation Sequencing library preparation using two kits: Illumina TruSeq Total Stranded RNA with Ribozero (TotalRNA) and Illumina TruSeq RNA v2 (mRNA) according to the manufacturer''s instructions. Completed libraries were sequenced on HiSeq 2500 with TruSeq SBS Kit v4- HS reagents (Illumina) as 100 bp single-end reads at the Australian Genome Research Facility (AGRF), Melbourne. Approximately 30 million 100 bp single-end reads were obtained for each sample. Reads were aligned to the human reference genome hg19 and mapped to known genomic features at the gene level using the Rsubread package (version 1.16.1) (Liao et al. 2013). Single reads were then summarized into gene-level counts using FeatureCounts (Liao et al. 2014). Overall design: Total RNA was extracted from lung adenocarcinoma cell lines NCI-H1975 and HCC827 (3 independent samples for each cell line) and mixed in known ratios. Both mRNA and Total RNA transcriptomes from these mixtures were profiled by RNA-Seq.	Co-expression
SRP051102	Comparison of poly(A) and capture RNA-seq: controlled degradation in vitro	We compare the performance of two library preparation protocols (poly(A) and exome capture) in in vitro degraded RNA samples Overall design: VcaP cell were grown, and treated with MDV3100 (enzalutamide) or DHT (dihydrotestosterone), intact RNA was isolated and samples were prepared in technical triplicates using two library preparation protocol. Also cells were subject to in vitro degradation through incubation of the whole cell lysate in 37C for increasing amounts of time. Following incbation paired capture and poly(A) libraries were prepared.	Co-expression
SRP051118	Homo sapiens	We used targeted RNA sequencing to identify gene fusions in various cell types	Co-expression
SRP051170	The activation of IL-1 induced enhancers depends on TAK1 kinase activity and NF-KB p65 [RNA-Seq]	The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-?B subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-?B p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-?B-dependent enhancers in epithelial cells. Overall design: RNA-seq of KB cells either untreated or treated with IL-1 alpha	Co-expression
SRP051182	Dual RNA-sequencing of nontypeable Haemophilus influenzae and host cell transcriptomes reveals new aspects of host-pathogen interface	Characterization of host-pathogen interactions is critical for the development of next-generation therapies and vaccines. Classical approaches involve the use of transformed cell lines and/or animal models which may not reflect the complexity and response of the human host. We reconstituted the ciliated human bronchial epithelium in vitro using primary bronchial epithelial cells to simultaneously monitor the infection-linked global changes in nontypeable Haemophilus influenzae (NTHi) and infected host epithelia gene expression by dual RNA-seq. Acquisition of a total of nearly 2,5 billion sequences allowed construction of high-resolution strand-specific transcriptome maps of NTHi during infection of host mucosal surface and monitoring of metabolic as well as stress-induced host-adaptation strategies of this pathogen. As a part of our screening, we identified a global profile of noncoding transcripts that are candidate small RNAs regulated during human host infection in Haemophilus species. Temporal analysis of host mRNA signatures revealed significant dysregulation of target cell cytoskeleton elicited by bacterial infection, with a profound effect on intermediate filament network of bronchial epithelium. Our data provide a robust and comprehensive catalogue of regulatory responses that drive NTHi pathogenesis and gives novel insights into complex crosstalk between the host and the invading pathogen. Overall design: Primary human bronchial epithelium was infected with NTHi at a multiplicity of 100:1. Total RNA was isolated at 1, 6, 24 and 72 h post-infection in three biologically-independent experiments and cDNA libraries were prepared and sequenced with Illumina HiSeq 2500 sequencer. At each time point, between 60 and 180 million total reads per sample were obtained of which approximately one-third could be aligned to non-rRNA regions of the bacterial and human genomes	Co-expression
SRP051249	Tissue-specific circular RNA induction during human fetal development	The pervasive expression of circular RNA from protein coding loci is a recently discovered feature of many eukaryotic gene expression programs.  Computational methods to discover and quantify circular RNA are essential to the study of the mechanisms of circular RNA biogenesis and potential functional roles they may play.  In this paper, we present a new statistical algorithm that increases the sensitivity and specificity of circular RNA detection.by discovering and quantifying circular and linear RNA splicing events at both annotated exon boundaries and in un-annotated regions of the genome  Unlike previous approaches which rely on heuristics like read count and homology between exons predicted to be circularized to determine confidence in  prediction of circular RNA expression, our algorithm is a statistical approach. We have used this algorithm to discover general induction of circular RNAs in many tissues during human fetal development.  We find that some regions of the brain show marked enrichment for genes where circular RNA is the dominant isoform. Beyond this global trend, specific circular RNAs are tissue specifically induced during fetal development, including a circular isoform of NCX1 in the developing fetal heart that, by 20 weeks, is more highly expressed than the linear isoform as well as beta-actin. In addition, while the vast majority of circular RNA production occurs at canonical U2 (major spliceosome) splice sites, we find the first examples of developmentally induced circular RNAs processed by the U12 (minor) spliceosome, and an enriched propensity of U12 donors to splice into circular RNA at un-annotated, rather than annotated, exons.  Together, our algorithm and its results suggest a potentially significant role for circular RNA in human development. Overall design: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kit.	Co-expression
SRP051320	Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma (RNA-Seq)	Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. Here, we demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Phenotypic effects are preceded by the direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4 and the subsequent down-regulation of the IRF4 transcriptional program. Ectopic expression of IRF4 antagonizes the phenotypic effects of CBP/EP300 bromodomain inhibition and prevents the suppression of the IRF4 target c-MYC. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network. Overall design: Through the use of CBP/EP300 bromodomain inhibitors (CBP/EP300i), we demonstrate that MYC expression in BETi-resistant cells is dependent on CBP/EP300 bromodomains and that treatment with CBP/EP300i restores phenotypic sensitivity.	Co-expression
SRP051331	Human DIS3 shapes the RNA polymerase II transcriptome degrading variety of unwanted transcripts.	Human DIS3 is a nuclear, catalytic subunit of the exosome complex containing exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide we conducted comprehensive transcriptomic analysis of HEK293 cells producing mutated DIS3 versions and Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) experiments. Pervasive transcription products like Promoter Upstream Transcripts (PROMPTs) accumulated robustly in catalytic DIS3 mutants, representing ~8% of PAR-CLIP reads. Importantly, RNAs originating from unannotated genomic regions increased ~2.5 times in double DIS3 mutants, covering ~70% of genome and allowing for discovery of thousands of  novel transcripts. The first intron of many pre-mRNAs accumulated in DIS3 mutants indicating a widespread premature RNA polymerase II termination. The short form of NEAT1 lincRNA was overexpressed in DIS3 mutants, leading to increased number of paraspeckles. Moreover, there was a global deregulation of mRNAs in DIS3 double mutant. Finally, snoRNA precursors accumulated, which correlated with a strong PAR-CLIP signal indicating that DIS3 but not RRP6 is a main snoRNA processing enzyme. In aggregate, we demonstrate that DIS3 is a major nucleoplasmic activity responsible for shaping the human transcriptome. Overall design: RNA-seq experiments were performed in triplicates for DIS3 wild type (control), DIS3 PIN, DIS3 RNB domain mutants and DIS3 PIN RNB double mutant. RNA-seq samples from DIS3 wild type and DIS3 double mutant were additionally sequenced in deeper resolution, also in triplicates. DIS3 PAR-CLIP experiment was performed in duplicate. Pol II ChIP-seq experiment in WT and DIS3 PIN RNB double-mutants cells was performed in triplicates.	Co-expression
SRP051333	Effect of PDZ domain binding Kinase inhibition using TOPK-32 (called PBKi) on C4-2 cell transcriptome	Analysis of C4-2 prostate cancer cell line after 6 hrs of treatment with TOPK-32. PBK is overexpressed in a number of solid tumours, including prostate cancer. Results provide insight into the molecular mechanisms of PBK in prostate carcinogenesis. Overall design: This experiment was designed to understand the regulation of transcriptome by PDZ domain binding kinase, which is an important kinase with role in cell cycle. The cells were treated with a catalytic inhibitor TOPK32 which inhibits the kinase activity of PBK protein.	Co-expression
SRP051359	Homo sapiens Transcriptome or Gene expression	investigation of lncRNAs deregulated in oncogenic induced senescence.	Co-expression
SRP051368	Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells (mRNA-Seq)	DNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Transcriptional profiles (polyA+) of 6 non-infected and 6 MTB-infected dendritic cell samples.	Co-expression
SRP051369	Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells (wtRNA-Seq)	DNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Transcriptional profiles (ribo-minus) of non-infected and MTB-infected dendritic cell samples, in triplicate.	Co-expression
SRP051380	Epigenomic profiling reveals the key function of histone H3K9 methylation during tumor transformation process	To understand transcriptome and epigenome profilings alteration during breast cancer initiation and development, we constructed a in vitro breast cancer transformation model. And then, we use mRNA-Seq to uncover differential expression genes during breast cancer transformation process. For epigenomic profilings, we specificly analysis genome wide H3K9me2, H3K9me3,H3K4me3 and H3K27me3 modifications using ChIP-Seq. We found that H3K9 di and tri methylation decrease both in vitro breast cancer cell transformation model and in vivo clinical samples. Further more, we found KDM3A, a demethylase for H3K9 mono and di methylation, increase during the breast cancer model transformation process and clinical samples. KDM3A deficiency impairs the growth of those transformed cell lines and its overexpression promotes tumor formation. Overall design: To study the underlying mechanisms of breast cancer transformation, we utilized a cell based cell transformation model. Large T antigen, TERT and HRAS(V12) were transfected into purchased primary breast cell, respectively. Four cell lines were used for the following study, named as HMC-p6 (breast primary cell passage 6), HMC-L (breast primary cell with stable large T expression), HMC-LT (breast primary cell with large T and TERT) and HMC-LTR (breast primary cell with large T, TERT and HRAS (V12)). HMC-p6 cell is a normal breast primary cell, and we proved HMC-LTR is a cancer cell by using colony formation and nude mouse tumor formation assay. And then, we performed mRNA-Seq and ChIP-Seq in those four cell lines using standard Illumina TruSeq Kit as the manufaturer''s suggested. For KDM3A function analysis, we performed knockdown of KDM3A in L.T and L.T.R by using shRNA and siRNA, respectively.  NC stands for negative control, briefly, for shRNA we used shGFP as control and for siRNA we used negative control RNA.	Co-expression
SRP051401	Human Schlafen 5 (SLFN5) is a Regulator of Motility and   Invasiveness of Renal Cell Carcinoma (RCC) Cells	There is some emerging evidence that members of the Schlafen (SLFN) family of  proteins mediate antineoplastic responses, but the mechanisms accounting for these  effects are not known. We provide evidence that human SLFN5, an interferon (IFN)-  inducible member of the family, exhibits key roles in controlling motility and  invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by  which this occurs, demonstrating that SLFN5 negatively controls expression of matrix  metalloproteinases (MMP)-1 and -13 and several other genes involved in the control of  malignant cell motility. Importantly, our data establish that SLFN5 expression correlates  with a better overall survival in a large cohort of patients with RCC. The inverse  relationship between SLFN5 expression and RCC aggressiveness raises the possibility of  developing unique therapeutic approaches in the treatment of RCC, by modulating  SLFN5 expression. Overall design: Examination of 2 SLFN5 knockdown cells and 2 controls, in triplicate.	Co-expression
SRP051468	HITS-CLIP analysis uncovers a link between the Kaposi''s sarcoma associated herpesvirus ORF57 protein and host pre-mRNA metabolism	The Kaposi''s sarcoma associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi''s sarcoma, primary effusion lymphoma (PEL), and some forms of multicentric Castleman''s disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5´ ends. The position of these 5´-bound fragments correlated closely with the 5´-most exonintron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9) and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation. Overall design: HITS-CLIP was performed on TREx BCBL-Rta cells 20 hpi using antibodies against ORF57. Three biological replicates were performed.	Co-expression
SRP051472	Induction of circular RNA in fetal heart development recapitulated in in vitro differentiation	We discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. Overall design: We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.	Co-expression
SRP051485	Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma	Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. Overall design: RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.	Co-expression
SRP051518	The transcriptome of Kawasaki Disease arteritis	Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes.  80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries	Co-expression
SRP051544	FOXD3 is a novel tumor suppressor in lung cancer	The transcription factor forkhead box D3 (FoxD3) is a transcriptional factor which belongs to forkhead box (Fox) transcription factor family. The functions of FOXD3 in embryogenesis and in the development of neural crest cells have been clearly defined. Its tumor suppressor function hasbeen found in many types of cancer in recent years. However, the study about its roles in lung cancerdevelopment is still lacking. Our study found that deficiency of FoxD3 in lung cancer enhanced cell growth and cell invasion. RNA-sequence analysis demonstrated that loss of FoxD3 mainly affected cell cycle progression related gene expression. Knockdown of FoxD3 led to G2-M cell accumulation with up-regulation of DNA replication licensing factor MCM5 and MCM4 as well as cell cycle regulator polo-like kinase-1 (PLK1) and CDC6. Over-expression of those genesin lung cancer was associated with poor clinical outcomes of lung cancer patients. We also identified high mobility group box-1(HMGB1), Hras and Ephrin B1 gene expression increase after FoxD3 silencing which may participate in enhanced lung cancer cell invasion. Our study identifiedtumor suppressor function of FoxD3 in lung cancer andwe did the first comprehensive analysis of the genes regulated by FoxD3 for cell proliferation and invasion in lung cancer. The identified genes regulated by FoxD3 through our analysis will provide valuable information to uncover the mechanism of FoxD3 tumor suppressor function. Overall design: Three control and three FOXD3 knockdown A549 cell lines were subjected to RNA sequencing.	Co-expression
SRP051583	Assembly of methylated LSD1 and CHD1 drives AR-dependent transcription and translocation [RNA-Seq]	The aim of the study is to identify AR target gens in LNCaP cells Overall design: 6 samples correponding to 2 times 3 replicates were used for the study	Co-expression
SRP051595	shRNA knockdown of YAP1 in HCC364 cells, various drug conditions	Through a genetic screen in BRAF mutant tumor cells, we show that the Hippo pathway effector YAP acts as a parallel survival input to promote resistance to RAF-MEK inhibitor therapy. Our data uncover YAP as a novel mechanism of resistance to RAF-MEK targeted therapy. The findings unveil the synthetic lethality of YAP and RAF-MEK co-suppression as a promising strategy to enhance response and patient survival. Overall design: RNAseq analysis of HCC364 (lung adenocarcinoma) cells in the context of drug treatment with PLX4720 (vemurafenib, a BRAF inhibitor) or Trametinib (a MEK inhibitor) alongside shRNA knockdown of the gene YAP1	Co-expression
SRP051599	RNA-seq of human fibroblasts during normal aging and during aging with rotenone perturbation	Human fibroblasts at different population doublings were treated with low amounts of rotenone (mild stress) and compared to untreated fibroblasts. Two different cell lines were used (MRC-5, HFF). Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 60 samples: 3 biological replicates for each group: MRC-5 cells at 4 different population doublings (PD) with and without rotenone; HFF cells at 6 different population doublings with and without rotenone	Co-expression
SRP051606	Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer [RNA-seq]	The histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Overall design: Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).	Co-expression
SRP051626	Molecular phenotyping of a test compound (small-molecule neurotransmitter receptor antagonist) in primary human hepatocytes	Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment. Overall design: Vehicle control, diclofenac, and three doses of the test compound (small-molecule neurotransmitter receptor antagonist) were applied to three primary cell lines, with three biological replicates in each group. In some treatment groups read-outs were only available for two samples. All together 41 samples were profiled.	Co-expression
SRP051628	Estrogen Receptor Beta Impacts Hormone-Induced Alternative mRNA Splicing in Breast Cancer Cells	Estrogens play an important role in breast cancer (BC) development and progression, where the two isoforms of the estrogen receptor (ERa and ERß) are generally co-expressed and mediate the effects of these hormones in cancer cells. ERß has been suggested to exert an antagonist role toward the oncogenic activities of ERa, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERß in cancer cells. We described previously the ERß and ERa interactomes of BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERa and ERß pathways. Guided by these findings, we investigated here in depth the differences in the early transcriptional events and RNA splicing patterns induced in ERa vs ERa+ERß cells, by expressing ERß in ERa+ human BC MCF-7 cells. High-throughput mRNA sequencing was then performed in both cell lines after stimulation with 17b-estradiol, and the results obtained were compared. Overall design: We investigated here in depth the differences in the early transcriptional events and RNA splicing patterns induced in ERa vs ERa+ERß cells, by expressing ERß in ERa+ human BC MCF-7 cells. High-throughput mRNA sequencing was then performed in both cell lines after stimulation with 17b-estradiol, and the results obtained were compared.	Co-expression
SRP051674	SIRT6 regulates redox homeostasis in human mesenchymal stem cells by the transactivation of NRF2	We investigated the effect of SIRT6-knockout on gene expression and H3K4me3 modification profile in human mesenchymal stem cells. Overall design: RNAs isolated from SIRT6+/+ and SIRT6-/- hMSCs at early and late passages were sequenced, respectively. And, H3K4me3 ChIP-seq was performed upon the SIRT6 deleted hMSC and WT at early stage, respectively.	Co-expression
SRP051688	A Cell-based Systems Biology Assessment of Human Blood to Monitor Immune Responses After Influenza Vaccination	Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination.  Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. Overall design: PBMC and six purified cell types from two vaccinated donors were isolated prior to (d0) and at days 1, 3, and 7 post-TIV vaccination for RNA-seq analysis	Co-expression
SRP051705	Hepatitis C virus functionally sequesters miR-122 [RNA-Seq]	Hepatitis C virus uniquely requires the liver specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (Ago) during HCV infection showed robust Ago binding on the HCV 5’UTR, at known and predicted miR-122 sites. On the human transcriptome, we observed reduced Ago binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 “sponge” effect could be relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and number of sites. We describe a quantitative mathematical model of HCV induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV. Overall design: mRNA-seq libraries were generated from mock or J6/JFH1 Clone2 infected Huh7.5 cells. Cells were infected at an MOI of 1-2 and harvested at 72 hours and 96 hours post-infection for CLIP. Libraries were generated using Illumina Truseq technology.	Co-expression
SRP051737	Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig	During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases.  However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Overall design: Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500	Co-expression
SRP051765	Therapy induced tumour secretomes promote resistance and tumour progression	Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. We found that targeted therapy with BRAF, ALK, or EGFR inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, infiltration and metastasis of drug-resistant cancer clones in the tumour. Additionally, the TIS supports the survival of drug-sensitive cells, contributing to incomplete tumour regression. We used transcriptomic analysis of sensitive tumour cells and xenograft tumours treated with vehicle, vemurafenib, or crizotinib to identify the transcriptional drivers and to dissect the TIS in melanoma (A375, Colo800, UACC62) and lung adenocarcinoma (H3122). In addition, we utilize cell type–specific mRNA purification by translating ribosome affinity purification (TRAP) to identify pathways that are up-regulated in resistant cells (A375R) in response to the regressing tumour microenvironment. Overall design: Analysis of the response of drug sensitive melanoma and lung adenocarcinoma cells to pharmacological inhibition of their driver oncogene and gene expression analysis of drug resistant cancer cells responding to different tumor microenvironments.	Co-expression
SRP051772	Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells	Purpose: We have succeeded in the generation and long-term expansion of SOX9-expressing CD271+PDGFRa+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1-CD271hiPDGFRaloCD73- neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/TGFb inhibitor (SB) and FGF2 (hereafter called FSB). When “primed” with TGFb, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. Under the FSB condition, ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages, maintained normal karyotype for at least 10 passages, which any conditions deviated from it (e.g. FGF2 alone or SB alone) failed to support. In order to address the molecular basis of such effects of FSB, a series of RNA-seq experiments were carried out. Methods: We generated and compared the transcriptome profiles of human ectomesenchymal cells expanded under FSB  with those cultured under FSB first then under FGF2 alone (F).  As a control, we also generated transcriptome of ectomesenchymal cells expanded from the begining under F conditions. RNA-sequencing libraries were prepared using a SureSelect Strand Specific RNA Library Preparation kit (Agilent technologies, Santa Clara, CA). Sequencing was performed on an Illumina HiSeq 1500 using a TruSeq Rapid SBS kit (Illumina, San Diego, CA) in a 50-base single-end mode. Sequenced reads were mapped against the human reference genome (GRCh37), using TopHat v2.0.12 (http://ccb.jhu.edu/software/tophat/index.shtml). Expression levels were calculated as fragments per kilobase of exon per million mapped fragments (FPKMs) using Cufflinks v2.1.1 (http://cole-trapnell-lab.github.io/cufflinks). Results: Ectomesenchymal cells maintained under FSB conditions preferentially expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B, MYCN), cranial mesenchymes (ALX1/3/4) and chondroprogenitors (SOX9, COL2a1) of the neural crest origin (SOX8/9, NGFR, NES). In contrast, those cultured under FSB then F, still expressed SOX4/11/12, but lost LIN28, MYCN, ALX1/3/4, NGFR, COL2a1 expression. Interestingl it enhances expresion ofTGFß-inducible genes such as THBS1/2 and DCN  and osteogenesis-related genes such as  COL1a1/2 and RUNX1/2. Conclusions: The CD271+CD73+ ectomesenchymal cells accumulated under FSB conditions possess an mRNA profile of proliferating primitive neural crest/ectomesenchymal cells, although they lacked SOX10 expression, which is critical for neural and melanocytic lineage commitment. Transition from FSB to F conditions supressed the proliferation-related genes expression and enhanced the ossification/mineralization, vasculogenesis/angiogenesis, and cardiac myogenesis-related gene expression. Thus, suppression of TGFß signaling by SB does not seem to freeze the developmental stage of the hPSC-derived neural crest during expansion. Such suppression may instead simply support the high proliferative potential of the cells as well as the expression of SOX9 (and COL2a1), and thereby maintain chondrogenic activity. SOX9 expression initiated at the specification and pre-migratory stages is transient in trunk neural crest but persists in cranial neural crest. The chondrogenic CD271+CD73+ ectomesenchymal cells that maintain SOX9 transcription and translation may therefore represent proliferating cranial neural crest, with a slight commitment to non-neural lineages. Overall design: Examination of human ES-derived neural crest-like progenies expanded in 3 different culture media. Each group contains three biological replicates.	Co-expression
SRP051819	Genomic analysis of Multiple Myeloma using RNA Sequencing	Multiple Myeloma (MM) is a fatal proliferation of plasma cells that primarily affects elderly individuals, afflicting over 21,000 patients and accounting for over 10,000 deaths in the US each year. Most patients with MM relapse and ultimately become refractory to chemotherapy. Molecular and cytogenetic stratification of patients can identify patients at high risk of relapse, who have a particularly poor survival. Even though gene expression profiling (GEP) has been shown to be better than standard criteria and leads to better treatment stratification, a notable proportion of patients with high-risk gene expression signature can also achieve very good long-term survival, whereas some patients with low-risk gene expression signature myeloma (MM) can experience early relapse. Thus, newer molecular markers are needed for better risk stratification and most importantly newer therapeutic targets are desperately needed for patients with high-risk and relapsed disease. We hypothesize that integrative genomic analysis can define biologically and clinically distinct forms of myeloma beyond what can be gleaned by gene expression profiling alone, and by bringing together multiple types of molecular measures and understanding their relationships, we can reveal a more complete picture of multiple myeloma pathology and therapeutic opportunities. We are performing high-resolution genome-wide genomic, exome and transcriptome and epigenomic characterization of primary MM using next-generation sequencing and correlating these data with survival outcomes in a well-annotated cohort of patients treated at Mt. Sinai. We expect our results to yield novel insights into pathogenesis of relapsed MM, improved prognostic models and new therapeutic targets not identified by current technologies, and to identify approved therapies that could be repurposed for improving the treatment of relapsed MM.	Co-expression
SRP051822	Type I interferon regulates the expression of long non-coding RNAs [RNA-seq]	Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNa2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNa2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNß also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response. Overall design: HuH7 cells were treated with 10000 units/ml of IFN a2 and RNA was isolated 3 days post-treatment	Co-expression
SRP051825	Common inflammatory pathways between NEC and Crohn''s disease	Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infant occuring in neonatal intensive care units. NEC is associated with severe intestinal inflammation, intestinal perforation leading to mortality. The challenge for neonatologists is to detect early clinical manifestations of NEC. Therefore, one of the strategies to prevent or treat NEC would be to develop an early diagnostic tool allowing identification of preterm infants either at risk of developing NEC or at the onset of the disease. Illumina’s deep sequencing technology (RNA-seq) was used to establish the gene expression profile between resected ileal healthy preterm (control, n=5) and NEC diagnosed preterm infant (NEC, n=9) and analyzed by IPA Core analysis system. IPA analysis indicated that the most significant functional pathways overrepresented in NEC neonates were associated with innate immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors in recognition of bacteria and viruses. Among genes that were strongly modulated in NEC neonates, we observed a high degree of similarity with those linked to the development of IBD. By comparing gene expression patterns between NEC and Crohn’s disease, we identified several new potential protein targets for helping to predict and/or diagnose NEC in preterm infant. Gene expression profile revealed an uncontrolled innate immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohn’s disease evidenced high degree of similarity between these two inflammatory diseases and allowed us to identify several new potential NEC biomarkers. Overall design: Illumina’s deep sequencing technology (RNA-seq) was used to establish the gene expression profile between resected ileal healthy preterm (control, n=5) and NEC diagnosed preterm infant (NEC, n=9)	Co-expression
SRP051844	mRNA-Seq Expression profiling of human post-mortem BA9 brain tissue for Huntington's Disease and neurologically normal individuals	Huntington's Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD. Overall design: 20 Huntington's Disease and 49 neurologically normal control samples from post-mortem human subjects	Co-expression
SRP051848	Gene Networks Specific for Innate Immunity Define Post-traumatic Stress Disorder [RNA-Seq]	The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used RNA-Sequencing gene expression to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects. Overall design: Peripheral blood luekocytes gene expression was subject to transcriptional analysis for 94 service members both prior-to and following-deployment to conflict zones. Half of the subjects returned with Post-traumatic stress disorder (PTSD), while the other half did not.	Co-expression
SRP051983	Molecular Biomarkers Screened by Next-generation RNA Sequencing for non-sentinel lymph node status predicting in breast cancer patients with metastatic sentinel lymph node	Six candidates (all ER/PR+, HER2-, Ki-67 <20 %) with metastatic SLNs selected from 305 patients were equally categorized as NSLN negative and positive. We identified 103 specifically expressed genes in the NSLN negative group and 47 in the NSLN positive group. Among them, FABP1 (negative group) and CYP2A13 (positive group) were the only 2 protein-encoding genes with expression levels in the 8th to 10th deciles. Using a false discovery rate threshold of <0.05, 62 up-regulated genes and 98 down-regulated genes were discovered in the NSLN positive group. Furthermore, 10 gene fusions were identified in this group with the most frequently fused 23 gene being IGLL5. Overall design: examination of transcriptome differences between NSLN positive and negative breast patients	Co-expression
SRP052034	Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor	Direct conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. Additionally, the single seeded induced NSCs were able to form NSC colonies with efficiency comparable to control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating and attaining neural phenotypes after transplantation into neonatal mouse- and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts. Overall design: RNA-Seq of 3 replicates each of iNSC, WT-NSC, and HNF	Co-expression
SRP052056	RNA-Sequencing of human papillary thyroid carcinomas	RNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors'' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Overall design: Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors'' thyroids.	Co-expression
SRP052201	Homo sapiens Colon cancer Cell line RNA-Seq	A growing body of genomic data on human cancers poses the critical question of how genomic variations translate to cancer phenotypes. We used standardized shotgun proteomics and targeted protein quantitation platforms to analyze a panel of 10 colon cancer cell lines differing by mutations in DNA mismatch repair (MMR) genes. In addition, we performed transcriptome sequencing (RNA-seq) to enable detection of protein sequence variants from the proteomic data. In addition, RNA-seq data also provide transcript expression information, which can be combined with protein expression levels to identify regulatory changes in biologic systems	Co-expression
SRP052229	Improved transcription and translation with L-leucine stimulation of mTORC1	Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 was inhibited and overall translation was reduced in RBS cells. Treatment of RBS cells with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division. In this study, we use RBS as a model for mTOR inhibition and analyze transcription and translation with ribosome profiling to determine genome-wide effects of L-leucine. The translational efficiency of many genes is increased with Lleucine in RBS cells including genes involved in ribosome biogenesis, translation, and mitochondrial function. snoRNAs are strongly upregulated in RBS cells, but decreased with L-leucine. Imprinted genes, including H19 and GTL2, are differentially expressed in RBS cells consistent with contribution to mTORC1 control. This study reveals dramatic effects of L-leucine stimulation of mTORC1 and supports that ESCO2 function is required for normal gene expression and translation. Overall design: 42 samples of human fibroblast cell lines with various genotypes (wt, corrected, and esco2 mutants) are treated with l-leucine or d-leucine (control) for 3 or 24 hours. Biological replicates are present.	Co-expression
SRP052294	Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion	The evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. Here, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a novel approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of the Rho GTPase-activating-protein–encoding ARHGAP11A on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal, and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex. Overall design: Gene expression profiles of mouse and human purified neocortical progenitor types and neurons were generated by RNA-seq and analyzed including inter- and intra-species comparison.	Co-expression
SRP052491	Transcriptome analysis of alveolar macrophages in asthma	Purpose: The goal of this study is to investigate the alteration of gene expression pattern of alveolar macrophages by allergen challenge in human asthmatics. Method: By using subsegmental bronchial provocation with allergen (SBP-AG) protocol, we obtained BAL fluids, before and 48 hours after allergen challenge in the subjects enrolled in the protocol. Alveolar macrophages were purified from the BAL fluids and total RNA was isolated. Next-generation sequencing data were generated by using the Illumina system. Results: Using an optimized data analysis workflow, we mapped about 75 million sequence reads per sample to the human genome and identified 29,691 transcripts in the macrophage mRNAs. Among them, the change in the expression profiles of 37 transcripts were statistically significant. Conclusions: It has been well accepted that Th2 cytokine enriched environment transforms the phenotype of macrophages into alternatively activated form. However, the details of a genome-wide gene expression profiles of macrophages were not well investigated. Using RNA-seq technology, we provided comprehensive data of macrophage gene expression profiles in allergic lung inflammation. Our data could offer a framework to study biologic functions of alternatively activated macrophage in chronic inflammatory diseases. Overall design: mRNA profiles of alveolar macrophages obtained from asthmatics, before and after allergen challenge.	Co-expression
SRP052612	Loss of endometrial plasticity in recurrent pregnancy loss (RNA-Seq)	In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women.  The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. Overall design: 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.Â	Co-expression
SRP052615	Diarrhea in lymphocytic colitis: ERK1/2-dependent ENaC dysregulation and claudin-4-, -5- and -8-related barrier defects	Background: Lymphocytic colitis (LC) causes watery diarrhea. This study aimed to identify the inherent pathomechanisms of epithelial transport and barrier dysfunction and regulatory inputs. Methods: 8 (4 LC samples and 4 unrelated control samples) biopsies of fresh sigmoid colon were analysed by paired end sequencing (Illumina High Seq 2500) Conclusions: ENaC-mediated Na+ malabsorption via ERK1/2 and epithelial barrier dysfunction from tight junction downregulation through claudin-4, -5, and -8 are mechanisms causing malabsorptive and leak flux diarrhea in LC resulting from the key effector cytokines TNFa and INFg. Overall design: Sigmoid colon mRNA profiles from 8 unrelated individuals (4 with LC, 4 as control) were generated using paired end sequencing with Illumina High Seq 2500	Co-expression
SRP052620	Genome-wide effect of inhibition of glutamine transporter ASCT2 in PC-3 cells by BenSer or GPNA	To determine the global effects of ASCT2 inhibition, we used next generation sequencing to determine mRNA expression changes in PC-3 cells treated with BenSer or GPNA for 48 h. Overall design: Examination of two different ASCT2 inhibitors BenSer and GPNA in prostate cancer cell line PC-3.	Co-expression
SRP052698	RNA Sequencing Reveals the Snail-Regulated Transcriptome in Head-and-Neck Squamous Cell Carcinoma.	The epithelial-to-mesenchymal transition (EMT) is a critical biological process in normal development and tumor progression. One of the EMT regulator, Snail is shown to suppress or activate its downstream genes to sustain migratory capacities while remodeling the tumor microenvironment. Identification of the Snail-regulated transcriptome through a robust sequencing technique will give a global direction for targeting Snail-driven malignancy. Overall design: The stable Snail-expressing and vector control HNSCC cells are generated by lentivirus transduction. The differential expression profiles of cell established are assessed to identify the enriched biological functions and hub genes.	Co-expression
SRP052706	Rapamycin induces chromosome reorganization and increases cytokine production in normal human fibroblasts	We report the effects of Rapamycin treatment on the transcriptome of normal human dermal fibroblasts isolated from foreskin (designated 2DD). We sequenced mRNA from 2 replicates of proliferative (PRO) quiescent (QUI, serum starved) or treated with 500nM Rapamycin for 5 days (RAP). Comparative analyses with PRO transcripts a baseline indicate that genes that changed expression from Rapamycin treated fibroblasts are significantly different from those of quiescence cells. Rapamycin treated cells showed a significant enrichment for cytokines from the Il-6 cascade. Overall design: Examination of mRNAs from proliferative, quiescent (serum starvation) and Rapamycin (5oonM, 5days) treated 2DD normal human dermal/foreskin fibroblasts.	Co-expression
SRP052713	Effect in HCT116 cells of 3hr cortistatin A treatment on gene expression.	We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on insensitive HCT116 cells of 3hrs exposure to CA. Overall design: HCT116 cells were treated in triplicate with either DMSO or CA for 3hrs after which RNA was harvested and prepared for RNA sequencing to assess transcriptional changes.	Co-expression
SRP052740	RNAseq changes in pre MAPKi treatment and post MAPKi resistance Melanomas	Melanoma resistance to MAPK- or T cell checkpoint-targeted therapies represents a major clinical challenge, and treatment failures of MAPK-targeted therapies due to acquired resistance often require salvage immunotherapies. We show that genomic analysis of acquired resistance to MAPK inhibitors revealed key driver genes but failedto adequately account for clinical resistance. From a large-scale comparative analysis of temporal transcriptomes from patient-matched tumor biopsies, we discovered highly recurrent differential expression and signature outputs of c-MET, LEF1 and YAP1 as drivers of acquired MAPK inhibitor resistance. Moreover, integration of gene- and signature-based transcriptomic analysis revealed profound CD8 T cell deficiency detected in half of resistant melanomas in association with downregulation of dendritic cells and antigen presentation. We also propose a major methylomic basis to transcriptomic evolution under MAPK inhibitor selection. Thus, this database provides a rich informational resource, and the current landscape represents a benchmark to understanding melanoma therapeutic resistance. Overall design: Melanoma biopsies pre and post MAPKi treatment were sent for RNAseq analysis	Co-expression
SRP052771	The activation of the NF-?B-JNK pathway is independent of the PI3K-Rac1-JNK pathway involved in the bFGF-regulated human fibroblast cell migration	Wound healing is a complex process that repairs organ-tissues including skin after injury. Cell migration is an important process of wound healing and fibroblast growth factor bFGF has been reported to accelerate cell migration. However, knowledge of how bFGF regulates cell migration is limited. Here, we used human foreskin fibroblast primary cells and RNA-Seq based transcriptome analysis to isolate bFGF-regulating signal pathways that regulate cell migration. Among the many pathways identified, an inflammatory response pathway was further examined for its role in fibroblast cell migration through analysis of function by the key regulator NF-?B. Application of Bay11-7082 and LPS, a typical inhibitor and inducer of inflammatory response, promoted and inhibited cell migration, respectively. Biochemical data showed that Bay11-7082 treatment induces the phosphorylation level of JNK,but PI3K inhibitor LY294002 application did not alter the I?Ba phosphorylation level. In addition, Bay11-7082 and JNK inhibitor SP600125 together inhibit while LY294002 together with Bay11-7082 maintains normal cell migration, indicating that NF-?B is independent of the PI3K pathway for regulation of JNK activity during cell migration. Taken together, the present study broadens our understanding of the bFGF-regulation mechanism and further identifies a new bFGF-regulating mechanism by which NF-?B regulates JNK during human fibroblast cell migration. Overall design: In this study, we utilized a RNA-Seq approach to isolate bFGF-regulating gene pools and to further identify target molecules that regulate human fibroblast cell migration.	Co-expression
SRP052781	Identification of transcripts regulated by CEBPA protein and its P30 isoform in K562	To investigate the effect of CEBPA and its mutant isoform P30 on the expression of mRNAs and long non-coding RNAs (lncRNAs), we utilized the K562 AML cell line carrying a stable and Tet-on inducible CEBPA  or P30 allele. Overall design: Based on the expression of known CEBPA transcriptional targets, we selected RNA extracted from 48 hours of induction (CEBPA or P30)  together with RNA extracted from control-induced cells (CTR).  2 biological replicates for each sample have been utilized.	Co-expression
SRP052817	Homo sapiens Transcriptome or Gene expression	Characterization of circular RNAs in Ovarian cancer	Co-expression
SRP052856	Genome-wide expression profiling of an in vitro model for studying esophageal epithelial differentiation	We used RNA sequencing to identify differentially expressed genes during esophageal epithelial differentiation and in the presence of interleukin 13 using an air-liquid interface culture system. Overall design: RNA sequencing was performed on a human esophageal epithelial cell line (EPC2-hTERT) grown submerged (day 8) or at the air-liquid interface (ALI) (day 14, untreated or treated with interleukin 13 [100 ng/mL])	Co-expression
SRP052874	SRSF2 mutations impair hematopoiesis and alter exon recognition	Mutations within genes encoding spliceosomal proteins are the most common class of mutations in patients with myelodysplastic syndromes, yet it is currently not well understood how these mutations impact hematopoiesis or RNA splicing. Here we report that mutations affecting the splicing factor SRSF2 alter its normal RNA recognition activity, resulting in impaired hematopoietic differentiation and myelodysplasia. Commonly occurring SRSF2 mutations impaired wildtype SRSF2’s normal RNA-binding avidity and preference for specific exonic splicing enhancer RNA motifs. Integration of murine and human transcriptome data identified recurrent mis-splicing of key transcriptional regulators in the presence of mutant SRSF2, including promotion of a highly conserved “poison” exon of EZH2 that results in nonsense-mediated decay and contributes to impaired hematopoiesis. These data provide a mechanistic basis for the enrichment of specific mutations in spliceosomal proteins in myelodysplasia, and suggest that altered RNA recognition activity is a novel mechanism of leukemogenesis. Overall design: mRNA profiles of murine model and K562 cells expressing SRSF2 WT, mutants and knockdown of SRSF2 in TF-1 cells generated by deep sequencing.	Co-expression
SRP052879	Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels by regulating NF-?B-dependent gene expression	Pro-inflammatory response of VSMCs is triggered by endothelial damage and a causative step for thrombosis and neointimal thickening in the arterial vessels. Therefore, we investigate a role of cytosolic Hsp60 as a novel pro-inflammatory mediator in VSMCs.  Hsp60 was detected in the cytosol of VSMCs. The selective depletion of cytosolic Hsp60 in VSMCs reduced the IKK activation, repressed the induction of NF-?B-dependent pro-survival genes (MnSOD and Bfl-1/A1), and enhanced apoptotic death in response to TNF-a. Moreover, a quantitative RNA sequencing revealed that the expression of 75 genes among the 774 TNF-a-inducible genes was significantly reduced by the depletion of cytosolic Hsp60. In particular, the expression of pro-inflammatory cytokines/chemokines, such as CCL2, CCL20, and IL-6, was regulated by the cytosolic Hsp60 in VSMCs. Finally, the depletion of cytosolic Hsp60 markedly inhibited the neointimal thickening in the balloon-injured arterial vessels by inducing apoptotic cell death and inhibiting chemokine production.  This study provides the first evidence that cytosolic Hsp60 could be a therapeutic target for preventing inflammation-driven VSMC hyperplasia in the injured vessels. Overall design: Hsp60 normal vs knockout with TNF-alpha treatment	Co-expression
SRP052896	SMARCA4-Deficient Thoracic Sarcoma Study	Caraterisation of tumors presenting SMARCA4 inactivation, underlying a group of undifferentiated thoracic malignancies transcriptomically related to BAF-deficient rhabdoid tumors.	Co-expression
SRP052950	Genetic and drug perturbation of components in the NFkB signaling pathway in 11-18 cells	Through the study of EGFR-mutant lung adenocarcinoma we show that NFkB signaling is rapidly engaged by EGFR oncogene inhibition to promote tumor cell persistence and therapy resistance. Unexpectedly, we found that EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NFkB-mediated transcriptional survival program. We identified a direct pharmacologic NFkB inhibitor, PBS-1086, that suppressed this adaptive survival program and increased both the magnitude and duration of initial EGFR TKI response in cellular and in vivo tumor models, including a novel patient-derived NSCLC xenograft. These findings unveil NFkB as a critical adaptive survival mechanism engaged in response to EGFR oncogene inhibition and identify PBS-1086 as a promising NFkB inhibitor to eliminate disease persistence and potentially prevent the emergence of resistance in patients. Overall design: RNAseq analysis of 11-18 (EGFR-mutant lung adenocarcinoma) cells in the context of drug treatment with erlotinib and/or genetic or pharmacological inactivation of NFkB	Co-expression
SRP052978	Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and cardiac-specific Bmi1 deletion [human]	To explore the primary cause of Dilated Cardiomyopathy in heart samples from DCM-diagnosed patients who had undergone heart transplant (hDCM), we set out to identify differentially expressed genes by massively parallel sequencing of heart samples. Overall design: Methods: Heart mRNA profiles from DCM-diagnosed patients who had undergone heart transplant (hDCM) were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP052983	Transfected HEK293 Transcriptome or Gene expression	To find the expression of transfected genes	Co-expression
SRP052991	RNA-seq and Microarray in Transcriptome Profiling of Anterior Cruciate Ligament Tears: Implications for Prognostic Biomarkers Discovery	Injury to anterior cruciate ligament (ACL) is common in young individuals and a frequent cause of functional instability and early onset of osteoarthritis. The healing potential of an injured ACL is known to decay over time. The molecular origin of this healing deficiency largely remains elusive but plausibly involves gene transcripts associated with tissue healing. To explore this possibility, we set out to identify transcript expression differences in injured ACL remnants recovered at the time of surgical reconstruction, via microarray (n=24) and RNA-seq (n=8) technologies in transcriptome profiling. We found that time-from-injury was an important determinant of changes in gene expression signatures predominately resulting in repression of several biological processes as identified by gene ontology. The most interesting observation was a time-dependent decline in the gene transcripts as well as the biological processes common to both microarray and RNA-seq analyses. Compared to acute tears, in chronic several important biological processes were namely extracellular matrix organization, angiogenesis, cell adhesion, wound healing, mesenchyme transition, and response to hypoxia. Furthermore, the cross-platform concordance in terms of differentially expressed transcripts or enriched pathways was linearly correlated (r=0.64). Microfluidic digital PCR confirmed the expression of selected differentially expressed transcripts. These intriguing findings suggest an initial attempt of the injured ACL to repair, which drops with time. These findings have implications for efforts to repair the ACL and may be relevant for its reconstruction. These findings also emphasize the utility of differentially expressed transcripts as prognostic biomarkers in patients with ACL injury. Overall design: Examination of transcript expression differences by time-from-injury in anterior cruciate ligament	Co-expression
SRP052998	Physical and functional CSL-p53 interactions underlie control of cancer stromal cell evolution [RNA-seq]	Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J? in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Overall design: Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.	Co-expression
SRP053004	Human Embryo Single Cell Transcriptome Analysis	We sorted 2PN stage human embryos by predicted viability using a noninvasive measurement we previously developed. We then performed RNA-seq on each embryo (which was a single cell) and looked for differences in expression between viable and nonviable embryos. Overall design: We sequenced the transcriptomes of 22 human zygotes (2PN stage) embryos, of which 11 were predicted nonviable and 11 were predicted viable. We excluded 5 which had no siblings in this data set. From the remaining 17 embryos, we analyzed the set of genes that was differentially expressed between those predicted viable and those predicted nonviable.	Co-expression
SRP053034	Homo sapiens Transcriptome or Gene expression	In response to DNA damage tissue homoeostasis is ensured by elaborate protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage-response signaling pathways coordinate these processes, in part, by propagating gene expression-modulating signals. DNA damage does not only influence abundance of mRNAs, but also their coding information through alternative splicing. This level of regulation is thus far poorly understood. Here we show that transcription-blocking DNA lesions promote displacement of activated spliceosomes and initiate a positive feedback loop centered on the DNA damage signaling kinase ATM. Pausing of elongating RNA polymerase at DNA lesions induces spliceosome displacement and R-loop formation. This in turn activates ATM, which signals to further impede splicing activity. These findings define the R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells and highlight a key role for spliceosome displacement in this process.	Co-expression
SRP053042	Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors	Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six FA patients with FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage, and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. Overall design: The investigation of the RNA-seq analysis of iPSC-derived HAPCs.	Co-expression
SRP053043	Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs (RNA-Seq)	Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations of the survival of motor neuron 1 (SMN1) gene. In the pathogenesis of SMA, pathological changes of the neuromuscular junction (NMJ) precede the motor neuronal loss. Therefore, it is critical to evaluate the NMJ formed by SMA patients’ motor neurons (MNs), and to identify drugs that can restore the normal condition. We generated NMJ-like structures using motor neurons (MNs) derived from SMA patient-specific induced pluripotent stem cells (iPSCs), and found that the clustering of the acetylcholine receptor (AChR) is significantly impaired. Valproic acid and  antisense oligonucleotide treatment ameliorated the AChR clustering defects, leading to an increase in the level of full-length SMN transcripts. Thus, the current in vitro model of AChR clustering using SMA patient-derived iPSCs is useful to dissect the pathophysiological mechanisms underlying the development of SMA, and to evaluate the efficacy of new therapeutic approaches.  Overall design: to evaluate the effects of VPA on the expression profiles of the MNs	Co-expression
SRP053048	Dynamic regulation of the histone variant H1.0 contributes to intratumor epigenetic and functional heterogeneity [RNA-Seq]	Identification of genes regulated by the histone variant H1.0 by RNA-seq analysis of cell lines expressing inducible specific shRNAs. Overall design: RNA-seq analysis of in vitro-transformed human skin fibroblasts expressing inducible shRNAs targeting H1.0. Two different cell lines expressing distinct shRNAs are analyzed. For ech cell line, uninduced cells (NT), cells induced with doxycycline for 16h  (SHOT), cells induced with doxycycline for 14 days (DOX) and cells washed out of doxycycline for 4 days (washDOX) are compared.	Co-expression
SRP053050	RNA sequencing (RNA-SEQ) of PSPC1 knockdown by shRNA in A549 cells	We show that PSPC1 is required for cancer cell motilities and stemness properties in vitro and lung metastasis in vivo. We used high throughput sequencing to analyze the PSPC1 regulated gene expression. Loss of PSPC1 results in significant gene expression level changes in thousands of individual transcripts in key regulators of the EMT, CSCs and TGFb signaling. Overall design: Methods: Gene expression profiles of A549 shPSPC1 knockdown cells were generated by Illumna RNA sequencing and compared to profiles derived from control cells (shLacZ knockdown).	Co-expression
SRP053052	Droplet barcoding for single cell transcriptomics applied to embryonic stem cells	Recently, RNA sequencing has achieved single cell resolution, but what is limiting is an effective way to routinely isolate and process large numbers of individual cells for in-depth sequencing, and to do so quantitatively. We have developed a droplet-microfluidic approach for parallel barcoding thousands of individual cells for subsequent RNA profiling by next-generation sequencing. This high-throughput method shows a surprisingly low noise profile and is readily adaptable to other sequencing-based assays. Using this technique, we analyzed mouse embryonic stem cells, revealing in detail the population structure and the heterogeneous onset of differentiation after LIF withdrawal. The reproducibility and low noise of this high-throughput single cell data allowed us to deconstruct cell populations and infer gene expression relationships. Overall design: A total of 8 single cell data sets are submitted: 3 for mouse embryonic stem (ES) cells (1 biological replicate, 2 technical replicates); 3 samples following LIF withdrawal (days 2,4, 7); one pure RNA data set (from human lymphoblast K562 cells); and one sample of single K562 cells.	Co-expression
SRP053098	BPTF is required for c-MYC-induced remodelling of target chromatin and transcriptional activation [RNA-Seq]	The c-MYC oncogene is a key transcription factor deregulated in most human tumors. Histone marks associated with transcriptionally active genes in euchromatic islands define the set of high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are not known but likely involve chromatin-remodelling and chromatin-modifying complexes. Here, we show that c-MYC interacts with BPTF, a core subunit of the NURF complex that binds active chromatin. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to a decrease in c-MYC recruitment to DNA and to changes in chromatin accessibility. Using BPTF-null MEFs we show that BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress, but not for c-MYC-driven apoptosis. Consistently, BPTF is required for the proliferation of cells driven by c-MYC, such as Burkitt lymphoma, and its expression in human cancer lines correlates with the activation of c-MYC gene signatures. Our findings point to the c-MYC-BPTF axis as a potential therapeutic target in cancer. Overall design: To assess whether BPTF is required for the transcriptional activity of c-MYC, human foreskin fibroblasts (HFF) were stably transduced with the chimeric MYC-ER cDNA (HFF MYC-ER) and infected with lentiviruses coding for either control (shNt) or BPTF-targeting shRNAs. Cells were serum-starved for 2 days to achieve quiescence and then treated with 4-hydroxytamoxifen (4-OHT)	Co-expression
SRP053101	Impact of bariatric surgery on RNA-seq gene expression profiles of adipose tissue in humans	Bariatric surgery is the most effective therapy of severe human obesity. It is associated with improvements in metabolic and non metabolic co-morbidities which are thought to be mediated by a decrease of adipose tissue inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. We analyzed expression profiles in subcutaneous adipose tissue from 22 obese women before and 3 months after surgery using the RNA-seq technology. Of 15,972 detected genes, 1214 were differentially expressed after surgery. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, we identified 26 modules of coexpressed genes. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue, including a general signature of innate immune cells, an adaptive immune response elicited by T lymphocytes, a neutrophil-mediated inflammatory signature and an interferon-signaling pathway, respectively. After surgery, a few crucial molecules involved in chemotaxis and activation of immune cells were disconnected from their respective networks. These molecules may represent therapeutic targets against adipose inflammation. Overall design: mRNA sequencing of subcutaneous adipose tissue (SAT) samples from 22 obese women before and 3 months after bariatric surgery	Co-expression
SRP053124	Homo sapiens Transcriptome or Gene expression	TNFa-induced inflammation is important in diabetic retinopathy. This study was performed to determine the effect of TNFa on human microvascular endothelial cells as well as the role of the PPARbeta/delta antagonist GSK0660 on TNFa-stimulated cells.	Co-expression
SRP053190	Whole cell mRNA expression profiling in control and complex I deficient patient fibroblasts incubated with DMSO, AICAR, chloramphenicol, and resveratrol	Background: Transcription control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study, we combined RNA sequencing of human complex I-deficient patient cells across 32 conditions of perturbed mitochondrial metabolism, with a comprehensive analysis of gene expression patterns, co-expression calculations and transcription factor binding sites. Results: Our analysis shows that OXPHOS genes have a significantly higher co-expression with each other than with other genes, including mitochondrial genes. We found no evidence for complex-specific mRNA expression regulation in the tested cell types and conditions: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of OXPHOS complex subunits compared to assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of six yet uncharacterized candidate transcription factors (ELK1, KLF7, SP4, EHF, ZNF143, and EL2). Conclusions: OXPHOS genes share an expression program distinct from other mitochondrial genes, indicative of targeted regulation of this mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. Overall design: RNA-SEQ of whole cell RNA in 2 control and 2 complex I deficient patient fibroblast cell lines treated with 4 compounds in duplicate, resulting in a total of 2x2x4x2=32 samples	Co-expression
SRP053227	The effect of HOXB13 CRISPR knockout on the transcriptome in G401 cells	We report the expression profiles of G401 rhabdoid tumor of the kidney cell lines with and without the expression of the homeobox transcription factor HOXB13. Overall design: Single samples of G401-sg-control and G401-sg1-HOXB13 cells were subjected to RNAseq	Co-expression
SRP053246	Sperm RNA: A window to idiopathic infertile couples	We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple. Overall design: NGS RNA-seq of 72 sperm samples from male partner of couples undergoing fertility treatment	Co-expression
SRP053274	Homo sapiens Transcriptome or Gene expression	Eosinophils are granulocytes that play a role in homeostasis and pathogenesis of heminth infection and allergic diseases. To gain insight into eosinophil development and function, we performed a RNA-seq analysis using developing cord blood (CB) eosinophils at day 18 and at day24.	Co-expression
SRP053296	Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction.	Recent technological advances have made transcriptome sequencing (RNA-seq) possible in cells with low RNA copy number including platelets. Resulting studies have used RNA-seq in platelets isolated from healthy individuals to characterize the platelet transcriptome. However, platelets, possibly through gene expression changes, contribute to the etiology of and response to cardiovascular disease and events. To address this, we performed the largest human platelet RNA-seq analysis to date in 34 platelet samples: 16 ST-segment elevation myocardial infarction (STEMI), 16 non-STEMI (NSTEMI), and 2 controls. Overall design: RNA-seq of platelet samples from 34 individuals: 16 with ST-elevation myocardial infarction (STEMI), 16 with non-STEMI, and 2 non-myocardial infarction controls	Co-expression
SRP053366	Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy [RNA-Seq]	Phospholamban R14del mutazion (PLN-R14del) has been identified in a large family pedigree in which heterozygous carriers exhibited inherited dilated cardiomyopathy (DCM) and death by middle age. To better understand the causal link between the mutations in PLN and DCM pathology, we derived induced pluripotent stem cells from a DCM patient carrying the PLN R14del mutation. We showed that iPSC-derived cardiomyocytes recapitulated the DCM-specific phenotype and demonstrated that either TALEN-mediated genetic correction or combinatorial gene therapy resulted in phenotypic rescue. Our findings offer novel insights into the pathogenesis caused by mutant PLN and point to the development of potential new therapeutics of pathogenic genetic variants associated with inherited cardiomyopathies. Overall design: iPSCs were derived from a female patient carrying a heterozygous mutation (R14del) in the PLN gene. Tree samples were analyzed: Cardiomyocytes derived from PLN-R41del iPSC cells (R14del-CM); R14del-CMs infected with AAV6-EGFP-miR-PLN and R14del-CMs infected with AAV6-EGFP-miR-luc used as a negative control	Co-expression
SRP053402	The Small Molecule ISRIB Reverses the Effects of eIF2a Phosphorylation on Translation and Stress Granule Assembly	We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2a phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498).  Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2a and induced no major changes in translation or mRNA levels in unstressed cells. eIF2a phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2a phosphorylation, SG formation and cognitive loss. Overall design: Ribosome profiling with paired RNA-seq	Co-expression
SRP053791	En bloc and segmental deletions of human XIST reveal X chromosome inactivation-involving RNA elements	RNA-seqs followed by whole and segmental deletions of XIST genes in human K562 cells. The XIST RNA is a non-coding RNA that induces X chromosome inactivation (XCI). Unlike the mouse Xist RNA, how the human XIST RNA controls XCI in female cells is less well characterized, and the XCI-involving RNA elements remain unclear. To systematically decipher the XCI-involving elements of XIST RNA, ten smaller XIST segments, including repeats A, D, and E; human-specific repeat elements; the promoter; and non-repetitive exons, as well as the entire XIST gene, were homozygously deleted using the Cas9 nuclease and paired guide RNAs at high efficiencies, followed by high-throughput RNA sequencing and fluorescence in-situ hybridization experiments on XIST RNA. Overall design: There are mock transfected cells as control and 24 clones containing whole and segmental deletion of XIST.	Co-expression
SRP053794	RNA-Seq atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications	Purpose: provide evidence that RNA-seq can add information to transcriptome profiling already discovered by other technologies for atopic dermatitis Methods: mRNA profiles of 20 atopic dermatitis were analyzed to compare lesional and non-lesional skin, then transcriptomes found by reads were compared to Microarray and RT-PCR Results:RNA-seq provided complementary genes to AD transcriptome IL-36 and TREM-1 Conclusions: Our study represents the first analysis of lesional AD tissue by RNA-seq and comparison to microarray and RT-PCR Overall design: paired biopsies from lesional and non-lesional tissue of 20 patients sequenced by RNA-seq	Co-expression
SRP054971	Ribosome profiling and RNA sequencing of MCF10A-ER-Src and fibroblast cell transformation	We applied ribosome profiling and RNA sequencing to examine gene expression regulation during oncogenic cell transformation. One model involves normal mammary epithelial cells (MCF10A) containing ER-Src. Treatment of such cells with tamoxifen rapidly induces Src, thereby making it possible to kinetically follow the transition between normal and transformed cells. The other model consists of three isogenic cell lines derived from primary fibroblasts in a serial manner (Hahn et al., 1999). EH cell is immortalized by overexpression of telomerase (hTERT), and exhibits normal fibroblast morphology. EL cell expresses hTERT along with both large and small T antigens of Simian virus 40, and it displays an altered morphology but is not transformed. ELR cell expresses hTERT, T antigens, and an oncogenic derivative of Ras (H-RasV12). Overall design: Ribosome profiling and RNA sequencing in two cancer cell models	Co-expression
SRP055005	RNA-seq of HEK293T over-expressing WWTR-CAMTA1 fusion	No description.	Co-expression
SRP055027	Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed	Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers. Overall design: To assess circRNA expression in mammalian brain, we sequenced and analyzed mouse brain regions (hippocampus, cerebellum, prefrontal cortex and olfactory bulb), various neuronal differentiation (mouse P19 and human SH-SY5Y cells) and maturation (mouse cortical neurons) stages, and subcellular compartments in mouse (synaptoneurosomal fraction, cytoplasmic fraction, whole brain lysate).	Co-expression
SRP055063	Transcriptome analysis of Advanced glycation end products treated ligament cells	Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL.  Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM). Overall design: mRNA profiles of Primary human posterior longitudinal ligament cells stimulated with various stimuli (Control, 1µM AGE-BSA, 5µM AGE-BSA, 1µM AGE-BSA with BMP2, 5µM AGE-BSA with BMP2) were generated by deep sequencing on Ion Proton	Co-expression
SRP055067	A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells [RNA-seq]	Here, in this study we systematically examined the patterns of DNA methylation and hydroxy-methylation with its functional implications in gene regulation for the cultured TK6 lymphoblastoid cells upon exposure to micro-gravity conditions. The results reported here indicate that simulated microgravity alters methylation  patterns in a limited way  and subsequently the expression of genes involved in stress response like ATF3, FBXO17, MAP3K13 and VCL in TK6 cells. Overall design: Examination of RNA-seq with 2 replicates each for 1 cell type	Co-expression
SRP055094	Pathogen-host transcriptome analyses of human papillomavirus 16 E6 variants in an organotypic epithelial model	Human papillomaviruses (HPVs) are double-stranded DNA viruses, a subset of which, the “high-risk” HPVs, cause 5% of human cancers. HPV16 is the most common type in cancer, with its tumourigenicity resultant of the oncoproteins E6 and E7. The Asian-American (AA) and European Prototype (EP) are common HPV16 genomic variants that differ in their risk for cancer development, likely due in part to their E6 proteins differing by three amino-acids. Presently, we sought to define if the tumourigenic differences between these variants reflect unique gene expression in differentiating epithelium. RNA-Seq analyses were performed on three-dimensional organotypic epithelia, containing the viral genome either with AAE6, EPE6, or no virus.	Co-expression
SRP055101	Transcriptomic analysis of cultured corneal endothelial cells as a validation for their use in cell-replacement therapy	The corneal endothelium plays a primary role in maintaining corneal homeostasis and clarity, and must be surgically replaced with allogenic donor corneal endothelium in the event of visually significant dysfunction. However, a worldwide shortage of donor corneal tissue has led to a search for alternative sources of transplantable tissue. Cultured human corneal endothelial cells (HCEnC) have been shown to restore corneal clarity in experimental models of corneal endothelial dysfunction in animal models, but characterization of cultured HCEnC remains incomplete. To this end, we utilized next-generation RNA sequencing technology to compare the transcriptomic profile of ex vivo human corneal endothelium (evHCEnC) with that of primary HCEnC and HCEnC lines, and to determine the utility of cultured and immortalized corneal endothelial cells as models of in vivo corneal endothelium. Multidimensional analyses of the transcriptome datasets demonstrated that primary HCEnC have a closer relationship to evHCEnC than do immortalized HCEnC. Subsequent analyses showed that the majority of the genes specifically expressed in HCEnC (not expressed in ex vivo corneal epithelium or fibroblasts) demonstrated a marked variability of expression in cultured cells compared with evHCEnC. In addition, genes associated with either corneal endothelial cell function or corneal endothelial dystrophies were investigated. Significant differences in gene expression and protein levels were observed in the cultured cells compared with evHCEnC for each of the genes tested except for AGBL1 and LOXHD1, which were not detected by RNA-seq or qPCR. Our transcriptomic analysis suggests that at a molecular level primary HCEnC most closely resemble evHCEC and thus represent a viable therapeutic option for managing corneal endothelial dysfunction. Our findings also suggest that investigators should perform an assessment of the entire transcriptome of cultured HCEnC prior to determination of the potential clinical utility of the cultured HCEnC for the management of corneal endothelial cell failure. Overall design: Transcriptomes from ex vivo corneal endothelium, primary cultures and three cell lines were compared. Three samples of each endothelial cell group were submitted for RNA sequencing for a total of 15 samples. The transcriptome for the ex vivo corneal endothelium was used as the reference (i.e., proxy for in vivo corneal endothelium). Transcript abundances for a subset of genes associated with corneal endothelial cell function or disease were validated with qPCR and western blot. Samples of ex vivo endothelium used for validation were independent replicates not used for RNA-sequencing.	Co-expression
SRP055103	Comparative genome-wide analysis of human BM IL3Ra-high precursors show a more MF-, DC- and OC committed gene expression profile, as compared to IL3Ra-low precursors	To clarify the lineage relationship between IL3Rahigh- and IL3Ralow precursor cells and to find potential molecules involved in their differentiation, we compared the IL3Rahigh- and IL3Ralow precursor populations from three independent donors by mRNA deep sequencing and used the Ingenuity Pathway Analysis (IPA)- and Multi-experimental Viewer (MeV) to analyze the differentially expressed genes (p<0.001). Analysis of the protein coding genes showed that the samples from IL3Rahigh precursor cells clustered together, as did the IL3Ralow samples. This indicated that the gene expression patterns of these cells are likely to be conserved. Further analysis revealed a list of (649) differentially expressed molecules between the two populations.  Among these, most notably, genes involved in the differentiation of cell in general, amongst which differentiation of MF, OC and antigen presenting cells appeared to be activation increased. Overall design: Examination of two hematopoietic precursor populations in human BM	Co-expression
SRP055105	The contribution of Alu exons to the human proteome	Alu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products. Our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution. Overall design: Comparing the A-I RNA editing levels of HEK293 cells transfected with empty vector (CV) control, Alu exon inclusion (long) isoform of ADARB1, and Alu exon skipping (short) isoform of ADARB1. Each group has 3 replicates.	Co-expression
SRP055108	Global Gene Expression analysis of CUTLL1 cell lines after treatment with Perhexiline	We identify perhexiline, a small molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1 induced leukemias in vitro and in vivo. Overall design: RNA-Seq from CUTLL1 cell lines treated with Perhexiline or vehicle for 3 days	Co-expression
SRP055153	Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms	We performed single-cell and bulk transcriptome profiling in two different human cell lines. We performed single-cell RNA sequencing in live and fixed cells. Overall design: Single cell RNA sequencing of live and fixed cells, bulk RNA sequencing in two cell lines.	Co-expression
SRP055176	m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveal the census and complexity of the m6A epitranscriptome	N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (“m6A levels”), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3’ untranslated regions (3’-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. Overall design: m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates	Co-expression
SRP055180	Homo sapiens Raw sequence reads	Effect of various synthetic ligands called diabodies on primary human megakaryocyte-erythrocyte progenitors (MEPs) isolated from bone marrow of a normal donor. The diabodies used in our studies act as either agonists or antagonists for erythropoietin receptor (EPOR) expressed on the surface of MEPs.	Co-expression
SRP055376	LARP4B is an mRNA stability factor that acts via AU-rich sequence elements	mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting “mRNP code” determines the fate of any given mRNA and thus determines the gene regulation at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA binding factors characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3´UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently to their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability. Overall design: RNAseq experiments of HEK293 cells which were transfected with siRNAs targeting LARP4B and firefly luciferase as controls. The experiment was performed in triplicates.	Co-expression
SRP055381	Suppression of NAF-1 in Breast Cancer Cells Reduces their Tumorigenicity by Interfering with Cellular Iron Distribution and Metabolism and Ensuing ROS Formation and Apoptosis	Nutrient autophagy factor 1 (NAF-1) is an iron-sulfur protein found on the outer mitochondrial membrane and the ER. Recent studies highlighted an important role for NAF-1 in regulating autophagy via interaction with BCL-2. We recently reported that the level of NAF-1 is elevated in cancer cells and that NAF-1 is required for tumor growth. Here we report that shRNA suppression of NAF-1 results in the activation of apoptosis in xenograft tumors and cancer cells grown in culture. Suppression of NAF-1 resulted in a depletion in the cytosolic iron pool, facilitated uptake of iron, and accumulation of iron and ROS in mitochondria, a shift to glycolysis and glutaminolysis, and the activation of cellular stress pathways associated with HIF1a, AMPK and mTOR. Suppression of NAF-1 in breast cancer cells appears therefore to reduce their tumorigenicity by interfering with cellular iron distribution and energy metabolism resulting in the activation of apoptosis. Overall design: Examination of the effect of suppression of NAF-1 in the breast cancer cell line MCF-7. Two sample types were analyzed, MCF-7 suppressed for NAF-1 and MCF-7 Empty vector control, three replicates for each.	Co-expression
SRP055390	Transcriptome analysis in chronic lymphocytic leukemia cells using RNA sequencing (RNA-seq)	Chronic lymphocytic leukemia (CLL) is a biologically and clinically heterogeneous disease. The somatic hypermutation status of the immunoglobulin heavy chain variable (IGHV) genes has been identified as one of the most robust prognostic markers in CLL. Patients with unmutated IGHV status (U-CLL) typically experience an inferior outcome compared to those whose clones express mutated IGHV genes (M-CLL). We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from a group of 43 CLL patients using reduced representation bisulfite sequencing (RRBS). Using base-pair resolution methylation sequencing, 2323 differentially methylated regions between CLL and normal B-cells (CLL-specific DMRs) and 569 between M-CLL and U-CLL samples (IGHV-specific DMRs) were identified in the CLL genomes. The IGHV-specific DMRs are mostly unique when compared to the CLL-specific DMRs. Less than 10% of the IGHV-specific DMRs are located in promoter regions; however, more than half of these overlap with known DNase I hypersensitive sites, enhancer regions marked by histone modification (H3K4Me1 and H3K27Ac), and transcription factor binding sites in the ENCODE datasets, which indicates that these DMRs contain regulatory sequences. Distinctive DNA methylation patterns were observed in M-CLL and U-CLL samples. Overall, U-CLL was found to contain 50% more hypermethylated regions than M-CLL samples. The hypermethylated loci observed in the U-CLL samples also appear to be hypermethylated in normal naïve B-cells as compared memory B-cells, suggesting that M-CLL and U-CLL differ in differentiation status corresponding to normal B-cell differentiation stages. RNA-seq analysis performed using matched samples (n=34), in which both DNA methylation and gene expression data were available, demonstrated excellent correlation between DNA methylation and gene expression. Several genes whose expression status was previously shown to be associated with CLL prognosis such as ZAP70, CRY1, LDOC1, SEPT10, LAG3, and LPL were differentially methylated in the promoter regions between M-CLL and U-CLL samples indicating that DNA methylation plays an important role in defining the gene expression patterns of these prognostic genes. We further validated 9 genes with IGHV-specific DMRs in the promoter regions using bisulfite pyrosequencing, and the results demonstrated excellent correlation between differential methylation and IGHV mutation status. These novel differentially methylated genes could be developed into biomarkers for CLL prognosis. In addition, DNA hypomethylation was observed in a significant number of genes involved in lymphocyte activation such as PDCD1, NFAT1, and CD5. DNA hypomethylation was observed in the proximal promoter and far up-stream enhancer regions of CD5, an important cell surface marker that uniquely identifies CLL. Overall, the DNA methylation landscape in CLL patients indicates that CLL B cells possess an active B-cell phenotype; at the same time, U-CLL and M-CLL are faithfully committed to their lineage resembling either naïve or memory B-cells.  In summary, this comprehensive DNA methylation analysis has identified a large number of novel epigenetic changes in CLL patients. The results from this study will further advance our understanding of the epigenetic contribution to molecular subtypes in CLL. Overall design: To perform a transcriptome analysis in CLL, we generated sequencing libraries from total RNA isolated from purified B-cells of CLL patients and healthy donnors. The RNA-seq libraries were sequenced using Illumina HiSeq2000 sequencer with a read length of 100bp.  11 CLL B-cell samples, 3 normal control samples including one each of normal CD19+ B cells were studied. We generated 20-30 million Illumina sequencing reads for each sample.	Co-expression
SRP055392	Genetic disruption of COX-1 inhibits multiple oncogenic pathways	We performed RNA sequencing in isogenic models of COX-1 proficient (OV3/SCR) and COX-1 deficient (OV3/COX1KD) OVCAR-3 ovarian cancer cells. COX-1 knockdown was associated with a coordinated anti-oncogenic phenotype, with growth, angiogenesis, migration/invasion, and epithelial-mesenchymal transition among the pathways down-regulated. Overall design: RNA sequencing was performed at Vanderbilt Technologies for Advanced Genomics (VANTAGE) using Illumina HiSeq 2500.	Co-expression
SRP055411	Oncogenic MYC induces a dependency on the spliceosome in human cancer	c-MYC (MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. Like other classic oncogenes, hyperactivation of MYC leads to collateral stresses onto cancer cells, suggesting that tumors harbor unique vulnerabilities arising from oncogenic activation of MYC. Herein, we discover the spliceosome as a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene, and demonstrate that BUD31 is a splicing factor required for the assembly and catalytic activity of the spliceosome. Core spliceosomal factors (SF3B1, U2AF1, and others) associate with BUD31 and are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total pre-mRNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Importantly, genetic or pharmacologic inhibition of the spliceosome in vivo impairs survival, tumorigenicity, and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers. Overall design: Examination of intron rentention in MYC-ER HMECs, in 4 conditions	Co-expression
SRP055413	Allele-selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-coding and Noncoding RNAs, and RNA Isoforms	Purpose:  mRNA translation into protein is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants has yet to be systematically studied. Using high-throughput sequencing (RNA-seq), we have measured cellular levels of mRNAs and ncRNAs, and their isoforms, in lymphoblast cell lines (LCL) and in polysomal fractions, the latter shown to yield strong correlations of mRNAs with expressed protein levels. Analysis of allelic RNA ratios at heterozygous SNPs served to reveal genetic factors in ribosomal loading. Methods: RNA-seq was performed on cytosolic extracts and polysomal fractions (3 ribosomes or more) from three lymphoblastoid cell lines.  As each RNA fraction was amplified (NuGen kit), and relative contributions from various RNA classes differed between cytosol and polysomes, the fraction of any given RNA species loaded onto polysomes was difficult to quantitate. Therefore, we focused on relative recovery of the various RNA classes and rank order of single RNAs compared to total RNA. Results: RNA-seq of coding and non-coding RNAs (including microRNAs) in three LCLs revealed significant differences in polysomal loading of individual RNAs and isoforms, and between RNA classes. Moreover, correlated distribution between protein-coding and non-coding RNAs suggests possible interactions between them. Allele-selective RNA recruitment revealed strong genetic influence on polysomal loading for multiple RNAs. Allelic effects can be attributed to generation of different RNA isoforms before polysomal loading or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Several variants and genes identified by this approach are also associated with RNA expression and clinical phenotypes in various databases. Conclusions:  These results provide a novel approach using complete transcriptome RNA-seq to study polysomal RNA recruitment and regulatory variants affecting protein translation. Overall design: cells from 3 samples were grown to 5x105 cells/mL density in T75 tissue culture flask and harvested, total RNA and polysome bound RNA was sequenced by Ion Proton	Co-expression
SRP055424	High-throughput RNA-sequencing analysis in human glioma stem cell	Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. To investigate gene expression including lncRNA (long non-coding RNA) in GSC, we have performed high-throughput RNA-sequencing (RNA-seq) experiment using Illumina GAIIx. Overall design: Profiles of gene expression including lncRNA in GSC were generated by RNA-seq using Illumina GAIIx.	Co-expression
SRP055435	Human Muscle tissue CTRL DMD CAGE-seq L1 and Alu profiling	Muscle tissue_CTRL_DMD_CAGEseq L1 and Alu profiling Nuclear_CTRL_MB_10006_07	Co-expression
SRP055438	mRNA and small RNA associated with Crohn''s disease behavior [RNA-Seq]	There is a need for reliable prognostic markers that can guide therapeutic intervention in Crohn’s disease (CD). We examined whether different behavioral phenotypes in CD can be classified based on colonic miRNA or mRNA expression and if miRNAs have prognostic utility for CD. We perform high-throughput sequencing of small RNA and mRNA isolated from colon tissue from CD patients and non-IBD (NIBD) controls. To identify miRNA and genes associated with specific behavioral phenotypes of CD, patients were stratified according to disease behavior (non-stricturing, non-penetrating; stricturing; penetrating) and compared miRNA profiles in each class with those of the NIBD group. Using a novel statistical simulation approach applied to colonic RNA-seq data for CD patients and NIBD controls, we identify at drivers of gene expression profiles associated with CD. Overall design: Macroscopically non-inflamed colon tissue from well-characterized Crohn''s disease patients and normal controls were obtained. Small RNA-seq and RNA-seq were performed on these samples. Additionally, we investigated the effect of inflammation on miRNA expression by performing small RNA-seq on matched colon samples obtained from macroscopically inflamed regions from a subset (six) of these patients with Crohn''s Disease.	Co-expression
SRP055440	Single Cell Analysis Reveals Unexpected Transcriptional Heterogeneity of Neural Progenitors in the Developing Human Cortex	The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans, but virtually absent in rodents, called ‘outer radial glia’ (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined cell type-specific sorting with transcriptome-wide RNA-sequencing to identify genes enriched in human ORG, including targets of the transcription factor Neurogenin, and previously uncharacterized, evolutionarily dynamic, long noncoding RNAs. Single-cell transcriptional profiling of human, ferret, and mouse progenitors showed that more human RGC co-express proneural Neurogenin targets than in ferret or mouse, suggesting greater self-renewal of neuronal lineage-committed progenitors in humans. Finally, we show that activating the Neurogenin pathway in ferret RGC promotes delamination and outward migration. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors. Overall design: Three biological replicates of human late mid-fetal cortex (18 to 19 weeks  of gestation) were dissociated and immunolabeled. Apical and outer radial glial cells were purified by FACS and compared to an immunonegative population, predominantly neurons.	Co-expression
SRP055444	Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in Chronic Lymphocytic Leukemia	IGHV mutation status is a well-established prognostic factor in chronic lymphocytic leukemia, and also provides crucial insights into tumor cell biology and function. Currently, determination of IGHV transcript sequence, from which mutation status is calculated, requires a specialized laboratory procedure. RNA sequencing is a method that provides high resolution, high dynamic range transcriptome data that can be used for differential expression, isoform discovery, and variant determination. In this paper, we demonstrate that unselected next-generation RNA sequencing can accurately determine the IGH@ sequence, including the complete sequence of the complementarity-determining region 3 (CDR3), and mutation status of CLL cells, potentially replacing the current method which is a specialized, single-purpose Sanger-sequencing based test. Overall design: CLL cells were sequenced by mRNA-seq on the Illumina platform then subjected to the costom bioinformatic pipeline Ig-ID which yields IGH data	Co-expression
SRP055454	RNA-Seq profiling of human fibroblasts treated with Novartis SMN2-splicing modulator NVS-SM1	Gene expression profiling of normal human fibroblasts treated with Novartis compound NVS-SM1, Novartis compound NVS-SM3 (NVS-SM1 inactive analog), and DMSO for 24 hours. This study allowed to elucidate the mechanism of action of NVS-SM1, a potent modulator of SMN2 splicing.	Co-expression
SRP055474	Expression and functions of long noncoding RNAs during human T helper cell differentiation	To improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions.  The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes.  These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies.  Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs.  Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes.  Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13.  Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Overall design: Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.	Co-expression
SRP055475	A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (RNA-seq)	In several developmental lineages, an increase in expression of the MYC proto-oncogene drives the transition from quiescent stem cells to transit amplifying cells. The mechanism by which MYC restricts self-renewal of adult stem cells is unknown. Here, we show that MYC activates a stereotypic transcriptional program of genes involved in protein translation and mitochondrial biogenesis in mammary epithelial cells and indirectly inhibits the YAP/TAZ co-activators that are essential for mammary stem cell self-renewal. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. PLD6 mediates a change in the mitochondrial fusion/fission balance that promotes nuclear export of YAP/TAZ in a LATS- and RHO-independent manner. Mouse models and human pathological data confirm that MYC suppresses YAP/TAZ activity in mammary tumors. PLD6 is also required for glutaminolysis, arguing that MYC-dependent changes in mitochondrial dynamics balance cellular energy metabolism with the self-renewal potential of adult stem cells. Overall design: RNA-Seq Experiments in 2 different primary breast epithelial cell lines (HMLE, which were sorted according to CD44/CD24 surface markers & unsorted IMEC). Both cell lines expressed a doxycycline-inducible version of MYC. For the HMLE cell line DGE analysis was performed for the uninduced (EtOH) situation, comparing CD44high vs CD44 low and for the induced situation Dox vs. EtOH for the CD44high population. For the IMEC cell line DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control which allows to filter out potential effects due to doxycycline treatment.	Co-expression
SRP055512	Gene expression profiling of patient's DCIS-IDC tandem lesions by RNA sequencing analysis	Tandem DCIS/IDC are defined as ductal carcicnoma in situ (DCIS) lesions that have concurrent invasive ductal carcinoma (IDC) within the same breast. These are identified radiologically by an area of clustered microcalcifications adjacent to (contiguous with) an invasive mass. Our radiologist (Dr. William P. Smith) has provided us with biopsy cores from each region. One core from each region (DCIS and IDC) has bas been collected and subjected to RNA sequencing for our studies to compare changes from DCIS to IDC in each individual patient. Overall design: 6 pairs of DCIS-IDC samples were collected, and analysed by RNA sequencing	Co-expression
SRP055514	Impact of bariatric surgery on RNA-seq gene expression profiles of peripheral monocytes in humans	Genome-wide expression profiles in peripheral monocytes (PM) from 19 obese women before and 3 months after bariatric surgery using the RNA-seq technology. This dataset is linked to the dataset GSE65540 providing expression profiles in subcutaneous adipose tissue (SAT) in the same population. Due to exclusion of some individuals for technical reasons, the overlap between the 2 datasets is of 18 women. Overall design: mRNA sequencing of peripheral monocyte (PM) samples from 19 obese women before and 3 months after bariatric surgery	Co-expression
SRP055517	Knockout human reveal an essential role for Paternally Expressed 10 (PEG10) in JEG3 cell line development	Tissue- and cell-type specific regulators of alternative splicing (AS) are an essential layer of posttranscriptional gene regulation necessary for normal cellular function, patterning, and development. Here we report the Paternally Expressed 10 (PEG10) are required for patterning of multiple organs, with loss of PEG10, resulting in increasingly severe phenotypes. Overall design: RNA from purified total placenta of human uterus were harvested by Trizol extraction. 1 ug of total RNA was used for  for RNA-seq library preparation using the TruSeqâ„¢ Stranded mRNA LT Sample Prep Kit (Illumina). 100x2 bp paired-end RNA-seq reads were generated on a HiSeq 2000 sequencer.	Co-expression
SRP055538	MicroRNA and gene expression changes in human cerebral aneurysms [RNA-seq]	Cerebral Aneurysm tissues and superficial temporal arteries were compared through RNA-Seq to identify differentially expressed genes, and through microRNA microarray to identify differentially expressed microRNAs. Significant miR:gene pairs were identified for potential microRNA silencing regualtory effects. Overall design: To study differentially expressed genes and microRNAs in cerebral aneurysms, we collected 7 cerebral aneurysm tisses and 10 superficial temporal artery (STA) tisses from 17 individuals. We performed RNA-Seq and microRNA microarray analysis on these samples, and compared them using STA as a control.	Co-expression
SRP055569	Scalable Microfluidics for Single Cell RNA Printing and Sequencing	Single cell transcriptomics has emerged as a powerful approach to dissecting phenotypic heterogeneity in complex, unsynchronized cellular populations.  However, many important biological questions demand quantitative analysis of large numbers of individual cells. Hence, new tools are urgently needed for efficient, inexpensive, and parallel manipulation of RNA from individual cells. We report a simple microfluidic platform for trapping single cell lysates in sealed, picoliter microwells capable of “printing” RNA on glass or capturing RNA on polymer beads. To demonstrate the utility of our system for single cell transcriptomics, we developed a highly scalable technology for genome-wide, single cell RNA-Seq. The current implementation of our device is pipette-operated, profiles hundreds of individual cells in parallel with library preparation costs of ~$0.10-$0.20/cell, and includes five lanes for simultaneous experiments. We anticipate that this system will ultimately serve as a general platform for large-scale single cell transcriptomics, compatible with both imaging and sequencing readouts.!Series_type = Expression profiling by high throughput sequencing Overall design: A microfluidic device that pairs sequence-barcoded mRNA capture beads with individual cells was used to barcode cDNA from individual cells which was then pre-amplified by in vitro transcription in a pool and converted into an Illumina RNA-Seq library. Libraries were generated from ~600 individual cells in parallel and extensive analysis was done on 396 cells from the U87 and MCF10a cell lines and from ~500 individual cells with extensive analysis on 247 cells from the U87 and WI-38 cell lines. Sequencing was done on the 3''-end of the transcript molecules.  The first read contains cell-identifying barcodes that were present on the capture bead and the second read contains a unique molecular identifier (UMI) barcode, a lane-identifying barcode, and then the sequence of the transcript.	Co-expression
SRP055675	Allogeneic mature human dendritic cells generate superior alloreactive regulatory T cells in the presence of  IL-15	Introduction: Expansion of antigen (Ag)-specific natural occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloAg-specific nTregs. Methods: A highly enriched nTreg-fraction (CD4+CD25brightCD127- T cells) was alloAg-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDC) or peripheral blood mononuclear cells (PBMC). The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the TSDR of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4 and cytokines. In addition, the antigen-specific suppressive capacity of these expanded nTregs was tested. Results: Allogeneic mature moDC and skin-derived DC were superior in inducing nTreg-expansion compared to immature moDC or PBMC in an HLA-DR and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2, could facilitate optimal mature moDC-induced nTreg-expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloAg-induced proliferation without significant suppression of completely HLA-mismatched-Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the TSDR within the FOXP3 gene and highly expressed of FOXP3, HELIOS and CTLA4.  A minority of the expanded nTregs produced IL-10, IL-2, IFN-g and TNF-a but very few IL-17 producing nTregs were found. Next generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Conclusions: Human allogeneic mature moDC are highly efficient stimulator cells, in presence of exogenous IL-15, for expansion of stable alloAg-specific nTregs with superior suppressive function. Overall design: Four different batches of highly pure regulatory T cells (all from the same donor) were expanded in two different ways, and compared to non-expanded samples.	Co-expression
SRP055677	RNA-seq analysis of add-back rescued TALEN-mediated LATS2 knockout HeLa-S3 cells	Chromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer. Overall design: mRNA of LATS2 KO HeLa-S3 cells rescued by empty vector, wild-type LATS2 or kinase-dead LATS2 were subjected to deep sequencing  profiling using Illumina HiSeq 2500	Co-expression
SRP055749	The Cushing's disease adipose gene expression profile reveals effects of long term glucocorticoids on adipose tissue lipid, protein and glucose metabolism	Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with non-functioning pituitary adenomas (n=11). We found higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings.  Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the co-morbidities associated with chronic elevations of glucocorticoids Overall design: DESIGN: Patients with cushing's (n=5) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012.	Co-expression
SRP055770	Biochemical fractionation of HEK293 nuclei and RNA-seq of chromatin-associated and soluble-nuclear RNA	Biochemical fractionation of HEK293 nuclei and RNA-seq of chromatin-associated and soluble-nuclear RNA. Overall design: Nuclei from three biological replicates were isolated by detergent lysis, fractionated, then three chromatin and three soluble RNA samples were converted to cDNA using Illumina TruSeq stranded protocol, and sequenced on Illumina HiSeq2000	Co-expression
SRP055809	Ectoderm specification of H1 human embryonic stem cells	In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum ?–secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions. Overall design: 6 samples were analyzed, 3 replicates of ETOH treated H1 HESCs and 3 replicates of DAPT treated H1 HESCs	Co-expression
SRP055810	Single-Cell RNA-seq Defines the Three Cell Lineages of the Human Blastocyst	Here we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Key components of the TGF-ß signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-ß signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although key trophectoderm factors Id2, Elf5, and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells. Overall design: Single-Cell RNA-seq	Co-expression
SRP055835	Patient-derived xenograft platform for metastatic melanoma: a model for studying resistance to targeted therapy.	The therapeutic landscape of melanoma is rapidly changing. While targeted inhibitors yield significant responses, their clinical benefit is often limited by the early onset of drug resistance. This motivates the pursuit to establish more durable clinical responses, by developing combinatorial therapies. But while potential new combinatorial targets steadily increase in numbers, they cannot possibly all be tested in patients. Similarly, while genetically engineered mouse melanoma models have great merit, they do not capture the enormous genetic diversity and heterogeneity typical in human melanoma. Furthermore, whereas in vitro studies have many advantages, they lack the presence of micro-environmental factors, which can have a profound impact on tumor progression and therapy response. This prompted us to develop an in vivo model for human melanoma that allows for studying the dynamics of tumor progression and drug response, with concurrent evaluation and optimization of new treatment regimens. Here, we present a collection of patient-derived xenografts (PDX), derived from BRAFV600E, NRASQ61 or BRAFWT/NRASWT melanoma metastases. The BRAFV600E PDX melanomas were acquired both prior to treatment with the BRAF inhibitor vemurafenib and after resistance had occurred, including six matched pairs. We find that PDX resemble their human donors' melanomas regarding biomarkers, chromosomal aberrations, RNA expression profiles, mutational spectrum and targeted drug resistance patterns. Mutations, previously identified to cause resistance to BRAF inhibitors, are captured in PDX derived from resistant melanomThis melanoma PDX platform represents a comprehensive public resource to study both fundamental and translational aspects of melanoma progression and treatment in a physiologically relevant setting. Overall design: Melanoma samples pre and post Vemurafenib treatment from patient and matching patient derived xenografts (PDX)	Co-expression
SRP055860	Identification of differentially spliced genes by wild type or S34F mutation of U2AF1	Identification of differentially spliced genes by wild type or S34F mutation of U2AF1 Overall design: Examination of effects on splicing events by overexpressing wipdtype or S34F mutation of two U2AF1 isoforms in A549 cells. All experimental conditions are performed in duplicate.	Co-expression
SRP055874	Defective structural RNA processing in relapsing-remitting multiple sclerosis	It is fundamentally unknown how normal cellular processes or responses to extracellular stimuli may invoke polyadenylation and degradation of ncRNA substrates or if human disease processes exhibit defects in polyadenylation of ncRNA substrates as part of their pathogenesis. Our results demonstrate that mononuclear cells from subjects with relapsing-remitting multiple sclerosis (RRMS) exhibit pervasive increases in levels of polyadenylated ncRNAs including Y1 RNA, 18S and 28S rRNA, and U1, U2, and U4 snRNAs and these defects are unique to RRMS. Defects in expression of both Ro60 and La proteins in RRMS appear to contribute to increased polyadenylation of ncRNAs. Further, IFN-ß1b, a common RRMS therapy, restores both Ro60 and La levels to normal as well as levels of polyadenylated Y1 RNA and U1 snRNA suggesting that aberrant polyadenylation of ncRNA substrates may have pathogenic consequences. Overall design: We extracted RNA from peripheral whole blood in healthy control subjects and patients with established relapsing-remitting multiple sclerosis using PaxGene tubes.	Co-expression
SRP055890	Epigenomic landscapes of human inflammation associated macrophages [RNA-seq]	We previously demonstrated by genomic and bioinformatical approaches that human macrophage (MF) activation is best described by a spectrum model (Xue et al, Immunity, 2014). MF integrate exogenous input signals on transcriptional level in a unique fashion to generate specific functional programs, enabling the plasticity in disease-related pathophysiologies. Such versatile responsiveness requires fast changes of transcription mediated by transcriptional regulators (TRs) or epigenomic changes. To better understand the principles of this regulation during human MF activation, we assessed histone modifications including H3K4me1, H3K4me3, H3K27me3, and H3K27Ac by ChIP-sequencing allowing us to characterize the functional state of promoters (active, poised, repressed) and enhancers (active, inactive, intermediate). Using transcriptome data from our MF spectrum model, we generated a co-regulation network of all TRs. Next, we overlaid epigenomic information and transcriptional changes of major TRs over time onto the TR network. We observed that input signals like IFN? or TNFa induce a specific network of TRs that are transcriptionally regulated themselves, the combination of regulated TRs changes over time with a boost of transcriptional regulation of dozens of TRs 4 to 12 hrs post input signal exposure, almost all TRs within the network show active promoters, even if the TR itself is not expressed, and similar results are obtained for enhancers with open or at least intermediated states. These findings strongly suggest that in MF, the TR-defined cellular ‘switch panel’ is always accessible thereby allowing MF to quickly respond to the diverse input signal repertoire from the environment. Overall design: Epigenetic analysis of promoter and enhancer sites in primary human macrophage subtypes and correlation to RNA-seq expression data	Co-expression
SRP055899	Homo sapiens Raw sequence reads	human embryonic carcinoma cell line	Co-expression
SRP055916	Multi-platform assessment of transcriptional profiling technologies utilizing a precise probe mapping methodology (RNA-seq_RiboZero)	We present a more extensive and yet precise assessment to elucidate differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.  Our results showed a fair degree of overall correlation between all 6 platforms evaluated; but, to varying degrees, two RNA-seq protocols outperformed three of the microarray platforms in most categories.  Notably, a fourth microarray platform, Agilent, was comparable, or marginally superior, to the RNA-seq protocols within these same assessments.  Furthermore, 3 platforms (Agilent and two RNA-seq methods) demonstrated over 80% concordance with the gold standard TaqMan assay in terms of fold-change accuracy.  Our study suggests that the use of transcript patterns can enhance a number of the observed cross-platform correlations, indicating a potential usefulness for similar evaluations. Overall design: The study assessed differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.	Co-expression
SRP055917	Multi-platform assessment of transcriptional profiling technologies utilizing a precise probe mapping methodology (RNA-seq_ClonTech)	We present a more extensive and yet precise assessment to elucidate differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.  Our results showed a fair degree of overall correlation between all 6 platforms evaluated; but, to varying degrees, two RNA-seq protocols outperformed three of the microarray platforms in most categories.  Notably, a fourth microarray platform, Agilent, was comparable, or marginally superior, to the RNA-seq protocols within these same assessments.  Furthermore, 3 platforms (Agilent and two RNA-seq methods) demonstrated over 80% concordance with the gold standard TaqMan assay in terms of fold-change accuracy.  Our study suggests that the use of transcript patterns can enhance a number of the observed cross-platform correlations, indicating a potential usefulness for similar evaluations. Overall design: The study assessed differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.	Co-expression
SRP055918	Evaluating intra- and inter-individual variation in the human placental transcriptome	Background: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively.  Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%). Conclusion: We apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection. Overall design: Placental mRNA was sequenced on an Illumina GAIIx. Samples were derived from 4 human groups, 10 individuals per group, 2 samples per individual	Co-expression
SRP055929	The regulartory role of ZCCHC24 in splicing machinery	ZCCHC24, Zinc Finger, CCHC domain containing 24. Showed mesenchymal cell specific expression, but no known function or phenotype associated with it. It required for mesenchymal cell growth, KD in mesenchymal cells induces drastic growth arrest. Its role in splicing machinery is not known. Overall design: 1 ug of total RNA was used for  for RNA-seq library preparation using the TruSeqâ„¢ Stranded mRNA LT Sample Prep Kit (Illumina). 100x2 bp paired-end RNA-seq reads were generated on a HiSeq 2000 sequencer.	Co-expression
SRP055932	Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes	Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. To address this, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes.  Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as unique to AT1 cells, while SCNN1G within lung is restricted to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence of mouse alveoli verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells. These new AT1 cell-specific genes, with GRAMD2 as a leading candidate, will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases. Overall design: RNAseq of purified primary human alveolar epithelial type 2 (AT2) and in vitro differentiated type 1 (AT1-like) cells.	Co-expression
SRP055938	Transcriptome Profiling of Pneumolysin Intoxication of Airway Epithelial Cells	Pneumonia remains one of the leading causes of death in both adults and children worldwide. Although viral and fungal acute airway infections can result in pneumonia, bacteria are the most common cause of community-acquired pneumonia, with Streptococcus pneumoniae isolated in nearly 50% of cases. Pneumolysin is a cholesterol-dependent cytolysin or pore-forming toxin produced by Streptococcus pneumonia and has been shown to play a critical role in bacterial pathogenesis. Airway epithelium is the initial site of many bacterial contacts and its barrier and mucosal immunity functions are central to infectious lung diseases. We decided to assess changes in the transcriptome of human airway epithelial cells exposed to toxin, statin or both. Our current work provides the first global view in human airway epithelial cells of the transcriptome under statin exposure that results in cellular protection from pneumolysin.	Co-expression
SRP055967	human embryonic and mesenchymal stem cells	Mesenchymal stem cells (MSC) are self-renewing multipotent cells which hold great potential in stem cell-based therapy. MSC can be derived from multiple adult tissues but require invasive harvesting and imply donor-to-donor differences. MSC derived from embryonic stem cells (ESC) may provide an alternative source not suffering from those limitations, but to what extend they correspond to the adult counterpart is not known. Here we characterized human ESC-derived MSC in-depth and compared them to human adult tissue-derived MSC (bone marrow BM-MSC) as well as to hESC using next-generation RNA sequencing. In MSC we observed enrichment of proteins involved in cell adhesion, wound healing, extracellular matrix generation, as well as vesicle-mediated transport and exosomes, with the latter pointing towards paracrine signaling. The enrichment and variety of developmental terms associated with MSC further suggest the support function in tissue regeneration. The observed differences between ESC-and adult tissue derived-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications.	Co-expression
SRP055981	RNA-Seq of HIV-infected human primary CD4+ T cells	RNA-Seq of mRNA from human primary CD4+ T cells infected with the low passage isolate HIV89.6 and uninfected controls	Co-expression
SRP056033	SF3B1 Degron knockdown RNA-seq	Knockdown of mutant and/or wild-type SF3B1 in MEL202 cell line by Degron knock-in, followed by RNA-seq, to identify splicing events governed by mutant SF3B1. Overall design: Control: parental MEL202 cell line. Experiments: mutant-SF3B1 knockdown; wildtype-SF3B1 knockdown; mutant SF3B1 knockout. Treatments: each of these four conditions plus and minus shld.	Co-expression
SRP056036	Epigenome Editing by a CRISPR/Cas9-Based Acetyltransferase Activates Genes from Promoters and Enhancers	Epigenetic modifications determine the structure and regulation of eukaryotic genomes and define key signatures of cell lineage specification. Technologies that facilitate the targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we have generated a programmable acetyltransferase based on the CRISPR/Cas9 gene regulation system, consisting of the nuclease-null dCas9 protein fused to the catalytic core of the human acetyltransferase p300. This fusion protein catalyzes acetylation of histone H3 lysine 27 (H3K27) at its target sites, leading to robust transcriptional activation of target genes from promoters, proximal enhancers, and distal enhancers. In contrast to conventional dCas9-based activators, the acetyltransferase fusion effectively activated genes from enhancer regions and with individual guide RNAs. The core p300 domain was also portable to other programmable DNA-binding proteins. This technology enables the targeted perturbation of native epigenetic architecture and will be useful for reprogramming the epigenome for applications in genomics, genetics, disease modeling, and manipulating cell fate. Overall design: HEK293T cells were transfected in triplicate with plasmids expressing synthetic transcription factors. The synthetic TFs were either (a) dCas9-VP64 fusion protein and a targeting guide RNA (gRNA), or (b)dCas9-p300 fusion protein containing the catalytic domain of p300 and a targeting guide RNA (gRNA).  As a control, cells were transfected with plasmids expressing dCas9 alone and dCas9 fused with a aceryltransferase null mutatnt form of the p300 catalytic domain (D1399Y, as in text). After transfection, RNA-seq was used to identify differential expressin at on-target and off-target  sites.	Co-expression
SRP056037	RNA-sequencing in OS-RC-2 cells under the knockdown of Arkadia or ESRP2	Tumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC). Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC. Overall design: Expression of mRNA in a ccRCC cell line OS-RC-2 under the knockdown of Arkadia or ESRP2. Knock-down of ESRP2 was confirmed by RT-PCR because of low expression of ESRP2 which resulted in non-quantitative FPKM value.	Co-expression
SRP056041	Decoding breast cancer tissue-stroma interactions using species-specific sequencing	Decoding genome-wide effects of experimental tissue-tissue or cell-cell interactions is important, for example, to better understand tumor-stroma interactions after transplantation (xenografting). Transcriptome analysis of intermixed human and mouse cells has frequently relied on the need to separate the two cell populations prior to transcriptome analysis, which introduces confounding effects on gene expression. To circumvent this problem, we perform a bioinformatics-based genome-wide transcriptome analysis technique separating the mouse and human transcriptome part of a dataset, which allows a mixed mouse and human cell population to be sequenced without prior cell sorting. We use the new technology – which we call S3 (“S-cube” for Species-specific sequencing) technology – to provide new insights into the Notch downstream response following Notch ligand-stimulation and to explore transcriptional changes following transplantation of luminal (MCF7) and basal-type (MDA-MB-231) human breast cancer cells into mammary fat pad tissue in mice. Overall design: Analysis of Notch response to ligand in three settings: co-culture, immobilized ligand and xenografted tumors	Co-expression
SRP056049	Functional Inflammatory Profiles Distinguish Myelin-Reactive T Cells from Patients with Multiple Sclerosis	Myelin-reactive T cells have been identified in patients with multiple sclerosis (MS) and healthy subjects with comparable frequencies, but the contribution of these autoreactive T cells to disease pathology remains unknown. A total of 13,324 T cell libraries generated from blood of 23 patients and 22 healthy controls were interrogated for reactivity to myelin antigens. Libraries derived from CCR6+ myelin-reactive T cells from patients with MS exhibited significantly enhanced production of IFN-?, IL-17, and GM-CSF compared to healthy controls. Single-cell clones isolated by MHC/peptide tetramers from CCR6+ T cell libraries also secreted more pro-inflammatory cytokines while clones isolated from controls secreted more IL-10. The transcriptomes of myelin-specific CCR6+ T cells from patients with MS were distinct from those derived from healthy controls, and of note, were enriched in Th17-induced experimental autoimmune encephalitis (EAE) gene signatures and gene signatures derived from Th17 cells isolated other human autoimmune diseases. These data, although not casual, imply that functional differences between antigen specific T cells from MS and healthy controls is fundamental to disease development and support the notion that IL-10 production from myelin-reactive T cells may act to limit disease progression, or even pathogenesis. Overall design: Four conditions of purified T cells with between 3 and 5 replicates per condition	Co-expression
SRP056066	Discovery of novel isoforms of Huntingtin reveals a new hominid-specific exon	Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell is still not well understood. Scrutiny of HTT function has been focused on a single, full length, mRNA.  In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HD-hESC lines as well as cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.  Furthermore, it provides a new human-specific target for drug screening in Huntington’s disease. Overall design: We performed RNAseq of human embryonic stem cells in pluripotency conditions to check expression of multiple HTT isoforms.	Co-expression
SRP056074	Epoxyeicosatrienoic Acids Enhance Haematopoietic Stem and Progenitor Cell Specification and Engraftment	Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions including leukemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here, we developed a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We used this system to conduct a chemical screen and identified epoxyeicosatrienoic acids (EET) as a family of lipids that enhance HSPC engraftment.  EETs’ pro-haematopoietic effects are conserved in the developing zebrafish, where this molecule promotes HSPC specification through activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect requires the activation of PI3K pathway, specifically PI3Kg. In adult HSPCs, EETs induce transcriptional programs including AP-1 activation, modulating multiple cellular processes, such as migration, to promote engraftment. Finally, we demonstrated that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study established a novel method to explore the molecular mechanisms of HSPC engraftment, and discovered a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation. Overall design: To analyze the effect of 11,12-EET on gene expression of human blood cells, we treated human CD34+ cells (positively selected from cord blood) and the human leukemic cell line U937 with 5uM 11,12-EET for 2 hrs. Control treatment was done with DMSO.	Co-expression
SRP056076	RNA-seq analysis of gene expression patterns responding to TSA treatment during hESC neural differentiation	We report the differential roles of an HDAC inhibitor-TSA during hESC nerual commitment. In the initiation of hESC differentiation, TSA could inhibit the downregulation of pluripotency genes to maintain pluripotency, whereas in the neural commitment stage, TSA could promote neural gene expression to assist hESC nerual determination. Overall design: Examination of gene expression patterns in hESCs, day 4 or day 8 differentiated cells without or with TSA treatment	Co-expression
SRP056084	RNA-seq analysis of control and Myc-induced U2OS cells	We used RNA-seq to examine the effect of Myc activation on U2OS cells transcriptome. We also examined these effects in the presence of Torin-1, an inhibitor of mTOR Overall design: We measure gene expression profiles in U2OS cells containing an inducible Myc expression vector that were induced or mock-treated in duplicates for 36 hours. In addition, we repeated the experiments in the presence of Torin-1, an inhibitor of mTOR.	Co-expression
SRP056086	CRISPR Display: A modular method for locus-specific targeting of long noncoding RNAs and synthetic RNA devices in vivo [RNA-Seq]	Noncoding RNAs (ncRNAs) comprise an important class of natural regulators that mediate a vast array of biological processes, including the modulation of chromatin architecture. Moreover, artificial ncRNAs have revealed that the functional capabilities of RNA are extremely broad. To further investigate and harness these capabilities, we developed CRISPR-Display ("CRISP-Disp"), a targeted localization strategy that uses Cas9 to deploy large RNA cargos to specific DNA loci. We demonstrate that exogenous RNA domains can be functionally appended onto the CRISPR scaffold at multiple insertion points, allowing the construction of Cas9 complexes with RNAs nearing one kilobase in length, with structured RNAs, protein-binding cassettes, artificial aptamers and pools of random sequences. CRISP-Disp also allows the simultaneous multiplexing of disparate functions at multiple targets. We anticipate that this technology will provide a powerful method with which to ectopically localize functional RNAs and ribonuceloprotein complexes at specified genomic loci. Overall design: Whole cell poly(A) selected RNA seq, from HEK293FT cells bearing lentivirally-integrated Gaussia and Cypridina luciferase reporter loci.  Cells were transiently transfected with dCas9~VP64 alone, or with dCas9~VP and one of several modified sgRNAs,each targeting the Gaussia reporter.	Co-expression
SRP056087	The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis	It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, It is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming, and show that mitosis may be a driving force of reprogramming. Overall design: Human BJ cells transduced with lentiviral particles of the conventional reprogramming factors (OCT3/4, SOX2 and KLF4) were used as controls. Two types of controls were used: 1) BJ transduced with OSK (OCT4, SOX2 and KFL4) viruses; 2) BJ cells transduced with OSK plus GFP viruses. Experimental treatment was BJ cells transduced with OSK plus BRD3R viruses. RNA was extracted from cells at day 3 of reprogramming because the reprogramming cells are still homogeneous and transgenes are well expressed at this time point.	Co-expression
SRP056098	IFN-g Regulates mTORC1, Cellular Metabolism and mRNA Translation to Potentiate Inflammatory Macrophage Activation [RNA-Seq]	IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. Overall design: RPF and RNAseq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with Pam3Cys and harvested at 4 hours. Libraries were generated using protocol modified from Illumina Truseq technology.	Co-expression
SRP056109	Homo sapiens Transcriptome or Gene expression	Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain largely unknown. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using high throughput RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to untreated control, metformin alone down-regulated 58 genes, and up-regulated 91 genes, aspirin alone down-regulated 12 genes only, while the combination of metformin and aspirin down-regulated 656 genes, and down-regulated 449 genes (fold-change > 2, P value < 10-5). Of the top 10 genes (fold-change > 10, P value < 10-10) regulated by the combination of metformin and aspirin, PCDH18, CCL2, RASL11A, FAM111B, and BMP5, were down-regulated more than 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated more than 10-fold. The ingenuity pathway analysis (IPA) was applied to explore the top signaling pathways regulated by metformin and aspirin. The top canonical pathways, “cholesterol biosynthesis”, “cell cycle: G1/S checkpoint regulation”, and “axonal guidance signaling” were the most statistical significant pathways that were modulated by the combination of metformin and aspirin. Although the results need further functional validation, these data provide, for the first time, a transcriptional profile of pancreatic cancer cells in response to metformin and aspirin.	Co-expression
SRP056146	Pancreatic cancer exosomes induce pre-metastatic niche formation in the liver	Pancreatic cancers (PCs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PC-derived exosomes induce liver pre-metastatic niche formation in naïve mice and consequently increase liver metastatic burden. Uptake of PC-derived exosomes by Kupffer cells caused transforming growth factor ß secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared to patients whose pancreatic tumors did not progress, MIF was markedly higher in exosomes from stage I PC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PC liver metastasis. Overall design: Normal pancreas and Pancreatic cancer exosomes education of human von Kupffer cells in vitro	Co-expression
SRP056153	RNA sequencing of SETD2 isogenic renal cell carcinoma cell lines	RNA sequencing of SETD2 isogenic renal cell carcinoma cell lines. Overall design: Examination of RNA expression in SETD2 isogenic cell lines	Co-expression
SRP056159	Disease-Associated SNPs From non-Coding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells [RNA-Seq]	We sequenced mRNA from 3 neutrophil cells taken from 3 male adult to generate the gene expression profile of human neutrophil cells Overall design: Examination of mRNA levels in human neutrophils.	Co-expression
SRP056197	Leucegene: AML sequencing (part 4)	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.	Co-expression
SRP056199	Homo sapiens Transcriptome or Gene expression	Anoikis resistance is a major contributor to triple negative breast cancer metastasis. In this study, the transcriptome of parental and anoikis resistant subclones of triple negative breast cancer cell lines were studied	Co-expression
SRP056200	Ribo_seq (aka ribosome profiling) analysis of control and Myc-induced U2OS cells	We used Ribo-seq to examine the effect of Myc activation on protein translation in U2OS cells and correalted these changes with alterations in RNA level measured by RNA-seq on tye same conditions. We also examined these effects in the presence of Torin-1, an inhibitor of mTOR Overall design: We measure ribosome occupancy profiles in U2OS cells containing an inducible Myc expression vector that were induced or mock-treated in duplicates for 36 hours. In addition, we repeated the experiments in the presence of Torin-1, an inhibitor of mTOR.	Co-expression
SRP056201	GRO-seq analysis of control and Myc-induced U2OS cells	We used GRO-seq to examine the effect of Myc activation on RNA transcription in U2OS cells. Overall design: We measure in duplicates gene transcription rates in U2OS cells containing an inducible Myc expression vector that were induced or mock-treated in duplicates for 5 hours.	Co-expression
SRP056220	Effect of OVO-like 1 knockdown on global transcript expression in differentiated BeWo trophoblast cells	We had previously discovered that the transcription factor OVO-like 1 (OVOL1) was highly induced during trophoblast differentiation. In this study, we used an lentiviral shRNA strategy to decrease OVOL1 expression in BeWo trophoblast cells. Control cells were transduced with shRNAs targeting no known mammalian transcript (shCont). Following stimulation of differentiation (48h exposure to 8-bromo-cyclic adenosine monophosphate), a RNA-seq approach was used to determine global transcript differences in OVOL1-knockdown cells compared to control cells. Overall design: Trophoblast cells transduced with control shRNAs were used as controls. Cells transduced with shRNAs targeting OVOL1 were used as treatment. All cells received 250 uM 8-bromo-cyclic adenosine monophosphate to stimulate differentiation. Three independent replicates of control and treatment groups were analyzed.	Co-expression
SRP056228	Homo sapiens Raw sequence reads	Deciphering targeting rules of splicing modulator compounds: case of TG003.	Co-expression
SRP056271	CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of exon junction complexes	In metazoan cells, spliced mRNAs are marked by the exon junction complex (EJC), a multi-protein complex that serves as a key regulator of post-transcriptional mRNA metabolism. Deposition of EJCs on mRNA is intimately linked to the splicing process. The spliceosomal protein CWC22 directly binds the core EJC-protein eIF4A3, guides it to the spliceosome and initiates EJC assembly. In addition, CWC22 is involved in the splicing process itself, but the molecular details of its dual function remain elusive. Here we analyze the mechanisms, by which CWC22 co-regulates pre-mRNA splicing and EJC assembly. We show that the core of CWC22 is sufficient to mediate both pre-mRNA splicing and EJC assembly. Nonetheless, both processes can be functionally uncoupled with an eIF4A3-binding deficient mutant of CWC22, which impedes EJC assembly. A C-terminal domain of CWC22 strongly enhances its spliceosomal interaction and likely regulates its function. High-throughput RNA-sequencing identifies global defects of pre-mRNA splicing and downregulation of diverse gene expression pathways in CWC22-depleted cells. We propose a model, in which CWC22 represents an integral component of the spliceosome and orchestrates pre-mRNA splicing and eIF4A3 binding to achieve global assembly of exon junction complexes.	Co-expression
SRP056281	RNA Sequencing of default, melanocyte biased and enteric human neural crest populations (NC) and neuroectoderm (CNS)	We have generated expression profiles of three different neural crest populations from human embryonic stem cells.  These profiles were compared to a neuroectoderm population.  We find that the neural crest populations are separable and distinct. Overall design: All cell types were differentiated from human embryonic stem cells.  Neural crest populations were sorted on day 12 for CD49.  The neuroectoderm cells were unsorted and harvested on day 12 of differentiation.	Co-expression
SRP056287	Evaluation of Inter-Batch Differences in Stem-Cell Derived Neurons	Development of an Induced Pluripotent Stem Cell Derived Human Neuronal Model of Chemotherapeutic Neuropathy	Co-expression
SRP056293	Homo sapiens Raw sequence reads	Gene expression pattern in follicular lymphomas	Co-expression
SRP056295	Leucegene: AML sequencing (part 5)	RNA sequencing of human leukemia Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.	Co-expression
SRP056330	Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer	The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome. Overall design: Human total RNA profiles of 3 pairs of benign prostatic basal and luminal populations freshly purified from prostate tissues of three prostate cancer patients by deep RNA-seq.	Co-expression
SRP056333	RNA sequencing of hiPSC derived neural crest populations from Familial Dysautonomia patients	We have generated expression profiles of induced pluripotent stem cells (iPSCs) and iPSC-derived neural crest populations from Familial Dysautonomia patients.  These profiles were compared to a normal iPSC line that does not harbor the IKBKAP mutation. Overall design: All cell types were differentiated from patient derived iPSCs.  Bulk iPSCs were harvested for RNA and the neural crest populations were sorted on day 18 for p75/HNK1 before RNA isolation.	Co-expression
SRP056369	Genome-wide RNA-expression analysis after p53 activation in colorectal cancer cells.	In order to comprehensively identify RNA-expression changes after p53-activation, total RNA was isolated and subjected to next generation seqencing (RNA-Seq) after activation of a conditional p53 allele in SW480 cells. Overall design: SW480/pRTR-p53-VSV cells were subjected to RNA-Seq analysis after 48 hours doxycycline-treatment.	Co-expression
SRP056395	Comparative whole-transcriptomic analysis between normal and AKAP-Lbc-depleted human embryonic stem cells	Human embryonic stem cells (hESCs) have the unique property of immortality, ability to infinitely self-renew and survive in vitro. In contrast to tumor-deribed cells, their immortality are free from any genomic abberations. Instead, they depend on the AKAP-Lbc/Rho signaling cascade. To understand the downstream way, we performed RNA-seq analyses between normal and AKAP-Lbc-depleted hESCs using the doxycyclin-inducible gene silensing strategy. Overall design: We use the genetically modified hESCs in which AKAP-13-targeting shRNA is induced by doxycyclin(dox) treatment. To minimize cell loss during treatment, anti-apoptotic factor Bcl-XL is overexpressed. We collected RNA from dox-treated and untreated cells in biological triplicate. We measured gene expression in these 2 sample groups using RNA-seq (illumina HiSeq) .	Co-expression
SRP056435	Proteogenomics-based identification of the repertoire of human MHC class I-associated peptides	We have develop a proteogenomics-based approach for identification of human MHC class I-associated peptides, including those deriving from polymorphisms, mutations and non-canonical reading frames Overall design: RNA-seq of human EBV-infected B lymphoblasts derived from peripheral blood mononuclear cells from volunteers Please note that GSM1641204 and GSM1641205 are reanalyzed and duplicated sample records of GSM1186811 and GSM1186812, respectively, for the convenient retrieval of the complete raw data from SRA	Co-expression
SRP056443	Transcription Profiling of Malaria-Naïve and Semi-Immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge [RNA-Seq]	We report two clusters in the overall profiles of expression among the samples. At the parasitemia onset, there is a strong interferon response reflected in up-regulation of co-regulated transcripts, while unexpectedly we also see down-regulation of transcripts related to TLR signaling and innate immunity. RNASeq also suggested differential expression of reticulocytes and a subset of T cell function. No obvious difference in the transcriptomes of naïve and semi-immune volunteers was seen, however several hundred genes were up-regulated in naïve individuals. Overall design: RNA-seq analysis was performed for 12 individuals (6 each from Buenaventura and Cali) for two of the time points, namely the diagnosis day and baseline (pre-challenge day).	Co-expression
SRP056477	Distinct brain transcriptome profiles in c9orf72-associated and sporadic ALS	Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Overall design: Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control	Co-expression
SRP056498	Study the effect of SUZ12 on the responsiveness of IFNg target genes in multiple cancer and non cancer cell lines	We studied the effect of knocking down SUZ12 on the responsiveness of IFNg target genes Overall design: 12 cell lines were transfected with siRNA against SUZ12 (siSUZ12) or siCtrl and left untreated or treated with IFNg for 6 hours	Co-expression
SRP056604	Transcriptomics profiling of Alzheimer’s disease reveal novel molecular targets	Our data provide a comprehensive list of transcriptomics alterations and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD Overall design: We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of 4 late onset Alzheimer''s diseas (LOAD) and 4 age-matched controls.	Co-expression
SRP056612	Homo sapiens Transcriptome or Gene expression	Gene expression profile in Calu-3 cells infected with MERS-CoV or SARS-CoV	Co-expression
SRP056665	Transcriptomic analysis of YAP1 knockdown glioblastoma cells	Gene expression analysis by RNA-Sequencing of SF268 glioblastoma cells. Total RNA was extracted from SF268 cells 48h after transfection with two individual siRNAs targeting YAP1 and unspecific control siRNAs.	Co-expression
SRP056696	Next Generation Sequencing Identification of HBV-MLL4 integration and its molecular basis in Chinese hepatocellular carcinoma	Purpose: To gain molecular insights of HBV integration that may contribute to HCC tumorigenesis, we performed whole transcriptome sequencing and whole genome copy number profiling of hepatocellular carcinoma (HCC) samples from 50 Chinese patients. Results: We identified a total of 33 HBV-human integration sites in 16 of 44 HBV-positive HCC tissues, which were enriched in HBV genotype C-infected patients. In addition, significantly recurrent HBV-MLL4 integration (18%; 8/44) was found in this cohort of patients. Conclusions: This is the first report on the molecular basis of the MLL4 integration driving MLL4 over-expression. HBV-MLL4 integration occurred frequently in Chinese HCC patients, representing a unique molecular segment for HCC with HBV infection. Overall design: mRNA profiles of 50 Chinese Hepatocellular Carcinoma patients and 5 adjacent tissues by Illumina Hiseq 2000.	Co-expression
SRP056733	Mycobacterial infection induces a specific human innate immune response	The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. Overall design: RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria:  Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC =  Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis	Co-expression
SRP056742	The MEF2B Regulatory Network - RNA-seq data	Myocyte enhancer factor 2B (MEF2B) is a transcription factor with somatic mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The recurrence of these mutations indicates that they may drive lymphoma development. However, inferring the mechanisms by which they may drive lymphoma development was complicated by our limited understanding of MEF2B’s normal functions. To expand our understanding of the cellular activities of wildtype (WT) and mutant MEF2B, I developed and addressed two hypotheses: (1) identifying genes regulated by WT MEF2B will allow identification of cellular phenotypes affected by MEF2B activity and (2) contrasting the DNA binding sites, effects on gene expression and effects on cellular phenotypes of mutant and WT MEF2B will help refine hypotheses about how MEF2B mutations may contribute to lymphoma development. To address these hypotheses, I first identified genome-wide WT MEF2B binding sites and transcriptome-wide gene expression changes mediated by WT MEF2B. Using these data I identified and validated novel MEF2B target genes.  I found that target genes of MEF2B included the cancer genes MYC, TGFB1, CARD11, NDRG1, RHOB, BCL2 and JUN.  Identification of target genes led to findings that WT MEF2B promotes expression of mesenchymal markers, promotes HEK293A cell migration, and inhibits DLBCL cell chemotaxis. I then investigated how K4E, Y69H and D83V mutations change MEF2B’s activity. I found that K4E, Y69H and D83V mutations decreased MEF2B DNA binding and decreased MEF2B’s capacity to promote gene expression in both HEK293A and DLBCL cells. These mutations also reduced MEF2B’s capacity to alter HEK293A and DLBCL cell movement. From these data, I hypothesize that MEF2B mutations may promote DLBCL and FL development by reducing expression of MEF2B target genes that would otherwise function to help confine germinal centre B-cells to germinal centres. Overall, my research demonstrates how observations from genome-scale data can be used to identify cellular effects of candidate driver mutations. Moreover, my work provides a unique resource for exploring the role of MEF2B in cell biology: I map for the first time the MEF2B ‘regulome’, demonstrating connections between a relatively understudied transcription factor and genes significant to oncogenesis. Overall design: RNA-seq was performed on cells expressing V5 tagged WT or mutant MEF2B and on empty vector control cells. One biological replicates was performed on cell treated with either ionomycin or a solvent-only control.	Co-expression
SRP056784	Omic Personality: Implications of Stable Transcript and Methylation Profiles for Personalized Medicine [RNA-Seq]	Background:   Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response.  We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N=1 phenotypes. Methods:  Whole blood samples from 4 African American women, 4 Caucasian women, and 4 Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays.  Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure that is among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. Results:  Longitudinal omic profiles are in general highly consistent over time, with an average of 67% of the variance in transcript abundance, 42% of CpG methylation level (but 88% for the most differentiated CpG per gene), and 50% of miRNA abundance among individuals, which are all comparable to 74% of the variance among individuals for 74 clinical traits.  One third of the variance can be attributed to differential blood cell type abundance, which is also fairly stable over time, and a lesser amount to eQTL effects, whereas seven conserved axes of covariance that capture diverse aspects of immune function explain over half of the variance.  These axes also explain a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that are significantly up- or down-regulated in each person and are in some cases enriched for relevant gene activities that plausibly associate with clinical attributes.  A similar fraction of genes have individually divergent methylation levels, but these do not overlap with the transcripts, and fewer than 20% of genes have significantly correlated methylation and gene expression. Conclusions:  People express an “omic personality” consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity.  Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions. Overall design: Whole blood samples from 12 subjects drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays.	Co-expression
SRP056792	CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous ovarian carcinoma	Recurrent gene fusions have been described in many tumor types but have been difficult to identify in high-grade serous ovarian cancer (HG-SC), a cancer known for its significant heterogeneity and genome instability. Here, we combined high-throughput transcriptome sequencing with experimental validation to identify a cancer-specific and inter-chromosomal fusion gene CDKN2D-WDFY2 that is recurrent at 25% among HG-SC patients. CDKN2D is a cell-cycle modulator that is also involved in DNA repair while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of the fusion construct led to loss of CDKN2D and WDFY2 protein expression, and gain of an aberrant short WDFY2 protein isoform under the control of CDKN2D promoter. This short WDFY2 in turn led to marked alterations of the PI3K/AKT pathway, a signaling pathway with major implications in oncogenesis. Thus, CDKN2D-WDFY2 fusion could be an important molecular signature for understanding and classifying sub-lineages among heterogenous HG-SC.	Co-expression
SRP056802	Genome-wide mapping of TEL-AML1 targets in acute leukemia	Around 20-25% of childhood acute lymphoblastic leukemias carry the TEL-AML1 (TA) fusion gene. It is a fusion of two central hematopoietic transcription factors, TEL (ETV6) and AML1 (RUNX1). Despite its prevalence, the exact genomic targets of TA have remained elusive. We evaluated gene loci and enhancers targeted by TA genome-wide in precursor B acute leukemia cells  using global nuclear run-on sequencing (GRO-seq). Overall design: Nascent RNA expression profiles were generated with GRO-seq after TEL-AML1 expression in the Nalm6 pre-B-ALL cell line in four different time points (0, 4, 12 and 24 h). TEL-AML1-mut and luciferase induction cell lines were used as controls. Two replicates were included for all six samples.	Co-expression
SRP056822	Evidence for proliferation and synaptogenesis impairments in neural cells derived from idiopathic autistic patients	Reprogramming of human somatic cells to a pluripotent state (induced pluripotent stem cells or iPSC) has provided an exciting opportunity to produce relevant cellular models of human complex neurogenetic diseases. Here we show the generation and characterization of iPSC lines from 8 sporadic ASD patients with early brain overgrowth and 5 age/gender-matched control lines. These cells were used to derive neural progenitor cells and neurons in culture. We reveal molecular and phenotypic evidence that both cell proliferation and synaptogenesis are affected in this model system. Specifically, we detected altered cell cycle and altered levels of excitatory and inhibitory markers in neural cells at early stages of differentiation. This work demonstrates that in a heterogeneous condition such as ASD, selection of subjects based on phenotype can improve power to detect biologically relevant pathway disruption that may help guide development of novel therapies. Overall design: mRNA profiles of iPSC-derived neural progenitors and neurons from 8 sporadic ASD patients with early brain overgrowth and 5 age/gender-matched controls	Co-expression
SRP056832	RNA polymerase in pre-B-ALL cell lines	[Gro-seq] Precursor B acute leukemia cells measured using global nuclear run-on sequencing [ChIP-Seq] The genome-wide occupancy of ser2 and ser5 phosphorylated RNA pol2 and H3K4me3 was measured in precursor B acute leukemia cells measured using chip-seq. Overall design: [Gro-seq] Nascent RNA expression profiles were generated at cells in various basal culture conditions. [ChIP-Seq] Performed from REH and Nalm6 cells cultured under basal culture conditions. Mnase digestion was used for DNA fragmentation. Antibodies against Ser2 and Ser5 phosphorylated RNA polymerase and H3K4me3 compared to input. ****************************** This study includes reanalysis of Samples in Series GSE39878 (GSM980645, GSM980644), GSE60454 (GSM1480326), and GSE41009 (GSM1006728, GSM100672). The processed data files for the reanalyses are linked to GSE67540 as supplementary files (see the GSE67540_README.txt file for additional information).	Co-expression
SRP056835	Novel Observations from Next Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets	Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic a and b cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase b cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify a, b, and d cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the sub-populations by flow cytometry and, using next generation RNA sequencing, we report on the detailed transcriptomes of fetal and adult a and b cells. We observed that human islet composition was not influenced by age, gender, or body mass index and transcripts for inflammatory gene products were noted in fetal b cells. In addition, within highly purified adult glucagon-expressing a cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet a and b cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes. Overall design: RNA-sequencing of highly purified human adult and fetal islet cell subset was performed using our newly developed method. Using this data, we can study and compare the detailed transcriptome or alpha and beta cells during development.	Co-expression
SRP056840	Renal systems biology of patients with systemic inflammatory response syndrome	A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on host response during critical illness. We examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Plasma metabolite values showed greater changes as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among HD patients. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate showed inverse correlations with the majority of significantly down-regulated genes. In conclusion, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness. These changes were not effectively mitigated by hemodialysis. These studies suggest several novel mechanisms whereby renal dysfunction contributes to critical illness. Overall design: We sequenced peripheral blood RNA of 133 representative subjects with systemic inflammatory response syndrome that had Acute Kidney Injury (AKI) or Hemodialysis (HD). No injury (AKI0; n= 58); AKI Stage 1 (AKI1; n= 36); AKI stage 2 and 3 (AKI23; n= 17); HD (N=22).	Co-expression
SRP056863	Homo sapiens Raw sequence reads	Sequencing samples from the brain bank of Emory University	Co-expression
SRP056912	A function for the hnRNP A1/A2 proteins in transcription elongation	The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes. Overall design: two treatements and one control	Co-expression
SRP056957	Transcriptome dynamics of developing photoreceptors in 3-D retina cultures recapitulates temporal sequence of human cone and rod differentiation revealing cell surface markers and gene networks	To define molecular mechanisms underlying rod and cone differentiation, we generated H9 human embryonic stem cell line carrying a GFP reporter that is controlled by the promoter of cone-rod homeobox (CRX) gene, the first known marker of post-mitotic photoreceptor precursors. CRXp-GFP reporter in H9 line replicates endogenous CRX expression when induced to form self-organizing 3-D retina-like tissue. We define temporal transcriptome dynamics of developing photoreceptors during the establishment of cone and rod cell fate. Our studies provide an essential framework for delineating molecules and cellular pathways that guide human photoreceptor development and should assist in chemical screening and cell-based therapies of retinal degeneration. Overall design: Undifferentiated CRXp-GFP HP hES cells and 3D-neural retina were collected at days 37, 47, 67 and 90 and dissociated into single cells. Cells were sorted at 4°C and by FACSAria (Becton Dickinson). GFP+ and GFP- cells were separately collected. Total RNA was extracted by RNA purification kit (Norgen Biotek) and analyzed by 2100 Bioanalyzer (Agilent Technologies Genomics). High quality of total RNA (RIN: 7.7-9.2) was subjected to libraries construction using 40-60 ng of total RNA as input. Libraries were constructed using a stranded modification of the Illumina TruSeq mRNA (Brooks, et al. Meth Mol Biol 2012). Each library was single-end sequenced in an independent lane of a GAIIx at a length of 76 bases.  Fastq files were generated from reads passing chastity filter.	Co-expression
SRP056966	Comparative transcriptomics of endometrial stromal fibroblasts	We sequenced mRNA of endometrial stromal fibroblasts from six mammalian species. Overall design: Examination of mRNA levels in endometrial stromal fibroblasts from six mammalian species grown in culture with two biological replicates for each species	Co-expression
SRP056969	RNA sequencing of total RNA from 20 human tissues	No description.	Co-expression
SRP056985	Homo sapiens Raw sequence reads	<p/>	Co-expression
SRP057020	DLX3 alters transcriptomic profile of adhesion, cell cycle, and cell death in Squamous Cell Carcinoma Cells	Reinstatement of DLX3 into SCC13 cells upregulates genes involved with cell cycle exit, signaling, and adhesion whiles downregulates genes involved with cell death, proliferation, and movement. Overall design: We used RNA-sequencing data analysis to assess gene expression in SCC13 cells infected with Adeno-GFP or Adeno-DLX3 in order to understand the effects of DLX3 in a Squamous Cell Carcinoma Cell Line.  We identified a specific subset of genes involved in regulation of cell cycle arrest and inhibition of apoptosis.	Co-expression
SRP057064	Dual RNA-seq – Pilot Dual RNA-seq	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: Pilot Dual RNA-seq: Infection of HeLa-S3 cells with wild-type Salmonella; 2 time points (4 h, 24 h p.i.; each sorted into invaded host cells [GFP+] and non-infected bystanders [GFP-]) and the respective human (4 h mock, 24 h mock) or bacterial reference controls (0 h LB,  0 h input), respectively. Three biological replicates were taken.	Co-expression
SRP057065	Dual RNA-seq – High-resolution comparative Dual RNA-seq time-course	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: High-resolution comparative Dual RNA-seq time-course	Co-expression
SRP057074	Splicing function of mitotic regulators links R-loop mediated DNA damage to tumor cell killing	We discovered that two mitotic regulators, BuGZ and Bub3, involved in splicing regulation during interphase Overall design: 8 samples from primary Human foreskin fibroblast cells (HFFs) , 12 samples from TOV21G cells. Control siRNA. BuGZ siRNA or Bub3 siRNA were transfected for 48 h before sample collection. Cells treated with pladienolide B served as positive controls.  For each RNAi experiment, we had two biological replicates.	Co-expression
SRP057087	Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance	Background: Psoriasis is a chronic disease characterized by the development of scaly red skin lesions and possible co-morbid conditions. The psoriasis lesional skin transcriptome has been extensively investigated, but mRNA levels do not necessarily reflect protein abundance.  Methods: Lesional (PP) and uninvolved (PN) skin samples from 14 patients were analyzed using high-throughput complementary DNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).  Results: We identified 4122 differentially expressed genes (DEGs) along with 748 differentially expressed proteins (DEPs). Global shifts in mRNA were modestly correlated with changes in protein abundance (r = 0.40). We identified similar numbers of increased and decreased DEGs, but 4-fold more increased than decreased DEPs. Ribosomal subunit and translation proteins were elevated within lesions, without a corresponding shift in mRNA expression (RPL3, RPS8, RPL11). We identified 209 differentially expressed genes/proteins (DEGPs) with corresponding trends at the transcriptome and proteomic levels. Most DEGPs were similarly altered in at least one other skin disease. Psoriasis-specific and non-specific DEGPs had distinct cytokine-response patterns, with only the former showing disproportionate induction by IL-17A in cultured keratinocytes.  Conclusions: Our findings reveal global imbalance between the number of increased and decreased proteins in psoriasis lesions, consistent with heightened translation. This effect could not have been discerned from mRNA profiling data alone. We have also identified high-confidence DEGPs and shown that only those most specific to psoriasis are enriched with IL-17A targets. Overall design: RNA-seq-based comparison between gene expression in psoriasis lesions and uninvolved skin from 14 patients	Co-expression
SRP057118	RNA sequencing of heart samples of myotonic dystrophic (DM1) patients	Analysis of alternative splicing in  heart (left ventricles) samples of 3 adult DM1 patients versus 3 adult controls Overall design: PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed by massive parrallel sequencing	Co-expression
SRP057156	RNA sequencing of cells treated with DMSO or Retinoic acid during cardiac differentiation	Analysis of transcriptional differences between control and RA-treated cells during cardiac differentiation. The hypothesis tested in these samples is that addition of RA during differentiation towards atrial-like cardiomyocytes while control cells treated with DMSO result in ventricular-like cardiomyocytes. Overall design: NKX2.5 (eGFP/w)-hESCs were differentiated to cardiomyocytes with spin EB protocol, with the addition of RA or DMSO. Cells were sorted at day-31 based on GFP resulting in CTplus, CTminus, RAplus or RAminus goups. RNA was isolated from each of these fractions for sequencing.	Co-expression
SRP057177	CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells [RNA-Seq]	CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human HSPC hematopoietic stem and progenitor cells (HSPC) and primary human erythroid cells from single donors. Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone 3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner. These genomic data support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. Overall design: CD34+-selected stem and progenitor cells were expanded for three days in the absence of EPO. The cells were further cultured in the presence of EPO, and cells differentiated into R3/R4 nucleated erythroid cells. RNA was isolated from three biological replicates of each cell type and sequencing libraries were prepared from poly A selected RNA.	Co-expression
SRP057196	A survey of human brain transcriptome diversity at the single cell level	We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained from epileptic patients during temporal lobectomy for medically refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. Overall design: Examination of cell types in healthy human brain samples.	Co-expression
SRP057199	Disruption of Na+/H+ exchanger regulatory factor 2 scaffold suppresses colon cancer proliferation	A key function of Na+/H+ exchanger regulatory factor 2 (NHERF2) is spatial organization of signaling proteins to facilitate signal transduction. The role of NHERF2 in cancer progress is not well understood. This study determines how loss of NHERF2 alter colon cancer progress. Overall design: We show that loss of NHERF2 decreases colon cancer cell proliferation. To compare the effects of NHERF2 and LPA2 at the molecular level, HCT116 colon cancer xenograft with knockdown of NHERF2 or LPA2 was analyzed by RNAseq. Please note that standard cufflinks/cuffdiff output files are provided in the compressed tar files as processed data and Cufflinks/Cuffdiff output file content/formats are described at: https://cole-trapnell-lab.github.io/cufflinks/cuffdiff/#cuffdiff-output-files https://cole-trapnell-lab.github.io/cufflinks/file_formats/ (also included in the ''readme.txt'' file)	Co-expression
SRP057205	Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming	Reprogramming of somatic cells produces induced pluripotent stem cells (iPSCs) that are invaluable resources for biomedical research. Transcriptional and epigenetic changes have been investigated to facilitate our understanding of the reprogramming process. Here, we extended the previous transcriptome studies by performing RNA-seq on cells defined by a combination of multiple cellular surface markers. We found that transcriptome changes during early reprogramming occur independently from the opening of closed chromatin by OCT4, SOX2, KLF4 and MYC (OSKM). Furthermore, our data identify multiple spliced forms of genes uniquely expressed at each progressive stage of reprogramming. In particular, we found a pluripotency-specific spliced form of CCNE1 that significantly enhances reprogramming. In addition, single nucleotide polymorphism (SNP) expression analysis reveals that monoallelic gene expression is induced in the intermediate stages of reprogramming while biallelic expression is recovered upon completion of reprogramming. Our transcriptome data provide unique opportunities in understanding human iPSC reprogramming. Overall design: RNA samples from intermediates of hiPSC reprogramming were obtained. Gene expression of those cells were analyzed.	Co-expression
SRP057244	Dual RNA-seq – sRNA profiling in various cell types	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: sRNA profiling in various cell types	Co-expression
SRP057248	Dual RNA-seq – Pulse-expression of pinT	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: Pulse-expression of pinT	Co-expression
SRP057249	Dual RNA-seq – Host response to pinT*	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: Host response to pinT*	Co-expression
SRP057250	Dual RNA-seq –  Dual RNA-seq of further sRNA mutants	Bacteria possess many small noncoding RNAs whose regulatory roles in pathogenesis are little understood due to a paucity of macroscopic phenotypes in standard virulence assays. Here, we use a novel Dual RNA-seq approach for a single-step simultaneous RNA profiling in both pathogen and host to reveal molecular phenotypes of sRNAs during infection with Salmonella Typhimurium. We identify a new PhoP/Q-activated small RNA which upon bacterial internalization acts to temporally control the expression of both, invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity is shown to adjust the human response to replicating Salmonella, and have a pervasive impact on host RNA expression both inside and outside protein-coding regions including infection-specific alterations of an array of long noncoding RNAs. Our study provides a paradigm for a comprehensive RNA-based analysis of intracellular bacterial pathogens without their physical purification from a host and a new discovery route for hidden functions of pathogen genes. Overall design: Dual RNA-seq of further sRNA mutants	Co-expression
SRP057251	Investigation about fibroblasts of different origins in culture	The goal of this study was to determine if fibroblasts from different origin (skin, colon, tumors) were keeping their characteristic while extracted and cultured ex vivo for several passages. HUVEC was used as a control, being cells from a different background. Surprisingly, fibroblasts from different origins are losing their independant characteristic to cluster in a similar way after 5-6 passages in culture in vitro, showing an activated status. Overall design: Fibroblasts were extracted from human skin, colon normal stroma and colon tumor stroma. HUVECs were extracted from human samples at the same time. All cells, each group from 3 different patients, were grown on plastic for 5 passages and mRNA was extracted to perform RNASeq analysis.	Co-expression
SRP057295	Reversal of persistent wound-induced retinal pigmented epithelial-to-mesenchymal transition by the TGFb pathway inhibitor, A-83-01.	Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus-independent wound response in retinal pigmented epithelial (RPE) cells, a cell-type central to the etiology of AMD. Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we have shown that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post-confluence and altered expression of more than 40% of the transcriptome (see GEO:GSE62224). In contrast, at subconfluence fewer than 5% of expressed transcripts have 2-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division.  Among the wound response genes are the TGFb pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and reverses the passage-dependent loss of epithelial potential. In this RNA-Seq based transcriptome analysis we show that the TGFb receptor kinase inhibitor, A-83-01, largely reverses the effects of passage and restores the transcriptome profile of Passage 4 RPE highly similar to that seen in differentiated Passage 0 RPE. Overall design: Examination of mRNA expression in three different primary fetal RPE donor lines in 32 day old  passage 0, passage 3, and passage 3 treated with 500 nM A-83-01 culutres	Co-expression
SRP057322	Homo sapiens Genome sequencing	Whole transcriptome sequencing (RNA-seq) of KMS11, MM.1S, and RPMI8226 multiple myeloma cell lines	Co-expression
SRP057381	Comparison of gene expression profiles between FRA1 knockdown and vector control Bel-7402 cells by RNA-sequencing	The purpose of this experiment is to search for the transcriptional target of FRA1. Overall design: We subjected FRA1 knockdown and vector control Bel-7402 cells to RNA-sequencing, and analyzed the genes that were shown to be differentially expressed between the two groups.	Co-expression
SRP057399	Targeted Analysis of Chromosome 21 Reveals Size and Diversity of the Mammalian Transcriptome	Human, mouse and Tc1 mouse (carries a near-complete copy of human Chr21)	Co-expression
SRP057446	Homo sapiens Raw sequence reads	<p/>	Co-expression
SRP057448	8p Loss of Heterozygosity triggers metastasis and drug resistance	Chromosome arm deletions are frequently observed in human cancers. Such large-scale aberrations may trigger phenotypes distinct from those that arise by loss of single genes. Using TALEN-based genomic engineering, we generated cell models with targeted 8p loss-of-heterozygosity (LOH) that mimics an 8p deletion commonly found in breast cancer patients. 8p LOH triggered up-regulation of the mevalonate pathway. The alterations in lipid metabolism led to increased metastatic potential and drug resistance of 8p-deleted cells that are in agreement with poorer survival rates of breast cancer patients harbouting 8p LOH. Our findings also suggest novel therapeutic strategies for treatment of 8p LOH tumors. Overall design: RNASeq Analysis of two Wt 8p Cell clones vs two 8p LOH cell clones generated via TALEN Approach	Co-expression
SRP057452	Nucleotide stress induction of HEXIM1 suppresses melanoma by modulating cancer cell-specific gene transcription [RNA-Seq1]	Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human A375 melanoma cells treated with either DMSO or 25 µM A771726 for 0-72 hrs.	Co-expression
SRP057453	Nucleotide stress induction of HEXIM1 suppresses melanoma by modulating cancer cell-specific gene transcription [RNA-Seq2]	Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human Tet-On HEXIM1-inducible A375 melanoma cells treated with either DMSO or 1 µg/mL doxycycline in triplicate for 48 hrs.	Co-expression
SRP057500	RNA-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass and molecular pathway cancer diagnostics	We report RNA-sequencing data of 283 blood platelet samples, including 228 tumor-educated platelet (TEP) samples collected from patients with six different malignant tumors (non-small cell lung cancer, colorectal cancer, pancreatic cancer, glioblastoma, breast cancer and hepatobiliary carcinomas). In addition, we report RNA-sequencing data of blood platelets isolated from 55 healthy individuals. This dataset highlights the ability of TEP RNA-based ''liquid biopsies'' in patients with several types with cancer, including the ability for pan-cancer, multiclass cancer and companion diagnostics. Overall design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the human reference genome using STAR, and intron-spanning reads were summarized using HTseq. The processed data includes 285 samples (columns) and 57736 ensemble gene ids (rows). The supplementary data file (TEP_data_matrix.txt) contains the intron-spanning read counts, after data summarization by HTseq.	Co-expression
SRP057512	Impact of flanking chromosomal sequences on localization and silencing by the ncRNA XIST	We performed RNA-seq and ChIP-seq on clones of human cell lines carrying an inducible XIST transgene on 1p, 8p, or 12q to study the effects of allelic silencing in cis Overall design: Total gene expression and allelic changes were examined in HT1080 clones carrying an inducible XIST transgene on 1p, 8p, or 12q after induction by doxycycline. A replicate was done for the 8p clone treated with DOX. An additional 1p clone integrated with an empty vector, and an 1p, 8p, and 12q clone without induction were included as controls. ChIP was performed on the 8p clone to investigate the changes in H3K27 acetylation and trimethylation.	Co-expression
SRP057571	Human pancreatic adenocarcinoma cell line Transcriptome or Gene expression	Human pancreatic adenocarcinoma cell line	Co-expression
SRP057579	Homo sapiens Transcriptome or Gene expression	Stimulation of the TLRs, IFNGR and TNFR with specific agonists	Co-expression
SRP057586	Unbiased evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity	Objective: Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for novel biomarker discovery of fetal development and maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation. Methods: We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18-24 weeks, 6 from 34-36 weeks, and 6 from at 39-40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway inference.  Results: Sample-level analysis at different time points in pregnancy yielded a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some genes and splice variants were present throughout pregnancy, an abundant number of transcripts were uniquely expressed at different time points in pregnancy and associated with distinct fetal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity. Conclusions: The AF transcriptome exhibits unique cell- and organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and better inform obstetrical decisions regarding delivery timing. Overall design: RNA-Seq from cell-free was used to idenitfy mRNA transcripts indicative of overall fetal maturity.	Co-expression
SRP057616	Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma [RNA-seq]	Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Overall design: Expression levels for non tumorigenic (Melanocytes) and human melanoma cell line SKmel147, before and after JQ1 treatement	Co-expression
SRP057628	Illumina sequencing of vaginal epithelial cells from women using depot medroxyprogesterone acetate or non-hormonal contraception	The use of the hormonal contraceptive DMPA has been associated with a moderate increase in sexually transmitted infections, including HIV-1. To better understand the biological mechanisms behind this phenomenon, we report here the use of mRNA-sequencing on the Illumina HiSeq2000 of vaginal epithelial cells from women using DMPA or controls. We found that women using DMPA demonstrate over 330-fold decrease in the anti-microbial peptide human beta defensin 3 (HBD3) and massive downregulation of genes involved in structural integrity, barrier function, and wound healing. CXCL6, CXCL1, and IL-1B among other inflammatory genes were up-regulated in the tissue of DMPA users compared to controls. Overall, these results demonstrate significant differences in basic epithelial functions following DMPA use. Overall design: Vaginal epithelial cells from four women using DMPA or non-hormonal contraception were isolated using laser capture microdissection for subsequent Illumina analysis	Co-expression
SRP057629	Small molecule inhibition of ERK dimerization prevents tumorigenesis by Ras-ERK pathway oncogenes	About 50% of human malignancies exhibit unregulated signalling through the Ras-ERK1/2 (ERK) pathway, as a consequence of activating mutations in members of Ras and Raf families. However, the quest for alternative Ras-ERK pathway-directed therapies is desirable. Upon phosphorylation ERK dimerize. We had previously demonstrated that dimerization is essential for ERK extranuclear but not nuclear signaling. Furthermore, by molecular biology approaches, we showed that specifically inhibiting ERK extranuclear component, by impeding ERK dimerization, is sufficient for curtailing tumor progression. Here, we have identified a small molecule inhibitor for ERK dimerization in vitro and in vivo that, without affecting ERK phosphorylation, prevents tumorigenesis driven by Ras-ERK pathway oncogenes, both in cellular and animal models. Importantly, this compound is unaffected by resistance-acquisition processes that hamper “classical” Ras-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two novel concepts in cancer therapy: 1) The blockade of sublocalization-specific sub-signals, rather than total signals, as a means of effectively counteracting oncogenic Ras-ERK signaling. 2) Targeting regulatory protein-protein interactions such as dimerization, rather than catalytic activities, within a signaling route, as an approach for producing effective anti-tumoral agents. Strategies aimed at preventing aberrant flux through this route remain an attractive option for therapeutic intervention in cancer. In this respect, drugs inhibiting the kinase activities of BRaf and MEK have yielded promising results. Overall design: A375p cells treated with10 µM of either DEL22379, SCH772984 or DMSO as a control for two hours. mRNA from A375p cells was extrated using RNeasy mini kit (Qiagen, Germany) according to the manufacturer''s instructions. Cells were previously treated with10 µM of either DEL22379, SCH772984 or DMSO as a control for two hours.	Co-expression
SRP057644	Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer.	Mutant p53 proteins, resulting from the missense mutations of the TP53 tumor suppressor gene, possess gain-of-function activities and are among the most robust oncoproteins in human tumors. They are potentially important therapeutic targets. No studies to date have distinguished common, therapeutically relevant mutant p53 gain-of-function effects from effects specific to different mutant variants and cell backgrounds. here we performed RNA-seq analysisin MDA-MB-231 (R280K) upon silencing TP53 or the control siRNA. Overall design: MDA-MB-231 (R280K) cell line was transfected with control or p53 siRNA.So The study comprises one experimental cell line,in triplicate.	Co-expression
SRP057660	RNA sequencing of TN Drosha-transfected human and mouse cell lines	The goal of this study is to generate RNA-seq data sets for assembling the structures of primary microRNA transcripts.	Co-expression
SRP057691	Transcriptome sequencing of human fetal heart	We sequenced 2 heart samples from human fetal donors and detected the differential expressed mRNAs and lncRNAs. The network of significant differential expressed transcripts could be associated to developmental program. Overall design: examination mRNA and lncRNA expression in heart tissues	Co-expression
SRP057708	PolyA RNAseq from HCT116 cells in normoxia and hypoxia	To determine the effects of depleting TIP60, CDK8, or HIF1A on the transcriptional response to hypoxia, we performed RNAseq analysis of four HCT116 colorectal carcinoma cell lines (shNT, HIF1A-/-, shTIP60 and shCDK8) in normoxic and hypoxic (24hrs, 1% O2) conditions. Overall design: PolyA RNA for two independent biological replicates was purified from HCT116 cells stably expressing an shRNA against a non-targeting control (shNT), TIP60 (shTIP60) or CDK8 (shCDK8), or genetically deleted HIF1A (HIF1A-/-) subjected to 24hrs 1% O2 (hypoxia) or maintained under ambient oxygen (21%; normoxia) was sequenced on the Ion Torrent platform. Reads were aligned to the human genome and gene-level counts were used for differential expression analysis.	Co-expression
SRP057721	RNA expression in primary huamn muscle cells treated with 1,25(OH)2D3 or vehicle	We report the effects of 1,25(OH)2D3 treatment on the mRNA expression in human muscle cells Overall design: Primary cultures of human muscle cells were treated with 1,25(OH)2D3 or vehicle for 48 hours.	Co-expression
SRP057735	Global Regulatory Network Controlling Human Somatic Cell Reprogramming [RNA-seq]	This is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state. Overall design: Examination of the Transcriptomic profiles of cells undergoing reprogramming.	Co-expression
SRP057745	Genome-Wide Specificity of DNA-Binding, Gene Regulation, and Chromatin Remodeling by TALE- and CRISPR/Cas9-Based Transcription Factors	Synthetic DNA-binding proteins have found broad application in gene therapies and as tools for interrogating biology. Engineered proteins based on the CRISPR/Cas9 and TALE systems have been used to alter genomic DNA sequences, control transcription of endogenous genes, and modify epigenetic states. Although the activity of these proteins at their intended genomic target sites have been assessed, the genome-wide effects of their action have not been extensively characterized.  Additionally, the role of chromatin structure in determining the binding of CRISPR/Cas9 and TALE proteins to their target sites and the regulation of nearby genes is poorly understood.  Characterization of the activity these proteins using modern high-throughput genomic methods would provide valuable insight into the specificity and off-target effects of CRISPR- and TALE-based genome engineering tools. We have analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators targeted to the promoters of two different endogenous human genes in HEK293T cells using a variety of high-throughput DNA sequencing methods. In particular, we assayed the DNA-binding specificity of these proteins and their effects on the epigenome. DNA-binding specificity was evaluated by ChIP-seq and RNA-seq was used to measure the specificity of these activators in perturbing the transcriptome. Additionally, DNase-seq was used to identify the chromatin state at target sites of the synthetic transcriptional activators and the genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these genome engineering technologies are highly specific in both binding to their promoter target sites and inducing expression of downstream genes when multiple activators bind to a single promoter. Moreover, we show that these synthetic activators are able to induce the expression of silent genes in heterochromatic regions of the genome by opening regions of closed chromatin and decreasing DNA methylation. Interestingly, the transcriptional activation domain was not necessary for DNA-binding or chromatin remodeling in these regions, but was critical to inducing gene expression. This study shows that these CRISPR- and TALE-based transcriptional activators are exceptionally specific. Although we detected limited binding of off-target sites in the genome and changes to genome structure, these off-target event did not lead to any detectable changes in gene regulation.  Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. Overall design: HEK293T cells were transfected in triplicate with plasmids expressing synthetic transcription factors. The synthetic TFs were either (a) dCas9-VP64 fusion protein and a targeting guide RNA (gRNA), or (b) a TALE-VP64 fusion protein engineered to bind to a specific target site in the genome. As a control, cells were transfected with plasmids expressing GFP. After transfection, RNA-seq was used to identify both on-target and off-target binding sites for the synthetic TFs. The data in this submission were generated using the TALE transfection experiments.	Co-expression
SRP057758	RNA-seq in two ER+ breast cancer cell lines with and without progestins	Exploring effect of progesterone/progestin treatment on gene expression Overall design: Two cell lines, three conditions (Full Media with E2, E2+ Progesterone, Full Media + R5020 Progestin)	Co-expression
SRP057766	Ambient O2 pressure induces NF-kB1/RelA related inflammatory response in human lung epithelial cells in vitro	Purpose: Oxygen (O2) levels in cell culture conditions is typically 2-5 fold higher than the physiological O2 levels that most tissues experience in vivo. The ambient atmospheric O2 (21%) is known to induce cell proliferation defects and cellular senescence in stem cell and primary cell cultures. Therefore, culturing these cells under lower O2 levels (2-9%) is currently a standard practice. However, the non-cancerous immortalized cells and cancer cells, which evade cellular senescence are normally cultured under 21% O2 levels and the effects of higher O2 levels on these cells are not fully understood. Methods: Gene expression (RNA seq transcriptomics) analysis of immortalized human bronchial epithelial (BEAS-2B) cells cultured at ambient 21% O2 and lower 10% O2 levels for 3 days and 3 weeks. Further the beneficial effects of cuturing cells under lower oxygen tension is evalulated Results: Our results show NF-?B/RelA mediated activation of pro-inflammatory cytokines as a major outcome of cells being cultured 21% O2. Moreover, we demonstrate increased RelA binding at the NF-?B1/RelA target gene promoters at 21% O2. Interestingly, contrary to cells cultutred at 21% O2, external stress induced by H2O2 exposure did not induce inflammatory response in cells grown at 10% O2, suggesting increased ability to handle external stress in cells cultured at lower O2 levels. Overall design: RNA Seq gene expression comparision done in replicates	Co-expression
SRP057793	RNA-seq performed on sarcomas to identify various alterations	No description.	Co-expression
SRP057794	RNA-seq analysis of gene expression patterns during hESC neural differentiation	Thousands of genes expression patterns were displayed. Overall design: Examination of gene expression patterns during hESC neural differentiation every 2 days	Co-expression
SRP057826	RNA-seq and small RNA-seq for samples in malignant transformation process of hematopoietic transplants induced by BCR-ABL1-positive microvesicles (human)	Microvesicles (MVs) are extracellular vesicles released by most cells and play critical roles in the progression and relapse of cancers. Our previous work demonstrated that MVs derived from K562 chronic myeloid leukemia cell lines could transform mononuclear cells (MNCs) from normal hematopoietic transplants to acute leukemia-like cancer cells. During the transformation, a new group of leukemia-like cells could be observed after 14 days consecutive incubation with MVs and most of them were transformed to leukemia-like cells after 21 days. To study the gene expression change and the mechanism of the process of K562-MVs transforming MNCs, we performed RNA-seq and small RNA-seq for 5 samples of the key time points, which were samples of K562-MVs, MNCs, 1 week/2 weeks/3 weeks cells after MVs incubation. The K562 cell line was purchased from the China Center for Type Culture Collection (Wuhan, China). MNCs were extracted from the peripheral blood mobilization provided by healthy volunteers. Sequencing of 5 samples were performed by WuXi AppTec Co Shanghai, China.	Co-expression
SRP057852	Role of cervicovaginal microbiota in genital inflammation	We performed gene expression analysis using the SCRB-Seq method from cervical and peripheral blood antigen presenting cells that were collected from women with different cervicovaginal bacterial community types. Overall design: Cervical and peripheral blood antigen presenting cells were FACS sorted using the gating strategy: FSC vs. SSC  -> Singlets -> Live CD45+ -> HLA-DR+ -> CD11c+ or CD14+. The genital bacterial microbiomes were characterized in the same women and categorized into Lactobacillus dominance, Gardnerella dominance, or Prevotella dominance.	Co-expression
SRP057855	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated With Glioblastoma Subtypes	In glioblastoma multiforme (GBM), brain tumor initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here, we applied a stem cell biology approach and compared self-renewal, marker expression, label retention and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptome signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a new framework for the study and use of BTIC lines and provides novel precursor biology insights into GBM.	Co-expression
SRP057945	High salt primes a specific activation state of macrophages, M(Na)	Purpose: Investigate effects of high salt on human macrophage activation Methods: Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton(Life tech). qRT–PCR validation was performed using SYBR Green assays. Results: High salt significantly promotes pro-inflammatory gene expressions,while suppresses the expressions of anti-inflammatory genes and pro-endocytic genes in human macrophages. Conclusions: Our results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na) Overall design: Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton(Life tech). qRT–PCR validation was performed using SYBR Green assays.	Co-expression
SRP057964	CFBE flip-in cells with CFTR of varying genotypes	CFBE cells with flip-in constructs to introduce WT, F508del, and G551D CFTR products underwent RNA-sequencing in hopes of elucidating their expression profiles.	Co-expression
SRP057996	Vammin induces a highly efficient angiogenic response through VEGFR-2/NRP-1 and bypasses the regulatory function of VEGFR-1	Rationale: VEGF family members mediate their effects through cell surface receptors VEGFR-1, VEGFR-2 and NRP. Specific ligands were used to stimulate specific combinations of the receptors to evaluate ligand and receptor properties. Objective: The properties of a novel VEGF family member Vammin were studied in level of receptor binding, gene expression in HUVECs by RNAseq and in vivo using adenoviral gene trasfers. Methods: HUVECs were trasduced using adenoviral vectors encoding VEGF-A109, VEGF-A165 and Vammin and with an empty vector as a control. Gene expression was measured using RNA sequencing. Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Results and conclusions: Vammin is a highly effective VEGFR2 ligand that induces differential gene expression of genes related to proliferation, survival, angiogenesis and blood vessel development in HUVECs. The effect is stronger than ones induced by VEGF-A165 and VEGF-A109.  Vammin induces highly efficient angiogenic responses when delivered into rabbit skeletal muscles using adenoviral gene transfers. Overall design: HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.	Co-expression
SRP058000	CXCR4 regulates extra-medullary myeloma through epithelial-mesenchymal transition-like transcriptional activation	We have developed EMD- and BM-prone and defined the presence of an EMT-like mRNA signature in both EMD- and BM-prone clones. Overall design: Evaluation of RNA sequencing of EMD- and BM-prone clones as compared to the parental cells the two clones were originated from.	Co-expression
SRP058026	Resistance to ROS1 Inhibition Mediated by EGFR Pathway Activation in Non-Small Cell Lung Cancer	The targeting of oncogenic ‘driver’ kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies invariably arises and is a major limitation to patient care. ROS1 fusion proteins are a recently described class of oncogenic driver, and NSCLC patients that express these fusions generally respond well to ROS1-targeted therapy. In this study, we sought to determine mechanisms of acquired resistance to ROS1 inhibition. To accomplish this, we generated a ROS1 inhibition-resistant derivative of the initially sensitive NSCLC cell line HCC78.	Co-expression
SRP058036	An atlas of ribosomal RNA-depleted RNA-Seq data from different normal adult and fetal human tissues	Gene expression is the most fundamental level at which the genotype leads to the phenotype of the organism. Enabled by ultra-high-throughput next-generation DNA sequencing, RNA-Seq involves shotgun sequencing of fragmented RNA transcripts by next-generation sequencing followed by in silico assembly, and is rapidly becoming the most popular method for gene expression analysis. Poly[A]+ RNA-Seq analyses of normal human adult tissue samples such as Illumina s Human BodyMap 2.0 Project and the RNA-Seq atlas have provided a useful global resource and framework for comparisons with diseased tissues such as cancer. However, these analyses have failed to provide information on poly[A]- RNA, which is abundant in our cells. The most recent advances in RNA-Seq analyses, use ribosomal RNA-depletion to provide information on both poly[A]  and poly[A]- RNA. In this paper, we describe the use of Illumina s HiSeq 2000 to generate high quality rRNA-depleted RNA- Seq sequence datasets from human fetal and adult tissues. The datasets reported here will be useful in demonstrating the different expression profiles in different tissues.	Co-expression
SRP058098	The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer (RNA-seq)	This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).	Co-expression
SRP058107	Homo sapiens Raw sequence reads	RNA sequencing of tumor transcriptomes	Co-expression
SRP058120	Differential regulation of alternatively polyadenylated isoforms	Alternative Cleavage and Polyadenylation (APA) plays a crucial role in the regulation of gene expression across eukaryotes. Although APA is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we employed a rigorous subcellular fractionation approach to compare APA profiles of cytoplasmic and nuclear RNA fractions from human cell lines. This comparison allowed us to extract APA isoforms that are subjected to differential regulation and provided us with a platform to interrogate the molecular regulatory pathways that shape the APA profiles in the subcellular locations. Subsequently, we depleted these cells of Dicer to compromise the miRNA biogenesis pathway to isolate the differentially regulated APA events that were regulated by miRNA. Overall design: Two biological replicates of Dicer-depleted and non-depleted HEK293 subcellular fractions were analysed using 3''region extraction and deep sequencing to quantitatively measure the usage of each cleavage and polyadenylation site transcriptome-wide. In addition, 3''READS was performed on the subcellular RNA fractions of HBL melanocyte cells to see if the pattern of differential APA regulation holds between cell lines. Furthermore, standard RNA-seq was performed using the Ion Proton system on HEK293 subcellular RNA fractions. Please note that the raw data from two replicates of Dicer-depleted and non-depleted HEK293 subcellular fractions samples were merged to generate processed data, which is linked to the first replicate sample record (i.e. *rep1.1). For example, the processed data files, C0d.p.bw and C0d.m.bw, were generated from both 3''READs cyto_rep1.1 and 3''READs cyto_rep1.2 sample data and linked to the  ''3''READs cyto_rep1.1'' sample records as supplementary data file.	Co-expression
SRP058128	Montelukast counteracts the influenza virus-induced block in unfolded protein stress response and reduces virus multiplication	Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and economy. Therefore, a large effort has been devoted to the development of new anti-influenza drugs directed to viral targets, as well as to the identification of cellular targets amenable for anti-influenza therapy. Here we describe a new approach to identify such potential cellular targets by screening collections of drugs approved for human use. We reasoned that this would most probably ensure addressing a cellular target and, if successful, the compound would have a well known pharmacological profile.  In addition, we reasoned that a screening using a GFP-based recombinant replicon system would address virus trancription/replication and/or gene expression, and hence address a stage in virus infection more useful for inhibition. By using such strategy we identified Montelukast as an inhibitor of virus gene expression, which reduced virus multiplication in virus-infected cells but did not alter virus RNA synthesis in vitro or viral RNA accumulation in vivo. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated or not with Montelukast, we identified the PERK-mediated unfolded protein response as the pathway responsible for Montelukast action. Accordingly, PERK phosphorylation was inhibited in infected cells but stimulated in Montelukast-treated cells. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection. Overall design: Comparison of gene expression measured by deep sequencing (single-ends, 50nt, RNA-seq) of "Infected", "Not infected", "Infected+Montelukast" and "Not infect+Montelukast" in human A549 cells. Infected means "Infected with influenza virus".	Co-expression
SRP058181	mRNA-Seq expression and MS3 proteomics profiling of human post-mortem BA9 brain tissue for Parkinson Disease and neurologically normal individuals	Parkinson disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein (SNCA) and other proteins in aggregates termed “Lewy Bodies” within neurons. PD has both genetic and environmental risk factors, and while processes leading to aberrant protein aggregation are unknown, past work points to abnormal levels of SNCA and other proteins. Although several genome-wide studies have been performed for PD, these have focused on DNA sequence variants by genome-wide association studies (GWAS) and on RNA levels (microarray transcriptomics), while genome-wide proteomics analysis has been lacking. After appropriate filters, proteomics identified 3,558 unique proteins and 283 of these (7.9%) were significantly different between PD and controls (q-value<0.05). RNA-sequencing identified 17,580 protein-coding genes and 1,095 of these (6.2%) were significantly different (FDR p-value<0.05), but only 166 of the FDR significant protein-coding genes (0.94%) were present among the 3,558 proteins characterized. Of these 166, eight genes (4.8%) were significant in both studies, with the same direction of effect. Functional enrichment analysis of the proteomics results strongly supports mitochondrial-related pathways, while comparable analysis of the RNA-sequencing results implicates protein folding pathways and metallothioneins. Ten of the implicated genes or proteins co-localized to GWAS loci. Evidence implicating SNCA was stronger in proteomics than in RNA-sequencing analyses. Notably, differentially expressed protein-coding genes were more likely to not be characterized in the proteomics analysis, which lessens the ability to compare across platforms. Combining multiple genome-wide platforms offers novel insights into the pathological processes responsible for this disease by identifying pathways implicated across methodologies. Overall design: The study consists of mRNA-Seq (29 PD, 44 neurologically normal controls) and three-stage Mass Spectrometry Tandem Mass Tag Proteomics (12 PD, 12 neurologically normal controls) performed in post-mortem BA9 brain tissue. The proteomics samples are a subset of the RNA-Seq samples.	Co-expression
SRP058191	RC3H1 posttranscriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kB pathway [RNA-Seq]	The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3''UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3''UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway. Overall design: We measured global mRNA decay rates in mock and RC3H1/RC3H2-depleted HEK293 cells. Transcription was blocked by Actinomycin D zero, one or two hours before harvesting. Total RNA was isolated in two biological replicates and subjected to polyA selection followed by high-throughput sequencing.	Co-expression
SRP058222	Expression profiles in 46BR.1G1 cell line	46BR.1G1 cell line is impaired in DNA ligase 1 (LIG1) activity resulting in an increased level of endogenous single (SSBs) and double stranded DNA breaks (DSBs). 46BR.1G1 fibroblastoid cells represent a suitable model system to investigate how cells cope with low levels of chronic DNA damage, a condition frequently encountered in tumors. Transcriptional alterations in 46BR.1G1 cells were determined by RNAseq by comparison with 7A3, a cell line in which the defect was rescued by stable expression of ectopic wild-type Lig1. The identification of genes differentially expressed in 46BR.1G1 cells would contribute to the elucidation of DNA damage response (DDR) mechanisms.	Co-expression
SRP058237	Reprogrammed myeloid cell transcriptomes in NSCLC	Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form.  Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value. Overall design: We sorted pure populations of the immature monocytic myeloid cells (IMMCs), neutrophils (Neu), and epithelial cells (Epi) from tumors and adjacent lung tissues of stage I-III lung adenocarcinoma patients. RNA samples (totally 17 samples) were sequenced: from tumor IMMC (n=3), Neu (n=2), Epi (n=2); from adjacent lung IMMC (n=3), Neu (n=4), Epi (n=3).	Co-expression
SRP058243	RNASeq identified human transcriptome alterations in Chinese Nasopharyngeal Carcinoma	Our study is the first transcriptome profiling of Chinese NPC patients. These results provide both molecular basis and therapeutic opportunities for Chinese NPC patients. Overall design: mRNA profiles of 42 Chinese Nasopharyngeal Carcinoma patients and 4 non-NPC tissues by Illumina Hiseq 2000.	Co-expression
SRP058244	The RNA-binding protein Musashi1 is a central regulator of adhesion pathways in glioblastoma	The conserved RNA-binding protein Musashi1 (MSI1) has emerged as a key oncogenic factor in numerous solid tumors, including glioblastoma. However, its mechanism of action has not yet been established comprehensively. We set out to map its impact on the transcriptome in U251 cells using RNA-seq and iCLIP. Overall design: Examination of gene expression and splicing changes upon KD of Musashi1 in U251 cells and link to iCLIP-identified Musashi1 RNA binding sites	Co-expression
SRP058310	BRCA1, R-loops and Recombination defects in Ewing''s sarcoma (RNA-seq)	Ewing's sarcoma family of tumors (ESFT) is an aggressive pediatric bone and soft tissue cancer. It is the prototypical example of mesenchymal tumors driven by a fusion oncogene involving the ewing sarcoma break point region 1 (EWSR1) gene, most frequently– EWS-FLI1. We have discovered that loss of EWSR1 leads to accumulation of R-loops, replication stress and impaired homologous recombination, recapitulating breast cancer 1, early onset (BRCA1) deficiency. EWS-FLI1 acts dominant negatively in ESFT to impart the same phenotypes. Further we demonstrate that in ESFT, BRCA1 predominantly associates with the elongating transcription machinery and is unavailable for DNA strand break repair. Gene expression profiling identified upregulated compensatory mechanisms in ESFT cells to process increased R-loops (RNASEH2 and FEN1) and replication stress (Fanconi Anemia). Taken together, our data identifies BRCA1 sequestration due to transcription stress as the mechanistic basis for ESFT chemosensitivity and suggests potential targets for the much lacking second-line therapy. Overall design: Examination of gene expression of four ESFT cell lines and two control cell lines. Cells were treated to LD65 dose of etoposideand samples collected at 6 hour intervals over 24 hours	Co-expression
SRP058319	Endogenous DUX4 Expression in FSHD Myotubes is Sufficient to Cause Cell Death and Disrupts RNA Splicing and Cell Migration Pathways.	Facioscapulohumeral Muscular Dystrophy (FSHD) is caused by chromatin relaxation that results in aberrant expression of the transcription factor Double Homeobox 4 (DUX4). DUX4 protein is present in a small subset of FSHD muscle cells, making its detection and analysis of its effects historically difficult. Using a DUX4-activated reporter we demonstrate the burst expression pattern of endogenous DUX4, its method of signal amplification in the unique shared cytoplasm of the myotube, and FSHD cell death that depends on its activation. Transcriptome analysis of DUX4 expressing cells revealed that DUX4 activation disrupts RNA metabolism including RNA splicing, surveillance, and transport pathways. Cell signaling, polarity, and migration pathways were also disrupted. Thus, DUX4 expression is sufficient for myocyte death and these findings suggest mechanistic links between DUX4 expression and cell migration, supporting recent descriptions of phenotypic similarities between FSHD and an FSHD-like condition caused by FAT1 mutations.	Co-expression
SRP058341	RNA-Seq analysis of Head and Neck Squamous cell carcinoma cell-lines	Analysis of gene-probe expression data (FPKM) for HNSCC cell-lines using single-end RNA-Seq Overall design: RNA was collected and analyzed from 6 HNSCC cell-lines ( SCC15, SCC4, SCC71, UMSCC103, UMSCC29, SCC351)	Co-expression
SRP058342	NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells	In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE associated protein VAMP8. NUPR1 depletion deregulates autophagic flux and impairs autolysosomal clearance, inducing massive cytoplasmic vacuolization and premature senescence in vitro and tumor suppression in vivo. Collectively, our data show that NUPR1 is a potent regulator of autolysosomal dynamics and is required for the progression of some epithelial cancers. Overall design: mRNA profiles of NUPR1-depleted A549 and control cells were generated by RNA-sequencing, using Illumina GAIIx or Illumina HiSeq 2000.	Co-expression
SRP058375	Tumor exosome integrins determine organotropic metastasis	Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins a6ß4 and a6ß1 were associated with lung metastasis, exosomal integrins avß5 and avß3 were linked with liver and brain metastases, respectively. Targeting a6ß4 and avß5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis. Overall design: Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes	Co-expression
SRP058387	RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships (RNA-seq)	Mapping of RNA:DNA hybrids in human cells reveals a number of characteristics of these non-canonical  nucleic  acid  structures.    A  directional  sequencing  approach  reveals  the  RNA component of the RNA:DNA hybrid to be purine-rich, indicating a thermodynamic contribution to the stability of these structures.  The RNA:DNA hybrids are enriched at loci with decreased DNA methylation  and  increased  DNase  hypersensitivity,  and  within  larger  domains  with characteristics of heterochromatin formation.  Studies of chromatin at RNA:DNA hybrids shows the  presence  of  the  ILF2  and  ILF3  transcription  factors,  supporting  a  model  of  certain transcription factors binding preferentially to the RNA:DNA conformation.  Overall, there is little to indicate a dependence for RNA:DNA hybrids forming co-transcriptionally, with results from the ribosomal DNA repeat unit instead supporting a model of RNA generating these structures in trans.  The results of the study indicate heterogeneous functions of these genomic elements and new insights into their formation and stability in vivo. Overall design: Investigation of expression data genome-wide in HEK293T and IMR-90 cells through RNA-seq, including rRNA	Co-expression
SRP058414	Homo sapiens Transcriptome or Gene expression	RNA-seq was performed to analyze whole genome transcriptome in pre-B cell acute lymphoblastic leukemia	Co-expression
SRP058445	RNA sequencing analysis of miR-603 overexpression	Alzheimer’s disease (AD) is a serious neurodegenerative disease in which miRNAs have been linked to its pathogenesis. miR-603 is a primate-specific miRNA. Through ADNI data analysis, we found a SNP rs11014002 in pre-miR-603 which promotes the biogenesis of mature miR-603 is associated with AD risk. We further identified that LRPAP1, a protein which antagonizes the function of LRP1 in Aß clearance and AD susceptibility, is a target gene of miR-603. Moreover, overexpression of miR-603 increased the protein level of LRP1, suggesting the protective role of miR-603 in AD. Both significant increase and loss of regulatory function of miR-603 hint the existence of a compensatory mechanism in hippocampus of AD subjects. Furthermore, we found that miR-603 could directly downregulate E2F1 and prevent cells from H2O2 induced-apoptosis. This work provides the first evidence that miR-603 may modulate AD susceptibility and the SNP rs11014002 (T-carrier genotype) might be a protective factor for AD. Overall design: There are two groups: Negative Control and miR-603 overexpression. We performed experiments on HEK293 cell and Hela cell.	Co-expression
SRP058479	Gene target specificity of the Super Elongation Complex (SEC) family: How HIV-1 Tat employs selected SEC members to activate viral transcription	The AF4/FMR2 proteins AFF1 and AFF4 act as a scaffold to assemble the Super Elongation Complex (SEC) that strongly activates transcriptional elongation of HIV-1 and cellular genes. Although they can dimerize, it is unclear whether the dimers exist and function within a SEC in vivo. Furthermore, it is unknown whether AFF1 and AFF4 function similarly in mediating SEC-dependent activation of diverse genes. Providing answers to these questions, our current study shows that AFF1 and AFF4 reside in separate SECs that display largely distinct gene target specificities. While the AFF1-SEC is more potent in supporting HIV-1 transactivation by the viral Tat protein, the AFF4-SEC is more important for HSP70 induction upon heat shock. The functional difference between AFF1 and AFF4 in Tat-transactivation has been traced to a single amino acid variation between the two proteins, which causes them to enhance the affinity of Tat for P-TEFb, a key SEC component, with different efficiency. Finally, genome-wide analysis confirms that the genes regulated by AFF1- and AFF4-SEC are largely non-overlapping and perform distinct functions. Thus, the SEC represents a family of related complexes that exist to increase the regulatory diversity and gene control options during transactivation of diverse cellular and viral genes. Overall design: RNA-seq in HeLa cells of wild-type and after RNAi of AFF1 or AFF4.	Co-expression
SRP058490	A positive regulatory loop between a Wnt-regulated non-coding RNA and ASCL2 controls intestinal stem cell fate	The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/ß-catenin transcriptional complex is the primary transforming factor in colorectal cancer. Despite significant recent inroads, the full complement of Wnt target genes and the mechanisms of regulation remain incompletely understood. Here we identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/ß-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its close neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/ß-catenin to mediate the juxtaposition/physical contact of its own promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 expression. This feedforward regulatory loop controls stem cell-related gene expression and is highly amplified in colorectal cancer. Overall design: Derivatives of Ls174T colon cancer cells, overexpressing the Tet repressor were used for the construction of inducible overexpressing a shRNA against the WiNTRLINC1 long non coding RNA upon treatment with doxyxycline. siRNAs against WiNTRLINC1 were designed with the siDesign center tool from Dharmacon and their sequences were used for the construction of the shRNA stem loop structure as described in EMBO Rep. 2003 Jun;4(6):609-15. The modified pTER vector was used as a backbone for constructing the shRNA cassette as described in EMBO Rep. 2003 Jun;4(6):609-15. Positive cell clones were screened with RT-PCR in order to validate the efficiency of the knockdown of WiNTRLINC1. The Ls174T derivative cell line inducibly overexpressing a shRNA against ASCL2 has been described previously  in Cell. 2009 Mar 6;136(5):903-12. RNA deep sequencing was performed in the WiNTRLINC1 KD and ASCL2 KD cells compared to controls cells in order to detect changes in gene expression due to the loss of either WiNTRLINC1 or ASCL2.	Co-expression
SRP058501	Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics	Ribosome profiling is a widespread tool for studying translational dynamics in human cells.  Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis.  Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics.  We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density.  This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone.  Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events.  These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics. Overall design: Timecourse experiment with six points over 48hr after bortezomib exposure in MM.1S myeloma cells.  mRNA-seq and ribosome profiling data at each time point.	Co-expression
SRP058534	ELAVL2-regulated transcriptional networks in human neurons link atlernative splicing, autism and human neocortical evolution	The role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution. Overall design: We carried out RNA-sequencing (RNA-seq) of human neural progenitors cells. For the RNA-seq, 5 indipendent replicates were used for the neural progenitor cells. Primary human neural progenitor cultures were derived from mid-gestation fetal brain. Cells were transduced with a lentivirus containing a specific shRNA to ELAVL2 or a control shRNA. Cells were differentiated into neurons for 4 weeks and then harvested.	Co-expression
SRP058567	Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte [RNA-seq]	We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly through a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Overall design: Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system	Co-expression
SRP058571	Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer [RNA-Seq]	Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Overall design: RNA-Seq in breast cancer cell-lines	Co-expression
SRP058587	The effect of knockdown Abl kinases on breast cancer cells'' global transcriptome	To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells. Overall design: Four samples were analyzed control, Abl single knockdown, Arg single knockdown, Abl/Arg double knockdown. Experiments were performed in triplicate.	Co-expression
SRP058619	RNA-Sequencing experiment for effects of PKF115-584 treatment on four T-ALL cell lines (RPMI8402, HPB-ALL, Jurkat, CCRF-CEM).	Notch activation is instrumental in the development of most T-cell acute lymphoblastic leukemia (T-ALL) cases, yet Notch mutations alone are not sufficient to recapitulate the full human disease in animal models. We here found that Notch1 activation at the fetal liver (FL) stage expanded the hematopoietic progenitor population and conferred it transplantable leukemic-initiating capacity. However, leukemogenesis and leukemic-initiating cell capacity induced by Notch1 was critically dependent on the levels of ß-Catenin in both FL and adult bone marrow contexts. In addition, inhibition of ß-Catenin compromised survival and proliferation of human T-ALL cell lines carrying activated Notch1. By transcriptome analyses, we identified the MYC pathway as a crucial element downstream of ß-Catenin in these T-ALL cells and demonstrate that the MYC 3'' enhancer required ß-Catenin and Notch1 recruitment to induce transcription. Finally, PKF115-584 treatment prevented and partially reverted leukemogenesis induced by active Notch1. Overall design: Four T-ALL cell lines (RPMI8402, HPB-ALL, Jurkat, CCRF-CEM)  were treated with DMSO (control) or PKF115-584 (310nM) for 3hrs. Gene expression changes were measured with Cufflinks comparing the 4 control with the 4 treated samples.	Co-expression
SRP058626	Comparative transcriptome analysis reveals that ECM-Receptor Interaction contributes to the venous metastases of hepatocellular carcinoma	Hepatocellular carcinoma (HCC) is the most common kind of liver cancer in the world. Portal vein tumor thrombus (PVTT) is one of the most serious complications of HCC and strongly correlated to a poor prognosis for HCC patients. However, the detailed mechanisms of PVTT development still remains to be explored. In this study, we presented the large scale transcriptome analysis of 11 HCC with PVTT patients by RNA-sequencing. The dysregulated genes between HCC and PVTT suggested that the ECM-Receptor Interaction was correlated to the venous metastases of HCC. Among all the recurrent alternative splicing events, we identified exon 6 skipping of RPS24, which is likely to be a cancer driver. We also identified five common fusion genes between HCC and its corresponding PVTT samples, including ARID1A-GPATCH3, MDM1-NUP107, PTGES3-RARG, PRLR-TERT and C9orf3-TMC1. All of the findings broaden our knowledge in PVTT development and may also contribute to the diagnosis and treatment for HCC patients with PVTT. Overall design: In this study, we presented the large scale transcriptome analysis of 11 HCC with PVTT patients by RNA-sequencing.	Co-expression
SRP058633	Homo sapiens Raw sequence reads	This study identified genomwide KCl inducible readthrough transcription. The project also includes a Cap-Seq experiment to identify transcriptional start sites, demonstrating that KCl does not activate downstream transcriptional start sites, but indeed does induce readthrough	Co-expression
SRP058647	Mastermind-like 3 controls proliferation and differentiation in neuroblastoma (RNA-seq)	Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas. Overall design: RNA-seq of SK-N-SH control and MAML3 overexpressing (SD3.23) cells, either untreated (UT) or treated with 1 µM RA (RA).	Co-expression
SRP058667	RNA sequencing of matched nephrectomy samples [RNA-seq]	To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes, nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91-95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing and after genome alignments, only 0.2-0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line, prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between the Mayo Clinic vs. TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes. Overall design: Examination of RNA expression in ccRCC	Co-expression
SRP058698	Comparing effects of perfusion and hydrostatic pressure on human chondrocytes using gene profiles	Hydrostatic pressure and perfusion have been shown to alter the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed applying loading (0.1 MPa for 2 h) and perfusion (2ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls were maintained in static culture. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. RNAseq identified similarities between the two treatments. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP-13 expression. Despite of the similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects Overall design: 9 samples	Co-expression
SRP058699	Gene expression of rhabdomyosarcoma cells infected with cytolytic and non-cytolytic variants of coxsackievirus B2 Ohio	In this study the gene expression in cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose of elucidating the effects of lytic and non-lytic viruses on host cell transcription. Total RNA was extracted from infected cells, next generation sequencing was performed, and the reads were subsequently mapped against the human and CVB2O genomes. The amount of intracellular virions was measured, showing a relative amount of virus RNA 13 times higher in the cells infected with the lytic variant, vVP1Q164K, compared to cells infected by the non-lytic CVB2Owt. Furthermore, differential gene expression in the cells infected with the two viruses was identified and a number of genes singled out as possible keys to the answer of how the viruses interact with the host cells, resulting in lytic or non-lytic infections. Overall design: 4 samples, two samples of one strain, one sample of a different strain, and one control sample	Co-expression
SRP058717	The lncRNA LUST promotes CCICs self-renewal stimulating the wnt/b-catenin signaling activation [RNA-Seq]	Comprehensive RNA-seq experiments in CD24bright/CD44bright (CCICs), CD24dim/CD44dim (more differentiated counterpart) cells and colonospheres delineate the role of the lncRNA LUST  in promoting CCICs self-renewal. Overall design: RNA-Seq study from HT-29 CD44bright/CD24bright and CD24dim/CD44dim sorted cells subpopulation	Co-expression
SRP058719	Long non-coding RNA profiling of human lymphoid progenitors reveals transcriptional divergence of B cell and T cell lineages	To elucidate the transcriptional ‘landscape’ that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNA (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus. Overall design: We performed RNA-Seq of 10 distinct cell types isolated by fluorescence activated cell sorting (FACS). From BM, we isolated CD34+CD38neglinneg cells, a population highly enriched for HSC, as well as three lymphoid progenitor populations; LMPP (CD34+CD45RA+CD38+CD10neg CD62Lhilinneg), CLP (CD34+CD38+CD10+CD45RA+linneg ) and fully B cell committed progenitors (BCP, CD34+CD38+CD19+). From thymus we isolated three CD34+ subsets; Thy1 (CD34+CD7neg CD1aneg CD4negCD8neg), Thy2 (CD34+CD7+CD1aneg CD4negCD8neg), and Thy 3 (CD34+CD7+CD1a+CD4negCD8neg), as well as fully T cell committed populations CD4+CD8+ (Thy 4), CD3+CD4+CD8neg (Thy5) and CD3+CD4neg CD8+ (Thy6).	Co-expression
SRP058722	A Molecular Portrait Of High-Grade Ductal Carcinoma In Situ (DCIS) [RNA-seq]	DCIS is a non-invasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer while others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor intrinsic subtypes, proliferative, immune scores and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immune suppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly ncRNA and methylation profiles reproduce changes observed post-invasion. Among the most significant findings we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and specific SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a pre-invasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. Overall design: RNAs from 25 out of 30 (83%) pure HG-DCIS and 10 normal breast organoids (total 35 samples) were subjected to RNA-Seq analysis by using Illumina HiSeq2000 platform Please note that description of samples employed for the NGS analyses including age, race, ER/PR immunohistochemistry results, ITIL/STIL scores and PAM50 classification is provided the ''Supplementary Data1_Samples data.xlsx'' (available on Superseries record)	Co-expression
SRP058740	Analysis of human, chimpanzee, macaque and mouse tissue transcriptomes using Next Generation Sequencing	We performed deep strand-specific sequencing of poly-adenylated RNA (polyA+ RNAseq) from human, chimpanzee, macaque and mouse tissues, with the goal of detecting numerous non-annotated poorly expressed and antisense genes. We identified thousands of annotated and novel genes, especially in testis. We discovered that ~2% of the human and chimpanzee multiexonic genes were specific from such species. Overall design: We generated RNA-Seq data (~2.10 billion paired-end reads, 25-100 bp length) for the polyadenylated RNA fraction of brain (cerebral cortex), heart, liver and testis. In human and chimpanzee, we generated 2 samples per tissue corresponding to different individuals. In macaque, only 1 sample per tissue was generated. In mouse, considered as the evolutionary outgroup, we generated three pools of brain samples, and one pool of heart, liver and testis samples.  We generated an additional sample in Testis without including reverse transcriptase as a control of DNA contamination.	Co-expression
SRP058771	RNA-seq 1,25(OH)2D3 time course in THP-1 cells	gene expression profiling by RNA-seq in THP-1 cells treated with 1,25(OH)2D3 for 2.5-24 h Overall design: three independent experiments of 1,25(OH)2D3 time course in THP-1 cells	Co-expression
SRP058773	Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [smartseq2]	Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: single cell RNA-seq profiles from 52 unfractionated hiF-T cells after 10 days of reprogramming	Co-expression
SRP058783	RNA-Seq experiment to identify genes regulated by ATF4	Activating Transcription Factor 4 (ATF4) is a transcription factor induced by the integrated stress response (ISR). This experiment is a genome-wide profiling of ATF4-dependent RNA expression in human HAP-1 cells. HAP-1 is a near-haploid human cell line that was derived from KBM-7 cells isolated from a patient with Chronic Myelogenous Leukemia. We analyzed WT and ATF4 KO cells. We induced ATF4 expression by mimicking amino acid starvation with the drug histidinol. Overall design: RNA expression profiles were generated for WT and ATF4 KO HAP1 cells. ATF4 genes were mutated using Cas9 genome editing technology. Amino acid starvation was mimicked by treating WT and ATF4 KO cells with 2 mM histidinol for 24 hours, which increases ATF4 expression.	Co-expression
SRP058787	Genome-wide maps of human OEC innate immune responses to Burkholderia	We report a transcriptional response in human OECs that encompasses multiple innate immune networks not previously associated with these cells. Major pathways included immune cell trafficking, and differential cytokine production Overall design: We used RNA-based sequencing technology for high-throughput profiling of innate immune responses in human OECs and the role of Burkholderia in triggering these responses	Co-expression
SRP058840	Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [SCRB-Seq]	Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: hiF-T cells are secondary reprogrammable cells derived from hiF cells  obtained thorough the directed differentiation of a dox-inducible OKMS  hIPSC line obtained from reprogramming BJ fibroblasts. After directed  differentiation, hiF cells were infected with a lentivirus expressing  the human telomerase and after clonal expansion individual hiF-T  clones were obtained. The multiplexed data is available at: https://refinery.stemcellcommons.org/data_sets/GSE69351_DGE/	Co-expression
SRP058841	Tunable protein synthesis by transcript isoforms in human cells (Transcript Isoforms in Polysomes sequencing: TrIP-seq)	Eukaryotic genes generate multiple mRNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex as each isoform can be translated differently. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and translational output of each transcript isoform. We extracted a panel of 5' and 3' untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5' untranslated regions exert robust translational control between cell lines, while 3' untranslated regions can confer cell-type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels. Overall design: Total cytoplasmic and eight polysomal fractions of RNA were purified from HEK 293T cells in biological duplicate. Ribosomal RNA was depleted using Ribo-Zero (Human/Mouse/Rat; Epicenter) and libraries were prepared using the TruSeq RNA v2 kit (RS-122-2001; Illumina) skipping the polyA selection step. Reads are paired-end 75bp and sequencing adapters are GATCGGAAGAGCACACGTCTGAACTCCAGTCAC (read1) and AGATCGGAAGAGCGTCGTGTAGGGAAAGAGTGT (read2).	Co-expression
SRP058856	The apoptotic network and expression of BH3-containing proteins predict phenotypic response to BET bromodomain inhibitors	Small molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are in clinical trials for a variety of cancers, but patient selection strategies are limited.  This is due in part to the heterogeneity of response following BET inhibition (BETi), which includes differentiation, senescence, and cell death in subsets of cancer cell lines.  To elucidate the dominant features defining response to BETi, we carried out phenotypic and gene expression analysis of both treatment naïve cell lines and engineered tolerant lines.  We found that both de novo and acquired tolerance to BET inhibition are driven by the robustness of the apoptotic response and that genetic or pharmacological manipulation of the apoptotic signaling network can modify the phenotypic response to BETi.  We further identify that ordered expression of the apoptotic genes BCL2, BCL2L1, and BAD significantly predicts response to BETi.  Our findings highlight the role of the apoptotic network in response to BETi, providing a molecular basis for patient stratification and combination therapies. Overall design: Gene expression profiling of A375 melanoma cells or NOMO-1 AML cells treated with DMSO or the BET inhibitor, CPI203.  Also, gene expression profiling of the respective derived BETi-tolerant cells treated with DMSO or CPI203.	Co-expression
SRP058911	Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival	Background and Aim: Fra-1 (Fos-related antigen-1) is a member of the AP1 (activator protein-1) family of transcription factors. We have recently shown that Fra-1 is necessary for breast cancer cells to metastasize in vivo, and that breast cancer outcome can be predicted by a classifier comprising genes that are expressed in a Fra-1-dependent fashion. Here, we show that Fra-1 plays an important role also in colon cancer progression. Methods: We compared proliferation rates of parental and Fra-1-depleted colon cancer cells in vitro under 2D, 3D, and attachment-free conditions and in vivo upon subcutaneous and intravenous injections into mice. We also compared RNA expression profiles of colon cancer cells with and without Fra-1 expression. Results: Fra-1 depletion impair colony outgrowth of human colon cancer cells in soft agar and in suspension, whereas it does not affect proliferation on 2D culture plates. Consistent with this, upon subcutaneous injection into mice, tumors formed by Fra-1-depleted colon cancer cells are only three times smaller than those produced by control cells. In contrast, when injected intravenously, Fra-1 depletion causes 200-fold reduction in tumor burden. Consistent with the more aggressive characteristics of Fra-1-proficient tumors, the prognosis of colon cancer patients can be predicted by a Fra-1 classifier generated by comparing RNA profiles of parental and Fra-1-depleted colon cancer cells. Conclusions: Our results demonstrate that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and suggest that a Fra-1 classifier can be used as a prognostic predictor in colon cancer patients. Overall design: HT29 cell line, two shRNAs against Fra-1, one empty vector control, three biological replicates	Co-expression
SRP058916	Finding missing proteins from epigenetically manipulated human cells	We performed transcriptome sequencing to assess the genes turn on in the cell under epigenetically manipulation. MHCC97H, A549 and HCT116 were treated by GSK126, S2101 and TSA respectively. We detected the missing proteins in the cells under epigenetically manipulation. Overall design: A549 and MHCC97H cells were cultured in the complete DMEM medium and epigenetically manipulation (1 µM TSA, 50 µM GSK126 and 100µM S2101 respectively); HCT116 cells were maintained in complete RPMI 1640 medium and epigenetically manipulation (1 µM TSA, 50 µM GSK126 and 100µM S2101 respectively). We detected and analyzed the missing protein with transcriptome and proteome.	Co-expression
SRP058941	The protein and transcript profiles of human semen	Transcriptome of testes was examined for comparison of transcript abundance with that of sperm/seminal fluid (as sequenced in separate study) Overall design: Commercially available (Ambion) human testes RNA was prepared and sequenced in two replicates	Co-expression
SRP059028	Chromatin-associated RNA-seq in MCF-7	Deep sequencing of total RNA isolated from the chromatin fraction of MCF-7 cells. Overall design: Stranded total RNA-seq (rRNA-minus) of chromatin-isolated RNA from estradiol starved and estradiol induced MCF-7 cells.	Co-expression
SRP059031	Transcriptome analysis of Jurkat T-ALL clones from control and CBAP-knockdown/knockout sets	We sequenced whole-genome mRNA from 8 different single stable clones of Jurkat cells modified with CBAP gene expression usng shRNA knockdown or CRISPR/Cas9-mediated knockout and their controls. Overall design: Examination of mRNA levels from individual cell line using high throughput sequencing	Co-expression
SRP059035	Single-cell RNA sequencing of lung adenocarcinoma patient-derived cells	To address how intratumoral heterogeneity affects anti-cancer drug responses, we profiled transcriptomes of single cancer cells originating from lung adenocarcinoma patient-derived xenograft (PDX) tumors. Overall design: We performed single-cell RNA sequencing (scRNA-Seq) together with bulk sequencing by applying Smart-Seq protocol (Ramsköld et al., Nat Biotechnol 2012). Enrichment of cancer cells in PDX from primary tumor (LC-PT-45: bulk RNA-Seq, n=1) was identified by histopathological examination and genomic signatures. Tumor cell-enriched PDX cells (LC-PT-45: scRNA-Seq, n=34; bulk RNA-Seq, n=9) were analyzed, and additional batch (LC-Pt-45-Re: scRNA-Seq, n=43; bulk RNA-Seq, n=7) was obtained to check comparable results. H358 human lung cancer cells (scRNA-Seq, n=50; bulk RNA-Seq, n=1) were used as cell line controls. Another lung cancer PDX case (LC-MBT-15: scRNA-Seq, n=49; bulk RNA-Seq, n=7) was prepared to validate our analytical strategy applied in the LC-PT-45 case.	Co-expression
SRP059039	Elucidating the etiology and molecular pathogenicity of infectious diarrhea by high throughput RNA sequencing	Diarrhea remains a major cause of death in children. Current diagnostic methods largely rely on stool culture and suffer from low sensitivity and inadequate specificity, often leading to inappropriate treatment. The objective of the present study was to use RNA sequencing (RNAseq) analysis to determine blood transcriptional profiles specific for several common pathogenic bacteria and viruses that cause diarrhea in children. We collected whole blood samples from children in Mexico having diarrhea associated with a single pathogen and without systemic complications. Our RNAseq data suggested that the blood signatures can differentiate children with diarrhea from healthy children either with or without bacterial colonization. Moreover, we detected different expression profiles from bacterial and viral infection, demonstrating for the first time the use of RNAseq to identify the etiology of infectious diarrhea. Overall design: 255 whole blood samples from 246 children including children with diarrhea caused by rotavirus (n=60 total; 5 repeated; 55 unique), E.coli (n=55), Salmonella (n=36), Shigella (n=37), adenovirus (n=8), norovirus (n=7), and control children (n=52 total; 4 repeated; 48 unique).	Co-expression
SRP059057	Transcriptome analysis of CD4+ T cells reveals imprint of BACH2 and IFN? regulation	We used RNA sequencing to profile over 70 transcriptomes of CD4+ T cells, a cell type crucial for Coeliac Disease CD pathogenesis, in both stimulated and resting samples from individuals with CD and unaffected controls The data gave us the opportunity to (i) compare gene expression between cases and controls; (ii) specifically assess whether genes that have been genetically associated with the disease were being DE; (iii) and also look for known and novel aspects of pathogenesis in the transcriptome of this specific cellular compartment. Overall design: RNA sequencing was performed on mRNA  extracted from the CD4+ T cells of 15 Coeliac patients and 11 Controls that had been stimulated with anti-CD3/anti-CD28, PMA and left unstimulated. In total we sequenced 74 transcriptome samples using 50bp reads on an Illumina HiSeqâ„¢ 2000.	Co-expression
SRP059066	Combinatorial Regulation Mediated by Biochemically Distinct Forms of SWI/SNF [RNA-Seq]	The precise makeup of chromatin remodeling complexes is important for determining cell type and cell function. The SWI/SNF chromatin remodeling complex is made up of multiple subunits that can be filled by mutually exclusive proteins. Inclusion or exclusion of these proteins has profound functional consequences, yet we currently understand little about the direct functional relationship between these biochemically distinct forms of remodeling complexes. Here we combine chromatin immunoprecipitation, transcriptome analysis, and transcription factor binding information from the ENCODE project to determine the functional relationship between three biochemically distinct forms of SWI/SNF. We find widespread overlap in transcriptional regulation and the genomic binding of the three ARID (AT-Rich Interacting Domain) subunits of SWI/SNF. Despite the numerous similarities in their transcriptional regulation and the co-factors bound with each ARID we identify several novel interaction modalities. Previous work has found examples of competition or subunit switching at individual loci, and we find this functional relationship is widespread, and in these cases gene expression changes following loss of one ARID depend on the function of another ARID. We also identify a previously unknown cooperative interaction between ARID1B and ARID2 in the repression of a large number of genes. Together these data help untangle the complicated combinatorial relationships between a highly heterogenous chromatin remodeling family. Overall design: We performed depletion of ARID subunits (ARID1A , n=5; ARID1B, n=3, ARID2, n=5) of SWI/SNF using siRNA or a Non-Targeting control (N=6) and performed expression analysis using polyA+ selected RNA and a strand-specific dUTP incorporation library protocol.	Co-expression
SRP059170	Gene expression analysis of CD4+ and CD4- ILC1 subsets by RNAseq	Innate lymphoid cell (ILC) subsets that mirror helper T cells in their effector cytokine profiles have recently emerged as central players in both homeostatic and inflammatory conditions.  Like their Th1, Th2 and Th17/Th22 helper T cell counterparts, ILC subsets are categorized based on their expression of specific transcription factors and effector cytokines:  group 1 ILC (ILC1) express T-bet and IFN-?; group 2 ILC (ILC2) express GATA-3 and type 2 effector cytokines such as IL-13 and IL-5; and group 3 ILC (ILC3) express RORgt and the cytokines IL-22 and/or IL-17.  Under this nomenclature, natural killer (NK) cells and lymphoid tissue inducers (LTi) are considered ILC1 and ILC3, respectively.  ILC1 contain both CD4+ and CD4- populations, but whether this phenotypic characteristic reflects functional differences between these two populations is unknown.  These studies examine the gene expression profiles of CD4+ vs CD4- ILC1 in a cohort of healthy control subjects. Overall design: ILC subsets were isolated from the peripheral blood of healthy control subjects.  cDNA was isolated and amplified from sorted populations, and gene expression was analyzed by RNAseq	Co-expression
SRP059172	Refining brucellosis diagnosis by blood transcriptional profiling.	Diagnosis of brucellosis remains challenging for several reasons, including lack of culture sensitivity, nonspecific symptomatology, and high prevalence of positive serology in endemic areas. The main objectives of this study were to identify blood biomarkers specific to brucellosis compared to other endemic infections and to monitor changes in blood biomarkers during treatment. To obtain a global profile of the disease, we employed RNA sequencing (RNAseq) of whole blood RNA to measure host response against brucellosis infection in patients from Macedonia and Spain. Long-term follow up of patients was used to classify patients as having acute or chronic/reinfection brucellosis and as treatment responders and non-responders. We observed distinct gene expression differences between samples from acute brucellosis and control donors. The magnitude of gene expression changes was associated with antibody titers determined by standard serological tests for brucellosis, including the rose Bengal and standard agglutination tests. The expression signature characteristic of acute brucellosis was also different from that of subjects with leishmaniasis. In depth integration of clinical data and serological findings with our gene expression data will be performed to provide insight into cellular and molecular mechanisms of brucellosis infection. Overall design: Whole blood from 169 subjects including 105 patients with suspected brucellosis, 17 patients with leishmaniasis, and 47 healthy controls.	Co-expression
SRP059176	Transcriptome analysis of PC9 cells with gefitinib or/and hypoxia treatment and comparison with gefitinib resistant PC9 cells and ALDH positive PC9 cells	Inevitable gefitinib resistance and relapse of the disease was the biggest hurdle to NSCLC treatment. Importantly, the role of hypoxia in solid tumor tissues in vivo in gefitinib acquired resistance and its relationship to lung cancer stem cells (LCSCs) has not been fully elucidated. Here, the PC9 cells were treated with short term gefitinib or/and hypoxia, also, PC9 gefitnib resistant (PC9-GR) cell line was established and ALDH positive PC9 cells were sorted by FACs. Transcriptome analysis among those PC9 cell groups revealed the important role of hypoxia in gefitinib acquired resistance and signaling transduction change, which may critical for NSCLC disease progression and recurrence. Overall design: The PC9 cells were treated with 0.1 uM gefitinib or/and hypoxia for 1 week, also, PC9 geifitnib resistant (PC9-GR) cells and ALDH positive PC9 cells were anlyzed by RNA-seq technology.	Co-expression
SRP059197	An orthologous epigenetic gene expression signature derived from differentiating embryonic stem cells identifies regulators of cardiogenesis	We report a time course of RNA-seq data from wild-type embryonic stem cells and embryonic stem cells in which the cardiogenic transcription factors ZNF503, ZEB2 and NKX2-5 are depleted with shRNAs differentiating along the cardiac lineage. Overall design: Biological replicates of RNA-seq data from embryonic stem cells differentiating along the cardiac lineage.	Co-expression
SRP059205	Landscape of Hematopoiesis Described in Induced Pluripotent Stem Cells and Human Bone Marrow	Granulopoietic differentiation of myeloid progenitor cells derived from control iPSCs  was performed in a two-step liquid culture. At the end of culture, stages of differentiation were identified by morphological analysis and submitted for RNA-sequencing analysis in order to provide insight into the genomic landscape of myeloid lineage hematopoiesis as modeled by the in vitro induced differentiation of iPSCs as compared to in vivo bone marrow-derived promyelocytes. Overall design: Peripheral blood from healthy controls was obtained and iPSC were generated from peripheral blood mononuclear cells.  Hematopoietic progenitors generated from control iPSCs when cultured in myeloid expansion medium containing 50ng/mL SCF, 10ng/mL IL-3 and 10ng/mL GM-CSF for 5 days at which point cells were stained for CD45-Pacific blue, CD34-PECy7, CD33-AP, CD11b-APC-Cy7, CD15-FITC.  7-AAD was used to eliminate the dead cells. The promyelocytic population (CD45+CD34-CD33+CD11b-CD15+/lo) was sorted and the RNA from control iPSC promyelocytes was isolated using QIAGEN RNAeasy mini kit. The RNA samples were processed for RNA-seq analyses using RNA-seq protocol from NuGEN and Illumina. The amplified products were sequenced to analyze the gene expression profile of each replicate sample.  A total of 20 samples were used in this analysis to characterize and compare iPSC in vitro differentiated myeloid cells with those isolated from human bone marrow.	Co-expression
SRP059215	Homo sapiens Raw sequence reads	Profile cell-free circulating RNAs in plasma samples from non-small cell lung cancer patients and healthy controls	Co-expression
SRP059217	RNA-seq identifies novel lncRNAs involved in vascular smooth muscle cell proliferation	Smooth muscle cell (SMC) phenotypic switching from a contractile to a synthetic state is implicated in diverse vascular pathologies, including neointimal formation. This study was designed to identify lncRNAs that may play a role in vascular pathologies. Primary smooth muscle cells cultured from surplus human saphenous vein tissue were treated with inflammatory and proliferative stimuli, IL1a and PDGF, for 72h and RNA extracted for RNA-sequencing. Using edgeR processed data we found expression of many lncRNAs was altered following treatment and could play a role in vascular disease. Overall design: 4 groups of samples, n= 3/group each replicate using cells cultured from a different venous patient sample. Cells were quiesced in 0.2% serum for 48h followed by addition of 10ng/ml IL1a , 20ng/ml PDGF or both 10ng/ml IL1a and 20ng/ml PDGF together. Cells were collected after 72h and RNA extracted using Qiagen RNeasy kits. RNA-sequencing was carried out by Beckman Coulter Genomics on the r-RNA depleted fraction.	Co-expression
SRP059242	An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates	Alternative splicing (AS) generates extensive transcriptomic and proteomic complexity. However, the functions of species- and lineage-specific splice variants are largely unknown. Here, we show that mammalian-specific skipping of exon 9 of PTBP1 alters its splicing regulatory activities and affects the inclusion levels of numerous exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity so as to facilitate activation of a brain-specific AS program. Engineered skipping of the orthologous exon in chicken cells induces a large number of mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a single exon skipping event in an RNA binding regulator directs numerous AS changes between species. The results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systems. Overall design: This study contains two sets of samples: (Set 1) mRNA profiling of human 293 cells subjected to four different conditions in two biological replicates: non-targetting control siRNA, PTBP1 and PTBP2 siRNA, PTBP1 and PTBP2 siRNA with overexpression of full-length human PTBP1, PTBP1 and PTBP2 siRNA with overexpression of exon-excluded human PTBP1. (Set 2) mRNA profiling of chicken DT40 cells with 3 genotypes in two bioligcal replicates: wildtype cells, cells with PTBP1 exon 8 (orthologous to human PTBP1 exon 9) deleted in one allele, and cells with PTBP1 exon 8 deleted in both alleles.	Co-expression
SRP059252	A systematic analysis of the time series gene expression in TGF-beta induced EMT by Next-generation sequencing	The goal of this study is to characterize time course gene expression profiles during TGF-beta induced EMT. In particular, we aim to identify and characterize master transcription factors regulate the transition into partial-EMT state. Overall design: A time series mRNA profile in A549 cells is generated from TGF-beta induced EMT samples during 0h,6h,12h,24h,36h,48h,72h and 96h by deep sequencing, in duplicate, using Illumina HiSeq 2500	Co-expression
SRP059266	TALENs-mediated gene disruption of FLT3 in leukemia cells: Using genome-editing approach for exploring the molecular basis of gene abnormality	Novel analytic tools are needed to elucidate the molecular basis of leukemia-relevant gene mutations in the post-genome era. We generated isogenic leukemia cell clones in which the FLT3 gene was disrupted in a single allele using TALENs. Isogenic clones with mono-allelic disrupted FLT3 were compared to an isogenic wild-type control clone and parental leukemia cells for transcriptional expression, downstream FLT3 signaling and proliferation capacity. The global gene expression profiles of mutant K562 clones and corresponding wild-type controls were compared using RNA-seq. The transcriptional levels and the ligand-dependent autophosphorylation of FLT3 were decreased in the mutant clones. TALENs-mediated FLT3 haplo-insufficiency impaired cell proliferation and colony formation in vitro. These inhibitory effects were maintained in vivo, improving the survival of NOD/SCID mice transplanted with mutant K562 clones. Cluster analysis revealed that the gene expression pattern of isogenic clones was determined by the FLT3 mutant status rather than the deviation among individual isogenic clones. Differentially expressed genes between the mutant and wild-type clones revealed an activation of nonsense-mediated decay pathway in mutant K562 clones as well as an inhibited FLT3 signaling. Our data support that this genome-editing approach is a robust and generally applicable platform to explore the molecular bases of gene mutations. Overall design: Global gene expression profiles of three isogenic K562 mutant clones (clones k20, k112, k324) and three randomly selected wild-type clones (clones kw1, kw2, kw3) were generated by RNA-seq, using Illumina Hiseq 2000.	Co-expression
SRP059275	Wnt addiction of genetically defined cancers reversed by PORCN inhibition	Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. Inhibition of PORCN in RSPO3-translocated cancers via treatment with ETC-159 causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell, and proliferation genes and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers. Overall design: RNA-seq of colorectal PDXs with confirmed R-spondin fusion genes. RNA-seq was performed in 2 conditions (Vehicle and treatment with ETC-159 (an inhibitor of PORCN) with 4 replicates per condition.	Co-expression
SRP059279	3D Chromosome Regulatory Landscape of Human Pluripotent Cells [RNA-Seq]	The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. Overall design: Polyadenylated RNA-seq from naive and primed human embroynic stem cells.	Co-expression
SRP059287	Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules [gene expression]	Endodermal stem/progenitor cells have diverse potential applications in research and regenerative medicine, so a readily available source could have widespread uses. Here we describe derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs show clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. The hiEndoPC-derived hepatocytes are able to rescue liver failure in Fah-/-Rag2-/- mice after transplantation, and, unlike hESCs, transplanted hiEndoPCs do not give rise to teratomas. Since human gastric epithelial cells are readily available from donors of many ages, this conversion strategy can generate clonally expandable cell populations with a variety of potential applications, including personalized drug screening and therapeutic strategies for liver failure and diabetes. Overall design: Gastric epithelial cells (GECs) were isolated from human stomach. Human induced endodermal progenitor cells (hiEndoPCs) were reprogrammed from GECs by small molecules. The hiEndoPC-Heps were differentiated from hiEndoPCs under hepatic differentiation protocol. Fetal-Heps were isolated from aborted fetal liver. Definitve endoderm (DE), primitive gut tube (PGT), and posterior foregut (PFG) were endodermal stem cells derived form human enbryonic stem cells (hESCs).We used RNA sequencing and DNA methylation analysis to detail the global gene expression profile of GECs, hiEndoPCs, hiEndoPC-Heps, Fetal-Heps, DE, PGT and PFG to delineate the difference of these cells.	Co-expression
SRP059322	Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia	We identified a novel recurrent genetic lesion in T-LGL. Mutations of the tumour suppressor gene TNFAIP3 causing amino-acid exchanges or protein truncations were seen in 3/39 cases (8%). Overall design: RNA sequencing (Illumina HiSeq 2500) of 5 index patients with paired tumor and non-tumor samples.	Co-expression
SRP059324	Gene expression analysis of human cell lines established from normal patient''s fibroblast and BWS patients with known mutations in the CDKN1C and KCNQ1OT1	Gene expression profiling was carried out in one normal human fibroblast cell line established from normal people and three different cell lines established from BWS patients to characterize the molecular mechanisms relevant to the etiology of BWS and tumor development. Whole-transcriptome sequencing of three BWS fibroblastic cell lines was established from patients with mutation in the CDKN1C mutation (CDKN1C+ cell line), and loss of methylation in the KCNQ1OT1 region (KvDMR+ cell line: with KvDMR molecular defect, and KvDMR- cell line: absence of KvDMR molecular defect but it had some clinical signs of BWS) Overall design: Whole-transcriptome RNA sequencing of the 4 different cell lines	Co-expression
SRP059327	Gene body H2B1ub regulates RNA Polymerase II pause release and is not needed for transcription elongation	Histone H2B monoubiquitylation (H2Bub1) is localized to transcribed regions of genes and spread in parallel with the progress of RNA polymerase II (Pol II). H2Bub1 levels are highly correlated both with transcription and elongation rates of mammalian genes. Although H2Bub1 correlate with elongation rates, it is not clear whether the correlation is due to causative role of H2Bub1 in regulating elongation rate or the vice versa. By utilizing our recently developed method to measure genomewide elongation rate – 4sUDRB-seq, we tested genomewide elongation rates in H2Bub1 depleted cells. Our results show that H2Bub1, although widely appreciate as an elongation factor, is not needed for proper transcription elongation. Although H2Bub1 depletion does not affect transcription elongation, its depletion results in the upregulation of more than 1000 genes. Our findings show that H2Bub1 regulates the pause release of Pol II at these genes. This specificity might be mediated through the relatively high proximity of H2Bub1 to paused Pol II at these genes. Overall, our data shed light on the regulation of transcription by H2Bub1 and suggest that the role of H2Bub1 in transcription elongation should be reconsidered. ------------------------------------------- see also: Fuchs G, Voichek Y, Benjamin S, Gilad S et al. 4sUDRB-seq: measuring genomewide transcriptional elongation rates and initiation frequencies within cells. Genome Biol 2014 May 9;15(5):R69. PMID: 24887486 see also Dataset GSE57116, Samples GSM1375518 – GSM1375525 Overall design: Pol II ChIP-seq, mRNA and 4sUDRB-seq were derived for different replicates of RNF20 siRNA and control siLacZ	Co-expression
SRP059357	Homo sapiens Raw sequence reads	The purpose of this study is to identify the transcriptome-wide functional targets of the splicing factor hnRNP L using mRNA sequencing and bioinformatic analysis.	Co-expression
SRP059363	Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers	Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P?<?1.0?×?10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers'' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P?=?1.13?×?10-62) and CYP1B1 (P?<?2.49?×?10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis. Overall design: RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.	Co-expression
SRP059379	Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity	Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Overall design: Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.	Co-expression
SRP059431	Perturbations of PIP3 signaling trigger a global remodeling of mRNA landscape and reveal a transcriptional feedback loop	PIP3 is synthesized by PI3Ks and regulates complex cell responses, such as growth and migration. Signals that drive long-term reshaping of cell phenotypes are difficult to resolve because of complex feedback networks that operate over extended times. It is clear PIP3-dependent modulation of mRNA accumulation is important in this process but is poorly understood. We have quantified the genome-wide mRNA-landscape of non-transformed, breast epithelium-derived MCF10a cells and its response to transient (EGF or PI3Ka-selective inhibitor) or chronic (isogenic cells expressing an oncomutant PI3Ka allele or lacking the PIP3-phosphatase /tumour-suppressor, PTEN) perturbations of PIP3.These results show that whilst many mRNAs are changed by long-term  genetic perturbation of PIP3 signaling (“butterfly effect”), a much smaller number change with a directional logic that aligns with different PIP3 perturbations, allowing discrimination of more directly regulated mRNAs. Our results also indicate that mRNAs can be differentially sensitive to specific features of PIP3 signals, that PIP3-sensitive mRNAs encode PI3K pathway components and identify the transcription factor binding motifs SRF and PRDM1 as important regulators of PIP3-sensitive mRNAs involved in cell movement. Overall design: RNA-seq on WT MCF10a, treated or not with A66 (Pi3Kalpha inhibitor), PIK3CA H1047R MCF10a and PTEN KO MCF10a. EGF time course stimulation applied (0, 15, 40, 90, 180, 300 min). A66 no EGF when A66 was applied for 300min w/o EGF simulation. All samples made in triplicate. Total of 75 samples.	Co-expression
SRP059448	Illumina Total RNA-seq in HeLa	Purpose: Examine the effect of the long non-coding RNA PARROT on the transcriptome in HeLa cells. Overall design: Total RNA-seq of  RNA from cells treated with the control knock-down (NK) or depleted of ENST00000046668 (PARROT) with two different siRNAs (si1 and si2) for 24h.	Co-expression
SRP059509	Genome-wide Circadian Control of Transcription at Active Enhancers Regulates Insulin Secretion and Diabetes Risk	The molecular clock is a transcriptional oscillator present in brain and peripheral cells that coordinates behavior and physiology with the solar cycle. Here we reveal that the clock gates insulin secretion through genome-wide transcriptional control of the pancreatic exocyst across species. Clock transcription factors bind to unique enhancer sites in cycling genes in beta cells that diverge from those in liver, revealing the dynamics of inter-tissue clock control of genomic and physiologic processes important in glucose homeostasis. Overall design: Transcriptome profiling in mouse and human islets at serial 4-hour time intervals by polyA RNA-Seq	Co-expression
SRP059511	Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor	Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) – the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. Overall design: RNA-seq profiles of prostate cancer cell lines to understand gene expression associated with enzalutamide treatment	Co-expression
SRP059518	Mini-kidneys from human pluripotent cells model normal human fetal kidney development and response to nephrotoxicity	Mini-kidneys from human pluripotent cells	Co-expression
SRP059531	The transcription and translation landscapes during human cytomegalovirus infection reveal novel host-pathogen interactions	During its long infection cycle, human cytomegalovirus (HCMV) extensively manipulates cellular gene expression to maintain conditions favorable for viral propagation. In order to reveal the signature of cellular genes that are manipulated by HCMV, we measured RNA abundance and rate of protein production through the course of HCMV infection. We characterized changes for most expressed cellular genes and although much of the regulation was transcriptional we uncover diverse and dynamic translational regulation for subsets of host genes, revealing unappreciated coordination in translational control that suggests common regulators Overall design: Ribosome profiling and mRNA-seq along HCMV infection	Co-expression
SRP059536	RNA-seq performed on sarcoma cell lines	No description.	Co-expression
SRP059557	Salivary adenoid cystic carcinoma RNA-seq	RNA-SEQ using RNA isolated from archived FFPE tissue slices on an Ion Proton (P1 chip). Examined differences in gene expression between normal salivary gland tissue and salivary adenoid cystic carcinoma tissue.	Co-expression
SRP059579	Human Brain CAGE and RNA-seq data	No description.	Co-expression
SRP059588	RNA-seq performed on FFPE sarcoma blocks	No description.	Co-expression
SRP059624	Primary cilium-autophagy-Nrf2 (PAN) axis links the cell cycle to neuroectoderm fate in human embryonic stem cells	Under defined differentiation conditions human embryonic stem cells (hESCs) can be directed toward a mesendodermal (ME) or neuroectoderm (NE) fate, the first decision during hESC differentiation. Coupled with G1 lengthening a divergent ciliation pattern emerged within the first 24 hours of induced lineage specification and these changes heralded a neuroectoderm decision before any neural precursor markers were expressed. By day 2, increased ciliation in NE precursors induced autophagy that resulted in the inactivation of Nrf2. Nrf2 binds directly to upstream regions of the OCT4 and NANOG genes to promote their expression and represses NE derivation. Nrf2 suppression was sufficient to rescue poorly neurogenic iPSC lines. Only after these events have been initiated do neural precursor markers get expressed at day 4. Thus we have identified a primary cilium-autophagy-Nrf2 (PAN) axis coupled to cell cycle progression that directs hESCs toward NE. Overall design: Transcriptome analysis of hESC-derived neuroectoderm and mesendoderm cells	Co-expression
SRP059633	HMM_MS1_SP and NSP cells_RNA-seq	Intratumoral heterogeneity is common in all tumor types and major barrier against effective cancer therapy. Especially, human malignant mesothelioma that is an environmental contaminant- induced disease is known to be extremely heterogeneous with regards to morphology as well as molecular phenotypes, resulting in poor response to cancer therapy. This study was performed to investigate the global gene expression profile of distinct subpopulations of MS1, a human malignant mesothelioma cell line	Co-expression
SRP059642	Homo sapiens Transcriptome or Gene expression	To investigate the paracrine effects of stromal elements on cancer cells, we developed a “stromal” culture system, which incorporates structural and diffusible stroma-derived elements into homotypic cultures amenable to functional genomics and metabolomics. Here we show that microenvironmental cues co-regulate cancer metabolism and gene expression. Stromal inputs broadly influenced histone acetylation in the cancer epigenome, which coincided with induction of genes implicated in anabolic metabolism and inflammation. The gene expression and metabolic changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental pathways. Finally, we implicate the BET family of epigenetic readers as key transducers of stromal inputs to drive alterations in gene expression. This work suggests paracrine epigenome regulation as a conduit through which stromal signals drive metabolic and immune adaptation to a challenging tumor microenvironment.	Co-expression
SRP059643	Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation (RNA-seq)	The MYC transcription factor is an unstable protein and its turnover is controlled by the ubiquitin system. Ubiquitination enhances MYC-dependent transactivation, but the underlying mechanism remains unresolved. Here we show that proteasomal turnover of MYC is dispensable for recruitment of RNA polymerase II (RNAPII), but is required to promote transcriptional elongation at MYC target genes. Degradation of MYC stimulates histone acetylation and recruitment of BRD4 and P-TEFb to target promoters, leading to phosphorylation of RNAPII CTD and the release of elongating RNAPII. In the absence of degradation, the RNA polymerase II-associated factor (PAF) complex associates with MYC via interaction of its CDC73 subunit with a conserved domain in the amino-terminus of MYC ("MYC box I"), suggesting that a MYC/PAF complex is an intermediate in transcriptional activation. Since histone acetylation depends on a second highly conserved domain in MYCs amino-terminus ("MYC box II"), we propose that both domains co-operate to transfer elongation factors onto paused RNAPII. Overall design: RNA-Seq Experiments were performed in a primary breast epithelial cell line (IMEC).The cell line expressed doxycycline-inducible versions of MYC (WT;Kless,Swap=WTN-KC). Where indicated cells were transfected with siRNAs (siCtrl;siSKP2). Where indicated cells were treaed with the proteasome inhibitor MG132 or EtOH as solvent control. DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control or comparing Dox-induced cells with EtOH (solvent control) treated cells.	Co-expression
SRP059689	Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with allergen specific modulation of immune reactivity	Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma. The aim of this study was to characterize changes in TG-specific T cell responses as a function of seasonality. Peripheral blood mononuclear cells (PBMC) obtained either during the pollen season or out of season, from allergic individuals and non-allergic controls were stimulated either with TG extract or a pool of previously identified immunodominant antigenic regions. PBMC from in season allergic subjects exhibit higher IL-5 and IL-10 responses compared to out of season donors. In the case of non-allergic subjects, as expected we observed lower IL-5 responses and robust production of IFN? compared to allergic individuals. Strikingly, non-atopic donors exhibited an opposing pattern with decreased immune reactivity in-season. The broad downregulation in non-allergic donors indicates that healthy individuals are not oblivious to allergen exposure but rather react with an active modulation of the responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen-specific T cells defined genes modulated in concomitance with allergen exposure and inhibition of responses in non-allergic donors. Magnitude and functionality of T-helper cell responses differ substantially for in season versus out of season in allergic and non-allergic subjects. The results indicate specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programs associated with health and allergic disease. Overall design: 11 allergen-specific T cell RNA samples were analyzed: 5 isolated from PBMC of allergic individuals and 6 from non-allergic individuals (considered as the control group).	Co-expression
SRP059695	RNA-Seq analysis of human neutrophils isolated by different protocols (Polymorphprep and negative selection) and incubated with and without in vitro cytokine stimulation	We report gene expression in human neutrophils isolated by two methods: Polymorphprep (~95% purity) and negative selection (~99% purity) from two healthy donors - one donor with low eosinophil contamination of neutrophils and one donor with high eosinophil contamination of neutrophils.  We report the effect of the presence of contaminating leukocytes in neutrophil preparations, and in reponse to inflammatory cytokines TNF-alpha and GM-CSF. Overall design: Healthy human neutrophils were isolated using Polymorphprep or negative selection, and incubated for 1h in the absence or presence of TNF-alpha or GM-CSF.  RNA was analysed by Illumina HiSeq 2000.  The results from n=2 donors were analysed as biological replicates for differential expression analysis.	Co-expression
SRP059701	Androgen receptor programming in human tissue implicates HOXB13 in prostate pathogenesis [RNA-Seq]	The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis Overall design: Gene expresion profiles when LHSAR with overexpressed FOXA1, HOXB13 or FOXA1 and HOXB13 together compared with LacZ control	Co-expression
SRP059712	RNA sequencing of mechanically strained NHEKs and control NHEKs	We sequenced mRNA from NHEKs that had been subjected to cyclic biaxial mechanical strain at 100 mHz for 12h together with unstrained control NHEKs, 3 biological replicates each Overall design: Examination of mRNA levels in control and mechanically strained NHEKs	Co-expression
SRP059732	Apoptosis enhancing drugs overcome innate platinum resistance in CA125 negative tumor initiating populations of high grade serous ovarian cancer	High grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSCs contain a CA125 negative population enriched for carboplatin resistant cancer initiating cells. Transcriptome analysis reveals up-regulation of homologous recombination DNA repair and anti-apoptotic signals in this population. While treatment with carboplatin enriches for CA125 negative cells, co-treatment with carboplatin and birinapant eliminates these cells in HGSCs expressing high levels of the inhibitor of apoptosis protein cIAP in the CA125 negative population. Birinapant sensitizes CA125 negative cells to carboplatin by mediating degradation of cIAP causing cleavage of caspase-8 and restoration of apoptosis. This co-therapy significantly improved disease free survival in vivo compared to either therapy alone in tumor-bearing mice. These findings suggest that therapeutic strategies that target CA125 negative cells may be useful in the treatment of HGSC. Overall design: mRNA profiles of CA125 positive and negative populations, generated by next generation sequencing of populations FACS isolated from 10 independent dissociated primary human high grade serous ovarian cancers, were compared.	Co-expression
SRP059733	Generation of low passage high grade serous ovarian cancer cell lines from primary tumors	High grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy.  Many commercially ovarian cancer cell lines are not good models for HGSC. Here we demonstrate that 3 low passage cell lines derived from HGSC have similar transcriptomes to their parental bulk tumors. These cell lines recapitulated tumor characteristics of the primary cancer and had responded to therapy in the same manner as primary HGSC cells, demonstrating they are accurate models for HGSCs. Overall design: mRNA profiles of low passage high grade serous tumor cell lines and their parental tumors, generated by next generation sequencing, were compared.	Co-expression
SRP059762	Time course of androgen-regulated transcripts in LNCaP cells	Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed RNA sequence analysis in AR positive prostate cancer cell line, LNCaP. Overall design: RNA sequence analysis of androgen-regulated transcripts in prostate cancer cells	Co-expression
SRP059775	C1 analysis using mixtures of human (HEK) and mouse (3T3) cells	A cell supsension containing an equal mix of HEK and 3T3 cells was used in the Fluidigm C1 Overall design: Suspensions of 3T3 and HEK cells were diluted down to a concentration of 250,000 per mL and mixed 1:1, then loaded onto two medium C1 cell capture chips.	Co-expression
SRP059835	The EGF Receptor Ligand Amphiregulin Controls Cell Division via FoxM1	We analyzed the effect of tetracycline (Tet)-inducible amphiregulin (AREG) silencing on the transcriptome of immortalized human N/TERT keratinocytes in the presence or absence of exogenous rhEGF. Tetracycline-mediated AREG silencing significantly altered the expression of 2,331 genes, 623 of which were not normalized towards normal by treatment with EGF.  Genes irreversibly up-regulated by suppression of AREG overlapped with genes involved in keratinocyte differentiation.  A significant proportion of the irreversibly down-regulated genes featured upstream binding sites recognized by FoxM1 Overall design: N/TERT-2G keratinocytes with tetracycline (Tet)-inducible expression of AREG shRNA were incubated for 60h in the presence (n=3) or absence of Tet (n=3) or with Tet and 20 ng/ml recombinant EGF (n=2).	Co-expression
SRP059880	RNA-seq of cytosolic and chromatin-associated transcripts following TNFa and Spt5 KD	We examined the effects of TNFa and Spt5, the major DSIF subunit, on nascent and mature transcripts using RNA-Seq of chromatin-associated and cytoplasmic transcripts. Overall design: RNA was extracted from the cytosolic and chromatin fractions of control and Spt5 KD cells that were treated with TNFa for 1 hour	Co-expression
SRP059887	Measure transcript integrity using RNA-seq data	Achieved biospecimens annotated with patient clinical characteristics are unique resources for translational research. However, RNA extracted from the achieved tissues is often degraded. RNA degradation can have a significant impact on the measure of transcript abundance that can lead to an increase rate of erroneous differentially expressed genes.  Here, we are presenting the transcript integrity number (TIN) algorithm to measure the RNA degradation at transcript level. When applied to RNA-seq datasets generated from human brain Glioblastome cell line, human peripheral blood mononuclear cells, and metastatic castration resistant prostate cancer (mCRPC) clinical tissues, TIN provided a more reliable and more sensitive measure of RNA degradation than RIN, as demonstrated by much higher concordance with the RNA fragment size estimated from read pairs. More importantly, when comparing 10 mCRPC samples with lower RNA quality to another 10 samples with higher RNA quality, we demonstrated that calibrating gene quantification with TIN scores could mitigate RNA degradation effects and greatly improve gene expression analysis. The detected differentially expressed genes before TIN correction were predominantly ribosomal genes. However, when we adjusted gene quantifications with the corresponding TIN scores, we found differentially expressed genes were highly enriched in prostate cancer specific pathways. When further evaluating the performance of TIN correction using synthetic spike-in transcripts with predetermined abundance in RNA-seq data generated from Sequencing Control Consortium (SEQC), we found TIN adjustment had a better control of false positives and false negatives (sensitivity = 0.89, specificity = 0.91), as compared to gene expression analysis results without TIN correction (sensitivity =0.98, specificity = 0.50). Overall design: RNA sequencing of 20 bone-metastatic castration resistant prostate cancer (mCRPC) using Illumina HiSeq 2500. Out of 20 mCRPC samples, 10 samples have relative low RNA integrity and another 10 samples have relative higher RNA integrity as measured by Agilent RIN score.	Co-expression
SRP059908	The evolution of N6-methyladenosine in primates	Phenotypic differences within populations and between closely related species are often driven by variation and evolution of gene expression. However, most analyses have focused on the effects of genomic variation at cis-regulatory elements such as promoters and enhancers that control transcriptional activity, and little is understood about the influence of post-transcriptional processes on transcript evolution. Post-transcriptional modification of RNA by N6-methyladenosine (m6A) has been shown to be widespread throughout the transcriptome, and this reversible mark can affect transcript stability and translation dynamics. Here we analyze m6A mRNA modifications in lymphoblastoid cell lines (LCLs) from human, chimpanzee and rhesus, and we identify patterns of m6A evolution among species. We find that m6A evolution occurs in parallel with evolution of consensus RNA sequence motifs known to be associated with the enzymatic complexes that regulate m6A dynamics, and expression evolution of m6A-modified genes occurs in a parallel evolutionary pattern with m6A evolution. Further, genes modified by evolved m6A in humans are significantly enriched in transcriptional regulatory processes and disease related pathways, suggesting an important role in human biology for the evolution of m6A modification. Overall design: Perform m6A-seq in human, chimpanzee and rhesus, and identify m6A evolutionary mode in primates.	Co-expression
SRP059925	ncRNA (non-coding RNA) signature in endothelial cells during hypoxia [RNA-seq]	To define ncRNA expression in hypoxic endothelial cells, we applied pro-angiogenic hypoxia to cultured endothelial cells. Afterwards, total RNA was isolated and underwent RNA-seq analysis. Overall design: HUVECs were subjected to normoxic or hypoxic (0.1-0.2% O2) cell culture conditions.	Co-expression
SRP059948	Transcriptome-wide mapping of cut sites of the viral endoribonuclease SOX from Kaposi''s sarcoma-associated herpesvirus (KSHV)	Purpose: identify sites in endogenous mRNAs that are cut by KSHV SOX; Method: parallel analysis of RNA ends (PARE, following Zhai et al., 2014); Results: SOX cuts at discrete locations in mRNAs Overall design: human Xrn1 was knocked down in HEK293T cells by shRNAs or siRNAs to stabilize degradation fragments with free 5'' ends; GFP-SOX or GFP were transfected for ~24 hrs; total RNA samples were collected and subjected to PARE protocol (Zhai et al., 2014)	Co-expression
SRP059950	Patient Derived Xenograft for Delivery of Precision Medicine in Castrate Resistant Prostate Cancer	Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period  and implanted subcutaneously and under the renal capsule in immuno-deficient mice.  To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data  suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. Overall design: RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.	Co-expression
SRP059957	Gene expression profiling of human and murine in vitro muscle differentiation	Total RNA sequencing of human and murine myoblasts and myotubes was extracted, depleted of ribosomal RNA and subjected to Illumina stranded paired end library prep and sequencing. Samples from Duchenne Muscular Dystrophy patients-derived myoblasts were included  in this study Overall design: 12 samples were analysed: murine C2C12 myoblasts and myotubes differentiated for 4 days, each in two biological replicates; human 9208 myoblasts and myotubes differentiated for 6 days, each in two biological replicates; human Duchenne Muscular Dystrophy patients derived myoblasts and myotubes differentiated for 10 days.	Co-expression
SRP059959	Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans	Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from ten healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at one or more than one month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in 2 independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. Overall design: We used PolyA+ RNA-seq data from human primary granulocytes of 10 healthy individuals to de novo annotate lncRNAs and mRNAs in this cell type and ribosomal depleted (total) RNA-seq data from seven of these individuals sampled three times to analyze lncRNA amd mRNA expression variability	Co-expression
SRP059963	Investigation about Monocytes in metastatic breast cancer patients under chemotherapy +/- Avastin	The goal of this study was to determine if blood circulating monocytes of metastatic breast cancer patient would express a different activation profile compared to healthy donors, in order to use this specific changesas biomarkers to monitor then response to therapy Overall design: CD11b+ cells were extracted from all blood of 4 healthy donors and 4 metastatic breast cancer patients using magnetic beads separation (Miltenyi). CD11b+ cells were then lysed and mRNA was extracted to perform RNASeq.	Co-expression
SRP059989	Homo sapiens Raw sequence reads	By means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.	Co-expression
SRP060016	Homo sapiens Raw sequence reads	to compare colorectal cancer to its metastase	Co-expression
SRP060205	UTRseq_human_brain	Alternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer's disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3' primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3'-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression; AD/NDWP increases in 3'-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers. Overall design: Examination of polyadenylation sites in brain tissues of Alzheimer`s disease patients, with 3 levels of pathology and 3 levels of cognition	Co-expression
SRP060235	Replicated transcriptome profiling of Normal and Cancerous Prostate Cells [RNA-Seq]	To identify differentially expressed transcripts  in Cancer and Normal Prostate cells global transcript abundance was assayed by replicated (n=3) stranded RNA-Sequencing Overall design: PolyA+ RNA profiles of LNCaP (n=3) and PrEC (n=3) cell lines were generated by deep sequencing. Libraries were generated by Illumina TruSeq kits (maintaining strand information). The resultant cDNA libraries were sequenced at the Kinghorn Center for Clinical Genomics (The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia) using the Illumina HiSeq 2500 platform.	Co-expression
SRP060253	AGS cell line RNA-seq	RNA-seq study of a gastric carinoma cell line (AGS) with or without Epstein-Barr Virus infection as well as AGS cells expressing only viral noncoding RNAs (BARTs).	Co-expression
SRP060284	Homo sapiens Raw sequence reads	NCCIT cell with EtOH treatment	Co-expression
SRP060348	Latency expression of the Epstein-Barr virus-encoded MHC class I TAP inhibitor, BNLF2a in EBV-positive gastric carcinomas	RNA Sequencing performed on EBV positive gastric cancer biopsies and cells lines to study expression of EBV specific genes. Overall design: Examination of two EBV postitive gastric carcinoma biopsies and two EBV positive gastric cancer cell lines, NCC24 and YCCEL1 by RNA-Seq.	Co-expression
SRP060355	Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines	Variation in the expression level and activity of genes involved in drug disposition and action (“pharmacogenes”) can affect drug response and toxicity, especially when in tissues of pharmacological importance.  Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-seq to determine the expression levels and alternative splicing of 389 PGRN pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines (LCLs), which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from different individuals across the 5 tissues (N = 139 samples) revealed substantial variation in both expression levels and splicing across samples and tissue types. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated.  Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use. Overall design: mRNA profile of 389 genes in 24 liver, 20 kidney (cortex), 25 heart (left ventricle), 25 adipose (subcutaneous) samples, and 45 lymphoblastoid cell lines (LCLs). The raw data for the LCL Samples will be available through dbGap under phs000481.	Co-expression
SRP060359	Identification of differentially expressed mRNAs in HCSC cell lines compared with HCC cell lines	Hep3B and Huh7 are two types of human hepatoma cell lines (HCC). In our laboratory, we cultured their stem-like cancer cells (HCSCs), Hep3B-C and Huh7-C. And we have demonstrated that these cells had enhanced stem cell properties, drug resistance, properties of EMT, and stronger tumor-initiating capabilities. To explore functionally crucial mRNAs in HCSCs, 2 samples of HCSCs and 2 samples of HCCs were sequenced by the Illumina Genome Analyzer II. Through differential expression analysis, we finally identified 115 up- and 402 down-regulated miRNAs which were consistently up- and down-regulated in two stem cells compared to the cancer cells. Overall design: Expression analysis using total RNAs extracted from 2 HCSC cell lines (Hep3B-C and Huh7-C), and 2 HCC cell lines (Hep3B and Huh7).	Co-expression
SRP060362	Homo sapiens Transcriptome or Gene expression	Umbrella BioProject forMARINA Hazard Theme on Systems Toxicology (Transcriptomics):Implementation of methods for toxicological profiling of engineered nanomaterials (ENMs) using transcriptomics, proteomics and metabolomics.This BioProject is an umbrella project for the studies on two human cell lines (A549 and THP-1.)	Co-expression
SRP060370	Transcriptional Signatures of Hypoxic and Inflammatory Renal Epithelial Injury	To identify RNA transcripts involved in acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing (RNA-seq) revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Overall design: Examination of transcriptomic response of human PTECs to hypoxic or inflammatory injury	Co-expression
SRP060416	Single cell RNA-sequencing of human tonsil Innate lymphoid cells (ILCs)	Single cell RNA-sequencing of human tonsil Innate lymphoid cells (ILCs) from three independent tonsil donors. Overall design: Sequencing libraries were prepared from FACS sorted individual ILCs with the Smart-Seq2 protocol  (Picelli et al. Nature Methods 2013)	Co-expression
SRP060462	Identifying lincRNA as prognostic biomarker for clear cell renal cell carcinoma	RNA sequencing libraries were made for A-498 and 786-O to detect the transcripts regulated by the lincRNA comparing knockdown and the non-targeting control. Overall design: Two siRNAs were designed, non-target control and the siRNAs were introduced to the cell lines A-498 and 786-O separately by Lipofectamine 2000. After 16 hours total RNA were extracted. Barcoded cDNA libraries were then prepared from total RNA using the Illumina TruSeq RNAseq kit, and sequenced (single-end 36-bp reads) on an Illumina HiSeq instrument.	Co-expression
SRP060499	Regulatory T cell modulation by CBP/EP300 bromodomain inhibition [RNA-seq]	Genome-wide gene expression changes in response to CBP inhibitor treatment in Treg cells using RNA sequencing (RNA-seq). Overall design: Expression profiling by RNA-seq of Treg cells treated with DMSO or CBP inhibitor	Co-expression
SRP060566	Integrated Profiling of mRNAs and microRNAs to Identify Potential Biomarkers for Oral Malignant Transformation [mRNA-Seq]	The purpose of this study was to systematically profile the expression of both mRNAs and miRNAs in OSCC and its premalignant disease to identify some novel potential biomarkers for the detection of malignant transformation. Overall design: NGS was applied to investigate the differential transcriptome. The expression of mRNAs and miRNAs were analyzed in tumor tissues, premalignant tissues and adjacent normal tissues obtained from same OSCC patients with long history of oral mucosal disease.	Co-expression
SRP060598	Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest	Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here we show that multinucleate OIS cells originated mostly from failed mitosis. Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase.  Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation. Overall design: We used RNA-seq of IMR90 cells with inducible expression of oncogenic RasV12 that were synchronised in mitosis, to characterise the nature of mitotic defects that lead to multinucleation of oncogene-induced senescent cells	Co-expression
SRP060605	Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells	A greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo. Overall design: 4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)	Co-expression
SRP060637	Cas9 gRNA engineering for selectable genome editing, activation and repression	RNA-Seq after Cas9-gRNA transfection with different length gRNAs Overall design: we performed PolyA Selection and RNA-Seq on cells transfected with dCas9-VPR and a gRNA of each length (20nt, 16nt, or 14nt) targeting ACTC1, MIAT, or HBG1/2	Co-expression
SRP060655	Differential expression profiles of type I JAK inhibitor persistent vs. naïve MPN cells	The type I JAK inhibitor ruxolitinib is approved for therapy of MPN patients but evokes resistance with longer exposure. Several novel type I JAK inhibitors were studied and we show that they uniformly induce resistance via a shared mechanism of JAK family heterodimer formation.Here we studied the expression profiles of SET2 cell lines persistent to several different type I JAK inhibitors in comparison to naive SET2 cells or in comparison to SET2 cells with acute exposure to ruxolitinib. Overall design: Analysis of RNA isolated from several type I JAK inhibitor SET2 cell lines in comparison to naïve SET2 cells	Co-expression
SRP060677	Total RNA profiles associated with DDX3 wild-type (WT) or R534H variant expression with or without sodium arsenite treatment [RNA-seq]	RNA expression profiles are not significantly altered by DDX3 WT or R534H expression as well as by 45 minute exposure of cells to sodium arsenite. Overall design: Cells expressing either DDX3 WT or R534H variant were treated with or without sodium arsenite and lysed in the presence of cyclohexime. Total cellular RNAs were extracted and sequenced.	Co-expression
SRP060708	Deregulation of HIF-Responsive Demethylases Causes Synthetic Lethality Between the VHL Tumor Suppressor Gene and the EZH1 Histone Methyltransferase	Comparison of ccRCC cells with high HIF or low HIF activity Overall design: Cells expressing control (VEC) were compared to cells with ARNT1 loss using sh/sgRNA targeting ARNT1 The samples labeled 'con' are parental Vhl-null cells and represent the 'high HIF' state. The other 2 cell lines represent the 'low HIF' state. The cell line labeled shArnt have loss of a protein named ARNT by virtue of RNAi-mediated knockdown using a shRNA targeting ARNT. The sample labeled lcARNT has loss of ARNT protein using a lenti-crispr mediated sgRNA.	Co-expression
SRP060715	Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens	Background: To determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed. Methods:  Ten CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system. Results: An average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q<0.05, fold change >2) were identified. Expression of selected DEGs (n=32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90% of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1). Conclusion: The RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR  for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis. Overall design: Ten CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.	Co-expression
SRP060719	MiR-26 dampens IL-6 production by down-regulating TNF-a/NF-kB signaling through silencing HMGA1 and MALT1 and not by directly targeting IL-6 mRNA	We found NF-kB signaling as a major target of miR-26 based on an analysis of the changes in gene activation by TNF-a in response to alteration of miR-26 levels. Overall design: Transcriptional profiling of genes in response to either a miR-26 mimic or miR-26 antagomir.	Co-expression
SRP060721	HCT116 MYC 3'' TBE1 (WT) and KO RNA-Seq	mRNA was sequenced from HCT116 MYC 3'' TBE1 (WT) and KO cells to identify genes differentially expressed after deletion of the MYC 3'' TBE1 Overall design: mRNA levels from two biological replicates of HCT116 MYC 3'' TBE1 (WT) and KO cells were examined	Co-expression
SRP061033	Recovery and analysis of nascent RNA	Nascent transcription profiles are shown for scaled megadomains and 100kb flanking regions before BRD4-NUT induction (0h) and at different time points (2h, 3h, 7h) following induction in 293T cells. Increase of the transcription from 0h to 7h after induction. Average level of transcriptional activity is reduced within the megadomains and their flanking regions following JQ1 treatment of TC-797 cells. Profile of nascent RNA-seq is shown for cells without JQ1 treatment, and for cells 1hr, 2.5hr and 4hr following JQ1 treatment. Overall design: Recovery and analysis of nascent RNA	Co-expression
SRP061037	Spontaneous single-copy loss of TP53 in human embryonic stem cells markedly increases cell proliferation and survival [RNA-Seq]	The potential safety issues related to the acquisition of common genomic aberrations in hPSC cultures are well-recognized, but these risks have not been evaluated for sporadic mutations. Here, we explore whether a sporadic mutation that spontaneously arose in a hESC culture consisting of a single-copy deletion of chr17p13.1 would confer a survival advantage to the mutant cells. Compared to wild-type cells with two normal copies of the chr17p13.1 region, the mutant cells displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of pluripotent cells after two weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. RNA sequencing analysis showed differential expression of genes in pathways related to proliferation and differentiation. Thus, phenotypic implications of sporadic mutations must be taken into consideration before using the hPSC for clinical applications. Overall design: Triplicate cDNA libraries of two mutant WA09 lines with a single-copy deletion of chr17p13.1, and two wild-type WA09 lines, for a total of 12 libraries were sequenced using Illumina HiSeq 2500. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.	Co-expression
SRP061163	The impact of oil spill to lung health – insights from an RNA-seq study of human airway epithelial cells	To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527 and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil + dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527 + oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on the transcriptomic perturbation of airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of genes involved in angiogenesis and immune responses and downregulation of genes  involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil or Corexit 9500 + oil mixture. Interestingly, these key molecular features coincide with those observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggested significant health impacts of the recent BP oil spill to those people involved in the cleaning operation. Overall design: We profiled with RNA-seq six groups of human airway epithelial cells. Each group contains three replicate samples. These groups are oil treatment group, 9500 treatment group, 9527 treatment group, oil+9500 treatment group, oil+9527 treatment group, and control group.	Co-expression
SRP061184	Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [RNA-Seq]	We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib. Overall design: Lymph node biopsies and peripheral blood samples were obtained from patients with previously untreated MCL.	Co-expression
SRP061192	Reduced CYFIP1 in human neural progenitors as 15q11.2 deletion model: donor specific dysregulation of schizophrenia/epilepsy genes	Deletions at 15q11.2 have been established to increase risk for multiple neurodevelopmental disorders (NDDs) including schizophrenia and epilepsy, yet show variable expressivity between individuals. To investigate the potential role of CYFIP1, a gene within the locus, we carried out knockdown experiments in human neural progenitor cells derived from 15q11.2 neutral induced pluripotent stem cells. Transcriptional profiling and cellular assays support a prominent role for CYFIP1 in cytoskeletal remodeling across all lines examined. Validating the utility of this model for study of disease, genes implicated in schizophrenia and epilepsy but not other disorders or traits unrelated to the deletion, were enriched among mRNAs dysregulated following knockdown. Importantly, and consistent with the variable expressivity of 15q11.2 deletions, the magnitude of disease-related effects varied between donor lines. Towards mechanisms, FMRP targets and synaptic genes were overrepresented among dysregulated mRNAs and as such may contribute to the schizophrenia and epilepsy effects we observe. Further model validation, and new candidate epilepsy genes, comes from machine-learning analyses showing a striking similarity between a subset of dysregulated transcripts and well-established epilepsy genes. Results provide support for an important contribution of CYFIP1 in 15q11.2 mediated risk for NDDs and demonstrate that disease-related biological signatures are evident prior to neuronal differentiation. This new human model of disease will be useful in identifying compounds that could ameliorate outcomes in deletion carriers. Overall design: Investigation of CYFIP1 shRNA knockdown in three neural progenitor cell lines derived from induced pluripotent stem cells  (3 control samples and 3 knockdown samples analyzed in each line)	Co-expression
SRP061240	Plasma extracellular RNA profiles in healthy and cancer patients	Extracellular vesicles such as exosomes are selectively enriched in RNA that has potential for use as disease biomarkers. To systemically characterize circulating extracellular RNA profiles, we performed RNA sequencing analysis on plasma extracellular vesicles derived from 192 individuals including 100 colon cancer, 36 prostate cancer and 6 pancreatic cancer patients along with 50 healthy individuals. Of ~12.6 million raw reads for each of these subjects, the number of mappable reads aligned to RNA references was ~5.4 million including microRNAs(miRNAs) (~40.4%), piwi-interacting RNAs(piwiRNAs) (~40.0%), pseudo-genes (~3.7%), long noncoding RNAs (lncRNAs) (~2.4%), tRNAs (~2.1%), and mRNAs (~2.1%). To select the best candidates for potential extracellular RNA reference controls, we performed abundant level stability testing and identified a set of miRNAs showing relatively consistent expression. To estimate biological variations, we performed association analysis of expression levels with age and sex in healthy individuals. This analysis showed significant sex association with seven small noncoding RNAs (false discovery rate, or FDR<0.05), while no small noncoding RNAs were statistically associated with age. To identify disease-associated RNA transcripts, we performed analysis of covariance by including disease status, age, sex, RNA isolation and gel size selection dates. We observed a gradual increase of significantly associated RNAs (in particular, miRNAs) with disease advancement as denoted by cancer staging. We found significant association of miR-125a-5p and miR-1246-3p with all cancer types tested (FDR<0.05). Based on the disease associations, we developed cancer type-specific multivariate statistical models to predict disease status with an area under the ROC curve from 0.67 in stage I colon cancer to 0.92 in advanced prostate cancer. To date, this is the largest RNA-seq study to systematically profile extracellular RNA species, which has not only provided a baseline reference profile for circulating extracellular RNA, but also a set of RNA candidates for reference controls and disease biomarkers. Overall design: RNAs fro plasma circulating microviscles in 192 individuals were sequenced and quantified. RNA expression stability testing was performed to identify stably expressed RNAs. Distribution of RNA species and individual RNA transcripts were compared in normal and cancer patients.	Co-expression
SRP061241	LIN28A modulates splicing and gene expression programs in breast cancer cells [RIP-Seq]	The goals of this study were to identify LIN28 downstream gene targets in breast cancer cells. We use a subclone of the MCF-7 breast cancer cell line, MCF-7M as our model system. Methods: mRNA-protein complexes (mRNP) lysates were prepared from MCF-7M cells and incubated with Protein-A Sepharose beads (Sigma-Aldrich) and either LIN28 (Abcam) or control normal rabbit serum IgG antibodies. LIN28 interacting mRNAs were identified by whole genome sequencing. Results: Using an optimized data analysis workflow, we mapped approximately 13 million sequence reads for LIN28-IP and CTL- IP (IgG), respectively to the to the human genome (build h19). Conclusions: mRNA were significantly bound by LIN28 if LIN28 RIP had 2.5 fold increase in normalized reads compared to IgG. We found that LIN28 was predominantly bound at coding exons and 3''UTRs, 38% & 45% respectively, in the 843 mRNAs within MCF-7M genome. Overall design: LIN28 mRNA enriched regions identified from LIN28/RNA complexes prepared from MCF-7M cells.	Co-expression
SRP061243	LIN28A modulates splicing and gene expression programs in breast cancer cells [RNA-Seq]	The goals of this study were to identify LIN28 downstream gene targets in breast cancer cells. We use a subclone of the MCF-7 breast cancer cell line, MCF-7M as our model system. Methods: mRNA profiles from MCF-7M breast cancer cells treated with siRNA against non-targeting control (NT), LIN28, hnRNP A1, LIN28 and hnRNPA1 (LIN28A1) for 72 hrs were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped over 200 million sequence reads per sample to the human genome (build h19). Each of the four groups had two biological replicates. We developed a custom method to identify alternative splicing events and identified 111 genes with significant (FDR<0.05) differential splicing for LIN28 depleted cells compared to non-targeting siRNA control, as well as 249 and 182 genes for hnRNP A1 and LIN28A1 respectively. RNA-seq data were validated with by qRT–PCR analysis of a subset of genes. Conclusions: Results reveal that LIN28 regulates alternative splicing and steady state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of ENAH exon 11a isoform. Expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Overall design: mRNA profiles of MCF-7M cells treated with siRNA for NT control, LIN28, hnRNP A1, and LIN28 plus hnRNP A1 (A1) (LIN28A1) were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000	Co-expression
SRP061286	Gene expression profiling in dentate granule cells from patients with mesial temporal lobe epilepsy with or without hippocampal sclerosis	Hippocampal sclerosis (HS) is the most common neuropathological finding of medically intractable cases of mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy. Within the dentate gyrus, HS may be associated with granule cell dispersion and aberrant mossy fiber sprouting, and these pathological changes are accompanied by a range of molecular changes. In this study, we analyzed the gene expression profiles of dentate granule cells of MTLE patients with and without HS to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations and to shed light on the transcriptional changes associated with HS. Overall design: 12 samples of dentate granule cells from patients with mesial tempora lobe epilepsy, 5 with hippocampal sclerosis and 7 without hippocampal sclerosis. 10 samples had replicates.	Co-expression
SRP061292	Treatment of prostate cancer cells with S-adenosylmethionine leads to genomewide alterations of transcription profiles	The analysis investigates the impact of methyl donor S-adenosylmethionin on transcription and methylation profiles of prostate carcinoma cells. Overall design: PC-3 cells (Prostate carcinoma cells) were treated with 160 micromolar S-adenosylmethionine or vehicle	Co-expression
SRP061310	CRISPR-Cas9 combinatorial KO of epigenetic regulators in human ovarian cancer cells	We sequenced polyA mRNA from OVCAR8-ADR-Cas9 cells in which one or two of 3 epigenetic regulators (BRD4, KDM4C, KDM6B) had been knocked out to examine how global gene expression was affected and evaluate potential synergistic effects at a molecular level. Overall design: Gene expression data (RNA-Seq) in OVCAR8-ADR-Cas9 cells infected with control vector or vectors expressing gRNAs targeting one of 4 epigenetic regulators (BRD4, KDM4C, KDM6B) with biological replicates.	Co-expression
SRP061322	Transcriptomics analysis of gene expression in normal and YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 or SRSF10 deficient human HeLa cells	RNA was isolated from and YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 deficient human HeLa cells using the TRIzol (Invitrogen) reagent by following the company manual. For all samples the RNA integrity was checked using an Agilent Bioanalyzer 2100. All samples showed a RIN (RNA integrity number) of higher than 9. Approximately 2.5 µg of total RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer’s protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read or paired-read mode, creating reads with a length of 101 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Overall design: Examination of gene expressive levels in normal and YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 or SRSF10 deficient Human HeLa cells	Co-expression
SRP061329	The LIN28B/let-7 axis is a novel therapeutic pathway in Multiple Myeloma	MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof-of-principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC dependent cancers as well. Overall design: RNA sequencing of MOLP-8 cells transduced with lentiCRISPRv2 scrambled control or containing a sgRNA against LIN28B. Both control and LIN28B KO cells were sequenced in triplicate.	Co-expression
SRP061380	Decrease in EZH2 histone methyltransferase mediates the effects of fluid shear stress (FSS) in endothelial cells	High uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level, remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knock down of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium. Overall design: Puromycin-selected HUVEC (Human Umbilical Vein Endothelial Cells, Lonza, Switzerland) cells, expressing either scrambled control (SCR) or anti-EZH2 short-hairpin (shEZH2) constructs (at total 7 days after the first viral transduction), were used in FSS experiments (72h of control static culture or exposure to 20 dynes/cm2 of fluid shear stress, using Ibidi pump system (in µ-Slides I 0.4 Luer, Ibidi, Planegg/Martinsried, Germany)). Each replicate experiment consisted of viral transductions and puromycin selection of a separate HUVEC batch, followed by the FSS experiment. Two FSS experimental sets of the same HUVEC batch were run every time in parallel and lysed at the same end time point, one in RNAse-free conditions with RNA-Easy Mini Plus kit RLT Plus lysis buffer (QIAGEN, Venlo, The Netherlands), and one with RIPA buffer. The RIPA-lysates were analyzed with Western blotting and confirmed the complete (no protein present) knock-down of EZH2. From the RNA-lysates, RNA was isolated using the RNA-Easy Mini Plus kit (QIAGEN, Venlo, The Netherlands). High quality RNA samples (pre-assessed by Nanodrop measurements) were further processed in the Genome Analysis Facility of the University Medical Center Groningen. The RNA quality and integrity were verified using PerkinElmer Labchip GX with a cut-off value of 9 (scale 1 to 10, where 9 is very high quality RNA). RNA library was created in accordance with the TruSeqTM RNA Sample Preparation v2 Guide (Illumina, San Diego, CA, USA), using the PerkinElmer Sciclone liquid handler, resulting in 330bp cDNA fragments. The paired-end sequencing (100bp reads) was performed using the Illumina HiSeqTM 2500. (Quoted from the Materials and Methods of the related manuscript, with adjustments).	Co-expression
SRP061403	EpCAM Based Capture Detects and Recovers Circulating Tumor Cells From  Subtypes of Breast Cancer Except Claudin-low	Circulating tumor cells (CTCs) potential utility as a liquid biopsy is of great interest in breast cancer.  The goal of this study is to use RNA-seq to show that we can capture CTCs  using EpCAM based gating for most of the breast cancer subtypes and detection of breast cancer specific genese are independent of sequencing plateformt. Using an optimized data analysis workflow, we mapped about 25 million sequence reads per sample to the hg 18.  Data analysis  revealed a significant detction of  breast cancer specific genes in CTCs and such signature genes  overlap between two sets of data yet provided complementary insights in transcriptome profiling. Overall design: CTCs can be sucessfuly isolated using EpCAm technique and represent an overall signature gene profile of breast cancer tumors.	Co-expression
SRP061405	Identification and characterization of MCF01A circular RNAs [RNA-seq]	Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Overall design: Detection of circRNAs from RNA-Seq – triplicate	Co-expression
SRP061412	Transcriptome analysis of RANK-positive and RANK-negative luminal progenitor subpopulations in the human breast	RANK-positive and RANK-negative luminal progenitor cells were isolated by FACS from histologically normal human breast tissue from wild-type human donors. RNA-seq gene expression profiling was used to find differentially expressed genes between the RANK-positive and RANK-negative cell populations. Overall design: Cells were isolated from 4 human patients. A paired analysis was used to compare RANK-positive and RANK-negative cells within patients.	Co-expression
SRP061416	Comprehensive analysis of microRNA expression in regionalized human neural progenitor cells reveals microRNA-10 as a caudalizing factor	MicroRNAs (miRNAs) have been implicated in regulating multiple processes during brain development in various species. However, the function of miRNAs in human brain development remains largely unexplored. Here, we provide a comprehensive analysis of miRNA expression of regionalized neural progenitor cells derived from human embryonic stem cells and human fetal brain. We found mir-92b-3p and mir-130b-5p to be specifically associated with neural progenitors and several miRNAs that display both age-specific and region-specific expression patterns. Among these miRNAs, we identified miR-10 to be specifically expressed in the human hindbrain and spinal cord, while absent from rostral regions. We found that miR-10 regulates a large number of genes enriched for functions including transcription, actin cytoskeleton and ephrin receptor signaling. When overexpressed, miR-10 influences caudalization of human neural progenitors cells. Together, these data confirms a role for miRNAs in establishing different human neural progenitor populations. This data set also provides a comprehensive resource for future studies investigating the functional role of different miRNAs in human brain development. Overall design: Human embryonic stem cells (hESCs) were transduced with lentiviral vectors expressing either miR10a-GFP or miR10b-GFP. The expression of the vectors is Tet-regulated and they will only be expressed in the presence of Doxycycline. In order to detect direct targets of the miR10a and miR10b, we differentiated the trasduced hESCs for 14 days, and added doxycycline to only half of the groups - resulting in groups that are overexpressing miR10a or miR10b and some groups that are not overexpressing these miRNAs.	Co-expression
SRP061425	Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells	We report nuclear receptor Esrrb''s responsive genes with or without Esrrb ligand DY131 in DU145 cells. Using Esrrb-null cells, we used RNA-Seq to find Esrrb responsive genes. In addition, we tested DY131-driven Esrrb-dependent genes to test the ligand dependency of Esrrb in regulating gene expression. Overall design: Control vector transfected cells with vehicle treatment, Esrrb expression vector transfected cell with vehicle treatment, control vector transfected cells with DY131 treatment, Esrrb expression vector transfected cell with DY131 treatment.	Co-expression
SRP061455	Next Generation Sequencing Facilitates Quantitative Analysis of PBX3 Regulated Transcriptomes	The goals of this study are to analyze the transcriptome profiling (RNA-seq) after PBX3 overexpression in SMMC-7721 cells. Overall design: SMMC-7721 cells were transfected by PBX3 expression lentivirus and blank lentivirus as control. Total RNA was extraced by Qiagen kit and the mRNA profiles were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000.	Co-expression
SRP061522	Truncation of LOC100288798 (SLC38A4-AS) lncRNA in human haploid KBM7 cell line	Many thousand long non-coding (lnc) RNAs are mapped in the human genome. Time consuming studies using reverse genetic approaches by post-transcriptional knock-down or genetic modification of the locus demonstrated diverse biological functions for a few of these transcripts. The Human Gene Trap Mutant Collection in haploid KBM7 cells is a ready-to-use tool for studying protein-coding gene function. As lncRNAs show remarkable differences in RNA biology compared to protein-coding genes, it is unclear if this gene trap collection is useful for functional analysis of lncRNAs. Here we use the uncharacterized LOC100288798 lncRNA as a model to answer this question. Using public RNA-seq data we show that LOC100288798 is ubiquitously expressed, but inefficiently spliced. The minor spliced LOC100288798 isoforms are exported to the cytoplasm, whereas the major unspliced isoform is nuclear localized. This shows that LOC100288798 RNA biology differs markedly from typical mRNAs. De novo assembly from RNA-seq data suggests that LOC100288798 extends 289kb beyond its annotated 3'' end and overlaps the downstream SLC38A4 gene. Three cell lines with independent gene trap insertions in LOC100288798 were available from the KBM7 gene trap collection. RT-qPCR and RNA-seq confirmed successful lncRNA truncation and its extended length. Expression analysis from RNA-seq data shows significant deregulation of 41 protein-coding genes upon LOC100288798 truncation. Our data shows that gene trap collections in human haploid cell lines are useful tools to study lncRNAs, and identifies the previously uncharacterized LOC100288798 as a potential gene regulator. Overall design: We cultured and processed 8 KBM7 cell lines in one batch. These cell lines were: two wild type KBM7 cells (WT2 and WT3), two monoclonal KBM7 cell lines with gene trap cassette insertions outside of the body of LOC100288798 (C1 and C2), two independently obtained KBM7 clones with gene trap cassette insertion 3kb downstream LOC100288798 transcriptional start site (TSS) (3kb1 and 3kb2), one independently obtained KBM7 clone with gene trap cassette insertion 100kb downstream LOC100288798 TSS replicated twice at the thawing step (100kb1 and 100kb2). We isolated total RNA from all th 8 cell lines, applied DNAseI treatment and ribosomal RNA depletion, and thhen prepared strand-specific RNA-seq libraries, which were pooled in equal molarities and sequenced using Illumina HiSeq 2000 (8 pooled samples were sequence on 2 lanes). We performed 50bp single-end RNA-seq. We used these 8 samples (4 untreated: WT2, WT3, C1, C2 and 4 treated:3kb1, 3kb2, 100kbk1, 100kb2) to analyze genome-wide gene deregulation associated with LOC100288798 lncRNA truncation	Co-expression
SRP061539	Disease-associated mutation in SRSF2 misregulates splicing by altering RNA binding affinities	SRSF2 is an RNA binding protein that plays important roles in splicing of mRNA precursors. Mutations in SRSF2 are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how they affect SRSF2 function has only begun to be examined. Here we used CRISPR/Cas9 to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these, 374 involve the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more included exons and a distinct motif (UGGA/UG) in the more excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG, but less tightly to UGGAG sites. The pattern of exon inclusion or exclusion thus correlated in most cases with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings not only shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation, but also reveal a group of mis-spliced mRNA isoforms for potential therapeutic targeting. Overall design: Examination of differentially spliced events in K562 CRISPR cell clones (with wild-type or mutant SRSF2) by RNA sequencing	Co-expression
SRP061560	A Surveillance System of Active Enhancers by a RACK7-histone Demethylase Complex (RNA-Seq I)	Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes.  Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer “brake” to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. Overall design: mRNA-seq of parental and RACK7-KO ZR-75-30 cells	Co-expression
SRP061561	A Surveillance System of Active Enhancers by a RACK7-histone Demethylase Complex (RNA-Seq II)	Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes.  Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer “brake” to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. Overall design: nascent RNA-seq of parental and RACK7-KO cells	Co-expression
SRP061566	mRNA differential expression in LNCaP cells expressing the wild-type androgen receptor (AR-WT) or the ligand-independent AR-V7 splice variant	Constitutively active AR variants are truncated proteins lacking the c-terminal region containing the ligand binding domain (LBD) and the activation function 2 (AF-2). The expression of these AR variants in CRPC was also associated with the resistance to novel therapies such as enzalutamide and abiraterone acetate. These variants are also involved in tumor progression. Overall design: LNCaP cells were transduced with lentival particles for expression of AR-WT or AR-V7 for 72 hours in complete medium containing 10 nM DHT. Libraries were sequenced using the Illumina Hiseq2500 technology The goal of this experiment was to delineate differential gene expression upon the expression of the AR-V7 in LNCaP cells compared with cells expressing the wild-type AR.	Co-expression
SRP061571	Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases	Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy. Overall design: tRNA was isolated from 35 omental tissue samples of HGSOC metastases either pre or post NACT treatment. RNASeq was performed on poly-A selected mRNA fragments, 100 b.p paired end, and strand specific, on average 40 million reads per sample.	Co-expression
SRP061614	RNA sequencing of T-ALL (COG study)	The clinical and cytogenetic features associated with T-cell acute lymphoblastic leukemia (T-ALL) are not predictive of early treatment failure or relapse.  We investigated 213 newly diagnosed patients who were treated in the Children''s Oncology Group (COG) T-ALL Studies 9404 and 0434 and identified a cluster cases characterized by increased expression of HOX9/10.  In samples with >8-fold HOXA9/10 deregulation, the presence of specific molecular lesions were confirmed through a systematic review of cytogenetic databases, FISH and PCR testing.  In cases with no identifiable lesions using the methods above, RNA sequencing was performed (Illumina and Ion Proton).  Fifteen cases selected for RNA sequencing met three criteria: HOXA9/10 expression =8-fold above the median, sufficient RNA, and an incomplete or absent molecular explanation for each sample’s HOXA9/10 deregulation.  Three cases were confirmed to have PICALM-AF10 fusions.  Two additional AF10-R cases showed DDX3X-AF10 lesions, one of which harbored a novel CASK gene fragment in a complex CASK-DDX3X-AF10 translocation.  Two cases harbored NUP98 fusions46 and one case each was identified for MLL-AF6, MLL-PICALM, HOXA10-(3’UTR)TRBC45, STAG2-LMO2, LOC338817-CCDC91.  We could not identify fusion transcripts in 3 cases. Overall design: Identification of novel fusion transcripts in HOXA9/10-deregulated T-ALL	Co-expression
SRP061634	RNAseq to identify TGF-beta and EGF regulated alternative splicing in Hela cells	No description.	Co-expression
SRP061636	Tracing the expression of circular RNAs in human preimplantation embryos	We systematically analyzed transcriptome in individual human oocytes and preimplantation embryos with a new single-cell RNA seq method we recently developed. Overall design: We sequenced individual single cells or embryos at seven consecutive stages (mature oocytes, zygotes, 2-cell, 4-cell, 8-cell embryos, morulae, and blastocysts) and single hESC using single-cell RNA seq.	Co-expression
SRP061639	Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation	We evaluated changes in mRNA stability and transcription using 4sU metabolic pulse labeling across a four hour time course following activation of Jurkat T cells with PMA and PHA Overall design: Measurement of total mRNA (T) and 4sU labeled mRNA (IP) in three biological replicates at five time points: prior to activation (U) and the first four hours after activation (1-4)	Co-expression
SRP061651	Tumor hypoxia causes DNA hypermethylation by reducing TET activity (RNA-Seq)	Hypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET gene expression, basal metabolism, HIF activity or nuclear reactive oxygen species, but directly depends on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro, while also in patients, gene promoters are markedly more methylated in hypoxic than normoxic tumors. Affected genes are frequently involved in DNA repair, cell cycle regulation, angiogenesis and metastasis, indicating cellular selection of hypermethylation events. Overall, up to 50% of the tumor-associated hypermethylation is ascribable to hypoxia across various cancer types. Accordingly, spontaneous murine breast tumors become hypermethylated when rendered hypoxic through vessel pruning, whereas vessel normalisation rescues this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation. Overall design: RNAseq of MCF7 cells grown under hypoxic and normoxic conditions. Submission includes data on 5 independent RNAseq experiments, each containing biological replicates grown under hypoxic conditions (0.5% oxygen), and under normoxic conditions.	Co-expression
SRP061670	Homo sapiens Raw sequence reads	We differentiated hESC into retinal pigment epithelial cells using two methods (three-dimensional culture and spontaneous differentiation methods). We investigated which kind of RPE cells derived from hESC showed similar gene expression patterns to those of human fetal native RPE.	Co-expression
SRP061682	Transcriptome profiling of human neural progenitor cells and neurons with DISC1 interruption	Purpose: Genetic and clinical association studies have identified disrupted-in-schizophrenia 1 (DISC1) as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11) translocation in a Scottish family, in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We sought to compare the gene expression profiles of human neural progenitor cells (NPCs) and neurons with interruption of the DISC1 gene in exon 2 (affecting all known coding transcripts) or exon 8 (near the site of the Scottish translocation, affecting longer transcripts). Methods: Wild-type and DISC1-targeted iPSCs (wild-type = "WT", exon 8 single allelic frameshift mutant = "ex8_wm", exon 8 biallelic frameshift mutant = "ex8_mm", exon 2 biallelic frameshift mutant = "ex2mm") were differentiated to NPCs and neurons using an embryoid aggregate method. NPC or neuronal cultures were used for RNA harvest and subsequent paired-end stranded sequencing of >50M reads/sample and 3-6 biological replicates per group. Results: We find that a subset of genes related to neuronal differentiation and development are dysregulated with DISC1 disruption at the NPC timepoint, whereas expression of genes related to neuronal function and signaling are altered at the neuronal timepoint. This study implicates DISC1 as a regulator of neuronal development. Overall design: mRNA profiles of wild-type and DISC1-targeted human iPSC-derived neural progenitor cells (day 17) and neurons (day 50) by paired-end sequencing, with 3-6 biological replicates, using Illumina HiSeq	Co-expression
SRP061689	EHMT1 and EHMT2 inhibition induce fetal hemoglobin expression [RNA-seq]	Using UNC0638 and genetic assays to inhibit EHMT1/2 and derepress fetal hemoglobin in adult hematopoietic cells. Overall design: RNA-Seq in primary adult human erythroid cells treated with UNC0638 or the vehicle control (DMSO) in biological triplicates.	Co-expression
SRP061701	Genome-wide Analysis of Human Constitutive Androstane Receptor (CAR) Transcriptome in Wild-type and CAR-knockout HepaRG cells	The constitutive androstane receptor (CAR, NR1I3) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pregnane X receptor (PXR), it is extremely difficult to decipher the exact role of human CAR (hCAR) in gene regulation, relying predominantly on pharmacological manipulations.  Here, utilizing a newly generated hCAR-knockout (KO) HepaRG cell line, we carried out RNA-seq analysis of the global transcriptomes in wild-type (WT) and hCAR-KO HepaRG cells treated with CITCO, a selective hCAR agonist, phenobarbital (PB), a dual activator of hCAR and hPXR, or vehicle control. Real-time PCR assays in separate experiments were used to validate RNA-seq findings. Our results indicate that genes encoding drug-metabolizing enzymes are among the main clusters altered by both CITCO and PB. Specifically, CITCO significantly changed the expression of 135 genes in an hCAR-dependent manner, while PB altered the expression of 227 genes in WT cells of which 94 were simultaneously modulated in both cell lines reflecting the dual effects of PB on hCAR/PXR. Notably, we found that many genes promoting cell proliferation and tumorigenesis were up-regulated in hCAR-KO cells, suggesting that hCAR may play an important role in cell growth that differs from mouse CAR. Together, our results reveal both novel and known targets of hCAR and support the role of hCAR in maintaining the homeostasis of metabolism and cell proliferation in the liver. Overall design: Compare the mRNA profiles of HepRG WT and hCAR-KO cells after DMSO, PB and CITCO treatment, each sample was done in duplicate.	Co-expression
SRP061707	Derivation and differentiation of haploid human embryonic stem cells [RNA-Seq 1]	Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution. Overall design: RNA sequencing analysis was performed on a total of 15 samples, including haploid and diploid human parthenogenetic embryonic stem cells at different differentiation states and cell cycle phases.	Co-expression
SRP061769	SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation [primary tissue_RNA-seq]	SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting     markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq for three primary Rhabdoid tumor samples	Co-expression
SRP061772	SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation [cell line_RNA-seq]	SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting     markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq in six Smarcb1 deficient rhabdoid tumor cell lines, before and after Smarcb1 re-expression.	Co-expression
SRP061830	Expression profile of wild type (WT) vs miR-155-/- in FLT3-ITD+ AML (MV4-11) cell lines	The expression profile in miR-155-/- FLT3-ITD+ AML is unknown. Using empty vector (EV) or two distinct miR-155 (S3 or S10) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing to determine the expression profile in these cells dependent on miR-155. We found a number of pathways dysregulated, including STAT5 activation. Overall design: RNAseq was performed on EV or miR-155 lentiviral CRISPR-Cas9 infected MV4-11 cell lines in triplicate cultures.	Co-expression
SRP061835	Characterization of t(15;21) translocations in myeloid disorders	We report on two novel t(15;21) alterations [t(15;21)(q24;q22) and t(15;21)(q21;q22)], which led to concurrent disruption of RUNX1 and two translocation partner genes encoding for transcription factors (SIN3A, TCF12) Overall design: Examination of four different patients with myeloid disorders. 2 out of 4 have been analyzed by means RNAseq	Co-expression
SRP061840	Epigenome Editing by CRISPR/Cas9 Repressors for Silencing of Distal Regulatory Elements	Epigenome editing with the CRISPR/Cas9 platform is a promising technology to modulate gene expression to direct cell phenotype and to dissect the causal epigenetic mechanisms that direct gene regulation.  Fusions of the nuclease-inactive dCas9 to the KRAB repressor domain (dCas9-KRAB) can effectively silence target gene expression.  We targeted dCas9-KRAB to the HS2 enhancer, a distal regulatory element that orchestrates the expression of multiple globin genes. Genome-wide analyses demonstrated that localization of dCas9-KRAB to HS2 specifically induced H3K9 tri-methylation (H3K9me3) at that enhancer and reduced the chromatin accessibility of both the enhancer and its promoter targets.  Targeted epigenetic modification of HS2 silenced the expression of multiple globin genes, with minimal off-target changes in gene expression. These results demonstrate that repression mediated by dCas9-KRAB is sufficiently specific to disrupt the activity of individual enhancers via local modification of the epigenome. This approach enables precise modulation of epigenetic function without modifying the underlying genome sequence. Overall design: K562 cells were transduced with in triplicate lentivirus encoding dCas9-KRAB with gRNA targeted to the HS2 globin enhancer.  Cells transduced with dCas9-KRAB without gRNA or dCas9 with gRNA targeted to the HS2 globin enhancer were included as controls.  RNA-seq was used to identify differential expression at on-target and off-target sites.	Co-expression
SRP061841	Prolyl hydroxylation regulates protein degradation, synthesis, and splicing in human induced pluripotent stem cell-derived cardiomyocytes	In this study we report the gene expression profile and MISO analysis for alternative splicing events such as exon skipping in iPSC-derived cardiomyocytes which were treated with a drug  inhibiting a-ketoglutarate-dependent hydroxylases (dimethyloxalylglycine) and compared to vehicle control. a-ketoglutarate-dependent hydroxylase inhibition plays a central role in cardiac hypoxia and the goal of this study was to identify new pathways in hypoxia beyond HIF-1a. Overall design: Biological replicates of RNA-seq data from iPSC-derived cardiomyocytes treated with dimethyloxalylglycine or vehicle control	Co-expression
SRP061848	Interactions of aCPs with Cytosine-rich Polypyrimidine Tracts Enhance Splicing of Cassette Exons	Alternative splicing comprises a robust generator of mammalian transcriptome complexity. Splice site specification and activity are controlled by interactions of cis-acting determinants on a transcript with specific RNA binding proteins. A major subset of these interactions comprises interactions localized to the intronic U-rich polypyrimidine tract located immediately 5’ to the majority of splice acceptors.  alphaCPs (also referred to as polyC-binding proteins (PCBPs) and hnRNP Es) comprise a subset of KH-domain proteins with high specificity and affinity for C-rich polypyrimidine motifs. Prior studies have revealed that binding of alphaCPs to C-rich motifs can modulate splicing and 3’ processing of the human alpha-globin mRNA transcript in the nucleus as well as stabilization of the halpha-globin mRNA in the cytoplasm. In the current report, we demonstrate that alphaCPs have a positive impact on the activity of splice acceptor sites in a defined subset of mammalian transcripts via binding to polypyrimidine tracts that are predominantly C-rich. These findings lead us to conclude that the alphaCPs play a global role in determining the splicing activity and levels of cassette exon inclusion within the mammalian transcriptome. Overall design: To test the impact of aCP proteins on alternative splicing, aCP proteins were knockdown from K562 cells by siRNA. Since aCP1 and aCP2 have redundent function, we therefore designed siRNAs capable of knockdown both isoform at the same time. 3 aCP1/2 combined knockdown and 3 control siRNA knockdown were performed in K562 cells. RNA-seq were then performed to identify alternative splicing pattern mediated by aCP proteins.	Co-expression
SRP061881	RNA-sequencing of cells derived from the site of inflammation of Juvenile Idiopathic Arthritis patients	Through RNA sequencing of CD4+ Tmemory/effector cells derived from the synovium of JIA patients and healthy controls, we analyzed the JIA gene expression signature. Treatment of autoinflammatory site-derived patient T cells with the BET-inhibitor JQ1 inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Overall design: RNA-sequencing of CD4+ memory/effector T cells derived from Healthy Controls (HC) and JIA patients upon JQ1 treatment.	Co-expression
SRP061888	RNA-Sequencing shows novel transcriptomic signatures in failing and non-failing human heart	The knowledge of an expression network signature in end-stage heart failure (HF) diseased hearts may offer important insights into the complex pathogenesis of advanced cardiac failure, as well as it may provide potential targets for therapeutic intervention. In this study, the NGS sequencing of RNA (RNA-Seq) method was employed to obtain the whole transcriptome of cardiac tissues from transplant recipients with advanced stage of HF. The analysis of RNA-Seq data presents novel challenges and many methods have been developed for the purpose of mapping reads to genomic features and quantifying gene expression. The main goal of this work was to identify, characterize and catalogue all the transcripts expressed within cardiac tissue and to quantify the differential expression of transcripts in both physio- and pathological conditions through whole transcriptome analyses. Expression levels, differential splicing, allele-specific expression, RNA editing and fusion transcripts constitute important information when comparing samples for disease related studies. Analysis methods for RNA-Seq data are continuing to evolve. Thus, in order to find the best solution for filter generated list of differentially expressed genes, an informatic approach of NOISeq BIO method has been applied in this RNA-Seq analysis. Most of the genes obtained by filtering differentially expressed gene list, have been experimentally validated by Real time RT-PCR. Noteworthy, these findings provide valuable resources for further studies of the molecular mechanisms involved in heart ischemic response thus leading to potential novel biomarkers and targets for therapeutic intervention in the onset and progression of cardiomyopathies. Overall design: Heart biopsies from candidates for solid organ transplantation were collected and their RNA samples were used for high-throughput sequencing purposes. Libraries were sequenced on the Illumina HiSeq2000 NGS platform.	Co-expression
SRP061932	Identification of global regulators of T-helper cell lineage specification (RNA-Seq)	The aim of the dataset was to identify genome-wide regulators of gene expression in early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) and Th2 (Act+IL4) polarizing conditions. Overall design: Total RNA from naive CD4+ T cells was compared to total RNA from cells cultured in the following three conditions: activating (antiCD3+antiCD28)+antiIL4+antiIFNG; activating (antiCD3+antiCD28)+IL12+antiIL4; activating (antiCD3+antiCD28) +IL4+antiIFNG. Samples from 3 biological replicates were analysed.	Co-expression
SRP061971	Homo sapiens Raw sequence reads	bone marrow-drived mesenchymal stem cells	Co-expression
SRP061972	Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets [RNA-Seq_AML]	Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of several AML cell lines	Co-expression
SRP061973	Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets [RNA-Seq_normal]	Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of normal cells (CD34+)  from different donors	Co-expression
SRP062010	Poly(A)-specific ribonuclease (PARN) mediates 3'' end maturation of the telomerase RNA component	Mutations in the poly(A) ribonuclease (PARN) gene cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita (DC)1,2, but how PARN deficiency impacts telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem (iPS) cells from DC patients with PARN mutations, we show that PARN is required for the 3' end maturation of the telomerase RNA component (TERC). Patient cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3' termini reveals that PARN is required for removal of posttranscriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results reveal a novel role for PARN in the biogenesis of TERC, and provide a mechanism linking PARN mutations to telomere diseases. Overall design: mRNA sequencing of fibroblasts, induced pluripotent stem cells, and 293 cell line.	Co-expression
SRP062025	Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo	Gene expression analysis of purified hematopoietic stem and progenitor cells isolated from low to intermediate risk MDS patients and age-matched normal healthy controls. Overall design: Analysis of lineage associated genes and PCA clustering of populations	Co-expression
SRP062046	Inhibitors of the histone lysine demethylase KDM1A are broadly efficacious in AML by evicting the enzyme from chromatin [RNA-Seq]	Investigating the effects of two different classes of KDM1A inhibitors on the transcriptome of AML cell lines Overall design: 16 different samples with biological replicates.  Treatment for 24 and 72 hours with an irreversible KDM1A inhibitor (RN-1) or a reversible KDM1A inhibitor (GSK690) or an inactive isomer of the latter (GSK690*).	Co-expression
SRP062062	The DNA methylation landscape of human melanoma [RNA-Seq]	Melanoma genomes are often characterized by large numbers of sunlight-induced mutations. However, epigenetic alterations, in the form of aberrant DNA methylation patterns, are also abundant. Using MIRA-seq, we have carried out a comprehensive characterization of the DNA methylome in a series of metastatic melanoma samples and catalogued the methylation changes relative to normal melanocytes, the presumed cells of origin for these tumors. Individual melanoma tumors contained up to several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks that were present in all (27/27) melanomas and may lend themselves as effective disease biomarkers, and 3124 methylation peaks were present in >40% of the tumors. We specifically examined the relationship between presence of the Polycomb mark, H3K27me3 in melanocytes and tumor-specific DNA methylation in melanoma. We found that 150 of the approximately 1,200 tumor-associated methylation peaks near transcription start sites (TSS) were H3K27me3-marked in melanocytes. Notably, DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for H3K27me3-enriched regions with broad genomic coverage. Yet, there were also numerous H3K27me3 peak-associated TSS regions that were completely resistant to DNA methylation in tumors. Furthermore, a rather large group of genes became methylated in melanoma but lacked H3K27me3 in melanocytes. There was no relationship between presence of BRAF V600 mutations and the number of methylation peaks in individual tumors. Gene expression analysis showed a strong signature of upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Genes down-regulated in tumors were enriched for melanocyte differentiation and pigmentation factors. Overall, there was limited correlation between tumor-associated DNA methylation changes and changes in gene expression although distinct melanocyte differentiation genes including KIT, PAX3 and SOX10 became methylated and downregulated in melanoma. Overall design: Genome-wide gene expression analysis of 17 melanomas and 3 melanocyte samples	Co-expression
SRP062099	RNASeq of MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946	Central to the molecular pathogenesis of MLL leukaemia is the abnormal co-optation of members of transcription complexes including disrupter of telomeric silencing 1-like (DOT1L) and bromodomain containing protein 4 (BRD4). Consequently, targeted therapies against DOT1L and BRD4 are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukaemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation we find that native BRD4 and DOT1L exist in largely separate protein complexes. Genetic disruption or small molecule inhibition of BRD4 and DOT1L shows marked synergistic activity against MLL-FP leukaemia cell lines, primary human leukaemia cells and murine leukaemia models. Mechanistically, we find a previously unrecognised functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in close proximity to superenhancers. DOT1L via H3K79me2 facilitates the deposition of histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide novel insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this poor prognostic disease. Overall design: RNASeq of MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946 in duplicate	Co-expression
SRP062132	Next Generation Sequencing Transcriptomes of breast cancer	We performed high throughput transcriptome of breast cancer and normal tissues, identifying lincRNA associated molecular subtype with powerful capacity to distinct breast cancer population and predict prognosis. We also identified subtype-specific lincRNAs that may be a useful complement to intrinsic molecular subtype classification when divergence emerges among pathologists.Paired-end transcriptome sequencing were carried out on a cohort of 33 breast tissues from 11 groups including five breast cancer subtypes including luminal A (LA), luminal B (HER2 negative)(LB, HER2-), luminal B (HER2 positive) (LB, HER2+), HER2 and tripple negative breast cancer (TNB), adjacent noncancerous breast tissue (ANT, three samples for each subtype) and the complete normal breast tissues (three samples) Overall design: Examination of transcriptomes in 15 breast cancer and 18 normal tissues.	Co-expression
SRP062144	Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets (RNA-seq AML development)	Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 AML	Co-expression
SRP062170	Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets (RNA-seq B-ALL)	Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 B-ALL	Co-expression
SRP062177	Fixed single-cell transcriptomic characterization of human radial glial diversity	The human neocortex is created from diverse progenitors that are intermixed with multiple cell types in the prenatal germinal zones. These progenitors have been difficult to profile with unbiased transcriptomics since progenitors-particularly radial glia (RG)-are rare cell types, defined by a combination of intracellular markers, position and morphology. To circumvent these problems, we developed a method called FRSCR for transcriptome profiling of individual fixed, stained, and sorted cells. After validation of FRSCR with human embryonic stem cells, we profiled primary human RG that constitute only 1% of the mid-gestation cortex. These data showed that RG could be classified into ventricle zone-enriched RG (vRG) that expressed ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that expressed HOPX. Our study identified the first markers and molecular profiles of vRG and oRG cells, and provides an essential step for understanding molecular networks that control the development and lineage of human neocortical progenitors. Furthermore, FRSCR allows targeted single-cell transcriptomic profiling of many tissues that currently lack live-cell markers. Overall design: 26 Llive and 19 Fixed cultured hESCs were prepared and sequenced using both FRISCR and TritonX-100 Lysis as proof of principal for FRSCR.	Co-expression
SRP062178	Homo sapiens Raw sequence reads	RNA-Seq of Endemic Burkitt Lymphoma	Co-expression
SRP062188	Differential Gene Expression between MCF10A and MCF7 cells	These RNA-seq data were generated to correlate with genomic interaction data in a related Hi-C analysis.  MCF10A is a normal-like mammary epithelial cell line and MCF7 is a transformed estrogen responsive breast cancer cell line derived from a metastatic site; both are commonly used in models of breast cancer progression.  Analysis revealed a set of genes related to repression of WNT signalling that were both up-regulated in MCF7 and located in genomic regions that had transitioned from closed to open structure in MCF7. Overall design: RNA-seq of MCF10A and MCF7 cells. 3 replicates each.  Sequencing was strand-specific and conducted on ribo-depleted RNA.	Co-expression
SRP062203	Homo sapiens Transcriptome or Gene expression	Human hepatocyte-like cells (HLCs) can be obtained from directed differentiation of human pluripotent stem cells (PSCs), including induced pluripotent stem cells and embryonic stem cells. However, the functional immaturity of HLCs prevents them from practical use. Here, we generated hepatocytes from both human embryonic stem cells (hESCs) and human induced pluripotent cells (hIPSCs) by in vitro directed differentiation respectively. By analysing of their transcriptome on a step-wise time course, we found that transcriptome of hESC and hIPSC have difference in expression of particular sorts of genes. Our study is the first one which jointly studied the in vitro directed hepatocyte differentiation process from both transcriptomic and methylomic aspects to our knowledge. These results can provides a comprehensive understanding about transcriptomic dynamics during differentiation process of human pluripotent cells into hepatocytes, as well as the difference between hESC and hIPSC during differentiation process.	Co-expression
SRP062212	Survival of pancreatic cancer cells lacking KRAS function	Activating mutations in the proto-oncogene KRAS are a hallmark of pancreatic ductal adenocarcinoma (PDAC), an aggressive malignancy with few effective therapeutic options. Despite efforts to develop KRAS-targeted drugs, the absolute dependence of PDAC cells on KRAS remains incompletely understood. Here we modeled complete KRAS inhibition using CRISPR/Cas-mediated genome editing. While KRAS knockout led to decreased in vitro proliferation and impaired in vivo tumorigenic growth, KRAS was dispensable in a subset of human and mouse PDAC cells. KRAS knockout cells exhibited hyperactivation of the PI3K pathway and induced sensitivity to phosphoinositide 3-kinase (PI3K) inhibitors. Mechanistically, PI3K inhibition in KRAS knockout cells led to transient mitogen-activated protein kinase (MAPK) blockade while impeding AKT-dependent 4EBP1 phosphorylation and cap-dependent translation. Furthermore, comparison of gene expression profiles of cells retaining or lacking KRAS revealed a novel functional role of KRAS in the suppression of metastasis-related genes. Accordingly, KRAS knockout gene expression signatures correlated with PDAC circulating tumor cell (CTC) signatures, and human PDAC tumors with gene expression patterns enriched in signatures from KRAS knockout cells were associated with worse survival in patients. Together, these data underscore the potential for resistance of PDAC to even the very best of KRAS inhibitors and suggest combination therapies with PI3K inhibitors as a viable strategy to circumvent resistance. Overall design: KRAS intact and knockout subclones from human 8988T and mouse A13 parental cell lines. Biologic replicates include 4 intact and 3 knockout clones from 8988T and 2 intact and 2 knockout clones from A13.	Co-expression
SRP062214	Transcript abundance in A-T-derived iPSC: Comparing isogenic cells to unrelated individual	Induced pluripotent stem cells (iPSC) were prepared from multiple subjects with Ataxia-telangiectasia (A-T).  iPSC were prepared from activated T-cells using commercial Sendai virus to deliver reprogramming factors.  ATM protein-expressing and non-expressing cultures would found in multiple sub-lines (sub-lines are generated from distinct founder colonies of cells) from a single subject (Q3).  Genetic analysis determined that all sub-lines originated from the same subject and were likely the product of spontaneous reversion by gene correction.  To compare gene expression profiles, three iPSC samples were assayed: (1) A reverted ATM+/- subline from subject Q3, (2) An ATM-/- subline from subject Q3, and (3) An iPSC line from an unrelated ATM-/- subject, Q1.  Analysis reveals that the majority of significantly-different genes between the unrelated ATM-/- line (Q1SA) and the reverted ATM+/- line (Q3SC) was due to genetic variation between individuals.  A more focused set of contrasting genes could be identified between the isogenic Q3-derived lines (Q3SA, ATM-/-, vs. Q3SC, ATM+/-).  The 206 transcripts that are significantly different point to a differential regulation of p53-associated pathways. Overall design: Total cellular RNA was prepared from each iPSC culture.  Different passage numbers or sister cultures were used as replicates (n=2).	Co-expression
SRP062223	The Polycomb protein BMI1 induces an invasive gene expression signature in melanoma that promotes metastasis and chemoresistance.	The epigenetic regulator BMI1 is upregulated in many human malignancies and has been implicated in cell migration, but the impact on autochthonous tumor progression is unexplored. Our analyses of human expression data show that BMI1 levels increase with progression in melanoma. We find that BMI1 expression in melanoma cells does not influence cell proliferation or primary tumor growth. In contrast, BMI1 levels are a key determinant of melanoma metastasis, whereby deletion impairs and overexpression enhances dissemination. Remarkably, BMI1’s pro-metastatic effect reflects enhancement of all stages of the metastatic cascade including invasion, migration, extravasation, adhesion and survival. Additionally, downregulation or upregulation of BMI1 induces sensitivity or resistance to BRAF inhibitor. Consistent with these pleiotropic effects, we find that BMI1 promotes widespread gene expression changes that encompass key hallmarks of the melanoma invasive signature,  including activation of TGFß, non-canonical Wnt, EMT and EGF/PDGF pathways. Importantly, for both primary and metastatic melanoma samples, this BMI1-induced signature identifies invasive subclasses of human melanoma and predicts poor patient outcome. Our data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance. Overall design: Three replicates of A375 BMI1 or GFP overexpressing cells.	Co-expression
SRP062230	AKT Inhibition Promotes Non-autonomous Cancer Cell Survival [RNA-Seq]	Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this “AKTlow” cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Overall design: Profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated, each in duplicate, using RNA-Seq.	Co-expression
SRP062278	Human macrophage-Leishmania infectome	The goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.	Co-expression
SRP062287	Research resource: global identification of estrogen receptor ß target genes in triple negative breast cancer cells	The goal of this work was to identify all estrogen receptor beta target genes using RNA sequencing in MDA-MB-468 triple negative breast cancer cells engineered with inducible expression of full length estrogen receptor beta. Overall design: MDA-MB-468 breast cancer cells with inducible ERb expression (MDA-468-ERb cells) were treated in triplicate with vehicle (control, no ERb) or doxycycline (plus ERb) for 48 hr prior to treatment with 0.1% DMSO vehicle or 10 nM 17b-estradiol for 4 hr.	Co-expression
SRP062298	Histamine footprint on the human exercise transcriptome	Transcriptome wide analysis of the skeletal muscle response to exercise in humans. Subjects performed one 60-min bout of moderate-intensity single-leg knee-extension exercise, and samples were obtained by biopsy of the vastus lateralis muscle before, immediately after, and at 3 hr post-exercise. Eight subjects were control (no drug), and eight received combined H1/H2-histamine receptor blockade prior to exercise. Overall design: Three time-points in each of 8 control and 8 histamine-blockade subjects. Time points are before exercise, immediately after exercise, and at 3 hrs post-exercise. Note: Alignments were re-run using an updated piece of software and the results are reported in PMID 29455450. The following supplementary files contain information on the differentially expressed genes that were identified by the new analysis of the data: GSE71972_Differential_Expression_Tables_Updated_20160830.xlsx GSE71972_Protein_Coding_Full_Counts_Updated_20160830.xlsx	Co-expression
SRP062331	Differential gene expression profiling of MIHA cells transfected with C-terminal truncated HBx mutants	To compare the differentially expressed transcriptomes between MIHA cells transfected with empty vector control or different C-terminal truncated HBx mutants (14 or 35 amino acid carboxyl-terminal truncation - i.e. d14 and d35) Overall design: mRNA profiles of MIHA cells stably overexpressing empty vector control or different C-terminal truncated HBx mutants (delta 14 and delta 35) were generated by PolyA mRNA sequencing using Illumina HiSeq 1500 platform	Co-expression
SRP062389	Human telomerase RNA processing and quality control	RNA sequencing of HeLa cells treated with siRNA against the RNA exosome components hRRP40, hRRP6, hDIS3, and hRRP6/hDIS3 or the splicing inhibitors Isoginkgetin and spliceostatin A, respectively. Overall design: Stranded, ribo-depleted RNA seq profiles of HeLa cells treated with exosome targeting siRNAs or splicing inhibitors using Illumina HiSeq. All experiments were carried out in triplicate starting with independent cell cultures	Co-expression
SRP062417	Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets (Leukemia Cell Bank)	Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of MLL-AF9 AML pediatric patients	Co-expression
SRP062444	Nef +/- infection and RNA transcriptome in different cell lines	Identification of the counterpart protein of Nef during HIV infection	Co-expression
SRP062555	Global analysis of pre-mRNA subcellular localization upon splicing inhibition by spliceostatin A	RNA-Seq analysis of SSA treated cells Overall design: HeLa cells, nuclear and cytoplasmic fractions, treated with SSA or MeOH	Co-expression
SRP062609	Homo sapiens Transcriptome or Gene expression	SRSF1-regulated splicing events in breast cancer	Co-expression
SRP062617	RNA-seq Profiles in Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells	Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo.  Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence. Overall design: RNA-seq of primary patient-derived GBM cancer stem cells and normal human neural progenitor cells	Co-expression
SRP062702	Potent and targeted activation of HIV-1 using the CRISPR/Cas9 activator Complex	Integration of the HIV-1 provirus in the host genome ensures a persistent supply of latently infected cells. This latent reservoir is recalcitrant to antiretroviral therapy (ART) making lifelong treatment the only option for patients. The “shock and kill” strategy aims to eradicate latent HIV by reactivating proviral gene expression followed by ART treatment. Gene specific transcriptional activation can be achieved using the RNA-guided CRISPR-Cas9 system comprising small guide RNAs (sgRNAs) with a nuclease deficient Cas9 mutant (dCas9) fused to the VP64 transactivation domain (dCas9-VP64).  We engineered this system to target 23 sites within the LTR promoter of HIV-1 and identified a “hotspot” for activation. We studied the functionality of activating sgRNAs to transcriptionally modulate the latent proviral genome across multiple different in vitro latency cell models including several J-Lat, ACH2 J1.1 and the CEM T cell model comprising a single clonal population of integrated mCherry-IRES-Tat from a full-length HIV LTR (LChIT).  While we observed variable responses of latent cell models to well-characterized chemical stimuli, we detected consistent efficient activation of latent virus mediated by activator sgRNAs.  In addition, transcriptome analysis of chemically treated cells revealed massive non-specific gene dysregulation whereas by comparison, dCas9-VP64/sgRNAs induced specific activation of the integrated provirus.  In conclusion, we show the potential for CRISPR-mediated gene activation systems to provide enhanced efficiency and specificity in a targeted latency reactivation strategy. This represents a promising approach to a “functional cure” of HIV/AIDS. Overall design: Three experimental conditions (sgRNA control, TNF treated and sgRNA against the LTR of HIV-1) were analyzed in triplicate using two sequencing lanes	Co-expression
SRP062714	Reprogramming postnatal human epidermal keratinocytes toward functional neural crest fates	During development, neural crest cells are induced by signaling events at the neural plate border of all vertebrate embryos.  Initially arising within the central nervous system, NC cells subsequently undergo an epithelial to mesenchymal transition to migrate into the periphery, where they differentiate into diverse cell types. Here we provide evidence that postnatal human epidermal keratinocytes, in response to FGF2 and IGF1 signals, can be reprogrammed toward a neural crest fate.  Genome-wide transcriptome analyses show that keratinocyte-derived NC cells are similar to those derived from human embryonic stem cells.  Moreover, they give rise in vitro and in vivo to neural crest derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes and smooth muscle). By demonstrating that human KRT14+ keratinocytes can form neural crest cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine. Overall design: mRNA profiles of KC and KC derived NC (from 3 biological replicates) were generated by deep sequencing using Illumina HiSeq 2500 platform (pair-end (2x50 bp) rapid run mode).	Co-expression
SRP062719	Globally construct ceRNA regulation network based on comparison with SHEE and SHEEC cell lines (RNA-Seq)	Long non-coding RNAs (lncRNAs), new star ncRNA class of mRNA-like transcripts, play complicate and critical roles in regulating various key biological processes including chromatin modification, transcription and post-transcriptional processing. Remarkably, some lncRNAs serve as a miRNA “sponge” to inhibit mediation of the differentiation of miRNA target in post-transcriptional regulation. Here, we firstly constructed the putative ceRNA network by integrating lncRNAs, miRNAs and mRNAs expression in compared with SHEE and SHEEC cell lines based on the high-though RNA sequencing data and microarray data. Though the biology function analysis, the result showed that ceRNA network mainly participate in PI3K-Akt pathway and may play a modulating role in regulation of essential signal molecules including SYK, FGF11, IL7R, MET, LAMB3, PRS6KB1, ITGB6, ITGB4, ITGA2, ITGA6, EPHA2, SOS2, VEGFA, GRB2, KRAS, CCDN1 and TP53 in primary ESCC. These results could provide us more essential clues for the development of novel therapeutic strategies and efficient drugs target in primary ESCC. Overall design: The SHEEC and SHEE cell lines were pooled with 5 cell lines respectively.	Co-expression
SRP062850	Conserved roles for murine mDUX and human DUX4 in activating cleavage stage genes and MERVL/HERVL retrotransposons [RNA-Seq]	To better understand transcriptional regulation during human oogenesis and pre-implantation embryonic development, we defined stage-specific transcription, which revealed cleavage stage as highly distinctive.  We present multiple lines of evidence that two cleavage-specific homologs, mouse mDUX and human DUX4, each activate hundreds of cleavage-specific endogenous genes (e.g. ZSCAN4, ZFP352, KDM4E) and retroviral elements (MERVL/HERVL-family).  Remarkably, mDux expression converts mouse ESCs into two-cell embryo-like (2C-like) cells by binding to MERVL promoters/enhancers and restoring the chromatin landscape (via ATACseq) to the pattern of mouse two-cell embryos Overall design: We derived and analyzed transcriptomes from seven stages of developing human oocytes and embryos. The blastocyst stage embryos were dissected into inner cell mass (ICM) and trophectoderm lineages and processed independently. Cells from each stage were pooled and RNA was extracted. Two stranded libraries were prepared from each stage. Each library was then split and amplied for 12 or 14 PCR cycles, resulting in four technical replicates per developmental stage. 12 and14 cycle replicates from the same library prep were merged after sequencing	Co-expression
SRP062871	NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence [N1ICD]	ER:RAS-G12V expressing IMR90 cells were transduced with N1ICD-containing or control vectors before treatment with either 100nM 4-OHT or vehicle for 6 days leading to Notch-induced senescence (NIS), RAS-induced senescence (RIS) or combined Notch and Ras-induced senescence (RNIS). Overall design: IMR90 cells expressing a 4-hydroxytamoxifen (4-OHT) inducible estrogen receptor (ER)-coupled RAS-G12V (ER:RAS-G12V) were transduced with N1ICD-FLAG-containing (residues 1758-2556 of human NOTCH1, as per Capobianco et al, Mol Cell Biol, 1997) or control vector before treatment with either 100nM 4-OHT or vehicle for 6 days , leading to RAS-induced senescence (RIS), NOTCH-induced senescence (NIS) or combined Ras & NOTCH-induced senescence (RNIS).  The total RNA was then analysed for transcriptional profiling using mRNA-sequencing. There were 6 (six) biological replicates for each experimental condition. Untreated, vector-transduced ER:RAS IMR90 cells were the control condition	Co-expression
SRP062872	NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence [CSM]	ER:RAS-G12V expressing IMR90 cells were treated with either 100nM 4-OHT for 6 days or 100uM Etoposide for 2 days, followed by further culture for 5 days, leading to RAS-induced senescence (RIS) and DNA-damage induced senescence (DDIS) respectively. Overall design: IMR90 cells expressing a 4-hydroxytamoxifen (4-OHT) inducible estrogen receptor (ER)-coupled RAS-G12V (ER:RAS-G12V) were treated with either 100nM 4-OHT for 6 days or 100uM Etoposide for 2 days, followed by further culture for 5 days, leading to RAS-induced senescence (RIS) and DNA-damage induced senescence (DDIS) respectively.  The total RNA was then analysed for transcriptional profiling using mRNA-sequencing. There were 8 (eight) biological replicatesfor each of the experimental conditions. Untreated ER:RAS IMR90 cells were the control condition	Co-expression
SRP062885	Transcriptome seuqnencing of hepatocellular carcinoma(HCC) patients associated with Hepatitis B Virus(HBV)	Transcriptome seqeunecing on 16 paired HCCs and non-tumorous livers to investigate the effect of HBV integration	Co-expression
SRP062902	Effect of Hypoxia in Severe Preeclampsia through Epigenetic Regulation	Though the pathophysiology of preeclampsia (PE) is unclear worldwide, placental hypoxia has been implicated in the pathologic processes of PE.In this study, we profiled the transcriptome in BeWo and JEG-3 cells cultured in hypoxic condition or normal ones based on the RNA sequencing dataset. After filtered the low-quality ones, the RNA readers was aligned to human genome hg19 by TopHat and then assembled by Cufflinks. The expression value of each transcript was calculated and consequently differentially expressed genes were screened out. CD39 and ZDHHC14 were found to have both different mRNA in hypoxic cells and abnormal methylation level in severely preeclamptic placentas. The mRNA expression of CD39 and ZDHHC14 in placental tissues were analyzed using qRT-PCR. The differential methylated regions (DMRs) of CD39 and ZDHHC14 were confirmed by MassARRY EppiTYPER. The effect of hypoxia on trophoblast cells was detected with western blotting and enzyme linked immunosorbent assay. The results showed CD39 and ZDHHC14were significantly lower in severe PE placenta, hypoxia significantly reduced the expression of CD39 and ZDHHC14 and the secretion of CD39 in trophoblast cells. Therefore, we believed hypoxia plays an important role in the processes of severe PE via decreasing the expression of CD39 and ZDHHC14 by changing their methylation level in placenta. Overall design: mRNA profiles of three cell lines at five stages and two different conditions were generated by deep sequencing, using HiSeq 2500.	Co-expression
SRP062910	Transcriptome of human ILC2s; primary vs IL-1b-primed	ILC2s regulate type2 immune responses and protect against helminth infection. We found that ILC2s can be expanded in the presence of a combination of cytokines IL-2 and IL-1b. To better understand the functional and phenotypic consequence of IL-1ß activation of ILC2s, we utilized whole transcriptome sequencing (RNA-seq) of freshly isolated ILC2s and IL-1ß-primed ILC2s. Differential expression analysis revealed a substantial number of genes underwent significant change between the two conditions (total 4,744 gene, FDR<0.01, Fold change >2), among which 3,871 genes were upregulated in IL-1ß –primed ILC2s. Overall design: Six samples were analyzed, three biological replicates of isolated ILC2s and three biological replicates of isolated ILC2s cultured with IL-1b	Co-expression
SRP062923	Identifying RBBP4-regulated transcriptome in T98G glioblastoma cells using RNA sequencing (RNA-seq)	Retinoblastoma-binding protein 4 (RBBP4) is a chromatin modifying protein regulating multiple cellular functions. We have identified RBBP4 as a critical modulator of therapy response in glioblastoma (GBM). The purpose of this study was to identify genes through which RBBP4 regulates this important role with expectation of identifying candidates for therapy sensitizing strategy in GBM, and perhaps in other human malignancies. Overall design: RNA was extracted from T98G cells expressing either a control shRNA (shNT) or RBBP4 shRNA (shRBBP4), and RNA-seq was used to evaluate the patterns of gene expression comparing T98G-shNT with the T98G-shRNA.	Co-expression
SRP062936	Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer''s disease	The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-sw) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer''s disease (AD). Here, we analyzed the effect of APP-sw in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-sw expressing H4-sw cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-sw. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase 3ß (GSK-3ß), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-relatedAquaporin 1 and presenilin 2 expression was regulated by APP-sw. Taken together, we propose that the expression of APP-sw modulates global gene expression directed to AD pathogenesis.	Co-expression
SRP062942	ROR-? drives androgen-receptor expression and represents a therapeutic target in castration-resistant prostate cancer	The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor–related orphan receptor ? (ROR-?) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-? drives AR expression in the tumors. ROR-? recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3)  to an AR–ROR response element (RORE) to stimulate AR gene transcription. ROR-? antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-? antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-? antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity in mice. Taken together, these results establish ROR-? as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa. Overall design: A total of 6 samples were analyzed in this study.  The study included one cell line C4-2B. C4-2B cells were cultured in medium containing vehicle control and/or SR2211 and/or XY011 and/or Enzalutamide (ENZ). The untreated C4-2B cells served as controls for the study.	Co-expression
SRP062950	Functional analysis of a novel human polymorphic inversion specific of Asian populations	Despite many years of study of inversions, very little is known about their functional consequences, especially in humans. A common hypothesis is that the selective value of inversions stems in part from their effects on nearby genes, although evidences of this in natural populations are almost nonexistent. Here we present a global analysis of a new 415-kb polymorphic inversion that is among the longest ones found in humans and is the first with clear position effects. This inversion is located in chromosome 19 and has been generated by non-homologous end joining between blocks of transposable elements with low identity. PCR genotyping in 541 individuals from eight different human populations allowed the detection of tag SNPs and inversion genotyping in multiple worldwide populations, showing that the inverted allele is mainly found in East-Asia with an average frequency of 4.7%. Interestingly, one of the breakpoints disrupts the transcription factor gene ZNF257, causing a significant reduction in the total expression level of this gene in lymphoblastoid cell lines. RNA-Seq analysis of the effects of this expression change in standard homozygotes and inversion heterozygotes revealed distinct expression patterns that were validated by quantitative RT-PCR. Moreover, we have found a new fusion transcript that is generated exclusively from inverted chromosomes around one of the breakpoints. Finally, by the analysis of the associated nucleotide variation, we have estimated that the inversion was generated approximately 43,450 years ago and, while a neutral evolution cannot be ruled out, its current frequencies are more consistent with those expected for a deleterious variant, although no significant association with phenotypic traits has been found so far.	Co-expression
SRP062956	Ro60-knockout cells	RNA-seq of Ro60-null GM12878 cell lines in order to determine the gene expression changes resulting from loss of Ro60. Overall design: 3 separate clones of Ro60(Trove2)-null cells derived from zinc finger nuclease targeting of exon 2, two wildtype biological replicates, +/- IFNa for 6 hours.	Co-expression
SRP062958	Healthy donor PBMC RNA-seq with or without interferon-alpha stimulation	Determine the gene expression profile in peripheral blood monocytes isolated from 3 healthy donors +/- 6 hours of interferon-alpha treatment. Overall design: 3 healthy donor PBMCs +/- interferon-alpha.	Co-expression
SRP062966	SLE lupus RNA-seq	RNA-seq of systemic lupus erythematosus (SLE) whole blood and healthy controls to determine the gene expression changes in these patients. Overall design: RNA-seq of PAXgene blood from SLE and healthy donors.	Co-expression
SRP062995	Effect of Hotair overexpression in human breast cancer cell lines	Study of the transcriptome changes upon Hotair overexpression in wt and Ezh2-/- Human breast cancer cell lines Overall design: 8 samples, 2 replicates for each	Co-expression
SRP063003	Modeling genome-wide transcriptional cis-regulation in n LNCaP-abl cell line after siRNA knock down of a series of gene factors [RNA-seq]	We describe, MARGE, Model-based Analysis of the Regulation of Gene Expression, a robust methodology that leverages a large library of genome-wide H3K27ac ChIP-seq profiles to predict key regulated genes and cis-regulatory regions in human or mouse. MARGE adopts a gene centric approach to define a regulatory potential that summarizes the aggregate activity of multiple cis-regulatory elements on each gene. This model is effective in describing cis-regulatory activity and, unlike the super-enhancer based approach, is highly predictive of gene expression changes in response to BET-bromodomain inhibitors. We show that linear combinations of H3K27ac defined regulatory potentials, selected from an extensive database of published H3K27ac profiles, can accurately model diverse gene sets derived from differential gene expression experiments. In addition, we demonstrate a novel semi-supervised learning approach for identifying transcription factor binding sites associated with the set of transcription factors that regulate the gene set. MARGE leverages published H3K27ac ChIP-seq data to enhance the interpretation of newly generated H3K27ac ChIP-seq profiles. MARGE can also be used to analyze gene expression studies, without the production of matched H3K27ac ChIP-seq data. Overall design: Transcriptome profiling in LNCaP-abl cell line after siRNA knock down of a series of gene factors.	Co-expression
SRP063006	Gene expression analysis of TIL rich HPV driven head and neck tumours reveals a distinct B-cell signature when compared to HPV independent tumours.	Purpose: Human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HPV(-) negative cancer. This may be due, in part, to the higher number of tumour infiltrating lymphocytes (TIL) in HPV(+) tumours. We used RNAseq to evaluate whether these differences in clinical behaviour could be explained simply by a numerical difference in TILs or whether there was a fundamental difference between TILs in these two settings. Patients and methods: Twenty-three consecutive HNSCC cases with high and moderate TIL density were subjected to RNAseq analysis.  Differentially expressed genes (DEG) between 10 HPV(+) and 13 HPV(-) tumours were identified with EdgeR. Immune subset analysis was performed using, FAIME (Functional Analysis of Individual Microarray Expression) and Immune gene transcript count analysis. Results: 1634 genes were differentially expressed. There was a dominant immune signature in HPV(+) tumours. After normalizing expression profiles for numerical differences in T cells and B cells, 437 significantly DEGs still remained. A B-cell associated signature emerged, which segregated HPV(+) from HPV(-) cancers  and included CD200, STAG3, GGA2, SPIB and ADAM28. Differential expression of these genes was confirmed  by real-time quantitative PCR and immunohistochemistry. Conclusion: In our dataset, the difference associated with T-cells between patients with HPV(+) and (-) HNSCC was predominantly numerical. However, when TIL numbers are corrected, a distinct differential B-cell signature was revealed. Overall design: mRNA profiles of 10 HPV driven (HPV+)  and 13 HPV independant (HPV-) head and neck squamous cell carcinoma (HNSCC) tumours were generated by RNA-Seq, using Illumina HiSeq 2000.	Co-expression
SRP063054	Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes	Recent studies have shown that circular RNAs (circRNAs) are abundant, widely expressed in mammals, and can display cell-type specific expression. However, how production of circRNAs is regulated and their precise biological function remains largely unknown. To study how circRNAs might be regulated during colorectal cancer progression, we used three isogenic colon cancer cell lines that differ only in KRAS mutation status. Cellular RNAs from the parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically-matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only) were analyzed using RNA-Seq. We developed a bioinformatics pipeline to identify and evaluate circRNA candidates from RNA-Seq data. Hundreds of high-quality circRNA candidates were identified in each cell line. Remarkably, circRNAs were significantly down-regulated at a global level in DLD-1 and DKO-1 cells compared to DKs-8 cells, indicating a widespread effect of mutant KRAS on circRNA abundance. This finding was confirmed in two independent colon cancer cell lines HCT116 (KRAS mutant) and HKe3 (KRAS WT). In all three cell lines, circRNAs were also found in secreted extracellular-vesicles, and circRNAs were more abundant in exosomes than cells. Our results suggest that circRNAs may serve as promising cancer biomarkers. Overall design: RNAseq deep sequencing for both cell and exosome mRNAs	Co-expression
SRP063059	Transcriptome-wide Quantitative Analysis of XLPDR-derived human dermal fibroblasts with POLA1 deficiency	The goal of this study is to analyzed transcriptome changes caused by POLA1 deficiency. Our data represents the first detailed analysis of molecular basis of XLPDR syndrome. We report than POLA1 deficiency leads to over-activation of IRF and NF-kB pathways with overexpression of typical markers of autoimmune syndromes. Overall design: Wild type and XLPDR-derived dermal fibroblasts are analyzed under non-stimulated (basal) conditions, after TNF treatment (2 and 12 h, 1000 U/mL), and poly(dA:dT) stimulation (16h, 1 mkg/mL). Obtained data were confirmed using the cellular model of XLPDR - normal dermal fibroblasts pretreated with control or anti-POLA1 siRNA and stimulated in analogous way.	Co-expression
SRP063075	Dissection of heterogeneity during cardiac maturation process by single-cell RNA sequencing	To improve the maturity and reduce the heterogeneity of iPSC-cardiomyocytes, we addressed the diversity of iPSC-cardiomyocytes by single-cell RNA sequencing and analyzed in detail about heterogeneity during cardiac maturation process. Overall design: mRNA profiles of differentiated iPSC-cardiomyocytes at several differentiation stages; day0, day21, day30.	Co-expression
SRP063090	Transcriptome profiles of moderate dysplasia in oral mucosa associated with malignant conversion	Oral malignancies are among the top most deadly cancers in the world. Early diagnosis of oral premalignant and malignant lesions is essential for treatment decision-making and prognosis improvement. In this study, we systematically evaluated the gene expression patterns during the pathogenesis of oral moderate dysplasia. RNA sequencing detected 21556 genes in moderate dysplasia and paired normal tissues from three patients. Hierarchical clustering analysis revealed distinct gene expression patterns between the moderate dysplasia samples. 346 differentially expressed genes that may contribute to the pathogenesis of moderate dysplasia were identified. Among these genes, ISG15 and MAGEA family showed different transcription profiles that close related with the alterations of gene expression patterns in moderate dysplasia samples and paired normal tissues. We speculated that, as the potential marker to signal the risk of malignant transformation, ISG15 and MAGEA together with their close related misexpressed genes may involve in two different pathways during the malignant conversion from oral dysplasia to oral squamous cell carcinoma. Overall design: six samples, including oral moderate dysplasia samples and paired normal samples from three patients	Co-expression
SRP063333	Syncytiotrophoblast generation from human pluripotent stem cells	Purpose: Syncytiotrophoblast (STB) is a multi-nucleated, terminally differentiated syncytium that covers the surface of the villous placenta and forms the major interface with maternal blood. It releases placental hormones and plays a primary role in exchange of gases, nutrients and waste products. Alterations in STB development and turnover have been implicated in placental diseases, including preeclampsia (PE). In vitro cell models are badly needed to study STB development and physiology due to inaccessibility to placental tissues during gestation. To establish in vitro STB model system, we generate STB and its mononucleated precursors from human embryonic stem cells (hESC) and profile for RNA content by RNAseq. Methods: H1 Human ESC (WA01) were treated with BMP4, the ALK4/5/7 inhibitor (A83-01), and the FGF2 signaling inhibitor (PD173074) (BAP) to direct them to the trophoblast lineage and provided both STB and extravillous trophoblast. Syncytial areas emerged at day 8 BAP treatment ranged in diameter from ~40 µm to > 100 µm. The intact syncytial areas were isolated by sieving successively through 70 µm and 40 µm mesh cell strainers. The captured cells are recovered by inverting the strainer and rinsing with culture medium to separate large (>70 µm) and middle size cell sheets (40-70 µm). The fraction that passes through both sieves represents cells of smallest diameter (< 40 µm), presumably cytotrophoblast. Total 12 RNA samples from triplicate three size-fractioned BAP treated and three untreated hESC cultured in a FGF2 supplemented medium in parallel were analyzed. Results: The larger > 70 µm areas stained positively for STB markers while ultrastructural analysis clearly revealed multi-nuclear cells with an extensive cytoplasm containing many prominent secretion granules.  The larger STB areas also had a larger DNA content that > 70 µm fraction contained 37 times more nuclear content and 40-70 µm fraction did 16 times more. Compared to the < 40 µm cell fraction, these larger cells over-expressed a full repertoire of genes characteristic of STB, e.g. CGA, CGB, PGF, ERVW1, GCM1. The smallest cell fraction had a DNA content consistent with mononuclear diploid cells, contained few secretory granules, and were only weakly positive for STB markers. Conclusion: The data are consistent with the > 70 µm cells being mature STB, while the intermediate fraction may represent a precursor population. Human ESC directed along the trophoblast lineage by BAP treatment offers a useful model for following STB formation in vitro and suggest that this protocol may have utility in studying the basis of certain placental diseases, especially preeclampsia, where placental tissue isolated at term or after pregnancy terminations can only offer limited information. Overall design: Three size fraction mRNA profiles of syncytial areas emerged at day 8 BAP treatment of hESC were generated by deep sequencing along with untreated hESC, in triplicate, using Illumina HiSeq 2500.	Co-expression
SRP063340	Transcriptome analysis of eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps reveals distinct lncRNA expression profiles	Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. Long noncoding RNAs (lncRNAs) play pivotal roles in various biological processes, but their roles in CRSwNP have not been explored. We performed systematic transcriptome analysis of mRNAs and lncRNAs of eosinophilic and noneosinophilic CRSwNP to deepen our understanding of the disease mechanism. Methods: We analyzed expression profiles of mRNAs and lncRNAs with next-generation high-throughput RNA sequencing in patients with eosinophilic CRSwNP (n=3), noneosinophilic CRSwNP (n=3), and healthy control subjects (n=3). Results were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an independent cohort of patients. The dysregulated mRNAs and lncRNAs were identified and characterized via bioinformatics analysis. Results: A total of 1917 novel lncRNA transcripts and 280 known lncRNA transcripts were identified. Sample groups were separated by unsupervised hierarchical clustering on differentially expressed lncRNAs or mRNAs. The qRT-PCR results of five dysregulated lncRNAs were consistent with the RNA-seq data. The dysregulated genes were significantly overrepresented in immune response and extracellular environment related terms in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The predicted functions of dysregulated lncRNAs were highly consistent with those of dysregulated mRNAs. Conclusion: The cross talk between inflammation and immune response and microenvironment is the key pathogenesis mechanism of CRSwNP. Patients with eosinophilic CRSwNP compared with noneosinophilic CRSwNP has distinct gene expression profiles. This highlights the necessity of designing personalized therapeutic strategies and suggests developing specific molecular biomarkers.  Overall design: Ribosomal RNA (rRNA) removed total RNA sequencing carried out in 3 groups of samples: ECRSwNP, non-ECRSwNP, CTRL.	Co-expression
SRP063363	Transcriptomes of peripheral blood mononuclear cells from a Guillain-Barre Syndrome patient and her healthy twin sampled at three different points of the disease evolution	Guillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy that debilitates the voluntary and autonomous response of the patient. In this study the transcriptome of peripheral blood mononuclear cells from a GBS patient and her healthy twin were compared to discover possible correlates of disease progression and recovery. Overall design: Blood samples were collected simultaneously from the Guillain-Barré patient (A) and from her control healthy twin (B) at three different time points during disease progression from hospitalization in the intensive care unit (T1), passing to intermediate care (T2),  and at conclusion of locomotion rehabilitation program when the patient was close to abandon the hospital (T3).	Co-expression
SRP063416	Homo sapiens Raw sequence reads	In the present study, the autologous cell based therapy for the compromised liver disease due to hepatitis B infection has been investigated. To perform this research, the HBsAg positive and nucleic acid test (NAT) positive blood samples along with healthy blood samples were utilized to generate hepatocyte-like cells (NeoHeps) from monocytes. The monocytes were sorted by MACS technology from the PBMCs so that the abundant non-monocyte cells were depleted.The isolated monocytes were cultured in two steps for 21 days. In the first step monocytes were incubated with serum supplemented IMDM medium containing cytokines like IL-3, MCSF and 2-ME for a period of six days for priming to induce plasticity in them. After six day in culture, the primed monocytes were termed as reprogrammed monocytes (RM). The reprogrammed monocytes were then differentiated for 15 days in serum supplemented IMDM medium containing mitogenic reagents like EGF, HGF and FGF-4 to generate NeoHeps.The RNA sequencing (RNASeq) of the Monocytes, RM and NeoHeps generated from both healthy and HBsAg positive blood samples were performed to analyse the kinetics of this differentiation process at the transcript level.	Co-expression
SRP063462	RNA-seq on HeLa cells after knockdown of NMD factor UPF1	In order to globally identify targets of the nonsense-mediated mRNA decay pathway (NMD), RNA-seq was performed on HeLa cells where NMD was inhibited by shRNA knockdown of UPF1 and on control cells (scrambled shRNA).	Co-expression
SRP063477	Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing	Here we present an RNAseq analysis of human bone samples, obtained from iliac crest needle biopsies, to yield the first in vivo interrogation of all genes and pathways that may be altered in bone with aging and E therapy in humans. Overall design: 58 healthy women were studied, including 19 young women (mean age ± SD, 30.3 ± 5.4 years), 19 old women (73.1 ± 6.6 years), and 20 old women treated with 3 weeks of E therapy (70.5 ± 5.2 years).  Using generally accepted criteria (false discovery rate [q] < 0.10), aging altered a total of 678 genes and 12 pathways, including a subset known to regulate bone metabolism (e.g., Notch).	Co-expression
SRP063493	Cancer associated SF3B1 hotspot mutations induce cryptic 3' splice site selection through use of a different branch point	Recurrent mutations in the spliceosome are observed in several human cancers but their functional and therapeutic significance remain elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3' splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3' ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer. Overall design: 72 samples, including two sets of patient data and cell lines with two additional technical replicates each	Co-expression
SRP063496	Gene expression of baseline biopsies from etrolizumab-treated ulcerative colitis (UC) patients	RNA sequencing was performed on RNA isolated from baseline biopsies from UC patients enrolled in the Phase II EUCALYPTUS study of etrolizumab. Gene expression differences were identified in a subset of anti-TNF naïve patients that achieved clinical remission at 10 weeks in response to etrolizumab. Overall design: Baseline colonic biopsies from UC patients treated with etrolizumab were sequenced by the Illumina HiSeq 2000 Sequencing System.	Co-expression
SRP063499	Gene expression analysis of human adenomas.	Gene expression profiling was carried out in 7 matched colon adenoma samples and normal mucosa to characterize the molecular mechanisms relevant to the etiology ofadenoma and human colorectal carcinoma development. Overall design: Whole-transcriptome RNA sequencing of the 7 matched colon adenoma samples and normal mucosas.	Co-expression
SRP063500	High-throughput RNA-sequencing of human macrophages infected with Mycobacterium abscessus Smooth and Rough variants	Mycobacterium abscessus is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and is associated with the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests as either a Smooth (MAB-S) or a Rough (MAB-R) morphotype, which differ in their levels of cell wall glycopeptidolipids (GPLs) and in their pathogenicity in vivo. As one of the primary immune cells encountered by MAB, we sought to examine the early transcriptional events within macrophages, following infection with both MAB-S or MAB-R. We sampled the small RNA (sRNA) transcriptome of THP-1-derived macrophages infected with both MAB-R and MAB-S at 1, 4 and 24 hours post-infection (hpi) using RNA-seq. MAB-S elicited a more robust transcriptional response at the miRNA level, reflecting higher cytokine levels in culture supernatants. However, and a direct comparison identified no differentially expressed miRNAs between MAB-R- and MAB-S-infected cells. Most of the induced miRNAs have previously been associated with mycobacterial infection and overall miRNA expression patterns were similarly highly correlated between the morphotypes. Overall design: THP-1-derived macrophages were infected in parallel with the MAB-R and MAB-S morphotypes. Poly-A selected RNAs were purified and sequenced at 1, 4 and 24 hours post-infection, and compared with uninfected controls.	Co-expression
SRP063510	Regulartory effect of HNRNPL and LARP on RNA expression in LNCaP prostate cancer cells	Analysis of RNA expression in LNCaP prostate cancer cells treated with different siRNAs to define the regulatory effect of HNRNPL and LARP on RNA expression. Overall design: LNCaP prostate cancer cells were treated with the control siRNA oligos and the siRNA oligos that knockdown the expression of HNRNPL and LARP. The polyA-RNA expression difference upon different siRNA oligo treatment was evaluted.	Co-expression
SRP063523	Next Generation Sequencing Facilitates Quantitative Analysis of mesoderm posterior bHLH transcription factor 1(MESP1)+ and MESP1- cells' Transcriptomes	Purpose: To compare the transcriptome of MESP1-mTomato reporter cells at undifferentiated state, cardiac differentiation day 3 and day 5. Methods: total RNA from sorted MESP1+, MESP1- and HESCs (in biological duplicates) was extracted using RNeasy Plus Mini Kit (Qiagen) and treated with RNase free DNase. RNA library was prepared following the instruction of TruSeqâ„¢ RNA Sample Preparation kit (Illumina) and sequenced on Illumina HiSeq 2000. Results: genes differentially expressed in MESP1-mTomato+ and mTomato- cells were identified. Conclusions: the gene expression profile of MESP1-mTomato cells indicates that they are cardiovascular progenitor cells. Overall design: Through RNA-seq of MESP1+, MESP1- and undifferentiated cells, perform bioinformatics analysis to identify differentially expressed genes,  then perform functional study.	Co-expression
SRP063573	Chromatin-remodelling complex NURF is essential for differentiation of adult melanocyte stem cells	MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf- mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes. Overall design: 5 samples corresponding to mRNA profiles of 501Mel and Hermes3A after BPTF shRNA-mediated knockdown were generated by deep sequencing in triplicate (Hermes 3A) or duplicate (501Mel), using HiSeq2500.	Co-expression
SRP063581	Homo sapiens Transcriptome or Gene expression	To profile gene expression affected by AKT3 p.E17K expression in human neural progenitor cells	Co-expression
SRP063600	Deciphering H3K4me3 Broad Domains Associated With Gene Regulatory Networks and Conserved Epigenomic Landscapes in the Human Brain [RNA-Seq]	Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. Overall design: We collected separately cortical gray (GM) and subcortical white matter (WM) from 6 adult human subjects without neurological disease and extracted total RNA processed by the RNA-Seq approach.	Co-expression
SRP063602	Bromodomain-containing Protein 4 (BRD4) is Required for the Maintenance of a Mammary Epithelial Phenotype [RNA-Seq]	Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Here we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of epithelial differentiation-specific genes. Interestingly, we show that BRD4 perturbation regulates the expression of Grainy Head-like transcription factor, GRHL3, whose depletion partially mimics BRD4 inhibition and blocks differentiated phenotype. By binding to the distal regions of GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of GRHL3 expression. Overall design: mRNA expression profiles of MCF10A cells under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.	Co-expression
SRP063620	Retroviral Replicating Vectors Deliver Cytosine Deaminase Leading to Targeted 5-FU-Mediated Cytotoxicity in Multiple Human Cancer Types	Toca 511 is a modified Retroviral Replicating Vector based on Moloney g-retrovirus with an amphotropic envelope. As an investigational cancer treatment, Toca 511 preferentially infects cancer cells without direct cell lysis and encodes an enhanced yeast cytosine deaminase that converts the antifungal drug 5-fluorocytosine to the anticancer drug, 5-fluorouracil. A panel of established human cancers cell lines, derived from glioblastoma, colon, and breast cancer tissue was used to evaluate parameters critical for effective anticancer activity. As part of these analyses, we profiled relative mRNA levels across these cell lines via RNA sequencing. Overall design: mRNA expression profiles across nine human cancer cell lines.	Co-expression
SRP063631	Homo sapiens Transcriptome or Gene expression	Here, we describe a strategy in which candidate functional risk variants are evaluated using genome-editing to create isogenic cell lines representing all possible genotypes. We created a panel of isogenic 22Rv1 prostate cancer cell lines representing all three rs339331 genotypes (TT, TC, CC). The risk allele causally increased transcription of the RFX6 gene, increased HOXB13 binding, and increased deposition of the enhancer-associated H3K4me2 histone mark. The cell lines also differed in cellular morphology: TT cells were more adhesive than the CC cells consistent with a cancer-related phenotype. Pathway analysis of differentially expressed genes between the CC and TTlines was predicted to be androgen regulated, a key pathway in prostatecancer biology.	Co-expression
SRP063658	TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses	The RNA-seq results reveal TMPyP4 and TPyP4 could promote cancer cell migration. Overall design: Examination of the gene expression of the following cells:A549-untreated and TMPyP4-treated or TPyP4-treated.	Co-expression
SRP063661	Expression profiles of cultured human epididymis cells reveal the functional diversity of caput, corpus and cauda regions.	Purpose: To compare the transcriptome profiles (RNA-seq) of cultured human epididymis cells and tissue from the caput, corpus and cauda regions of the human epididymis. Methods: Human epididymis tissue was obtained with Institutional Review Board approval from 3 patients (UC05, UC06, UC09, range: 22 - 36 years) undergoing inguinal radical orchiectomy for a clinical diagnosis of testicular cancer. None of the epididymides had extension of the testicular cancer. The three anatomical regions: caput, corpus and cauda, were separated and segments of each snap frozen. Adult human epididymis epithelial (HEE) cultures were also established from  tissue. RNA was extracted from both tissue and cultured HEE cells and RNA-seq libraries prepared (TruSeq RNA Sample Preparation Kit v2, Low-Throughput protocol, Illumina). Libraries were sequenced on Illumina HiSeq2500 machines. Data were analyzed using TopHat and Cufflinks. Results: Libraries generated ~19-39 million reads per library from the cells (95-99% mapping to the human genome) and ~14-39 million reads from the tissue samples (84-99% mapped). Raw reads were aligned to the genome with Tophat and gene expression values were processed using Cufflinks as Fragments Per Kilobase per Million mapped fragments (FPKM). FPKM values were subject to principle component analysis, which revealed that though caput, corpus and cauda cell samples respectively from UC05, UC06 and UC09 clustered together. RNA-seq data from the 3 biological replicas (UC05, UC06 and UC09) of caput, corpus and cauda were pooled for further analysis. Cufflinks was used to determine differentially expressed genes (DEGs) between caput, corpus and cauda cells, combined from the 3 donors. The gene expression profiles of corpus and cauda are remarkably similar and both differ from the caput to a similar degree. We identified ~40 genes differentially expressed between corpus and cauda and more than 1600 DEGs between caput and cauda. The DEGs for each comparison (caput and corpus/cauda) were analysed using a gene ontology process enrichment analysis (DAVID, Huang et al., NAR 2009;37:1-13, Huang et al., 2009 Nat Prot 4:44-57). Conclusions: Here we describe an in depth analysis of the gene expression repertoire of primary cultures of epithelial cells and intact tissues from each region of the adult human epididymis. These data will be valuable to decipher pathways of normal epididymis function and aspects of epididymis disease that cause male infertility. Overall design: RNA-seq was performed on libraries generated from caput, corpus and cauda-derived cultured cells (passage 2 or 3) from 3 donors and on caput, corpus and cauda tissue from 2 of the same donors. Donor age range: 22 - 36 years.	Co-expression
SRP063667	Homo sapiens Raw sequence reads	we treated Homo sapiens UMUC-3 cells with 5-AZA-CdR for 5, 9, 13 and 17 days and employed deep sequencing method to analyze alterations in gene expressions and alternative splicing	Co-expression
SRP063669	Human stem cell based models of neuronal migration provide insight into neurological disease pathogenesis and potential treatment	Neuronal migration defects (NMDs) are among the most common and severe brain abnormalities in humans. Lack of disease models in mice or in human cells has hampered the identification of underlying mechanisms. From patients with severe NMDs we generated iPSCs then differentiated neural progenitor cells (NPCs). On artificial extracellular matrix, patient-derived neuronal cells showed defective migration and impaired neurite outgrowth. From a cohort of 107 families with NMDs, sequencing identified two homozygous C-terminal truncating mutations in CTNNA2, encoding aN-catenin, one of three paralogues of the a-catenin family, involved in epithelial integrity and cell polarity. Patient-derived or CRISPR-targeted CTNNA2- mutant neuronal cells showed defective migration and neurite stability. Recombinant aN-catenin was sufficient to bundle purified actin and to suppress the actin-branching activity of ARP2/3. Small molecule inhibitors of ARP2/3 rescued the CTNNA2 neurite defect. Thus, disease modeling in human cells could be used to understand NMD pathogenesis and develop treatments for associated disorders. Overall design: 2 biological replicates per individual (2 iPSC clone differentiations), excluding 1263A, which has one sample	Co-expression
SRP063834	RNA-sequencing analysis of human fibrolamellar hepatocellular carcinoma and 4 maturational stages of the human hepatobiliary system	The etiology of fibrolamellar hepatocellular carcinoma (FL-HCC), a liver cancer occurring increasingly in children to young adults, is poorly understood. We performed high-throughput sequencing on mRNA isolated from a newly developed model of FL-HCC and 4 different maturational lineages of the hepatobiliary system. Our results indicate that the transcriptome of FL-HCC is most similar to that of biliary tree stem cells. Overall design: mRNA profiles of a newly developed model of FL-HCC and 4 maturational stages of the human hepatobiliary system (biliary tree stem cells, hepatic stem cells, hepatoblasts, and adult hepatocytes) were generated by high throughput sequencing using the Illumina HiSeq 2500.	Co-expression
SRP063838	Select correlative genes involved in pathogenesis of idiopathic interstitial pneumonia by high-throughput sequencing analysis	We report abonormally expressed genes of idiopathic interstitial pneumonia by RNA-seq analysis. BMP3 was found down-regulated in idiopathic intestital pneumonia patients, and it closely correlated with pathogenesis of disease. The role of BMP3 in advancement of idiopathic interstitial pneumonia was verified by a series of experiments. Overall design: Examination of differentially expressed genes in idiopathic interstitial pneumonia. Verification the function of selected gene in pathogenesis of idiopathic interstitial pneumonia in vivo and invitro.	Co-expression
SRP063840	Single-cell transcriptome profiling for metastatic renal cell carcinoma patient-derived cells [RNA-seq]	Clear cell renal cell carcinoma (ccRCC) initiated from the renal epithelium is the most prevalent histological type of adult kidney cancers. Dissecting intratumoral heterogeneity (ITH) of ccRCC has leveraged to extend our knowledge on how primary tumors harboring driver mutations evolve and spread to other sites. The cellular fractions within and across the primary (pRCC) and metastatic RCC (mRCC) are heterogeneous in both their genetic and biological features determining the variability in clinical aggressiveness and sensitivity to the therapy. To achieve sustainable therapeutic benefit with targeted agents in mRCC, the effective target should focus on signaling pathways that are related to driver mutations occurred early in the clonal evolution of the disease and thus should be common to primary tumor and metastatic sites. Considering that extensive genetic heterogeneity may result in drug response variability among patients and treatment resistance, the tailored strategies for metastatic RCC is urgently needed. Here, we analyze single-cell RNA-seq (scRNA-seq) data from a matched primary RCC (pRCC) and lung metastasis (mRCC) to dissect ITH at the highest resolution to date with the objective of discovering the better therapeutic regimen. Overall design: In order to identify successful clonal propagation from patient to PDX samples and understand pathogenesis from primary to metastatic RCC, we performed whole-exome sequencing (WES, n=4) and matched aCGH (n=4) on bulk tumor samples. And we utilized single-cell RNA sequencing (scRNA-seq) to model and dissect functional heterogeneity acroass primary and metastatic RCC tumors. We checked whether of capturing live one cell, not more cells, in microfluidics by fluorescent microscopic observation. To construct RNA sequencing libraries, we performed further quality controls including adequate quantities and qualities of amplified transcriptomes respectively from single cells. Tumor cells from the parental mRCC (n=34), PDX-mRCC (n=36) and PDX-pRCC (n=46) were finally analyzed in this study after filtering out poor quality cells.	Co-expression
SRP063851	High-throughput RNAi cell viability screen to identify selective targets for EWS-FLI1 positive Ewing sarcoma	We have performed a high-throughput RNA interference screen to identify targets inhibiting EWS-FLI1 driven cell proliferation in Ewing sarcoma cells. EWS-FLI1 expressing A673 Ewing sarcoma cells were screened both in presence and absence of EWS-FLI1 shRNA induction with druggable siRNA library. Leucine rich repeats and WD repeat Domain containing 1 (LRWD1) targeting siRNA pool was the strongest anti-proliferative hit identified only in presence of EWS-FLI1. Validation experiments confirmed the anti-proliferative effect of LRWD1 depletion especially in EWS-FLI1 expressing cells. Functional analysis of differentially expressed genes in LRWD1 depleted Ewing sarcoma cells showed over-representation of connective tissue development, cell projection morphogenesis and neuronal processes. Overall design: Examination of the effect of two LRWD1 targeting siRNA molecules vs. scrambled siRNA in one cell line	Co-expression
SRP063860	RNAseq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells	The specialized corneal epithelium requires differentiated properties, specific for its role at the anterior surface of the eye, thus tight maintenance of the differentiated qualities of the corneal epithelial is essential.  Our studies have focused on pinin (PNN), an exon junction component (EJC) that has dramatic implications on corneal epithelial cell differentiation and may act as a stabilizer of the corneal epithelial cell phenotype. Our studies revealed that PNN is involved in both transcriptional repression complexes and the spliceosomal complexes, placing PNN at the fulcrum between chromatin and mRNA splicing.  Transcriptome analysis of PNN-knockdown cells revealed clear and reproducible alterations in transcript profiles and splicing patterns of a subset of genes that would significantly impact the epithelial cell phenotype.  Here, we further investigate PNN’s role in the regulation of gene expression and alternative splicing (AS) in a corneal epithelial context.  We used human corneal epithelial cells (HCET cells) that carry doxycycline-inducible PNN-knockdown shRNA vector and performed RNA-seq to determine differential gene expression and differential AS events. Multiple genes and AS events were identified as differentially expressed between PNN-knockdown and controls cells. Genes up-regulated by PNN-knockdown included a large proportion of genes that are associated with processes associated with enhanced cell migration and ECM remodeling including: MMPs, ADAMs, HAS2, LAMA3, CXCRs and UNC5C.  Genes down-regulated in response to PNN depletion included: IGFBP5. FGD3, FGFR2, PAX6, RARG and SOX10. AS events in PNN compared to controls was also more likely to be detected, and uregulated in PNN-knockdowns.  In particular, 60% of exon skipping events detected in only one condition were detected in PNN-knockdowns and of the shared exon skipping events, 92% of those differentially expressed were more frequent in the PNN-knockdown. This suggests that in the absence of PNN the epithelial cells are dramatically transformed in the amount and composition of isoforms and that PNN plays a crucial role in the selection of which isoforms differentiating cells produce.   Many of the genes affected by PNN-knockdown are known to affect epithelial phenotype. This window into the complexity of RNA splicing in the corneal epithelium implies that PNN exerts broad influence over the regulation and maintenance of epithelial cell phenotype. Overall design: We used HCET cells that carry doxycycline-inducible PNN knockdown shRNA vector and performed RNA-seq to determine differential gene expression and differential alternative splicing events.	Co-expression
SRP063867	Comparing isogenic pairs of hESC and hiPSC lines reveals genetic background and reprogramming method as primary sources of transcriptional variation	The equivalency of human induced pluripotent stem cells (hiPSCs) with human embryonic stem cells (hESCs) remains controversial. Here, we devised a strategy to assess the contribution of clonal growth, reprogramming method and genetic background to transcriptional patterns in hESCs and hiPSCs. Surprisingly, transcriptional variation originating from two different genetic backgrounds was dominant over variation due to the reprogramming method or cell type of origin of pluripotent cell lines. Moreover, the few differences we detected between isogenic hESCs and hiPSCs neither predicted functional outcome, nor distinguished an independently derived, larger set of unmatched hESC/hiPSC lines. We conclude that hESCs and hiPSCs are transcriptionally and functionally highly similar and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional comparisons of pluripotent cell lines, explaining some of the previously observed expression differences between unmatched hESCs and hiPSCs. Overall design: Expression profiling of human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and fibroblasts, mostly in triplicates.	Co-expression
SRP063875	Promoter H3K4 methylation reveals the dynamic reinforcement of activation-induced pathways in human CD4 T cells with differential kinetics in na誰ve and memory cells (RNA-Seq)	The epigenetic determinants driving the rapid responses of memory CD4 T cells to antigen are currently an area of active research.  While much has been done to characterize various Th subsets and their associated genome-wide epigenetic patterns, the dynamics of histone modifications during CD4 T cell activation and the differential kinetics of these epigenetic marks between na誰ve and memory T cells have not been evaluated.  In this study we have detailed the dynamics of genome-wide promoter H3K4me2 and H3K4me3 over a time course during activation of human na誰ve and memory CD4 T cells.  Our results demonstrate that changes to H3K4 methylation predominantly occur relatively late after activation (120 hours) and reinforce activation-induced upregulation of gene expression affecting multiple pathways important to T cell activation, differentiation, and function.  The dynamics and mapped pathways of H3K4 methylation are distinctly different in memory cells. Memory CD4 have substantially more promoters marked by H3K4me3 alone, and that is influenced by promoter CpG content, reinforcing their more differentiated state.  Our study provides the first data examining genome-wide histone modification dynamics during T cell activation, providing insight into the cross-talk between H3K4 methylation and gene expression, and underscoring the impact of these marks upon key pathways integral to CD4 T cell activation and function. Overall design: RNA-Seq of na誰ve and memory CD4 T cells at rest and at 3 time points after activation with anti-CD3/CD28.	Co-expression
SRP063881	EZH2 and BCL6 cooperate to assemble CBX8-BCOR Polycomb complex to repress bivalent promoters, mediate germinal center formation and promote lymphomagenesis [RNA-seq]	EZH2 mediates the humoral immune response and drives lymphomagenesis through de novo formation of bivalent chromatin domains and critical germinal center (GC) B cell promoters.  We show that such formation is dependent on the presense of BCL6 and the presence of non-canonical PRC1-BCOR complex.  We observe that BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in vitro, in vivo, and in primary human DLBCLs. Overall design: DLBCL cell lines treated with BCL6 inhibitor 79-6.1085	Co-expression
SRP063885	Primary human trophoblast from term placenta	We compare two groups of transcriptome profiles. They are 1) primary human trophoblasts (PHT) and 2) syncytiotrophoblast from human pluripotent stem cells. This data set represents the former data set and the latter has been deposited separately at GSE72712. Primary human trophoblasts (PHT) were purified cytotrophoblast populations from whole term placentas and then cultured in vitro.  The cytotrophoblasts were cultured for short (9 h) or long (48 h) term that show undifferentiated (PHTu) or differentiated (PHTd) phenotype that led syncytialization, respectively. Transcriptome profiles of PHTu and PHTd were compared with three size fractioned syncytiotrophoblasts and trophoblasts from human pluripotent stem cells that are named ESCd_gt70 (greater than 70 µm), ESCd_40-70 (size between 40 and 70 µm), ESCd_lt40 (smaller than 40 µm) and undifferentiated progenitor (ESCu; see GSE72712). Overall design: Primary human trophoblasts (PHT) were derived and cultured from three term human placentas obtained by the Obstetrical Specimen Procurement Unit from women after a healthy pregnancy, labor, and delivery at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Isolated PHT lines obtained from three individual (1 female and 2 male) placentas were cultured separately.	Co-expression
SRP063889	Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2	Inhibition of H3K27 methyltransferase EZH2 enhances osteogenic commitment of human mesenchymal progenitors and Ezh2 inactivation in mouse calvarial cells induces a post-proliferative state concomitant with increased production of a bone-related mineralizing extra-cellular matrix. Overall design: Expression of genes of interest, including Ezh2, was assessed during osteogenic differentiation of human adipose-derived mesenchymal (AMSCs) on plastic (2D) and on porous-sintered titanium discs (3D). We also assessed gene expression when AMSCs were differentiated into the adipogenic lineage. In addition, the effect of GSK126 on osteogenic differentiation of AMSCs was also evaluated. Finally, we compared gene expression in calvarial bones obtained from wild type mice and mice lacking functional Ezh2 in the mesenchymal lineage (Prrx1-Cre, 3 day old female mice).	Co-expression
SRP063899	Transcriptome analysis of AGS cells infected with Helicobacter pylori P12	Transcriptome analysis of AGS cells infected with Helicobacter pylori P12 Overall design: Cultured AGS cells infected with wildtype H. pylori P12 for 2,5 h. 3 biological replicates (non-infected vs. infected)	Co-expression
SRP063938	Next Generation Sequencing Facilitates Quantitative Analysis of HCC cells transfected with NCsiRNA or ODC1siRNA	We investigated if targeting of ODC1 with siRNA could inhibit HCC progression. To accomplish this, Huh1 and Huh7 human HCC cells were transfected with ODC1 siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to ODC1 knockdown, global changes in gene expression were examined using RNA sequencing. Our results show that ODC1 silencing caused inhibition of HCC cell growth through blockade of cell cycle progression and a strong induction of apoptosis. Subsequent Western blotting revealed that ODC1 silencing decreased the levels of cell cycle regulator cyclin E1, PARP-1, and pro-caspase 3 accelerating apoptotic signaling in HCC cells. In addition, ODC1 silencing resulted in a strong inhibition in the expressions of important regulators of glycolysis and lipogenesis, GLUT4 and ChREBP, and caused a marked decrease in fat accumulation. These findings suggest that ODC1 can be a promising target for systemic therapy of HCC by modulating tumor metabolism. Overall design: Examination of 2 different siRNA transfected cells in 2 cell lines.	Co-expression
SRP063948	hTERT promotes cell adhesion and migration independent of telomerase activity	We sequenced mRNA from 6 human cell lines stably over-expressed specific gene or empty vector, and searched for differently expressed genes after gene over-expression as compared to empty vector. Overall design: mRNA levels were compared as following pairs: U2OS+hTERT vs U2OS+vector; U2OS+hTERTmut vs U2OS+vector; VA-13+hTERT vs VA-13+vector; VA-13+hTERTmut vs VA-13+vector.	Co-expression
SRP063973	TSLP acts on neutrophils to drive complement-mediated killing of methicillin-resistant Staphylococcus aureus	Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention.  Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .	Co-expression
SRP063977	RNA-sequencing transcriptome profiling of normal human keratinocytes differentiation	In this study, we used a RNA-sequencing (RNA-seq) approach to analyze the whole transcriptomes of human primary Keratinocytes (KC) at different differentiation stages.    An average of 72.56 million reads were collected for each sample: 87.68% of the sequences could mapped to the human genome, and 66.70% of sequence mapped to known human genes.  A total of 17,446 ± 220 genes were expressed during the course of differentiation.  1024 transcription factors (TF) and genes encoding TF binding proteins were detected during the course of differentiation were expressed during the course of KC differentiation. Overall design: Foreskin normal human keratinocytes were differentiated in vitro by increasing Ca2+ concentration in culture media from 0.06mM to 1.3 mM.  Undifferentiated cells and cells under differentiation for 24 hrs, 48hrs, 72 hours, 96 hours and 120 hours were harvested for total RNA extraction.  RNA sequencing libraries were made using eukaryotic long non-coding RNA sequencing library construction protocol.  RNA libraries were deep sequenced by 100bp paired-reads on Illumina His-seq 2000.	Co-expression
SRP063978	Gene expression analysis of BRD4 knockdown in HT-29 and HCT116 cells	RNAseq is performed (50bp single end reads) on HT-29 and HCT-116 cell lines utilizing two independent shRNAs against BRD4 and a non-targeting control shRNA (NTC) Overall design: Examination of transcriptomic changes after knockdown of BRD4	Co-expression
SRP063980	Gene expression analysis following JQ1 treatments in colon cancer lines	RNAseq is performed (50bp single end reads) on SW480, HT-29, HCT-15, HCT-116, COLO 205, and COLO 320 cell lines after DMSO or JQ1 treatment Overall design: Examination of transcriptomic changes after JQ1 treatment	Co-expression
SRP063998	4sUDRB-seq of human PA1 cells, undifferentiated H9 cells and H9 differentiated FB neurons	We have optimized the metabolic tagging of newly transcribed RNAs by 4-thiouridine (4sU) to identify newly-transcribed (nascent) circRNAs from human PA1 cells, undifferentiated H9 cells and H9 differentiated FB neurons. Overall design: Ribo-4sUDRB-seq for characterizing nascent circRNA biogenesis.	Co-expression
SRP064121	Histone Demethylase-Assisted Somatic Cell Nuclear Transfer  Facilitates Derivation of Human Pluripotent Stem Cells	The extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing derivation of NTESCs from all oocyte donors tested using adult AMD patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine. Overall design: Here we perform RNA-seq based transcriptome profiling in human Donor (fibroblast cells), in vitro fertilized embryos at 8-cell stages (IVF_8Cell), somatic cell nuclear transfer embryos at 8-cell stages (SCNT_8Cell), SCNT assisted by KDM4A 8-cell embryos (SCNT_KDM4A_8Cell). Besides, we also perform RNA-seq in Control human ES cells (CTR_hES) and SCNT assisted by KDM4A derived human ES cells (NTK) with duplicates.Â	Co-expression
SRP064131	FOXM1 Cistrome Predicts Breast Cancer Metastatic Outcome Better Than FOXM1 Expression Levels or Tumor Proliferation Index [RNA-Seq]	FOXM1 is a key transcription factor regulating cell cycle progression, DNA damage response, and a host of other hallmark cancer features, but the role of the FOXM1 cistrome in driving estrogen receptor-positive (ER+) vs. ER- breast cancer clinical outcomes remains undefined. Overall design: Chromatin immunoprecipitation sequencing (ChIP-Seq) coupled with RNA sequencing (RNA-Seq) analyses was used to identify FOXM1 target genes in breast cancer cells (MCF-7) where FOXM1 expression was either induced by cell proliferation or repressed by p53 upregulation.	Co-expression
SRP064138	Homo sapiens Raw sequence reads	RNA-seq of liver samples from biliary atresia patients and controls	Co-expression
SRP064149	Homo sapiens Transcriptome or Gene expression	The goal of the study is to identify transcriptional differences between human induced motor neurons with 2, 1, or 0 full length copies of C9ORF72.	Co-expression
SRP064187	Redifferentiation of expanded human islet ß cells by inhibition of ARX	We applied RNA-seq analysis to human islet cells, received from 3 independent donors, treated with either redifferentiation cocktail + ARX shRNA, or redifferentiation cocktail + control shRNA or left untreated. Overall design: Examination of the effect of ARX inhibition on redifferentiation of ß-cell-derived (BCD) cells	Co-expression
SRP064207	The whole transcriptome analysis in a replicative senescence model.	RNA-Seq was performed to screen transcripts in whole lyastes or mitoplast fraction prepared from young and senescent WI-38 human fibroblast Overall design: A whole or mitoplast RNA was extracted from both young and senescent WI-38 cells, and used for RNA-Seq.	Co-expression
SRP064217	Identification of Resistance Genes to BRAF Inhibitor in Melanoma by piggyBac Transposon Activation Mutagenesis Screen	Genotype directed anti-cancer therapies such BRAF inhibitor in BRAF mutant melanoma can show remarkable clinical efficacy but resistance limits their benefit. We show that a transposon activation screen efficiently identifies resistance genes to BRAF and captures a number of previously uncharacterized resistance mechanisms, including an E3 ubiquitin ligase NEDD4L and the Hippo pathway effector WWTR1 (TAZ). Resistance can be reversed by combining BRAF inhibition with tyrosine kinase inhibitors as observed previously for other resistance genes. Moreover, an integrative analysis of several gain- and loss-of-function genetic screens performed in the same context reveals smaller functional diversity of resistance mechanisms to MAPK inhibition than suggested by the broad range of resistance genes identified, implying common therapeutic strategies. Overall design: A375 cells with lentiviral vector controls or WWTR1 cDNA plasmid.	Co-expression
SRP064222	The bromodomain protein BRD4 regulates splicing during heat shock	During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4''s role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors. Overall design: WI38 cells have been treated by heatshock and anti BRD4 siRNA and combination.	Co-expression
SRP064258	Modulation of Indoleamine 2, 3-dioxygenase 1 Expression by Activated Human T cells in Breast Cancer Cells is Controlled by DNA Promoter Methylation	Tumor infiltrating lymphocytes (TILs) play a critical role in modulating the immunoediting features in certain malignancies like triple negative breast cancer (TNBC). Nevertheless, much is still unknown concerning the specific responses of tumors when challenged by lymphocyte infiltration.  Based on this void, we conducted a immuno-phenotype comparison using mRNA sequencing between the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were co-cultured with activated human T-cells. We found that, though the cytokine-induced immune signature of the two cell lines was similar, MDA-MD-231 cells were able to transcribe IDO1 at a significantly higher level than MCF7 cells. Though no differences occurred in upstream JAK/STAT1 signaling or IDO1 mRNA stability between the two cell lines, stimulation with IFN? was able to differentially induce IDO protein expression and enzymatic activity in ER- cell lines compared to ER+ cell lines. Further experiments show that 5-aza-deoxycytidine treatment was able to reverse suppression of IDO1 expression in MCF7 cells, suggesting DNA methylation as a potential determinant in IDO1 induction. By analyzing TCGA breast cancer datasets, we discovered subtype-specific mRNA and promoter methylation differences in IDO1, with TNBC/basal subtypes exhibiting lower methylation/higher expression and ER+/luminal subtypes exhibiting higher methylation/lower expression. We confirmed this trend of IDO1 methylation by bisulfite pyrosequencing breast cancer cell lines and an independent cohort of primary breast tumors. Taken together, these findings suggest that IDO1 methylation regulates anti-immune responses in breast cancer subtypes and could be used as a predictive biomarker for IDO inhibitor-based immunotherapy. Overall design: To determine the immunomodulatory effects of cytokines secreted by activated human T-cells on breast cancer cells, we performed RNAseq analysis in MCF7 and MDA-MB-231 cells, after co-culturing them with normal PBMCs activated with anti-CD3/CD28 antibodies in a contact-independent manner. MDA-MB-231 or MCF7 cells were co-cultured with PBMCs alone or the conditioned-media or a combination of both for 24 hrs, and then total RNA was harvest for RNA-seq analysis.	Co-expression
SRP064259	The Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance (RNASeq)	Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations, translocations, and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole genome shRNA “dropout screens” on 77 breast cancer cell lines. Using a new hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify novel vulnerabilities in breast cancer, including new candidate “drivers,” and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, novel effects of existing anti-cancer drugs, and new opportunities for combination therapy.  Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer, and PIK3CA mutations as a resistance determinant for BET-inhibitors. Additional formatted data can be found at http://neellab.github.io/bfg/. Code and tutorials for the siMEM algorithm can be found at http://neellab.github.io/simem/. Overall design: RNA-Seq expression profiling of 82 breast cancer cell lines without replicates or control samples	Co-expression
SRP064264	Differentiation of human neural progenitor cells	The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. These cells were collected at two time-points of differentiation (24 h and 72h post transfection with an empty pIRES2-AcGFP vector).	Co-expression
SRP064305	Genes regulated by TAZ in a lung fibroblast cell line	To investigate the roles of TAZ in lung fibroblasts, we compared the expression profiles of a lung fibroblast cell line, HFL-1, transfected with control siRNA and siTAZ. Overall design: We collected RNA from HFL-1 cells transfected with control siRNA and siTAZ. Two kinds of TAZ siRNAs (siTAZ #1 and siTAZ #2) were used. Two biological replicates (rep1 and rep2) were used for each condition.	Co-expression
SRP064313	Complementary Post Transcriptional Regulatory Information is Detected by PUNCH-P and Ribosome Profiling	Two novel approaches were recently suggested for genome-wide identification of protein aspects synthesized at a given time. Ribo-Seq is based on sequencing all the ribosome protected mRNA fragments in a cell, while PUNCH-P is based on mass-spectrometric analysis of only newly synthesized proteins. Here we describe the first Ribo-Seq/PUNCH-P comparison via the analysis of mammalian cells during the cell-cycle for detecting relevant differentially expressed genes between G1 and M phase. Our analyses suggest that the two approaches significantly overlap with each other. However, we demonstrate that there are biologically meaningful proteins/genes that can be detected to be post-transcriptionally regulated during the mammalian cell cycle only by each of the approaches, or their consolidation. Such gene sets are enriched with proteins known to be related to intra-cellular signalling pathways such as central cell cycle processes, central gene expression regulation processes, processes related to chromosome segregation, DNA damage, and replication, that are post-transcriptionally regulated during the mammalian cell cycle. Moreover, we show that combining the approaches better predicts steady state changes in protein abundance. The results reported here support the conjecture that for gaining a full post-transcriptional regulation picture one should integrate the two approaches. Overall design: Two Ribo-Seq experiments, which included parallel RNA-Seq, one with 3 replicates, and the other with one replicate, totalling 4 technical replicates for the G1 and M phases of the cell cycle, respectively (totalling 16 samples), were performed.	Co-expression
SRP064316	Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood	Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. Overall design: Sequencing of blood RNA from five healthy individuals (biological replicates) plus technical replicate of one sample and detection of circRNAs.	Co-expression
SRP064317	Expression data for KDM1B knockdown in Glioma-Initiating Cells (GICs)	Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs'' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities. Overall design: We used RNA-Sequencing to detail the global change of gene expression in GICs with knockdown of KDM1B, and identified de-regulated genes and pathways downstream of KDM1B. CD133+ D456MG GICs were infected with non-targeting control and shRNA of KDM1B. Then RNA was extracted and gene expression was profiled by RNA-Seq.	Co-expression
SRP064321	Illumina Human Polycystic Liver Disease and Normal Biliary Stem Cell RNAseq	Background & aims: Polycystic liver disease (PLD) is an autosomal dominantly inherited disorder caused by mutations in genes such as PRKCSH and SEC63. It has been thought that cysts develop from biliary progenitor cells due to loss-of-heterozygosity (LOH), leading to aberrant proliferation or defects in differentiation. Cyst expansion can be suppressed by somatostatin analogues such as lanreotide. There is no human in vitro model available that truly recapitulates polycystic liver disease. We hypothesize that PLD progenitors can form bipotent liver organoids that carry key features of cyst development. To find gene expression differences between Human Polycystic Liver Disease and Normal Biliary Stem Cells. Methods: Cells from normal biliary duct (n=6), cyst biliary epithelium (n=60) and cyst fluid (n=31) were isolated and placed under conditions suitable for expansion of human adult liver stem cells. We analyzed genetic LOH, gene expression, differentiation capacity, response to lanreotide and cilium formation of these organoids. Results:  Cholangiocytes from cyst biliary epithelium (47/60) and cyst fluid (9/31) proved capable of expanding as bipotent liver organoids. Multiple cyst organoids displayed LOH surrounding PRKCSH or SEC63 regions. Organoids formed cilia when proliferation was inhibited. Neither hepatocyte nor biliary differentiation of PLD organoids was impaired. RNAseq revealed no significantly dysregulated pathway in PLD organoids. Lanreotide significantly decreased expansion of liver organoids in comparison to negative control (197% ± 46% versus 547% ± 28%; p: 0.038). Conclusion & discussion: Biliary progenitor cells from patient cyst epithelium and fluid can expand into liver organoids. They recapitulate key characteristics of PLD, and are a promising human in vitro model for research, diagnostics and treatment of polycystic liver diseases and cholangiociliopathies. Overall design: 8 polycystic liver disease samples versus 4 control samples RADBOUDUMC	Co-expression
SRP064329	Depletion of mitochondrial genome on gene expression patterns in human glioblastoma and multiple myeloma tumours	RNA-seq on both undepleted and mtDNA-depleted HSR-GBM1 and U266 cells and tumours	Co-expression
SRP064353	RNA-Seq data for AKT, BAD, ERBB2, IGF1R, RAF1 and ERK1 over-expressed samples with twelve green fluorescent protein control samples using human mammary epithelial cells	The goal was to capture the transcriptional activity due to over-expression of AKT, BAD, ERBB2, IGF1R, RAF1 and ERK1 genes.Over-expressions were validated using Western Blots. Illumina RNA-Seq technology was used to capture the downstream transcriptional activity. Reads were 101 base pairs long and single ended. An R open source package “Rsubread” was used to align and quantify the read using UCSC hg19 annotation. The integer-based gene counts were later normalized in TPM . Overall design: Profiles of gene expression, downstream of  AKT, BAD, ERBB2, IGF1R, RAF1 and ERK over-expression, were generated in cells derived from breast and used to generate a gene-expression signatures.	Co-expression
SRP064356	Comparative analysis of Rtf1- and PAF1C-regulated genes	Paf1 and Ski8 were selected as representative subunits of the Paf1 complex (PAF1C), and RNA-seq analysis was performed in triplicate to compare the genes affected by Paf1, Ski8, and Rtf1 knockdown in HeLa cells. Overall design: Total RNA was harvested from control HeLa and Ski8 knockdown cells at day 4 and from Rtf1 or Paf1 knockdown cells at day 7 and was subjected to RNA-seq in triplicates.	Co-expression
SRP064378	TGIRT-Seq profiling of human plasma nucleic acids	RNA-Seq datasets for human plasma RNAs obtained by using thermostable group II intron reverse transcriptase	Co-expression
SRP064391	Development of Pathway Preferential Estrogens Affording Beneficial Metabolic and Vascular Actions without Reproductive Tissue Stimulation in Mice	There is great medical need for estrogens having favorable pharmacological profiles, supporting desirable activities for menopausal women such as metabolic and vascular protection but lacking stimulatory activities on the breast or uterus. Here, we report the development of structurally novel estrogens with favorable target tissue-selective estrogenic activity. Through a process of structural alteration of the hormone estradiol that preserves essential chemical and physical features of estradiol but greatly moderates its binding affinity for the estrogen receptors (ERs), we obtained Pathway Preferential Estrogens (PaPEs) capable of having interaction with ER that is sufficient to activate the extranuclear-initiated signaling pathway preferentially over the direct nuclear-initiated pathway. PaPE modulate a pattern of gene regulation and cellular and biological processes that result in essentially no stimulation of reproductive and mammary tissues and breast cancer cells, but have a favorable pattern of activity on metabolic tissues and the vasculature. The structural permutation process represents a novel approach to govern the balance in utilization of extranuclear vs. nuclear pathways of ER action to obtain tissue-selective/non-nuclear pathway-preferential estrogens, which should prove to be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily. Overall design: 24 samples; inhibitor and time course experiments	Co-expression
SRP064410	Canonical poly(A) polymerase activity promotes the decay of a wide variety of mammalian nuclear RNAs	The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 stimulates hyperadenylation by poly(A) polymerase, and this activity is thought to be required for decay. Here, we inactivated hyperadenylation by two distinct mechanisms and examined changes in gene expression in HEK293 cells by RNAseq. We observed the upregulation of various ncRNAs, including snoRNA host genes, primary miRNA transcripts, and upstream antisense RNAs, confirming that hyperadenylation is broadly required for the degradation of PABPN1-targets. In addition, we found that mRNAs with retained introns are susceptible to PABPN1 and PAPa/?-mediated decay (PPD). Transcripts are targeted for degradation due to inefficient export, which is a consequence of reduced intron number or incomplete splicing. We conclude that PPD is an important mammalian nuclear RNA decay pathway for the removal of poorly spliced and nuclear-retained transcripts. Overall design: Poly(A)+ RNA from HEK293 cells was analyzed by next generation sequencing following depletion of PAPa and PAP? or expression of a dominant negative allele of PABPN1 (LALA) designed to inhibit polyadenylation. For each condition, we collected both total RNA and a nuclear-enriched sample. Each sample was collected in duplicate.	Co-expression
SRP064418	Effects of NSD2 depletion on gene expression and H3K36me2 in a lung cancer cell line	The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. Co-treatment with MEK and BRD4 inhibitors causes co-operative inhibitory responses on cell growth. While these inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition complements their action by affecting the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs. Overall design: H1299 cells were transduced with doxycycline (dox) inducible shRNAs (sh3 or sh5) againts NSD2 and with non target shRNA (shNT). Changes in gene expression (RNA-seq) and H3K36me2 (ChIP-seq) caused by depletion of NSD2 and indicated treatments were assessed. Two replicates (Rep) for RNA-seq and three replicates for ChIP-seq were included.	Co-expression
SRP064431	Gene expression analysis of human hepatocellular cancers	Gene expression profiling was carried out in 4 matched human hepatocellular cancer samples/normal liver smapls, and 4 human hepatocellular cancer samples to characterize the molecular mechanisms relevant to the etiology of human hepatocellular cancer development. Overall design: Whole-transcriptome RNA sequencing of the 4 matched human hepatocellular cancer samples/normal liver samples, and 4  human hepatocellular cancer samples.	Co-expression
SRP064454	RNA-Seq of human astrocytes	Astrocytes were purified from fetal and adult human brain tissue using an immunopanning method with the HepaCAM antibody. Samples were taken from otherwise 'healthy' pieces of tissue, unless otherwise specified. Overall design: 6 fetal astrocyte samples, 12 adult astrocyte samples, 8 GBM or sclerotic hippocampal samples, 4 whole human cortex samples, 4 adult mouse astrocyte samples, and 11 human samples of other purified CNS cell types	Co-expression
SRP064457	Transcriptome profiling of HEK 293T cells depleted of endogenous miRNAs	To assess the impact of AdV-VP55 mediated degredation of host miRNAs on the cellular transcriptome. Overall design: mRNA profiles of HEK 293T cells treated with type 5 Adeno vectors expressing either GFP or GFP-VP55 for 24 hours	Co-expression
SRP064464	Single-cell transcriptomics reveals unique features of human pancreatic islet cell subtypes	We report the single-cell RNA-seq based identification of 6 known human islet cell types (alpha cells, beta cells, delta cells, pp cells, acinar cells and duct cells) based on the expression of known marker genes. We further assess cell type specific gene expression and suggest novel marker genes for several cell types. Overall design: Transcriptional dissection of human pancreatic islets of one donor using single-cell RNA-seq	Co-expression
SRP064474	Patient-derived xenograft platform for metastatic melanoma: RNA sequencing of 4 melanoma PDX samples	The therapeutic landscape of melanoma is rapidly changing. While targeted inhibitors yield significant responses, their clinical benefit is often limited by the early onset of drug resistance. This motivates the pursuit to establish more durable clinical responses, by developing combinatorial therapies. But while potential new combinatorial targets steadily increase in numbers, they cannot possibly all be tested in patients. Similarly, while genetically engineered mouse melanoma models have great merit, they do not capture the enormous genetic diversity and heterogeneity typical in human melanoma. Furthermore, whereas in vitro studies have many advantages, they lack the presence of micro-environmental factors, which can have a profound impact on tumor progression and therapy response. This prompted us to develop an in vivo model for human melanoma that allows for studying the dynamics of tumor progression and drug response, with concurrent evaluation and optimization of new treatment regimens. Here, we present a collection of patient-derived xenografts (PDX), derived from BRAFV600E, NRASQ61 or BRAFWT/NRASWT melanoma metastases. The BRAFV600E PDX melanomas were acquired both prior to treatment with the BRAF inhibitor vemurafenib and after resistance had occurred, including six matched pairs. We find that PDX resemble their human donors’ melanomas regarding biomarkers, chromosomal aberrations, RNA expression profiles, mutational spectrum and targeted drug resistance patterns. Mutations, previously identified to cause resistance to BRAF inhibitors, are captured in PDX derived from resistant melanomThis melanoma PDX platform represents a comprehensive public resource to study both fundamental and translational aspects of melanoma progression and treatment in a physiologically relevant setting. Overall design: RNA sequencing of 4 melanoma PDX samples to validate the effects of a structural variant on BRAF mRNA in BRAF inhibitor resistant melanoma.	Co-expression
SRP064475	Homo sapiens isolate:WA09 Raw sequence reads	Two human pluripotent stem cell lines (hPSC) were generated from the human embryonic stem cell line WA09. These independent hPSC lines were designated Line A and Line B for the purpose of this study. Line A and Line B hPSC cells were each cultured in 2D (monolayer) or 3D (spheroid culture) conditions (experiment 1) and this procedure was repeated in a second independent experiment (experiment 2). RNA was isolated from these culture conditions (total of 8 samples) and RNA transcripts were sequenced as described in the publication accompanying this data.	Co-expression
SRP064478	Illumina Total Stranded RNA sequencing reads from 15 postmortem cervical spinal sections (7 ALS and 8 healthy controls)	We isolated total RNA using postmortem cervical spinal section homogenates from 7 sporadic ALS and 8 neurologically healthy control samples. We next prepared individual Illumina Total Stranded RNA-sequencing libraries for each sample. We sequenced each library with >50 million 2X150 sequencing reads on the NextSeq500. Our goal was to generate gene expression data for use in systems biology analyses to elucidate differences between the sALS and neurologically healthy control groups that may contribute to disease pathology.	Co-expression
SRP064515	Widespread shortening of 3' untranslated regions and increased exon inclusion characterize the human macrophage response to infection [mRNA]	Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. However, post-transcriptional mechanisms involved in mRNA processing have been poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Overall design: Transcriptomic profiles of 198 infected (Listeria and Salmonella) and non-infected samples at multiple time points.	Co-expression
SRP064527	Three-dimensional disorganisation of the cancer genome occurs coincident with long range genetic and epigenetic alterations [RNA-seq]	A three-dimensional chromatin state underpins the structural and functional basis of the genome by bringing regulatory elements and genes into close spatial proximity to ensure proper, cell-type specific gene expression profiles. Here, we perform HiC chromosome conformation, ChIP-seq and RNA-seq to investigate how the three-dimensional organization of the cancer genome is disrupted in the context of epigenetic remodelling and atypical gene expression programs. Overall design: Hi-C, ChIP-seq and RNA-seq were conducted in three human prostate cell lines: normal prostate epithelial cells (PrEC) and prostate cancer cells (PC3 and LNCaP).	Co-expression
SRP064538	Transcriptome sequencing of progenitor and differentiated human epidermal layers	The goal of the study is to identify genes whose expression are enriched in the progenitor or differentiated layers of human skin, with an ultimate aim to find new molecular regulators of skin development and differentiation.	Co-expression
SRP064547	Homo sapiens Transcriptome or Gene expression	Transcriptome of CALML5-depleted human organotypic epidermis	Co-expression
SRP064562	Synergistic gene expression signature observed in TK6 cells upon co-exposure to UVC-irradiation and protein kinase C-activating tumor promoters, a dosage study (study 2/2)	The purpose of this study, including this dosage series and another  time course series, was to establish gene expression signatures representing the interaction of pathways deregulated by tumor promoting agents and pathways induced by DNA damage.  Human lymphoblastoid TK6 cells were pretreated with the protein kinase C activating tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and exposed to UVC-irradiation.  The time and dose-responsive effects of the co-treatment were captured with RNA-sequencing (RNA-seq) in two separate experiments.  TK6 cells exposed to both TPA and UVC had significantly more genes differentially regulated than the theoretical sum of genes induced by either stress alone, thus indicating a synergistic effect on global gene expression patterns.  Further analysis revealed that TPA+UVC co-exposure caused synergistic perturbation of specific genes associated with p53, AP-1 and inflammatory pathways important in carcinogenesis.  The 17 gene signature derived from this model was confirmed with other PKC-activating tumor promoters including phorbol-12,13-dibutyrate, sapintoxin D, mezerein, (-)-Indolactam V and resiniferonol 9,13,14-ortho-phenylacetate (ROPA) with quantitative real-time PCR (QPCR).  Here we show a novel gene signature that may represent a synergistic interaction in the tumor microenvironment that is relevant to the mechanisms of chemical induced tumor promotion. Overall design: mRNA profiles of TK6 cells treated with tumor promoting agent at different dose, co-exposed to UVC	Co-expression
SRP064610	Functional characterization of RNA-binding protein IMP2 in primary Glioma cell lines [HTS]	Cancer stem cells (CSC) dictate tumor cell heterogeneity in diverse cancer types and arise, in part, from microRNA (miRNA)-dependent alteration of gene expression. The let-7 miRNA family induces differentiation by silencing genes that maintain stemness and is repressed by the RNA-binding proteins LIN28A/B, which preserve stemness in normal embryonic and malignant cells. Here, we observed that LIN28A/B is undetectable in glioma stem cells (GSC) whereas let-7 and, paradoxically, their target genes are highly expressed. Using photoactivatable-ribonucloside-enchanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) protects let-7 target genes from silencing and provides a mechanistically distinct alternative to LIN28A/B toward both GSC and neural stem cell specification. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism by which it supports GSC maintenance. Overall design: We characterized RNA binding sites of IMP2 in MGG8 Glioma cancer stem cells and differentiated cells. To profile changes upon IMP2 modulation we performed RNA-Seq in MGG4 and 8 cells in both states upon IMP2 knockdown and overexpression. Furthermore we investigated changes during differentiation from cancer stem cells to adherent cells in 6 and 7 RNA-Seq datasets in MGG4 and 8 cells.	Co-expression
SRP064625	Newly constructed network models of different WNT signaling cascades applied to breast cancer expression data	RNA-Seq profiling of MCF-7 and MDA-MB-231. We profiled RNA expression in the estrogen-receptor-positive (ER+) MCF-7 and the triple-negative MDA-MB-231 breast cancer cells. The objective was to find genes differentially expressed between these cell lines as potential drivers of invasiveness of the triple-negative MDA-MB-231. We further utilized the identified differential genes to validate expression-responsive module of non-canonical Wnt signaling pathway. Overall design: 2 biological replicates of MCF-7 and 3 biological replicates of MDA-MB-231	Co-expression
SRP064735	Limiting cholesterol biosynthetic flux engages type I IFN signaling in a STING-dependent manner	Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling rapidly shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol, and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. Overall design: shRNA to SREBF1 (shSREBP1) or SREBF2 (shSREBP2) were stably introduced via 3rd generation lentivirus into human THP1 monocytic cells under puromycin selection. Non-targeting shRNA scramble was used for a control (shControl). shControl, shSREBP1 and shSREBP2 modified cell types were analyzed by RNA-seq in duplicate.	Co-expression
SRP064738	Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome	N1-Methyladenosine (m1A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topol- ogy and dynamics in mRNA. Here, we show that m1A is prevalent in Homo sapiens mRNA, which shows an m1A/A ratio of ~0.02%. We develop the m1A-ID-seq technique, based on m1A immunoprecipitation and the inherent ability of m1A to stall reverse tran- scription, as a means for transcriptome-wide m1A profiling. m1A-ID-seq identifies 901 m1A peaks (from 600 genes) in mRNA and noncoding RNA and reveals a prominent feature, enrichment in the 5'' untranslated region of mRNA transcripts, that is dis- tinct from the pattern for N6-methyladenosine, the most abundant internal mammalian mRNA modification. Moreover, m1A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, we show that m1A methylation responds dynamically to stimuli, and we identify hundreds of stress-induced m1A sites. Collectively, our approaches allow comprehensive analysis of m1A modification and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m1A methylation. Overall design: Identification of m1A sites in human embryonic kidney cells. Comparisons of m1A profiles of wild type HEK293T with ALKBH3 knock out cell line reveals the ALKBH3 specific sites. Stress inducible m1A sites are also identified by comparing the profiles of untreated cells with stress treated cells.	Co-expression
SRP064747	RNA-seq of YB5 cells treated with epigenetic therapy	RNA-seq was performed after YB5 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples	Co-expression
SRP064761	A Primate lncRNA Mediates Notch Signaling During Neuronal Development by Sequestering miRNA [SHSY5Y cells]	Long non-coding RNAs (lncRNAs) are a diverse category of transcripts with poor conservation and have expanded greatly in primates, particularly in their brain. We identified a lncRNA, which has acquired 16 microRNA response elements (MREs) for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) gets expressed in neural progenitor cells and then declines in mature neurons. Binding and release of miR-143-3p, by LncND, can control the expression of Notch. Its expression is highest in radial glia cells in the ventricular and outer subventricular zones of human fetal brain. Down-regulation of LncND in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression and supported by RNA-seq analysis. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling in the expansion of the neural progenitor pool of primates and hence contributing to the rapid growth of the cerebral cortex. Overall design: SHSY5Y cells treated either with miR-143-3p mimic or 100 nM of siRNA specific for LncND were sequenced on NextSeq500 platform. Scrambled siRNA or miRNA sequences were used as a negative control.	Co-expression
SRP064783	An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell	Toxoplasma gondii is an obligate intracellular Apicomplexan parasite capable of invading and surviving within nucleated cells in most warm-blooded animals. This remarkable task is achieved through the delivery of effector proteins from the parasite into the parasitophorous vacuole and host cell cytosol that rewire host cellular pathways, facilitating parasite evasion of the immune system. Here, we have identified a novel export pathway in Toxoplasma that involves cleavage of effector proteins by the Golgi-resident aspartyl protease 5 (ASP5) prior to translocation into the host cell. We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has some similarity to the PEXEL motif of Plasmodium parasites. We show that ASP5 can mature effectors at both the N- and C-terminal ends of proteins and is also required for the trafficking of proteins without this motif. Furthermore, we show that ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the parasitophorous vacuole membrane. Global assessment of host gene expression following infection reveals that ASP5-dependent pathways influence thousands of the transcriptional changes that Toxoplasma imparts on its host cell. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell. Overall design: Three groups of human foreskin fibroblasts are compared. Each group has 3 replicates giving a total of 9 samples. The first group of samples are infected with wild type (GRA16HA) Toxoplasma gondii, the second group with Asp5 knock-out Toxoplasma gondii, and the final group remain uninfected. All fibroblasts are generated from one donor sample.	Co-expression
SRP064802	Genome-wide MAF1-dependent regulation of RNA polymerase III transcription [RNA-Seq]	In higher eukaryotes, an important mechanism to tune translation in different tissues and conditions is mTORC1-dependent regulation of tRNAs transcription by RNA polymerase III (Pol III), as the relative amount of tRNAs tightly coordinates with the translational needs of the cell. mTORC1 contributes to regulate protein synthesis through its direct substrate MAF1, which functions as a negative regulator of Pol III transcription in response to stimuli such as serum starvation or rapamycin treatment. Here, we applied ChIP-seq to examine the Pol III occupancy profile in human fibroblasts and report evidence of a genome wide, MAF1-dependent coordinated response to favorable or stress growth conditions. Strikingly, while a set of genes is extremely responsive in terms of Pol III binding, other genes are mostly unperturbed, yet associated with transcriptionally engaged polymerases as revealed by nascent EU-labeled RNA-seq (neuRNA-seq). As shown by DamIP-seq, the responsiveness of a subset of genes is tightly connected to the rapid and transient interaction of MAF1 with DNA-bound Pol III. Overall design: We performed duplicate ChIP-seq experiments for the Rpc4 (POLR3D) subunit of RNA polymerase III in IMR90hTert cells grown in the presence of fetal bovine serum (FBS), serum starved (SS), serum starved and treated with insulin (SS+I), serum starved and treated with insulin and rapamycin (SS+R+I). Additional ChIP-seq profiles were generated in cells treated with MAF1 siRNAs and serum starved. MAF1 binding was addressed by DamIP-seq, using two replicates per clone of IMR90hTert cells expressing HA-tagged MAF1-DamK9A (2 different clones) or EGFP-DamK9A (2 different clones). To monitor dynamic transcription profiles we did neusRNA-seq in IMR90hTert cells EU-labeled or mock (DMSO)-labeled. For both DamIP-seq and neusRNA-seq, cells were either unperturbed or serum starved.	Co-expression
SRP064809	Dynamics of the human and viral m6A RNA methylomes during HIV-1 infection of T cells	Significance of RNA methylation in the context of HIV-1 infection in human T cells Overall design: MeRIP-Seq of Control and HIV-infected MT4 T-Cells	Co-expression
SRP064820	Quadruplex ligand Tetra-Pt(bpy) Induces the Death of Human ALT Cancer Cells by Inhibiting Homologue Recombination-Mediated Telomere Elongation	The RNA-seq results reveal Tetra-Pt(bpy) has no effect on gene expression. Overall design: Examination of the gene expression of the following cells: MRC5-untreated and Tetra-Pt(bpy)-treated HeLa-untreated and Tetra-Pt(bpy)-treated U2OS-untreated and Tetra-Pt(bpy)-treated	Co-expression
SRP064825	Genes regulated by dimethyl-2-ketoglutarate (DKG) in breast cancer cells	We report the gene expression profile of DKG-treated MDA-MB-231 cells. Overall design: 2 replicates of parental MDA-MB-231 cells and MDA-MB-231 cells treated with DKG (10 mM, 4-days) were subjected to RNA-seq	Co-expression
SRP064832	RNA-seq of MCF7 cells treated with epigenetic therapy	RNA-seq was performed after MCF7 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples	Co-expression
SRP064847	RNA-seq transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs)	Advances in sequencing-based genomic profiling present a new challenge of explaining how changes in DNA/RNA are translated into proteins linking genotypes to phenotypes. The developing erythroid cells require highly coordinated gene expression and metabolism, and serve as a unique model in dissecting regulatory events in development and disease. Here we compare the proteomic and transcriptomic changes in human hematopoietic stem/progenitor cells and lineage-committed erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Two principal mitochondrial factors TFAM and PHB2 are tightly regulated at the protein level and indispensable for mitochondria and erythropoiesis. mTORC1 signaling is progressively enhanced to promote translation of mitochondrial proteins during erythroid specification. Genetic and pharmacological perturbation of mTORC1 or mitochondria impairs erythropoiesis. Our studies suggest a new mechanism for regulation of mitochondrial biogenesis through mTORC1-mediated protein translation, and may have direct relevance to the hematological defects associated with mitochondrial diseases and aging. Overall design: Transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs) by RNA-seq analysis.	Co-expression
SRP064863	RNA-seq of Human lung cell line A549 infected with Adenovirus	RNA-seq of Human lung cell line A549 alone as control, or infected with human adenovirus serotype 6, or infected with human adenovirus serotoype 26	Co-expression
SRP064894	Homo sapiens Raw sequence reads	High-throughput sequencing of RNA (RNA-Seq) in human cancer shows remarkable potential to simultaneously identify expression levels of protein-coding genes and long non-coding RNAs (lncRNAs). We performed RNA-Seq to investigate expression level of lncRNAs and protein-coding genes in 30 esophageal samples, including 15 esophageal squamous cell carcinoma (ESCC) tissue samples and 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE (for unsupervised random walk with each dysregulated lncRNA/PCG), to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. By this method, multiple known cancer and novel potentially functional lncRNAs were effectively identified. Quantitative reverse-transcription PCR was performed to confirm the lncRNA expression level of eight novel functional lncRNAs in an additional 120 paired ESCC patient samples. Finally, we characterized lncRNA625 as a novel ESCC regulator of cell proliferation, invasion and migration. Moreover, we identified E1A-binding protein p300 (EP300) as playing a key role in executing lncRNA625-induced transcriptional responses. These findings establish the utility of integrative bioinformatics analyses of RNA-Seq to identify cancer-associated functional lncRNAs.	Co-expression
SRP064952	Transcriptomics of adult human small bowel grafts	Objective: the objective of this work was to determine different gene expression patterns in small bowel grafts biopsies with “minimal changes” histology that could identify patients with high rejection risk Methods: 24 samples (17 stable and 7 non stable grafts) from 8 adult patients with small bowel transplantation were included for RNA-Sequencing.Total RNA extracted from intestinal biopsies was used with the TruSeq RNA Sample Preparation v2 Kit to construct index-tagged cDNA libraries. Libraries were sequenced on the Genome Analyzer IIx following the standard RNA sequencing protocol with the TruSeq SBS Kit v5. Fastq files containing reads for each library were extracted and demultiplexed using Casava v1.8.2 pipeline. Sequencing adapter contaminations were removed from reads using Cutadapt software v1.6 and the resulting reads were aligned to the reference human genome (Ensembl gene-build GRCh37.75) using TopHat2 v2.0.13. Gene expression values were calculated as counts using HTSeq v0.6.1. Only genes with at least 1 count per million in all samples were considered for statistical analysis. Data were then normalized and differential expression tested using the R Bioconductor package edgeR. We selected all biopsies from 4 of the patients (18 biopsies, 11 stable and 7 non stable) as the discovery set. The other 6 biopsies from 4 patients (all stable) were used as the test set. Differences in the discovery set were tested by generalized linear model analysis,and results were considered significant when the Benjamini-Hochberg adjusted p-value was < 0,05. Results: We obtained 816 differentially expressed genes (DEGs) between stable and non stable biopsies in the discovery set: 369 upregulated and 447 downregulated in the non stable group. The classification and prediction with the Nearest Shrunken Centroids method identified 5 genes (ADH1C, CYP4F2, PDZK1, SLC39A4 and OPTN) from the 816 DEGs that could classify both groups with an error rate of 11% and classified correctly all samples from the test set. These results were confirmed by Supoprted Vector Machine (SVM), bagSVM and Random Forest methods, showing high accuracy, sensitivity and specificity. Conclusions: We identified 5 genes from the DEGs as possible biomarkers to classify patients with normal histology  that could be however in a higher risk of rejection. In this way, gene expression assays are powerful tools with high sensitivity that allow more accurate diagnosis. Overall design: The study included 24 samples from 8 adult patients with small bowel transplantation. Samples correspond to RNA extracted from intestinal biopsies obtained at different post-transplantation time. All biopsies have an histological diagnosis of "minimal changes" and they were classified in two groups according their immunological stability (stable and non stable). Stable group comprised biopsies of patients that never rejected and biopsies obtained at least 15 days after rejection if no other rejection episode occurred in at least the next six months. Non stable group included biopsies obtained between rejection episodes (separated less than six months) and also those biopsies collected within the 15 days before the first rejection episode.	Co-expression
SRP064956	mammalian cell-lines Transcriptome or Gene expression	Gene expression studies of two mammalian cell lines that display primary cilia. Primary cilia are microtubule-based organelles that are hubs for receiving and intergrating signalling cascades during embryonic development and in maintaining tissue homeostasis. Defects in the structure of function of cilia can cause a group of comparitively common human inherited conditions known as ciliopathies. The cell-lines that have been profiled are standard model systems in the ciliary biology field, and gene expression profiles are important to understand the processes of forming, maintaining and resorbing cilia.	Co-expression
SRP065022	Positional proteomics reveals differences in N-terminal proteoform stability	To understand the impact of alternative translation initiation on a proteome, we performed the first study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. Overall, we monitored the stability of 1,941 human N-terminal proteoforms, including 147 N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. Study design: ribosome profiling of lactimidomycin and cycloheximide treated human Jurkat T-lymphocytes	Co-expression
SRP065040	A Primate lncRNA Mediates Notch Signaling During Neuronal Development by Sequestering miRNA [single cell sequencing analysis]	Long non-coding RNAs (lncRNAs) are a diverse category of transcripts with poor conservation and have expanded greatly in primates, particularly in their brain. We identified a lncRNA, which has acquired 16 microRNA response elements (MREs) for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) gets expressed in neural progenitor cells and then declines in mature neurons. Binding and release of miR-143-3p, by LncND, can control the expression of Notch. Its expression is highest in radial glia cells in the ventricular and outer subventricular zones of human fetal brain. Down-regulation of LncND in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression and supported by RNA-seq analysis. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling in the expansion of the neural progenitor pool of primates and hence contributing to the rapid growth of the cerebral cortex. Overall design: Cerebral organoids were generated as in Lancaster et al. (Lancaster and Knoblich, 2014). Organoids were dissociated into single cells and captured on C1 Single-Cell Auto Prep Integrated Fluidic Circuit (IFC) (Fluidigm). The RNA extraction and amplification was performed on the chip as described by the manufacturer. We captured 68 single-cells on a C1 Single-Cell Auto Prep System (Fluidigm) and sequenced the RNA on a NextSeq500 System (Illumina) (Pollen et al., 2014). Out of 68 cells, we obtained 60 high quality cells.	Co-expression
SRP065114	Homo sapiens Raw sequence reads	Normoxic (21% O2) and hypoxic (1% O2, 24 hr) U87MG human glioblastoma cells were subjected to polysome fractionation. Total RNA were isolated from individual fractions by standard phenol/chloroform extraction and ethanol precipitation following proteinase K treatment. Equal volumes of individual fractions from four independent experiments were pooled to yield the monosome/oligosomes (MO) and polysome (P) samples.	Co-expression
SRP065146	Homo sapiens Raw sequence reads	RNA-seq of peripheral blood leucocyte samples from Immune Thrombocytopenia patients and controls	Co-expression
SRP065153	Homo sapiens Transcriptome or Gene expression	Several studies have shown that long non-coding RNAs (lncRNAs) may play anessential role in Epithelial-mesenchymal transition (EMT), which is an important step in tumor metastasis, however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alteration contributes to EMT progression regulation, we performed a whole-transcriptome strand-specific RNA deep sequencing of MCF10A induced EMT by TGF-ß. Deep sequencing results showed that the long RNA (>=200-nt) transcriptome of MCF10A was undergone a global changed in EMT, and this alteration was determined as early as 8h after being induced using TGF-ß. 8703 linear novel genes with ambiguous protein-coding potential were identified, 512 of which were further determined to be novel lncRNAs. After analyzing the expression of 5473 known and novel lncRNAs, as well as 2208 known and novel circRNAs during EMT, we found a large numbers of lncRNAs might be involved in the regulation of EMT. Intriguingly, we identified 216 gene clusters constituted by lncRNAs and/ornovel genes in “gene desert” region. The expressions of all genes in these clusters were changed concurrently during EMT, indicating that these clusters might play important role in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome in EMT and provides clues to the study of the molecular mechanism of EMT.	Co-expression
SRP065193	RNA sequencing of Formalin-Fixed, Paraffin-Embedded Specimens for Gene Expression Quantification and Data Mining	We compared the RNAseq data consistency between Ribo-Zero and RNase H kits Overall design: RNA libraries were prepared using both Ribo-Zero and RNase H kits on breast cancer FFPE specimens. We sequenced these libraries and compared their data consistencies.	Co-expression
SRP065194	Hydroxychloroquine inhibits responses to group A streptococcus in peripheral blood mononuclear cells	Immune responses to group A streptococcus in humans can lead to the development of acute rheumatic fever and rheumatic heart disease. Immune pathways that are activated by group A streptococcus are potential targets for inhibiting autoimmune responses to group A streptococcus. This experiment tests the impact of the drug hydroxychloroquine on immune responses to group A streptococcus in peripheral blood mononuclear cells Overall design: Peripheral blood mononuclear cells from three healthy participants were stimulated with rheumatogenic, heat-killed group A streptococcus for 24 hours, MOI 10. The effect of hydroxychloroquine (20 µM) (HCQ) was measured, both alone and in combination with group A streptococcus (GAS).	Co-expression
SRP065196	Global gene expression differences between blood- and lymphatic-specific human dermal microvascular endothelial cells	We performed high throughput RNA-sequencing on blood and lymphatic HMVECs to identify differences in gene expression between these two cell types that may provide insight into their respective differentiation and roles in angiogenesis and lymphangiogenesis. Overall design: RNA was isolated from blood-specific HMVEC and lymphatic-specific HMVEC cell lines 3 separate times each	Co-expression
SRP065202	The effect of Heterogeneous Transcription Start Sites (TSS) on the Translatome: Implications for the Mammalian Cellular Phenotype.	Sequencing of total RNA and polysomal RNA of two cell lines, MCF7 (tumoral) and MCF10A (non-tumoral) Overall design: Polysomal and total RNA was prepared from biological triplicates from the two cell lines.  For each biological triplicate sub-confluent cell monolyers were lysed to produce cytoplasmic extracts. Half of each extract was fractionated on a sucrose gradient and the polysomal fraction recovered. Polysomal-associated RNA was recovered by Trizol extraction. From the second half of each sample total cyoplasmic RNA was recovered (Trizol extraction).	Co-expression
SRP065204	mRNA-seq Analysis of Transcriptomes of the PC9R and PC9 cells	The goals of this study is to compare the whole genome transcriptome of gefitinib-resistant NSCLC cell line (PC9R) with its gefitinib-sensitive counterpart (PC9) using RNA-seq tecnology Methods: Genome-wide mRNA profiles of the PC9R and PC9 cells were generated by deep sequencing, using Illumina Hiseq2000. The sequence reads that passed quality filters were analyzed in the following steps: 1) RNA-seq reads were aligned to the hg19 genome assembly using TopHat (http://bioinformatics.oxfordjournals.org/content/25/9/1105.short) with the default parameters; 2) Expression index was generated using GFOLD V1.0.9 job count (http://bioinformatics.oxfordjournals.org/content/early/2012/08/23/bioinformatics.bts515); 3) Differential expression were calculated using GFOLD V1.0.9 job diff.  Gene expression was quantified in rpkm (reads per kilobase of exon per million mapped sequence reads); 4) GFOLD, a generalized fold change, was used to rank the differentially expressed genes from the RNA-seq data. The GFOLD value can be considered as a reliable log2-fold change when only a single biological replicate is available Results: We found that hundreds of genes were either down- or up-regulated in the PC9R cells compared with the PC9 cells. Specifically, 6% of the total detected genes (1487 genes) were up-regulated in the PC9R cells, with a GFOLD value over 1, and 5% of the total detected genes (1112 genes) were down-regulated, with a GFOLD value less than -1. Conclusions: Our study reveals the differentially expressed genes in gefitinib-resistant NSCLC cells comparing with the sensitive cells in a genome-wide scale. This results help to provide the novel insight into the gefitinib-resistant mechanism. Overall design: The genome-wdie transcriptome study of gefitinib-resistant NSCLC cells (PC9R) comparing with the sensitive cells (PC9) using mRNA-seq technology	Co-expression
SRP065206	BRD4 connects enhancer remodeling to senescence immune surveillance (RNA-seq)	Cellular senescence is a homeostatic program associated with tumor suppression, wound healing, and certain age related pathologies. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes, while at the same time activate an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program. Overall design: Analysis of RNA isolated from human fibroblasts (IMR90) in proliferating, quiescent or senescent (HrasV12) conditions upon knockdown of Brd4, p65, p53, p53/RB, p16/21 or Vehicle and JQ1 treatment	Co-expression
SRP065216	GEO accession GSE74246 is currently private and is scheduled to be released on Mar 01, 2016.	If GEO accession GSE74246 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP065219	Transcriptome response to 4h IL-1b stimulation of primary chondrocytes	Using RNA sequencing (Illumina Hi-Seq 2000 sequencer) we report the transcriptome profile of primary human chondrocytes isolated from patients with hip osteoarthritis (OA), and the transcriptome response of these cells to 4h stimulation with IL-1ß (1ng/ml).  In total, 983 long non-coding RNAs (lncRNAs) were identified, which included 642 intergenic lncRNAs (lincRNAs), 124 antisense and pseudogenes.  Less than 4% of the identified lncRNAs overlapped with putative eRNAs regions, and visual inspection showed that they were uni-directional and multi-exonic.  Upon  IL-1ß stimulation 499 protein-coding genes were differentially expressed, and 158 lncRNAs were differentially expressed, including 92 lincRNAs, 13 antisense and 18 psudogenes.  This study demonstrates that IL-1ß induces a rapid and widespread change in the transcriptome of the primary human OA chondrocyte. Overall design: RNA sequencing analysis of primary human chondrocytes isolated from n=3 patients with hip osteoarthritis, with and without 4h IL-1b (1ng/ml) stimulation	Co-expression
SRP065220	RNA-seq of YB5 and MCF7 treated with different doses of decitabine	RNA-seq was performed after YB5 cells were treated with 1uM decitabine, and MCF7 cells were treated with 100nM decitabine Overall design: Biological triplicates were performed for a total of 6 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples from GSE73966 for YB5, and GSE74036 for MCF7. These control samples have been re-accessioned here for convenient access to the entire study.	Co-expression
SRP065236	Transcriptome analysis of diverse cell types infected with human cytomegalovirus [RNA-Seq]	Comprehensive RNA sequencing and splicing-sensitive microarray analysis of three diverse cell types infected with human cytomegalovirus (HCMV), including primary fibroblasts (HFFs), endothelial cells (ECs), and neural progenitors (NPCs) derived from embryonic stem cells. This global analysis includes both host and viral gene expression measurements, and an in-depth assessment of alternative RNA processing events. Extended comparisons were conducted through RNA sequencing analysis of human herpes simplex virus (HSV)-2 and human immunodeficiency virus type 1 (HIV-1) infections. Overall design: Deep sequencing analysis component of the study. RNA-seq measurements of host and virus gene expression, and RNA processing events.	Co-expression
SRP065258	Assessment of ability of hTSLP to maintain primary CRLF2 B-ALL cells in a xenograft model in a state more similar to the parent leukemia	Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells. Overall design: Three different classes of samples were analyzed. 1) The primary leukemia sample without any culture or treatment 2) Xenograft samples (2) of the primary leukemia that were exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment and 3) Xenograft samples (2) of the primary leukemia that were NOT exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment.	Co-expression
SRP065260	RNAseq analysis of genes regulated by GDE2 in neuronal cells	We analyze differentially expressed genes in wild-type versus GDE2 knockdown neuroblastoma cells Overall design: Stable knockdown of GDE2 in Shep2 neuroblastoma cells, followed by mRNA expression profiling	Co-expression
SRP065273	Transcriptome organization of primate neocortical layers and its human-specific change	We developped the unsupervised sectioning coupled with RNA-seq to generate data to estimate the laminar transcriptome profiles for primate prefrontal cortex. Each cortical cube was cut into 17-18 sections (DS1) or 10 sections (DS2) which are horizontal to the cortical layers. RNA-seq was then applied to profile transcriptome in each section sample. With this data, we were able to estimate and compare the laminar transcriptome profiles in three primate species: human, chimpanzee and macaque, which also provided the power to identify the genes with human-specific laminar expression profile.	Co-expression
SRP065282	Ribosomal profiling in Cystic Fibrosis Bronchial Epithelial cells	We performed ribosome profiling in Cystic Fibrosis Bronchial Epithelial cells which data set is used to calcualte codon-specific ribosome occupancy using the approach described by Lareau et al. eLife 2014. Overall design: Ribosome profiling of cells at steady state. 3 biological replicates.	Co-expression
SRP065305	Overexpression of PHF8 promotes an EMT-related gene signature in MCF10A cells	PHF8 exerts distinct functions in different types of cancer. However, the mechanisms underlying its specific functions in each case remain obscure. To establish whether overexpression of PHF8 regulates the TGF-ß induced the epithelial-mesenchymal transition (EMT), we treated MCF10A-Mock (control) and MCF10A-PHF8wt (overexpressing wild-type PHF8) cells with TGF-ß1 for 0, 24, 48 and 72 hours and performed RNA-seq in biological duplicates. Our data indicated that EMT gene signatures were significantly enriched in MCF10A-PHF8 cells with TGF-ß1 treatment at all time points, strongly indicating that PHF8 overexpression induces a sustained EMT signaling program. Overall design: mRNA profiles of MCF10A-Mock (control) and MCF10A-PHF8 with TGF-ß1 treatment for 0, 24, 48 and 72 hours were generated by RNA-seq, in duplicate, using HiSeq2500 instrument.	Co-expression
SRP065310	Targets of ROR2 overexpression in MCF-7 cells revealed a differentially regulated module of non-canonical WNT signaling pathway	RNA-Seq profiling of estrogen-receptor-positive MCF-7 cell lines with different perturbations of non-canonical WNT signaling . The MCF-7 cells were either transfected with an empty vector (pcDNA) or with a ROR2 overexpression construct, in parallel with or without stimulation with recombinant WNT5A. The objective was to find expression-responsive targets of these perturbations as potential drivers of increased cell invasiveness. Overall design: Four conditions of MCF-7 cells each in 3 replicates:  1. empty vector (pcDNA),  2. empty vector (pcDNA) with WNT5A stimulation, 3. ROR2 overexpression construct, 4. ROR2 overexpression construct with WNT5A stimulation	Co-expression
SRP065317	Tumor-derived circulating endothelial cell clusters in colorectal cancer	Circulating tumor cells (CTCs) are the subject of several translational studies and clinical trials because their examination could offer an insight into tumor progression and clinical outcomes. Circulating tumor microemboli (CTM) are clusters of CTCs that have been described as malignant entities for over 50 years, although a comprehensive characterization of these cells is still lacking. Contrary to current consensus, we demonstrate that CTM isolated from colorectal cancer patients are not cancerous, but represent a discrete population of tumor-derived endothelial cells. CTM express epithelial and mesenchymal markers that are consistent with previous reports on circulating tumor cell phenotyping. However, they do not mirror the genetic variations of matching tumors. Transcriptome analysis of single-CTM reveals that these structures exhibit an endothelial phenotype, with further results supporting a tumor-derived endothelial lineage. CTM are widespread in blood sampled from preoperative cancer patients but not in healthy donors, suggesting CTM count as a potential biomarker of interest for colorectal cancer. CTM should not be confused with bona fide circulating epithelial tumor cells. The characterization of tumor derived endothelial cell clusters (TECCs) is likely of high diagnostic value, and may provide direct information about the underlying tumor vasculature at the time of diagnosis, during treatment and the course of the disease. Overall design: Profiling of 18 TECCs/CTM from 8 colorectal cancer patients. In addition profiling of  matched 7 normal colonic mucosa, 9 primary colorectal tumor samples (of which three from the same patient), one colorectal cancer metastatis. Additionally,  14 laser-capture-dissected endothelia from the same patients and tissues, and 3 commercially available  normal endothelial cell lines	Co-expression
SRP065330	Caco-2 human transcriptome. 3-dimensional cell culturing and/or coxsackievirus B3 infection	Transcriptomic Sequence from Caco-2 colon carcinoma cell lines grown in monolayers or in the rotating wall vessel 3D bioreactor	Co-expression
SRP065337	Global gene expression measurements in stem cell derived motor neurons treated with various neurotrophic compounds	In this study, we differentiated H9 stem cells into motor neurons, and collected RNA-Sequencing reads to assess how different neurotrophic compounds influenced gene expression profiles. These compounds included DMSO, BDNF (brain derived neurotrophic factor), NGF (nerve growth factor), and three microneurotrophins designed to mimic the effects of NGF.	Co-expression
SRP065338	Global gene expression measurements in induced pluripotent stem cell (iPSC) derived motor neurons treated with various neurotrophic compounds	These sequencing reads come from induced pluripotent stem cell (iPSC)-derived motor neurons treated with either DMSO, brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), or three microneurotrophins designed to mimic nerve growth factor (BNN50, BNN93, BNN124). The original cell type reprogrammed into iPSCs were mononuclear blood cells from a 62 year old human donor without any known diseases.	Co-expression
SRP065445	Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms	Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans Cell (LCH) and non-Langerhans (non-LCH) histiocytoses, respectively. The discovery of BRAFV600E mutations in ~50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of BRAFV600E-wildtype, non-LCH patients are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in BRAFV600E-wildtype, non-LCH patients. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of MAP2K1- and ARAF-mutated, non-LCH patients using MEK and RAF inhibitors, respectively, resulted in clinical efficacy demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. Overall design: 13 patient samples were analyzed by RNA-seq and had 2 replicates.	Co-expression
SRP065449	Direct Isolation and Characterization of Human Nephron Progenitors.	Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA-labeling probes, we isolated SIX2+CITED1+ cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes Overall design: Single cell suspensions from 3 freshly isolated human fetal kidneys ( 17 weeks of gestation) were labelled overnight with RNA probes for SIX2 and CITED1 and sorted to obtain a 1) double positive population and2)  a negative fraction. Long term goal is to investigate the transcription profile that differentiate positive versus negative selections.	Co-expression
SRP065451	A Dual Molecular Analog Tuner for Dissecting Mammalian Protein Function	Loss-of-function studies are fundamental for dissecting gene function. Yet, methods to rapidly and effectively perturb genes in mammalian cells are scarce. We present a novel system, deliverable with only two lentiviral vectors, which enables simultaneous control over two different proteins in the same cell. By harnessing the plant auxin and jasmonate hormone-induced degradation pathways, combined with RNA interference, this system allows constitutive depletion of two endogenous proteins and their replacement with two exogenous proteins whose degradation is rapidly and reversibly induced by external ligands, representing a dual analog molecular tuner. Focusing on NANOG, CHK1 and NOTCH1 in embryonic stem cells and p53 in cancer cells we have validated the efficiency, rapidity, reversibility, titratability and multiplicity of the engineered tuners, and demonstrated their potential to facilitate previously-unfeasible experimental approaches and to generate novel biological insights. Overall design: For mRNA-Seq preparation, coronatine/DMSO treated cells were collected.	Co-expression
SRP065491	Gene expression profiling in metabolically heterogeneous human lung tumors	To investigate the impact of genetic and environmental factors that influence cancer cell metabolism in vivo, we conducted intra-operative 13C-glucose infusions in NSCLC patients. We determined that regional glucose metabolism was correlated with tumor perfusion as assessed by pre-surgical dynamic gadolinium enhancement.  Tumors or tumor regions showing high or low perfusion were collected and subjected to RNA-seq analysis. Overall design: RNA-seq analysis was performed to evaluate gene transcriptional levels in human non-small cell lung cancer (NSCLC) tissues showing high or low perfusion as measured by dynamic contrast-enhanced (DCE) MRI.	Co-expression
SRP065500	Downregulation of LATS kinases alters p53 to promote cell migration	p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. Overall design: MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates	Co-expression
SRP065539	RNA-seq Profiles in Transcription elongation factors are in vivo-specific cancer dependencies in glioma	Glioblastoma ranks as one of the most lethal human cancers, with no effective therapies.  To discover novel  therapeutic targets, here we performed parallel in vivo and in vitro RNA interference screens of epigenetic regulators and show that transcription elongation factors are essential for human glioblastoma cell survival in vivo, but not in vitro.  Context-specific dependency in vivo is driven by microenvironment-induced global changes in the cancer epigenome. JMJD6, a top in vivo-specific hit, binds at enhancers and correlates with increased transcription of known pause-controlled genes.  JMJD6 knockdown in patient-derived glioblastoma cells enhances survival of mice bearing orthotopic tumors.  Moreover, elevated levels of JMJD6 alone, as well as transcription elongation factors collectively, informs tumor grade and predicts poor prognosis for patients.  Our work provides a rationale for targeting transcription elongation as a therapeutic strategy in glioblastoma and, more broadly, the power of in vivo phenotypic screening to identify therapeutically relevant targets in cancer. Overall design: RNA-seq of primary patient-derived GBM cells grown in in vivo tumor microenvironment or in vitro in serum free cell culture	Co-expression
SRP065559	A designed inhibitor of p53 aggregation rescues p53 tumor-suppression in ovarian carcinomas	Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. Overall design: Vehicle vs. ReACp53 treatment in 4 different samples: 2 cell lines (MCF7 w/ WT p53 as negative control and OVCAR3 w/ R248Q p53) and 2 clinical specimens (primary cells from patient #8 w/ WT p53 as negative control and primary cells from patient #1 w/ R248Q p53)	Co-expression
SRP065566	Modulation of immunomodulatory peptide activity by 2-deoxy-d-glucose	The goal of this study was to identify the role of glycolysis in the activity of immunomodulatory peptides with respect to macrophage function using the glycolytic inhibitor 2-deoxy-d-glucose Overall design: Primary human monocyte derived macrophages were treated with 2-deoxy-d-glucose, the immunomodulatory peptide IDR-1018 or a combination of the two for 4 hours. Control samples of untreated macrophages were included. The study was completed in tripiclate (three independent, healthy donors).	Co-expression
SRP065678	ATRX is necessary for cellular senescence and represses HRAS to drive cells from quiescence into senescence [RNA-Seq]	Senescence is a state of stable cell cycle exit that has important implications for development, physiology and disease.  It is distinct from quiescence in which cells can be induced to re-enter the cell cycle. Although it is well known that there are massive changes in the heterochromatin of senescent cells, the molecular mechanisms underpinning the transition from reversible quiescence into irreversible senescence have remained elusive. Here, we demonstrate that the chromatin-remodeling enzyme ATRX is required for senescence. ATRX accumulates in nuclear foci during both replicative and cellular senescence. Using ChIP-seq and RNA-seq we identified HRAS as part of an ATRX regulated gene expression program associated with senescence. Repression of HRAS is sufficient to promote the transition of quiescent cells into senescence. Thus we conclude that the repression of HRAS is likely a direct consequence of ATRX binding and critical to how it mediates its role in senescence. Overall design: mRNA expression profiles were analyzed in dedifferentiated liposarcoma cell lines under cycling, quiescent and senescent (using two unique inducers) conditions via RNA-seq	Co-expression
SRP065758	Homo sapiens  raw sequence reads	Aim to identify the potential relationship between DNA methylation and gene expression.	Co-expression
SRP065763	IFN-kappa inhibits HPV31 transcription by inducing Sp100 proteins	Using doxycycline-inducible IFN-kappa expression in CIN612-9E cells, which maintain extrachromosomally replicating HPV31 genomes, we demonstrate that IFN-kappa inhibits the growth of these cells and reduces viral transcription and replication. Interestingly, the initiation of viral early transcription was already inhibited 4-6h after IFN-kappa expression. This was also observed with recombinant IFN-beta suggesting a common mechanism of IFNs. RNA-seq analysis identified 1367 IFN-kappa regulated genes of which 221 were modulated >2-fold. The majority of those (71%) matched known ISGs confirming that IFN-kappa acts as a bona fide type I IFN in hr-HPV-positive keratinocytes. RNAi and co-transfection experiments indicate that the inhibition of viral transcription is mainly due to the induction of Sp100 proteins by IFN-kappa. Overall design: CIN612-9E/pInd-IFN-kappa were induced for 4h with 1µg/ml doxycyclin or not. Three biological replicates were analyzed.	Co-expression
SRP065774	CD13 and ROR2 permit isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells	The resultant heat map demonstrates the maturation of CD13+/ROR2+ cells as they proceed through cardiac differentiation. Overall design: RNA-seq analysis was preformed on RNA samples from undifferentiated hESCs, 13R2+ and 13R2- populations from day 3, 13R2+/NKX2-5+ and 13R2+/NKX2-5- from day 7, and 13R2+/NKX2-5+/a-MHC+ and 13R2+/NKX2-5+/MHC- from day 14	Co-expression
SRP065795	A novel tumor-associated myeloid cell population inhibits antigen-specific immune responses in cancer patients	Tumor progression is associated with an immunosuppressive microenvironment that consists of several elements, such as regulatory T cells, type 2 macrophages and myeloid-derived suppressor cells. Here, we identify for the first time a BDCA1+CD14+ population of immunosuppressive cells that resides both in the blood and tumor of melanoma patients. We demonstrated that the presence of these cells in dendritic cell (DC)-based anti-tumor vaccines significantly suppresses CD4+ T cells in an antigen-specific manner. In an attempt to reveal the mechanism of this suppressive activity, we noticed that BDCA1+CD14+ cells express elevated levels of the check-point molecule PD-L1, which thereby hinders T cell proliferation. Importantly, although this suppressive BDCA1+CD14+ population expresses markers of both BDCA1+ DCs and monocytes, functional, transcriptome and proteome analyses clearly revealed that they comprise a unique population of cells that is exploited by tumors to evade immunity. Thus, targeting these cells may improve the efficacy of cancer immunotherapy.	Co-expression
SRP065812	Long non-coding RNAs  in psoriatic and healthy skin	In this study, we used RNA-sequencing to profile the long non-coding RNA (lncRNA) transcriptome in lesional skin from psoriasis patients before (PP) and after treatment (PT) with adalimumab and in normal skin from healthy individuals (NN). For this we sequenced total RNA from 18 psoriasis patients (before and after treatment) and 16 healthy controls. We created our own reference set of long non-coding RNAs by merging three long non-coding RNA reference data sets. The combined reference had 67,157 lncRNA transcripts with no overlaps. We identified differential expression of 971 lncRNAs between PP and NN, 157 between PP and PT, and 377 between PT and NN. Based on differentially expressed (DE) lncRNAs between PP and NN, we identified a molecular lncRNA signature that distinguishes psoriatic skin from healthy skin . Overall design: We recruited 18 psoriatic patients in our study. We took 5 mm punch biopsies from the edge of a psoriatic plaque before treatment and after one month of treatment with adalimumab. The mean improvement in the PASI over this time period was 53.1%. We obtained sixteen normal skin samples (N=16) from healthy control surgical discard specimens.	Co-expression
SRP065815	Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors That Can Function as a Cell of Origin for Prostate Cancer	Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulkNHPluminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates. Such functionally defined luminal progenitors can be transformed by distinct sets of genetic perturbations (i.e., AR+AKT/ERG or c-MYC+PTEN knockout) to form tumor glands. Genome-wide RNA-Seq analysis of freshly purified unperturbed human benign prostatic basal and luminal cells and culture-expanded lineage specific stem/progenitor populations reveals that the luminal progenitors possess a distinct gene expression profile that is greatly enriched in advanced, castration-resistant, and metastatic PCa, and it associates with poor patient survival. The ability of the simple two-dimensional culture system reported herein to greatly enrichNHPprogenitor-like cells should facilitate biological and biochemical studies as well as high-throughput screening in these cells and in progenitor-like PCa cells. Overall design: Human total RNA profiles of HPCa167N benign prostatic bulk epithelial cells and freshly purified basal and luminal populations cultured primarily in WIT and PrEGM media by deep RNA-seq.	Co-expression
SRP065825	Heterogenous ribonucleoprotein C suppresses cleavage and polyadenylation at poly(A) sites located in poly(U)-rich regions	Human transcripts can typically be processed at multiple polyadenylation sites to yield mRNA isoforms with distinct 3  ends. A multitude of factors contributes to the choice of individual polyadenylation sites in different cell types and tissues. In this study we have found that the heterogenous ribonucleoprotein C (hnRNP C), an RNA binding protein that was previously linked to splicing and polyadenylation at Alu repeat elements, is a general regulator of pre-mRNA cleavage and polyadenylation. By sequencing mRNA 3  ends from cells expressing normal and reduced levels of hnRNP C we found that transcripts that contain poly(U) tracts around their poly(A) sites respond in a manner indicative of hnRNP C repressing cleavage and polyadenylation. The 3  UTR isoforms whose abundance is modulated by hnRNP C contain U-rich elements and can thereby interact with A/U-rich element binding proteins that have been shown to alter transcript stability, sub-cellular localization and even the localization of the translated proteins.	Co-expression
SRP065849	A novel RAF kinase inhibitor with DFG-out binding mode: high efficacy in BRAF-mutant tumor xenograft models in the absence of normal tissue hyperproliferation	Purpose: Seek for differential gene expression in vemurafenib-resistant A375 tumors vs. untreated controls to provide a rationale for resistance mechanism Methods: mRNA profiles of vemurafenib-resistant A375 tumors and untreated control tumors were generated by transcriptome sequencing of A375 melanoma bearing mice. Since our xenograft samples contain a mixture of human and mouse RNAs we mapped RNASeq reads against a hybrid human/mouse genome. We than removed reads of potential mouse origin by taking only reads that map uniquely to human chromosomes. On average 23% of reads were removed as potential mouse reads. We than took the remaining reads (on average 77% per sample) to determine the gene expression levels for each sample. Normalized expression levels of 5 resistant samples were compared to 4 untreated control samples to detect differnetially regulated genes which may contribute to vemurfenib resistance Results: Expression levels of several genes were consistently altered in all resistant samples. Expression of e.g. genes encoding SPRY2, SPRY4, DUSP6, CCND1, PIK3R3, FGFR1, EPHA4, MCL1, and IGF1R was down-regulated, whereas expression of PDGFC, VEGFC, ABCB9 and KITLG was increased. Conclusions: Our study reports several differentially expressed genes which may contribute to vemurafenib resistance in A375 tumor bearing mice Overall design: RNA sequencing of genes expressed in A375 tumors bearing mice treated with vemurafenib until in vivo resistance appeared vs. untreated A375 tumors	Co-expression
SRP065865	Gene Networks and Blood Biomarkers of Methamphetamine-Associated Psychosis: A Preliminary Integrative RNA-Sequencing Report	The clinical presentation, course and treatment of methamphetamine-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in accurately diagnosing MAP at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH-dependency without psychosis (MA) (N=10) and healthy controls (N=10). We used RNA-Sequencing gene expression to characterize molecular signatures associated to METH and MAP status compared to healthy control subjects. Overall design: Peripheral blood luekocytes gene expression was subject to transcriptional analysis for 10 MAP subjects, 10 subjects with METH-dependency without psychotic symptomics and 10 healthy controls.	Co-expression
SRP065892	Comprehensive Evaluation of AmpliSeq Transcriptome, a Novel Targeted Whole Transcriptome RNA Sequencing Methodology for Global Gene Expression Analysis.	Background: Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis.  However, RNA-seq carries a few limitations, e.g., the requirement of a significant amount of input RNA and complications led by non-specific mapping of short reads. The Ion AmpliSeqTM Transcriptome Human Gene Expression Kit (AmpliSeq) was recently introduced by Life Technologies as a whole-transcriptome, targeted gene quantification kit to overcome these limitations of RNA-seq.To assess the performance of this new methodology, we performed a comprehensive comparison of AmpliSeq with RNA-seq using two well-established next-generation sequencing platforms (Illumina HiSeq and Ion Torrent Proton). We analyzed standard reference RNA samples and RNA samples obtained from human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Results: Using published data from two standard RNA reference samples, we observed a strong concordance of log2 fold change for all genes when comparing AmpliSeq to Illumina HiSeq (Pearson’s r=0.92) and Ion Torrent Proton (Pearson’s r=0.92). We used ROC, Matthew’s correlation coefficient and RMSD to determine the overall performance characteristics. All three statistical methods demonstrate AmpliSeq as a highly accurate method for differential gene expression analysis. Additionally, for genes with high abundance, AmpliSeq outperforms the two RNA-seq methods. When analyzing four closely related hiPSC-CM lines, we show that both AmpliSeq and RNA-seq capture similar global gene expression patterns consistent with known sources of variations. Conclusions: Our study indicates that AmpliSeq excels in the limiting areas of RNA-seq for gene expression quantification analysis. Thus, AmpliSeq stands as a very sensitive and cost-effective approach for very large scale gene expression analysis and mRNA marker screening with high accuracy. Overall design: Comprehensive, performance evaluation of AmpliSeq Transcriptome to standard whole-transcriptome RNA-sequencing methods for large-scale, genome-wide differential gene expression analysis. We analyzed standard reference RNA samples and RNA samples obtained from human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).	Co-expression
SRP065894	An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma	Changes in cellular metabolism contribute to the development and progression of tumors, and can render tumors vulnerable to interventions. However, studies of human cancer metabolism remain limited due to technical challenges of detecting and quantifying small molecules, the highly interconnected nature of metabolic pathways, and the lack of designated tools to analyze and integrate metabolomics with other –omics data. Our study generates the largest comprehensive metabolomics dataset on a single cancer type, and provides a significant advance in integration of metabolomics with sequencing data. Our results highlight the massive re-organization of cellular metabolism as tumors progress and acquire more aggressive features. The results of our work are made available through an interactive public data portal for cancer research community. Overall design: 10 RNA samples from human ccRCC tumors analyzed from the high glutathione cluster	Co-expression
SRP065895	Transcriptomics analysis of gene expression in multiple human and mouse cells and tissues	RNA was isolated from siCTRL, siNSUN2 HeLa or 3T3-L1 cells, human cells (embryonic kidney T cell line 293T; colon cancer cell line HCT116; hepatocellular carcinoma cell line Huh7; embryonic lung fibroblast cell line MRC-5; glioma cell line SNB19), mouse cells (kidney collecting duct cell line M-1; cervical cancer cell line U14) and multiple mouse tissues using the TRIzol (Invitrogen) reagent by following the company manual. For all samples the RNA integrity was checked using an Agilent Bioanalyzer 2100. All samples showed a RIN (RNA integrity number) of higher than 9. Approximately 2.5 µg of total RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer's protocol.The libraries were sequenced using HiSeq2000 (Illumina) in paired-read mode, creating reads with a length of 101 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Overall design: Examination of gene expressive levels in mammalian transcriptome	Co-expression
SRP065931	Functional Genomic Analyses of Hep-G2 Cell Line after FTO knockdown	To explore the molecular mechanism underlying glucose regulation by hepatic FTO, we used the human hepatocyte Hep-G2 cell line as an experimental platform and analyzed transcriptome changes following FTO knock-down. Overall design: Examination of three Hep-G2 cell lines: FTO is knocked down more efficiently in sh7 and less efficiently in sh2. The control is the scramble.	Co-expression
SRP065951	Tumor-Specific Retrogene NANOGP8 Reprograms Prostate Cancer Cells to Castration Resistance by Engaging the FOXA1/AR Signaling Axis and MYC [RNA-seq]	Targeted disruption of the embryonic stem cell (ESC) self-renewal and pluripotency factor NANOG diminishes cancer cell clonogenic growth in vitro and tumor development in vivo. NANOG has also been shown to augment CSC properties and propel the emergence of castration-resistance prostate cancer (CRPC) phenotypes. Here, we investigate the molecular mechanisms underlying NANOG-mediated oncogenesis and prostate cancer progression to androgen independence.  ChIP-Seq analysis of LNCaP prostate cancer cells overexpressing doxycycline-inducible NANOG (either NANOG1 or NANOGP8 vs pLVX control) reveal that NANOG coordinately occupies regions of chromatin regulated by AR signaling steroid-receptor complex proteins AR, FOXA1 and NKX3.1. Taken together with the NANOG-induced changes in the prostate cancer transcriptome (RNA-Seq), NANOG appears to reprogram prostate cancer cells to castration resistance by converging on steroid-hormone receptor signaling. Overall design: LNCaP empty vector (pLVX) vs NANOG overexpressing (NANOG1 or NANOGP8) cells cultured +doxycycline under androgen dependent (AD) or androgen independent (AI) conditions for the indicated period of time and subject to RNA extraction and Illumina sequencing	Co-expression
SRP066009	RNA-Seq of human reference RNA samples using a thermostable group II intron reverse transcriptase	Next-generation RNA sequencing (RNA-seq) has revolutionized our ability to analyze transcriptomes. Current RNA-seq methods are highly reproducible, but each has biases resulting from different modes of RNA preparation, reverse transcription, and adaptor addition, leading to variability between methods. Moreover, the transcriptome cannot be profiled comprehensively as highly structured RNAs, such as tRNAs and snoRNAs, are refractory to conventional RNA-seq methods. Recently, we developed a new method for strand-specific RNA-seq using thermostable group II intron reverse transcriptases (TGIRTs). TGIRTs have high processivity and fidelity plus a novel template-switching activity that enables addition of an RNA-seq adaptor during cDNA synthesis without using RNA-ligase. Here, we used TGIRT-seq to obtain RNA-seq datasets from well-characterized human RNA reference samples and compared them to previous datasets obtained for these RNAs by the Illumina TruSeq v2 and v3 methods. We find that TGIRT-seq recapitulates the relative abundance of human transcripts and RNA spike-ins in ribo-depleted, fragmented RNA samples similarly to the non-strand-specific TruSeq v2 and better than the strand-specific TruSeq v3 method. Moreover, TGIRT-seq is simpler and more strand-specific than TruSeq v3, gives more uniform 5’ to 3’ gene coverage than either TruSeq method, and eliminates sequence biases from random hexamer priming inherent to TruSeq. TGIRT-seq also detects more splice junctions, particularly near the 5’ ends of genes than does TruSeq v3, even in fragmented RNAs. Finally, TGIRT-seq enables simultaneous profiling of mRNAs and lncRNAs in the same RNA-seq as structured small ncRNAs, including tRNAs, which are essentially absent from TruSeq libraries.	Co-expression
SRP066012	RNA-Seq comparisons of gene expression profiles of epithelial and mesenchymal cells - HMLE, N8, N8-CTx	We find that treating mesenchymal NAMEC8 cells with cholera toxin (CTx) to elevate intracellular cAMP levels and activate PKA induces a mesenchymal-to-epithelial transition whereby the cells assume an epithelial state (N8-CTx). NAMEC8 cells undergo epigenetic reprogramming triggered by active PHF2, a histone demethylase, which demethylates H3K9me2 and H3K9me3 regions of epithelial genes silencing in the mesenchymal state Overall design: Performing RNASeq with HMLE (immortalized human mammary epithelial cells), their mesenchymal CD44hi counterparts, NAMEC8 and the CTx-reverted versions of NAMEC8 a.k.a N8-CTx	Co-expression
SRP066026	The conserved transcriptional landscapes in human spermatogenesis	Spermatogenesis is a complex and highly orchestrated combination of processes in which male germline proliferation and differentiation result in the production of mature spermatozoa. If recent genome-wide studies have contributed to the in-depth analysis of the male germline protein-coding transcriptome, little effort has yet been devoted to the systematic identification of lncRNAs expressed during spermatogenesis in human. We report high-resolution expression profiling of human male germ cells using Illumina next-generation sequencing technology and highly enriched testicular cell populations. 25,161 high-confidence transcripts were reconstructed and classified into eleven expression patterns.  Our study provides new insights in transcriptional profiling of the male germline and represents a high-quality resource of novel loci expressed during spermatogenesis that significantly contributes to the human genome annotation. A graphical display of the data is conveniently accessible through the ReproGenomics Viewer (RGV) at http://rgv.genouest.org. Overall design: Genome-wide expression profiling analysis using Illumina next-generation sequencing technology and highly enriched testicular cell populations	Co-expression
SRP066083	Calcineurin-dependent lateral transfer of Aspergillus fumigatus through a VASP tunnel during human macrophage cell death enables control of fungal germination	We sequenced total RNA from human monocyte derived macrophages (n = 6, healthy donors) pre-treated with calcineurin inhibitor FK506 (10 ng/ml) for 1h and stimulated with live Aspergillus fumigatus swollen conidia (MOI=1) for 1h and 6h. Overall design: We sequenced total RNA from human monocyte derived macrophages from six healthy donors. For each donor, we had six conditions (Unstimulated control, FK506 pre-treated control, 1 hour stimulation with live Aspergillus fumigatus, 1 hour stimulation with live Aspergillus fumigatus with FK506 pre-treatment, 6 hour stimulation with live Aspergillus fumigatus, 6 hour stimulation with live Aspergillus fumigatus with FK506 pre-treatment. In total we analysed 36 samples (6 healthy donors with 6 conditions).	Co-expression
SRP066090	Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number variations, PIK3CA mutation, and pathway signatures. [RNA-Seq]	Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons.  Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. Overall design: 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.	Co-expression
SRP066095	Inhibition of uPA expression by CRISPR-dCas9 DNA methyltransferases	We report the generation of CRISPR-dCas9 DNA methyltransferases to mediate targeted DNA methylation. Using the dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B methyltransferases, we have demonstrated that these two methyltransferase can mediate targeted methylation in three human genes tested: uPA, TGFBR3, and CDKN2A in human HEK293T cells. We also showed that these methyltransferases could mediate gene inhibition. Overall design: five samples co-transfected with five uPA sgRNAs and each of the four dCas9 fusions, or control transfection with pUC19 plasmid	Co-expression
SRP066099	Homo Sapiens Transcriptome or Gene expression	Epstein-Barr virus (EBV) establishes lifelong infections in its human host. The virus is associated with a broad range of malignancies of lymphoid and epithelial origin, including Burkitt's lymphoma, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma and gastric carcinoma. During the latent phase of its life cycle, EBV expresses more than 40 mature miRNAs that are highly abundant in tumor cells and may contribute to oncogenesis. Although multiple studies have assessed the relative expression profiles of EBV miRNAs in tumor cells, data linking these expression levels to functional target knockdown is mostly lacking. Therefore we set out to systematically assess the EBV miRNA expression levels in EBV+ tumour cell lines, and correlate this to their functional silencing capacity in these cells. We provide comprehensive EBV miRNA expression profiles of the EBV+ cell lines C666-1 (nasopharyngeal carcinoma), SNU-719 (gastric carcinoma), Jijoye (Burkitt's lymphoma), and AKBM (Burkitt's lymphoma) and of EBV- cells ectopically expressing the BART miRNA cluster. By deep sequencing the small RNA population and conducting miRNA-reporter experiments to assay miRNA potency, we were able to compare the expression profiles of the EBV miRNAs with their functional silencing efficacy. We observe a strong correlation between miRNA expression levels and functional miRNA activity. There is large variation in expression levels between EBV miRNAs in a given cell line, whereas the relative expression profiles are well maintained between cell lines. Furthermore, we show that miRNA arm selection bias is less pronounced for viral miRNAs than for human miRNAs. In addition to encoding the largest number of precursor miRNAs of all human herpesviruses, EBV expresses many miRNAs precursors that yield two functional miRNA strands, rather than one guide strand and a non-functional passenger strand. This reduced strand bias may increase the size of the EBV miRNA targetome.	Co-expression
SRP066102	Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer [RNA-seq]	Approximately 75% of breast cancers express estrogen receptor a (ERa) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit estrogen receptor signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the up-regulation of alternative growth signals. The mechanisms that drive this resistance - especially epigenetic events that alter gene expression - are however not well understood. Here we performed a genome-wide DNA methylation and expression analysis of cell line models to find epigenetically regulated genes involved in acquired aromatase inhibitor resistance. We discovered that prostaglandin E2 receptor 4 (PTGER4) is up-regulated after demethylation and promotes phosphorylation and activation of ERa. Knockdown and inhibitor studies demonstrate that PTGER4 promotes AI resistance via ligand independent activation of the ERa-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate that PTGER4 is a potential drug target in AI resistant cancers. Additionally, the epigenetic component of PTGER4 regulation suggests that further study of PTGER4 may yield valuable insights into how DNA methylation-targeted diagnoses and/or treatments can improve AI resistant breast cancer treatment. Overall design: RNA-Seq was used to generate mRNA expression profiles of MCF7-LTED (long-term estrogen deprived) cells grown in charcoal stripped serum. Two replicates were performed.	Co-expression
SRP066118	Generation of Patient-Matched Malignant and Normal Primary Cell Cultures from Clear Cell Renal Cell Carcinoma Patients	Transcriptome profiling of de novo-derived ccRCC cell cultures and their matching parental tumours.  VHL-mutant and VHL wild-type cultures were established by isolating CA9+ and CA9- cells from tumor samples using FACS. Overall design: RNASeq expression profiling of 18 renal cell carcinoma samples, including 6 patient tumours, 6 VHL mutant and 6 VHL WT derivative cell cultures	Co-expression
SRP066150	Global Trabscriptome Analaysis Reveals that Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2	Post-translational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the Polycomb Repressive Complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2 that resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2-target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to occupancy loss of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2. Overall design: Examination of the effect of PARP inhibition on global gene expression in LCLs cell lines. mRNA profiles of LCLs cells lines treated at different time points with olaparib were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP066152	Transcriptome-wide regulation of pre-mRNA splicing and expression by the RNA-binding protein Quaking during monocyte to macrophage differentiation [RNA-Seq]	Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Overall design: RNA-seq analysis of primary monocytes and macrophages from a  QKI haploinsufficient patient and their (control) sibling.	Co-expression
SRP066197	Transcriptional profiling of TH2 cells identifies pathogenic features associated with asthma	Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4+ T cells that produce type 2 cytokines (TH2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Since TH2 cells play a pathogenic role in both these diseases and are also present in healthy non-allergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in TH2 cells from subjects with allergic asthma, rhinitis and healthy controls. TH2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. In addition, genes that enhanced TH2 polarization and TH2 cytokine production were also upregulated in asthma. Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of TH2 cells from asthmatic subjects. Many novel genes with poorly defined functions were also differentially expressed in asthma. Thus, our transcriptomic analysis of circulating TH2 cells has identified several molecules that are likely to confer pathogenic features to TH2 cells that are either unique or common to both asthma and rhinitis. Overall design: RNA-sequencing of circulating TH2 cells isolated from a cohort of patients with allergic rhinitis (25), asthma (40) patients and healthy non allergic subjects (15). Cells were directly isolated from blood by flow cytometry. Total RNA was extracted, messenger RNA was selected and cDNA was amplified linearly with a PCR based method (Picelli et al. 2014). Libraries were prepared using the NexteraXT Illumina sequencing platform.	Co-expression
SRP066204	Next generation sequencing to elucidate the novel function of RORC (RORgamma) in breast cancer	Exploring the novel role of RORC (RORgamma) in breast cancer, utilizing NEXTseq with genetic gain and loss of function and pharmacological treatment. Overall design: For loss of function, control-siRNA or RORC-siRNA was transfected for 48h in three cell lines (MCF-7, T-47D and MDA-MB-231). For gain of function, CMV-empty or CMV-RORC was transfected for 48h in MDA-MB-231 cells. Furthermore, the selective RORC antagonist, SR2211 was utilized. MCF-7 cells were treated either DMSO or SR2211 (5uM) for 24h. Total RNA was extracted with the RNeasy kit. NEXTseq was performed for transcriptome analysis.	Co-expression
SRP066238	Lipid degradation promotes prostate cancer cell survival	Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p=0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. Overall design: Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing. The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.	Co-expression
SRP066242	A novel tumor-associated myeloid cell population inhibits antigen-specific immune responses in cancer patients	Tumor progression is associated with an immunosuppressive microenvironment that consists of several elements, such as regulatory T cells, type 2 macrophages and myeloid-derived suppressor cells. Here, we identify for the first time a BDCA1+CD14+ population of immunosuppressive cells that resides both in the blood and tumor of melanoma patients. We demonstrated that the presence of these cells in dendritic cell (DC)-based anti-tumor vaccines significantly suppresses CD4+ T cells in an antigen-specific manner. In an attempt to reveal the mechanism of this suppressive activity, we noticed that BDCA1+CD14+ cells express elevated levels of the check-point molecule PD-L1, which thereby hinders T cell proliferation. Importantly, although this suppressive BDCA1+CD14+ population expresses markers of both BDCA1+ DCs and monocytes, functional, transcriptome and proteome analyses clearly revealed that they comprise a unique population of cells that is exploited by tumors to evade immunity. Thus, targeting these cells may improve the efficacy of cancer immunotherapy. Overall design: mRNA profiles of BDCA1+ DCs, BDCA1+CD14+ cells and monocytes, isolated from 3 healthy volunteers, were generated by deep RNA sequencing using HiSeq 2000 System (TruSeq SBS KIT-HS V3,Illumina)	Co-expression
SRP066260	Transcriptional profile changes by Prox1 expression in thyroid cancer cells	Human thyroid cancer cell line BCPAP was engineered for doxycyclin-mediated inducible expressoin of Prox1 and next generation sequcing was performed to study the transcriptional regulation by Prox1 Overall design: BCPAP cells were infected with rTTA2 lentivirus. The resulting cell populations were then stably transfected either with pIRES-hygromycin vector (Clontech) to generate BCPAP-Ctr cells, or with Flag-PROX1-IRES-hygromycin vector to generate BCPAP-Prx cells. PROX1 expression was induced or not in BCPAP-Ctr and BCPAP-Prx cells with 0.5 µg/ml doxycycline (Dox) for 48 hours and the total RNA samples were collected for sequencing.	Co-expression
SRP066262	Homo sapiens Transcriptome or Gene expression	Study the effect of transfection reagent and control siRNA in Human aortic smooth muscle cells	Co-expression
SRP066267	Increased Wnt and Notch signaling: A clue to the renal disease in Schimke immuno-osseous dysplasia? [RNA-Seq]	Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD. We tested this hypothesis by transcriptome analysis and quantitative reverse transcription PCR (qRT-PCR) of an SIOD patient kidney, a genetic screen and immunofluorescence. These showed increased expression of genes in the Wnt and Notch signaling pathways in an SIOD patient kidney, interaction of Marcal1 with genes encoding components of the Wnt and Notch signaling pathways, and increased levels of unphosphorylated b-catenin and Notch1 intracellular domain (NICD) in the glomeruli of SIOD patient kidneys. Given that increased Wnt and Notch activity are established causes of FSGS, we hypothesize that SMARCAL1 deficiency increases the activity of one or both of these pathways to cause the renal disease of most SIOD patients. Overall design: Comparison of mRNA levels between the kidney tissue of a Schimke immuno-osseous dysplasia (SIOD) patient and an unaffected control	Co-expression
SRP066280	Homo sapiens Transcriptome or Gene expression	To gain the transcriptome alteration caused by knockdown of PHF8 and USP7 in MCF-7 cells	Co-expression
SRP066356	Characterization of macrophage - cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer	We performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive (ER+) or triple-negative (TNBC) breast cancer cell lines and studied the biological responses related to the differential gene activation in both cell types to understand how different cancer cells educate host cells to support tumor growth Overall design: To characterize the differences in macrophage activation under the influence of either ER+ or TNBC breast cancer cells, we cultured freshly isolated human peripheral monocytes with two breast cancer cell lines (T47D, ER+ and MDA-MB-231, TNBC) in an in vitro transwell co-culture assay. The transwell setting allowed us to investigate the effect of soluble mediators on macrophage activation since direct cell contact of these cells was inhibited by a (PET) membrane (pore size 0.4 µm).	Co-expression
SRP066363	Characterization of parental and rociletinib-resistant derived H1975 cell lines	Through development of an in vivo orthotopic lung cancer model, we reveal an unanticipated pathway driving spontaneous metastasis that is orchestrated by the developmentally-regulated transcriptional repressor, Capicua (CIC). Overall design: RNAseq and DNA copy number analysis of H1975 (EGFR-mutant lung adenocarcinoma) cells in the context of drug resistance to rociletinib	Co-expression
SRP066365	Nudt3 is a mRNA Decapping Enzyme That Modulates Cell Migration	The Dcp2 and Nudt16 Nudix hydrolases, are mRNA decapping enzymes that preferentially modulate stability of a subset of mRNAs.  Here we report Nudt3 is a third Nudix protein that possess mRNA decapping activity in cells and is a modulator of cell migration in MCF-7 breast cancer cells.  Genome-wide analysis of Nudt3 compromised cells identified increases in mRNAs involved in cell motility including integrin ß6, lipocalin-2 and fibronectin.  The increase in mRNA levels was dependent on Nudt3 decapping activity where integrin ß6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled.  Moreover, increased cell migration observed in Nudt3 depleted cells was mediated through the extracellular integrin ß6 and fibronectin protein nexus.  We conclude, Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals. Overall design: Stably transformed MCF-7 cell lines constitutively expressing either a short hairpin RNA (shRNA) directed against Nudt3 (Nudt3KD) or a non-targeted control shRNA (ConKD) were used, with three replicate cultures used per group (n=3).	Co-expression
SRP066371	RNA splicing alteration on glioblastoma and normal neural stem cells	We identified PHF5A as a functional synthetic-lethal hit in glioblastoma stem cells compared to normal neural stem cells. We wanted to perform analysis of RNA isoforms present in glioblastoma or normal neural stem cells with or without PHF5A depletion. We performed shRNA knockdown of PHF5A or used non-silencing shRNA as a control, selected infected cells with puromycin, and isolated RNA for sequencing. Overall design: We analyzed RNA from either normal neural stem cells or two different glioblastoma specimens aster either control knockdown, or two different shRNA sequences against the PHF5A gene transcript.	Co-expression
SRP066387	Histone H3 lysine 4 acetylation-methylation dynamics define breast cancer subtypes [RNA-seq]	The onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that results in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was overrepresented at promoters of genes associated with cancer-related phenotypic traits, such as estrogen response and epithelial-to-mesenchymal transition pathways. Our findings highlight an important role for H3K4ac in predicting epigenetic changes associated with early stages of transformation. In addition, our data provide a valuable resource for understanding epigenetic signatures that correlate with known breast cancer-associated oncogenic pathways. Overall design: RNA-Seq of cell lines MCF10A, MCF7 and MDA-MB-231.	Co-expression
SRP066415	A transcriptional regulatory network connects mitochondrial biogenesis and metabolic shift with stem cell commitment to hepatic differentiation	Mitochondrial biogenesis and metabolism recently emerged as critical modulators of stemness properties and differentiation programmes. The increase in mitochondrial biogenesis and metabolic shift toward increased oxidative phosphorylations (OXPHOS) appear as hallmarks of stem cell differentiation processes. While several mechanisms support the involvement of mitochondrial biogenesis and function in the regulation of stem cell differentiation, the mechanisms triggering mitochondrial biogenesis in the context of cell differentiation remain elusive. In this study, we performed transcriptomic and bioinformatic analyses in order to get deeper insights into the cross-regulation of mitochondrial biogenesis and hepatogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). We identified a transcriptional regulatory network involved in the co-regulation of stem cell differentiation and mitochondrial biogenesis. Overall design: Transcriptomics analyses performed at early time points of the hepatogenic differentiation of BM-MSC	Co-expression
SRP066424	High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities	The ability to perturb genes in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. To extend the catalog of human core and context- dependent fitness genes, we have developed a high-complexity second-generation genome-scale CRISPR-Cas9 gRNA library and applied it to fitness screens in five human cell lines. Using an improved Bayesian analytical approach, we consistently discover 5-fold more fitness genes than were previously observed. We present a list of 1,580 human core fitness genes and describe their general properties. Moreover, we demonstrate that context-dependent fitness genes accurately recapitulate pathway-specific genetic vulnerabilities induced by known oncogenes and reveal cell-type-specific dependencies for specific receptor tyrosine kinases, even in oncogenic KRAS backgrounds. Thus, rigorous identification of human cell line fitness genes using a high-complexity CRISPR-Cas9 library affords a high-resolution view of the genetic vulnerabilities of a cell.  Additional data can be found at tko.ccbr.utoronto.ca Overall design: RNAseq of five human cell lines with Cas9 knock-ins.	Co-expression
SRP066428	Homo sapiens Transcriptome or Gene expression	The study was undertaken to compare the gene expression profile in mesenchymal stem/stromal cells from bone marrow of healthy donors and patients with newly diagnosed acute acute myeloid leukemia	Co-expression
SRP066444	RNA deep sequencing to compare genome-wide differences between PRMT5/knockdown and control AML cells	We report the pro-leukemic activities of PRMT5 in AML partly via modulating the transcription of key genes. The goal of this experiment is to confirm the changes observed in expression of genes targeted by PRMT5 activities. RNA Deep sequencing was employed to validate and reproduce the changes measured by quantitative reverse transcription polymerase chain reaction (qRT–PCR) techniques. Overall design: Total RNA samples from MV4-11 cell line (FLT3-ITD AML) following PRMT5 knockdown using specific short hairpin RNA (shRNA) was used to compare gene expression pattern between PRMT5/Knockdown and control (control: MV4-11 cells transduced with scramble control).	Co-expression
SRP066449	Homo sapiens Transcriptome or Gene expression	BJAB cells over expressing KSHV PAN RNA	Co-expression
SRP066450	4sU metabolic labeled transcripts in 65 YRI LCLs	Noncoding variants play a central role in the genetics of complex traits, but we still lack a full description of the main molecular pathways through which they act. Here we used molecular data to quantify the contribution of cis-acting genetic effects at each major stage of gene regulation from chromatin to proteins, within a population sample of Yoruba lymphoblastoid cell lines (LCLs). We performed 4sU metabolic labeled transcripts in 65 YRI LCLs to identify genetic variants that affect transcription rates. As expected, we found an important contribution of genetic variation via chromatin, contributing ~65% of eQTLs (expression Quantitative Trait Loci). The remaining eQTLs, which are not asso- ciated with chromatin-level variation, are highly enriched in transcribed regions, and hence may affect expression through co- or post-transcriptional processes. Overall design: International HapMap lymphoblastoid cell lines (LCLs) derived from YRI (Yoruba in Ibadan, Nigeria); We adapted the 4sU labelling method from (PMID 21516085). Briefly, cell cultures were grown to log phase in volumes sufficient to yield about 300 ng of 4sU-labeled RNA. Cells were incubated with 4sU for the required length of time (0, 30, or 60 minutes), then washed, pelleted, and frozen. Total RNA was extracted, and 4sU-labeled RNA was separated from total RNA using a bead-based biotin-streptavidin purification protocol. We sequenced metabolic labeled transcripts in 65 YRI LCLs 30 minutes and 60 minutes after incubation.	Co-expression
SRP066487	Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation	The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt. Overall design: triplicate experiment of 3 conditions (untreated, GTPP treatment, CDDO treatment)	Co-expression
SRP066534	RNA-seq analysis upon ARID1B overexpression	We transduced either an empty vector or ARID1B cDNA in IMR90 cells. Cells were selected with puromycin and 6 days after the infection we collected the RNA. ARID1B is a member of the SWI/SNF chromatin-remodeling complex. Our previous experiments showed that knockdown of ARID1B allows cells to bypass cellular senescence. By performing RNA-seq we have shown that ARID1B expression can induce a set of genes involved in the senescence response. Overall design: 2 samples examined: IMR90 cells expressing an empty vector and IMR90 cells expressing ARID1B cDNA	Co-expression
SRP066571	Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment (RNA-seq)	Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively). Tumor cell-intrinsic reprogramming attenuated MAPK-dependency, while enhancing mesenchymal, angiogenic and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations. Overall design: Paired melanoma biopsies/cell lines before treatment, during treatment and after resistance to MAPKi were sent for transcriptomic analysis by paired end 2x100bp HiSeq 2000 RNAseq analysis	Co-expression
SRP066600	GEO accession GSE75329 is currently private and is scheduled to be released on Nov 24, 2018.	If GEO accession GSE75329 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP066619	A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation [human cell line RNA-seq]	We report gene expression data for human melanoma cell lines using RNAseq. Overall design: RNAseq was performed on 8 melanoma cell lines and one normal human melanocyte cell line.  All done as single replicates, except for two biological replicates of A375.	Co-expression
SRP066623	Reprogramming by de-bookmarking somatic transcriptional program via targeting the BET bromodomains	One critical task in pluripotent reprogramming is to erase the somatic transcriptional program of starting cells.  No strategy or theory exists for achieving erasure of somatic gene expression memory.  Here, we present a proof-of-principle strategy in which reprogramming to pluripotency is facilitated by small molecules that erase somatic cell transcription memory.  We show that mild chemical targeting of the acetyllysine-binding pockets of the BET bromodomains, the transcriptional bookmarking domains, robustly enhances reprogramming. Furthermore, we show that chemical targeting of the transcriptional bookmarking BET bromodomains dramatically downregulates specific somatic gene expression programs in both naïve and reprogramming fibroblasts. Chemical blocking of the BET bromodomains also resulted in loss of fibroblast morphology early in reprograming. In this study, we experimentally demonstrate a concept for cell fate conversion: facilitating the conversion by chemically targeting the transcriptional bookmarking BET bromodomains responsible for transcriptional memory. Overall design: human BJ cells were treated with JQ1 at 50 nM for 48 hours. Differential expression was compared with DMSO treatment. The same treatments and comparsion were conducted for reprogramming BJ cells, which were transduced with OCT4, SOX2, and KLF4. JQ1iPSC5 is a iPSC (induced pluripotent stem cell) line generated in this study using small molecules JQ1.	Co-expression
SRP066625	Comparing The Transcriptomes of Granulocytic and Macrophage Differentiated Forms of HL-60/S4 Cells	The acute myeloblastic leukemia cell line HL-60 can be differentiated in vitro from a rapidly growing promyelocytic form to a nongrowing form, resembling neutrophils with segmented (lobulated) nuclei, by the addition of retinoic acid. Treating the undifferentiated cells with phorbol ester (TPA) leads to rapid cessation of cell division and attachment of the treated cells to culture dishes, exhibiting characteristics of macrophage. The rapidly differentiating subline HL-60/S4 has been used to study nuclear shape, chromatin structure and cytoskeletal changes during differentiation induced by RA and TPA. This study seeks to understand phenotypic properties of the differentiated granulocyte and macrophage forms of HLA-60/S4 by examining through RNA-Seq the transcriptional differences between RA- TPA- and untreated cells 4 days after exposure.	Co-expression
SRP066632	HER2 expression identifies dynamic functional states within circulating breast cancer cells	Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2- primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2+ and HER2- subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2- circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2- circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2+ and HER2- circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2- phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance. Overall design: Seventy-four single candidate CTCs from two representative ER+/HER2- patients (BRx-42 and BRx-82) and 14 triple negative patients were isolated via micromanipulation and subjected to single-cell RNA-sequencing. Thirteen candidate CTCs expressed PTPRC at a level higher than 10 reads-per-million, so were deemed potential White Blood Cells and therefore dropped from further consideration. Expression profiles of CTCs expressing ERBB2 at a level greater than 10 RPM were compared with those expressing ERBB2 at a level less than 10 RPM.	Co-expression
SRP066663	Aberrant downstream mechanisms following loss of KMT2C and KMT2D in Pancreatic Ductal Adenocarcinoma	Genes encoding the histone H3 lysine 4 (H3K4) methyltransferases KMT2C and KMT2D are subject to deletion and mutation in pancreatic ductal adenocarcinomas (PDAC). We examined the functional and transcriptional consequences of loss of these methyltransferases in patients with PDAC. Patients with low KMT2C and KMT2D expression demonstrated a much-improved outcome compared with those expressing high levels. RNA-seq analysis of KMT2C or KMT2D loss in three cell lines (PANC1, SUIT2 and COLO357) identified 31 and 124 differentially expressed genes respectively, with 19 genes common to both methlytransferases. Gene set enrichment analysis, and correlation with publicly available patient gene expression (GEP) datasets, highlighted significant reductions in pathways relating to cell-cycle and cell growth, where gene expression correlated with KMT2C/D depletion. Furthermore, loss of Kmt2d in three murine cell lines increased sensitivity to the nucleoside analogue 5-fluorouracil (5FU). These experiments support critical, non-redundant, roles for KMT2D and KMT2C in PDAC, where depletion impacts cell-cycle to reduce cell proliferation, enhance response to specific chemotherapy, which may improve patient survival. Overall design: Investigation of changes in whole transcriptomes with KMT2C/D loss by siRNAs using RNA-seq in three human cell lines	Co-expression
SRP066672	Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation	The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt. Overall design: triplicate experiment of 2 conditions (untreated, GTPP treatment)	Co-expression
SRP066729	Muscle transcriptome analysis following Total Knee Arthroplasty with Tourniquet	Transcriptome profiling was performed on muscle biopsies from patients immediately before Total Knee Arthroplasty and two hours after TKA and tourniquet application. Overall design: RNA was isolated from 10 patients who were give vastus lateralis muscle biopsies immediately before surgery and 2 hours post surgery with tourniquet	Co-expression
SRP066737	Pan-cancer transcriptomic analysis associates long non-coding RNAs with key driver mutational events	We transfected the lung cancer cell line A549 with either siRNAs targeting NFE2L2 or ctrl siRNAs.The total RNA was extracted from the cells (3 siRNAs targeting NFE2L2, 2 ctrl siRNAs (each with two replicates), and one Mock) and RNA-seq was performed on RNA from these cells.	Co-expression
SRP066781	Single-cell indexed RNA-Seq of human hematopoietic stem and progenitors	To characterize early human hematopoiesis on a single-cell level we developed an approach termed index-omics, which combines flow-cytometric, single-cell transcriptomic and single-cell lineage fate data. Healthy human bone marrow was labeled with a panel of up to 11 FACS surface markers commonly used to identify human hematopoietic stem and progenitor cells (HSPCs). Lin-CD34+38+ progenitors and Lin-CD34+CD38- stem cell enriched HSPCs were individually sorted, their surface marker fluorescence intensities recorded, and subjected to single-cell RNAseq or single-cell ex vivo cultures. Overall design: For transcriptomics, human bone marrow was stained with antibodies against Lineage markers (CD4, CD8, CD11b, CD14, CD19, CD20, CD56 and CD235a), CD7, CD10, CD34, CD38, CD45RA, CD49f, CD90 and CD135. For individual 1, 8 96-well plates of Lin-cd34+cd38+ and 6 96 well plates of Lin-cd34+cd38- cells were sorted into lysis buffer and subjected to a modified smart-seq2 protocol. For individual 2, 4 96-well plates of Lin-cd34+cd38+, 7 plates of Lin-cd34+cd38- and 1 plate of Lin-cd34+cd38-cd45RA-cd90+ were sorted into lysis buffer and subjected to QUARTZ Seq (Sasagawa et al 2013). For single-cell culture, human bone marrow from a third individual was stained with antibodies against CD2, CD34, CD38, CD45RA, CD71, CD90, CD130, CD135, FCER1A, KEL and a Lineage cocktail as above, plus CD10. Lineage output was then determined by automated FACS following prolonged ex-vivo cultivation. The files transcriptomics_raw_filtered_I1.csv and transcriptomics_raw_filtered_I2.csv contain the raw read counts for the cells that passed quality control. transcriptomics_normalized_filtered_I1.csv and transcriptomics_raw_filtered_I2.csv contain the readcounts normalized by posterior odds ratio (POR) as described in our manuscript. The files transcriptomics_facs_indeces_filtered_I1.csv and transcriptomics_facs_indeces_filtered_I2.csv contain the FACS surface marker expression for the cells that passed filter. Additionally, FACS surface marker expression is given as a characteristic of each sample. The file culture_data.csv contains the FACS surface marker expression, quantification of cell types in the mature colony, and scoring of colony type of the cells that were subjected to ex-vivo culture.	Co-expression
SRP066789	Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [ESRP KD]	Epithelial specific splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) are important regulators of alternative splicing during EMT. To study the alternative splicing events regulated by ESRP1/2 at a genome wide scale, we used lentiviral shRNAs to knockdown ESRP1/2 in H358 cells and performed RNA-seq in biological triplicates. Overall design: We used lentiviral based shRNAs targeting ESRP1 and ESRP2 to knockdown both regulators in human H358 cells. We harvested total RNA and protein from ESRP1/2 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.	Co-expression
SRP066793	Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [RBM47 KD]	RBM47 is a RNA binding protein that is known to regulate alternative splicing. To study the genome wide regulatory role of RBM47 in alternative splicing and determine the potential function of RBM47 during EMT, we used lentiviral shRNAs to knockdown RBM47 in H358 cells and performed RNA-seq in biological triplicates. Overall design: We used lentiviral based shRNAs to knockdown RBM47 in human H358 cells. We harvested total RNA and protein from RBM47 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.	Co-expression
SRP066794	Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [EMT.time course]	The epithelial to mesenchymal transition (EMT) is an essential biological process during embryonic development and has also been implicated in cancer metastasis. Previous studies have characterized transcriptional regulation and key transcription factors that impact EMT. However, the role of alternative splicing (AS) regulation in EMT has only recently emerged and remains relatively uncharacterized. Here we used a robust in vitro EMT model to dynamically and comprehensively characterize splicing switches during EMT in a temporal manner. Overall design: We generated a H358 clone stably expressing a doxycycline (Dox)-inducible cDNA encoding a Zeb1-mCherry fusion protein. Over a 7-day time course following Dox treatment, cells have undergone EMT. We harvested total RNA and protein at each day of the EMT time course and a no Dox-treated control in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.	Co-expression
SRP066818	Activation of the IGF1 pathway mediates changes in cellular contractility and motility in single-suture craniosynostosis	We examined the effect pg IGF1 actibation on cellular contractility and migration in SSC osteoblast cells. Based on microarray levels of IGF1 expression, we selected fifteen cases and nine controls spanning from the highest IGF1 expression to the lowest in cases and controls. Subsequently, the pattern of IGF1 expressions in these cells was assessed using high throughput RNA sequencing. Overall design: RNA-seq based gene expression profiling of fifteen SSC osteoblasts and nine control osteoblasts.	Co-expression
SRP066834	Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.	Cerebral organoids – three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells – have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. Overall design: 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).	Co-expression
SRP066865	miRNA-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors [RNA-seq]	miRNA-1343 is an uncharacterized miRNA predicted to target a number of genes involved in epithelial cell function including TGF-beta signaling, cell adhesion, and cell proliferation. We transiently overexpressed miRNA-1343 or a non-targeting control miRNA in A549 and 16HBE14o- human airway cell lines. As predicted, RNA-seq following miRNA-1343 overexpression showed significant downregulation of genes involved in these pathways. Furthermore, genes involved in cholesterol and lipid biosynthesis were found to be significantly upregulated by miRNA-1343 overexpression. Overall design: mRNA profiles from A549 and 16HBE14o- cells transiently transfected with miRNA-1343 or a negative control (NC) miRNA, in quintuplicate.	Co-expression
SRP066895	Gene expression profiles in NORAD knockout and PUMILIO overexpressing cells	Purpose: PUMILIO proteins are known to repress target genes by specifically binding to PUMILIO response elements (PREs) in target mRNAs.  NORAD is a noncoding RNA that negatively regulates PUMILIO activity. The goal of this study was to determine the gene expression changes that result from knockout of NORAD or overexpression of PUMILIO and to test whether NORAD knockout causes PUMILIO hyperactivity. Methods: RNA-seq libraries were prepared using the TruSeq Stranded Total RNA with Ribo-Zero Human/Mouse/Rat Sample Preparation kit (Illumina) and sequenced using the 100 bp paired-end protocol on an Illumina HiSeq 2000.  For comparing NORAD+/+ and NORAD-/- HCT116 cells, 3 biological replicates per genotype were sequenced.  For PUM overexpression experiments, 3 replicates of GFP-expressing HCT116 cells (negative control) and 2 independent PUM1- or PUM2-overexpressing clones (2 replicates each) were sequenced. Results: Gene expression profiles show that PUMILIO target genes are downregulated in both NORAD knockout cells and PUMILIO overexpressing cells. Conclusions: These data indicate that NORAD sequesters PUMILIO, preventing excessive repression of PUMILIO target genes that are important for maintaining genomic stability. Overall design: Gene expression profiles of genetically modified HCT116 cells were determined by RNA-seq.	Co-expression
SRP066912	DNA repair in species with extreme lifespan differences	We compared RNA-seq expression patterns in liver, an organ with high oxidative metabolism and abundant spontaneous DNA damage, from humans, naked mole rats, and mice, differing in maximum lifespan over a range of ~100, 30, and 3 years, respectively, for 130 genes involved in DNA repair. The results show that the longer-lived species, human and naked mole rat, share higher expression of these DNA repair genes, including core genes in several DNA repair pathways. A more systematic approach of signaling pathway analysis (SPA) indicates statistically significant upregulation of several DNA repair signaling pathways in human and naked mole rat compared with mouse. Overall design: Compare steady-state RNA levels from 3 samples each of adult liver tissue of human, naked mole rat, and mouse. Mouse samples available in the Short Reads Archive: SRX871336, SRX871370, SRX871395 (SRP053350) and BioProject PRJNA274780.	Co-expression
SRP066917	CRISPR-Cas9 based screen for p53-bound enhancers that function in oncogene-induced senescence	We exained using RNA-seq the effect of targeting selected p53-bound enhancers on the p53-induced response to oncogenic stress Overall design: RNA-seq was applied to examine transcriptional response to oncogenic stress (induced by RASG12V activation) in control and genetically manipulated hTERT-immortalized BJ cells	Co-expression
SRP066934	Homo sapiens cultivar:Caki-1 Transcriptome or Gene expression	Human cancer cells are subjected to hypoxic conditions in many tumours. Hypoxia causes alterations in glycolytic pathway activation through stabilization of hypoxia-inducible factor-1. Currently, two approaches are commonly used to model hypoxia: alternatively to generating low-oxygen condition in an incubator, cells can be treated with CoCl2. We performed RNA-seq experiments to study transcriptomes of human Caki-1 cells under real hypoxia and after CoCl2-treatment. Despite causing transcriptional changes of much higher order of magnitude for the genes in hypoxia regulation pathway, CoCl2-treatment fails to induce alterations in glycolysis/gluconeogenesis pathway. Moreover, CoCl2 caused aberrant activation of other oxidoreductases in Glycine, Serine and Threonine metabolism pathways.	Co-expression
SRP066947	Massive reshaping of genome - nuclear lamina interactions during oncogene induced senescence	Background. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene.Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL.Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.	Co-expression
SRP066956	Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition	Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic. Overall design: Examination of mRNA levels of PC9 parental, drug-tolerant, PC9-GR2 and PC9-GR3 cells after treatment with vehicle, gefitinib or WZ4002 for 24 hours.	Co-expression
SRP066963	Dissecting the clonal nature of allelic expression in somatic cells by single-cell RNA-seq	Cellular heterogeneity can emerge from the expression of only one parental allele, however it has remained unknown to what degree patterns of random monoallelic expression of autosomal genes (aRME) are mitotically inherited (clonal) or stochastic (dynamic) in somatic cells. Here, we resolved this by applying allele-sensitive single-cell RNA-seq on primary mouse fibroblasts and in vivo human T-cells to simultaneously investigate clonal and dynamic aRME. Dynamic aRME affected a considerable portion of the transcriptome, with levels dependent on the cell’s transcriptional activity, but clonal aRME was surprisingly scarce (<1% of genes) and affected mainly lowly expressed genes. Consequently, the overwhelming portion of aRME occurs transiently and is scattered throughout somatic populations rather than, as previously hypothesized, confined to spatially restricted patches of clonally related cells. Overall design: Cells were collected from in vitro clonal expansions, or from tissue or blood, to study the effect of relatedness and cell size on allele-specific expression	Co-expression
SRP066966	IL-10 dysregulation in acute mountain sickness revealed by transcriptome analysis	Acute mountain sickness (AMS), which may progress to life-threatening high altitude cerebral edema, is a major threat to millions of people who live in or travel to high altitude. Although studies have revealed the risk factors and pathophysiology theories of AMS, the molecular mechanisms of it do not comprehensively illustrate. Here, we used a system-level methodology, RNA sequencing, to explore the molecular mechanisms of AMS at genome-wide level in 10 individuals. After exposure to high altitude, a total of 1,164 and 1,322 differentially expressed transcripts were identified in AMS and non-AMS groups, respectively. Among them, only 328 common transcripts presented between the two groups. Immune and inflammatory responses were overrepresented in participants with AMS, but not in non-AMS individuals. Anti-inflammatory cytokine IL10 and inflammation cytokines IF17F and CCL8 exhibited significantly different genetic connectivity in AMS compared to that of non-AMS individuals based on network analysis. IL10 was down-regulated and both IF17F and CCL8 were un-regulated in AMS individuals. Moreover, the serum concentration of IL10 significantly decreased in AMS patients after exposure to high altitude (p = 0.001) in another population (n=22). There was a large negative correlation between the changes of IL10 concentration, r(22) = -0.52, p =  0.013,  and Lake Louise Score. Taken together, our analysis provides unprecedented characterization of AMS transcriptome and identifies that genes involved in immune and inflammatory responses were disturbed in AMS individuals by high altitude exposure. The reduction of IL10 after exposure to high altitude was associated with AMS. Overall design: Transcriptome from blood samples of AMS and non-AMS individuals were measured and analyzed before their departure and upon their arrival at high altitude (5300m).	Co-expression
SRP066968	Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers	We examined the transcriptional chagnes modulated by ECBI-11 by perfroming global transcriptome analysis. ZR75 cells were treated with either control or ECBI-11 in the presence of E2 for 48 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that ECBI modulated several genes that are involved in cell cycle, breast cancer signaling, estrogen signaling and apoptosis. Overall design: Total RNA was isolated from the ZR75  cells that were treated with vehicle or ECBI for 48 h. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.	Co-expression
SRP066982	Single cell RNA sequencing of primary breast cancer.	We performed single cell RNA sequencing (RNA-seq) for 549 primary breast cancer cells and lymph node metastases from 11 patients with distinct molecular subtypes (BC01-BC02, estrogen receptor positive (ER+); BC03, double positive (ER+ and HER2+); BC03LN, lymph node metastasis of BC03; BC04-BC06, human epidermal growth factor receptor 2 positive (HER2+); BC07-BC11, triple-negative breast cancer (TNBC); BC07LN, lymph node metastasis of BC07) and matched bulk tumors. We separated these single cells into epithelial tumor and tumor-infiltrating immune cells using inferred CNVs from RNA-seq. The refined single cell profiles for the tumor and immune cells provide key expression signatures of breast cancer and the surrounding microenvironment. Overall design: All single-cell mRNA expression profiles were acquired from eleven patients (BC01-BC11) including two lymph node metastases (BC03LN, BC07LN) (549 samples). We applied four filtering criteria so as to remove samples with low sequencing quality and finally obtained 515 single cell sequencing data. Matched bulk tumor tissues and/or pooled cells were also sequenced and analyzed by the single cell RNA-seq pipeline (14 samples). Bulk tumor transcriptomes showed significant correlations with the average of single cell transcriptomes.	Co-expression
SRP066992	Transcriptome profiling of influenza virus-infected human bronchial epithelial cells	We report the whole genome sequencing of human bronchial cells infected with influenza A (PR/8/34) for 8 or 24 h. Overall design: Examination influenza virus-specific human gene profiling at early or late stage of viral infection.	Co-expression
SRP066994	Human Embryoid Body Transcriptomes Reveal Maturation Differences Influenced by Size and Formation in Custom Microarrays	Stem cell differentiation strategies and optimization for generating lineage-specific cells and tissues most frequently rely on a three-dimensional embryoid body (EB) intermediate. We previously applied nanotechnology tools of photolithography to generate custom microarrays that allow high throughput uniform formation of EBs of custom size for precise downstream analysis. Formation of EBs of 200 or 500 micron size revealed distinct morphological differences that are single or multicystic cores, respectively, independent of method of formation from single cells or two-dimensional (2D) clusters. Here we utilize photolithographic array generated EBs to obtain 3D cultures under a standardized platform for transcriptome analysis to compare EB size and the method of EB formation from single cells or mechanically passaged 2D clusters. Our analysis evaluates RNA expression in EBs formed from the human embryonic stem cell (hESC) line WA09 and from ethnically diverse human induced pluripotent stem cell lines (ED-iPSC) of African American and Hispanic Latino ethnicity recently derived in our laboratory. This is the first comprehensive study on EB transcriptomes including multiple size parameters, EB formation methodologies, and ethnicities. Our analysis indicates upregulation of genes involved in wound healing for mechanically passaged cells and of genes for embryonic tube formation in 500 micron multicystic EBs. We propose that EB maturation may be a longer process then previously realized. In addition, the type or extent of maturation possible may be influenced by EB size, with larger EBs capable of more extensive remodeling as revealed by multicystic morphology and initiation of early tube formation pathways while retaining pluripotency status. We anticipate that this information will be broadly useful to the stem cell and bioengineering communities in optimization of tissue engineering with pluripotent stem cells and understanding sources of variation. Overall design: mRNA profiles by RNA-seq from embryoid bodies generated by different methods	Co-expression
SRP067004	Generation of nephronal cells from human pluripotent stem cells via renal-vesicle formation	Human pluripotent stem cells (hPSC) provide a possible source for generation of kidney cells and organoids applicable in regenerative medicine, disease modeling and drug screening. By analyzing the effect of different factors on renal differentiation, we established an 8-day-protocol that steered hPSCs to the renal lineage by a step-wise process, segmented into mesoderm induction, intermediate mesoderm specification and metanephric induction outlining renal organogenesis. The differentiated cells contain populations of SIX2+/CITED1+ metanephric mesenchyme- (MM) and of HOXB7+/GRHL2+ ureteric bud (UB)-like cells at the end of 6 days. Transcriptome analysis corroborated that the in vitro generated precursor cell types at day 8 resemble their renal vesicle counterparts in vivo. The cells were further differentiated in 2-dimensional culture into podocyte- and diverse tubular epithelial-like cell types, showing their nephrogenic potential. In 3-dimensional culture, the progenitors gave rise to renal vesicles, and upon mouse embryonic kidney re-aggregation they form tubular structures. Overall design: Assessment of the progress of pluripotent stem cells towards a renal lineage at regular time points of a novel differentiation protocol.	Co-expression
SRP067012	Transcription profiling of neuronal metabolic reprogramming	we explored the changes in metabolic gene expression during neuronal differentiation from neural progenitor cells (NPC). Overall design: Examination of transcription profile in NPC and neurons.	Co-expression
SRP067017	Transcriptomic profiling of HeLa cells infected with Shigella flexneri	We evaluated the transcriptome changes induced by infection of Hela 229 cells with Shigella flexneri. The sample set consists of a control (mock), total population of infected sample and infected sample sorted into Shigella positive and Shigella negative population. Overall design: Transcriptmic profiles of HeLa cells infected with Shigella were generated by high throughput sequencing using Illumina HiSeq2000.	Co-expression
SRP067018	Transcriptomic profiling of HeLa cells treated with miR-29b-2-5p and control-miR	To have a global picture of the targets of the mir-29b-2-5p, we assessed transcriptome changes, by deep-sequencing, of HeLa cells transfected with this miRNA or a control miRNA (cel-miR-231). Overall design: Transcriptmic profiles of HeLa cells treated miR-29b-2-5p and control-miR  were generated by deep sequencing, using Illumina HiSeq2000.	Co-expression
SRP067025	The role of PRMT5/WDR77 complex in promoting breast cancer oncogenesis [RNA-Seq_HPTB]	Comprehensive RNA-seq experiments in DMSO and HPTB (inhibitor of PRMT5) treated cells delineate the role of PRMT5 complex in promoting breast cancer oncogenesis Overall design: RNA-seq was used to measure gene expression levels in DMSO and HPTB (inhibitor of PRMT5) treated human breast cancer cells	Co-expression
SRP067026	The role of PRMT5/WDR77 complex in promoting breast cancer oncogenesis [RNA-Seq]	Comprehensive RNA-seq experiments in control and PRMT5 and WDR77 shRNA infected cells delineate the role of PRMT5/WDR77 complex in promoting breast cancer oncogenesis Overall design: RNA-seq was used to measure gene expression levels in scrambled control, PRMT5 and WDR77 short hairpin RNA (shRNA) infected human breast cancer cells	Co-expression
SRP067036	Snapshot and temporal scRNA-seq of progenitor cells to dissect human embryonic stem cells entry into endoderm progenitors	Human pluripotent stem cells (hPSCs) offer a unique cellular model to study lineage specifications of the primary germ layers during human development. We profiled single-cell RNA-seq (scRNA-seq) on four lineage-specific progenitor cells derived from hESCs. Our scRNA-seq analyses revealed each type of progenitors display various extend of heterogeneity. Specifically, definitive endoderm cells (DECs) not only show a greater degree of heterogeneity, but are also enriched in metabolic signatures. Followed by detailed temporal scRNA-seq profiling along DEC differentiation, we reconstructed a differentiation trajectory using a novel statistical pipeline named Wave-Crest. Wave-Crest further identifies candidate regulators during the transitioning phase from Brachyury (T)+ mesendoderm towards CXCR4+ DEC state. To functionally test identified novel regulators; we generated a live cell monitoring system, a T-2A-EGFP knock-in reporter cell line via CRISPR/CAS9. We demonstrated that, among the top candidate genes, KLF8 plays a pivotal role modulating mesendoderm to DEC differentiation. In this submission, 1810 raw fastq files are provided; 212 are re-analysis from GSE64016. Four expected count matrices are provided - 1) 1018 single cells from snapshot progenitors; 2) 758 single cells from time couse profiling; 3) 19 bulk RNA-seq sample from snapshot progenitors; 4) 15 bulk RNA-seq sample from time course profiling. Overall design: Total 1018 single cells from snapshot progenitors and 758 single cells from time couse profiling. Matchd population bulk RNA-seq samples for both the progenitors snapshot (19 samples) and time course profiling (15 samples) also included in this submission. These data set are used to detect the transitioning phase from mesendoderm to definitive endoderm.	Co-expression
SRP067050	RNA-seq of poly(A)+, poly(A)- and poly(A)-/RNaseR RNAs from human PA1 cells	We have used RNA-seq to examine circular RNAs from poly(A)- and poly(A)-/RNaseR RNAs in human PA1 cells Overall design: In order to identify novel circular RNAs from PA1 cells	Co-expression
SRP067119	TT-Seq captures the human transient transcriptome	A large portion of the genome is transcribed but many of the resulting RNAs live only transiently and can generally not be mapped. Here we develop transient transcriptome sequencing (TT-Seq), a protocol that maps transcriptionally active regions in a nearly uniform manner and allows for unbiased monitoring of cellular RNA synthesis activity. Application of TT-Seq to human K562 cells recovers stable mRNAs and long intergenic non-coding RNAs, and additionally maps over 10,000 transient RNAs including enhancer RNAs, antisense RNAs, promoter-associated upstream antisense and convergent RNAs. TT-Seq also provides RNA half-lives, and reveals that transient RNAs are short and lack U1 motifs and secondary structure. TT-Seq further uncovers transcription termination sites and reveals a universal DNA motif for RNA polymerase II release. Overall design: TT-Seq is an adaptation of 4sU-Seq for human cells. The labeled RNA is fragmented prior to 4sU-purification, which leads to an overall enrichment of transient transcripts. 8 RNA-Seq (TT-Seq, 4sU-Seq, total RNA-Frag-Seq and total RNA-Seq; in biological duplicates) were sequenced on a HiSeq 1500	Co-expression
SRP067129	Image based identification and targeting of cancer stem cells in pancreatic adenocarcinoma (PDAC)	Purpose: The goals of this study were to identify quantitative gene expression differences between wild type,  Musashi1 null, Msuashi2 null and Musashi1/Musashi2 null MIAPaCa2 pancreatic cancer cells Overall design: mRNA profiles of MIA PaCa-2 cancer cells were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.	Co-expression
SRP067137	Homo sapiens Transcriptome or Gene expression	Transcriptome comparisons between two-dimensional and three-dimensional cultured JEG-3 trophoblasts, primary human trophoblast cells, and human brain microvascular endothelial cells (HBMEC).	Co-expression
SRP067154	Sequencing Universal Human Reference RNA by Smart-seq and early barcoding library preparation methods	Many library preparation methods are available for gene expression quantification. Here, we sequenced and analysed Universal Human Reference RNA (UHRR) prepared using Smart-Seq2, TruSeq (public data) and a protocol using unique molecular identifiers (UMIs) that all include the ERCC spike-in mRNAs to investigate the effects of amplification bias on expression quantification. Overall design: UHRR 10 and 12 replicates for Smart-seq2 and UMI-seq library preparation methods, respectively.	Co-expression
SRP067173	HSB-2 cells stably expressing LDB1 or mutant LDB1 proteins	LMO2 is a component of multisubunit DNA-binding transcription factor complexes that regulate gene expression in hematopoietic stem and progenitor cell development. Enforced expression of LMO2 causes leukemia by inducing hematopoietic stem cell-like features in T-cell progenitor cells, but the biochemical mechanisms of LMO2 function have not been fully elucidated.  In this study we systematically dissected the LMO2/LDB1 binding interface to investigate the role of this interaction in T-cell leukemia.  Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif R320LITR required for LMO2 binding. Most strikingly, co-expression of full length, wild type LDB1 increased LMO2 steady state abundance, whereas co-expression of mutant proteins deficient in LMO2 binding compromised LMO2 stability. These mutant LDB1 proteins also exerted dominant negative effects on growth and transcription in diverse leukemic cell lines. Raw gene expression data on HSB-2 cells is presented here. Overall design: RNAseq were performed on HSB cell lines to examine their expression patterns	Co-expression
SRP067175	Transposon mutagenesis reveals fludarabine-resistance mechanisms in chronic lymphocytic leukemia	Purpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools	Co-expression
SRP067184	Cerebellar differentiation in Ataxia-Telangiectasia	Control (CRL2429 C11) and A-T (MC3/AT30) iPSC were differentiated according to Erceg et al to generate cerebellar precursors Overall design: Examination of changes in gene expression after a 34 day differentiation protocol in control and A-T iPSC	Co-expression
SRP067192	Activation of Wnt/beta-catenin in Ewing sarcoma cells antagonizes EWS/ETS function and promotes phenotypic transition to more metastatic cell states	Ewing sarcomas are characterized by the presence of EWS/ETS fusion genes in the absence of other recurrent genetic alterations and mechanisms of tumor heterogeneity that contribute to disease progression remain unclear. Mutations in the Wnt/beta-catenin pathway are rare in Ewing sarcoma but the Wnt pathway modulator LGR5 is often highly expressed, suggesting a potential role for the axis in tumor pathogenesis. We evaluated beta-catenin and LGR5 expression in Ewing sarcoma cell lines and tumors and noted marked intra- and inter-tumor heterogeneity. Tumors with evidence of active Wnt/beta-catenin signaling were associated with increased incidence of tumor relapse and worse overall survival. Paradoxically, RNA sequencing revealed a marked antagonism of EWS/ETS transcriptional activity in Wnt/beta-catenin activated tumor cells. Consistent with this, Wnt/beta-catenin activated cells displayed a phenotype that was reminiscent of Ewing sarcoma cells with partial EWS/ETS loss of function. Specifically, activation of Wnt/beta-catenin induced alterations to the actin cytoskeleton, acquisition of a migratory phenotype and up regulation of EWS/ETS-repressed genes. Notably, activation of Wnt/beta-catenin signaling led to marked induction of tenascin C (TNC), an established promoter of cancer metastasis, and an EWS/ETS-repressed target gene. Loss of TNC function in Ewing sarcoma cells profoundly inhibited their migratory and metastatic potential. Our studies reveal that heterogeneous activation of Wnt/beta-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing sarcoma. Significantly, this is mediated, at least in part, by inhibition of EWS/ETS fusion protein function that results in de-repression of metastasis-associated gene programs. Overall design: Differential gene expression in highly Wnt-responsive cells.	Co-expression
SRP067214	Human RNase L Tunes Gene Expression by Selectively Destabilizing the MicroRNA-Regulated Transcriptome	Purpose: The goal of this study was to map the pathway of mRNA decay by human RNase L Methods: Total RNA was extracted (RNeasy kit, Qiagen). RNA integrity was verified by an RNA 6000 Nano Chip, using BioAnalyzer and 2100 Expert software (Agilent Technologies). The mRNA was enriched by oligo-dT pulldown from total RNA, followed by fragmentation, adapter ligation, PCR amplification, and finally sequencing on Illumina HiSeq 2000 platform. For sequencing introns, the oligo-dT pulldown step was replaced with Ribo-Zero rRNA removal (Illumina). Sequencing reads were mapped to the human genome hg19 using TopHat 2  set to map stranded reads with default parameters. Mapped read counts were obtained using HTseq-count run in union mode. Results: We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and non-targets. We show that this RNase L-dependent decay (RLDD) selectively affects transcripts regulated by miR-17/miR-29/miR-200 and other microRNAs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these microRNAs and acts as a suppressor of proliferation and adhesion in mammalian cells. Conclusions: Our data suggest that RLDD serves to establish an anti-proliferative state via destabilization of the microRNA-regulated transcriptome. Overall design: Human mRNA profiles from HeLa, T47D and HAP1 cells were generated by deep sequencing using Illumina Illumina HiSeq 2000.	Co-expression
SRP067221	RNA sequencing of human neural progenitor cells, SK-N-SH, following CHD8 knockdown	Chromodomain helicase DNA-binding protein 8 (CHD8) was previously identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. The present study used small interfering RNA-mediated knockdown of CHD8 in the human neural progenitor cell line, SK-N-SH, in order to determine the consequences of altered expression of this gene. RNA sequencing was performed following CHD8 knockdown to identify differentially expressed genes and affected molecular pathways resulting from this manipulation. This study sheds light on the functional consequences of altered CHD8 expression and may provide insight into the molecular underpinnings of autism spectrum disorder.	Co-expression
SRP067289	RNA-seq analysis of the human fetal kidney.	Micro-dissection and FACS were used to isolate tissue and cells, respectively, for RNA-seq analyses of the developing human kidney. Specifically, ITGA8 and ROR2 antibodies were used to isolate cells of the nephron progenitor lineage, and representative tissue samples of the outer cortex and whole kidney were collected, to obtain information on the transcripts expressed within these cell populations. These data will further our understanding of human kidney development. Overall design: Total RNA was obtained from micro-dissected and FACS isolated cells from 15-17 week human fetal kidneys. ITGA8 and ROR2 were used to enrich for nephron progenitors. Micro-dissected samples were representative of the outer cortex and whole kidney. Isolated RNA was subjected to high throughput sequencing analyses to identify expressed transcripts.	Co-expression
SRP067312	Transcriptome analysis of human, pig and bat cell lines infected with Zaire ebolavirus	RNAseq of human, bat and pig following ebolavirus infection	Co-expression
SRP067318	Homo sapiens Transcriptome or Gene expression	A549 RNA-seqs	Co-expression
SRP067329	RNA-seq Generated Transcriptional Profile of H2O2 Treated HCT116 vs. Untreated HCT116	Oxidative stress, is considered to be a key risk state for a variety of human diseases, which can upregulate transcriptional expression of DNA repair genes. However, it remains elusive whether all or just a portion of DNA repair genes can be upregulated in response to oxidative stress. Therefore, the changes in expression pattern of DNA repair genes and how they are regulated in response to oxidative stress need to be elucidated. In this study, we performed RNA-seq to generate expression profile and identified subsets of induced and repressed DNA repair genes in colorectal cancer cell line exposure to hydrogen peroxide. Overall design: Total RNAs were extracted from H2O2-treated HCT116 and untreated HCT116 cells with RNeasy Mini Kit (QIAGEN, Germany). Quality control was performed using Bioanalyser 2100 (RNA nano kits, Agilent). mRNA-Seq libraries were generated from total RNA with polyA+ selection of mRNA using the TruSeq RNA Sample Prep Kit v2 (Illumina, San Diego, CA), and then subjected to transcriptome sequencing on the Illumina Hiseq 2000	Co-expression
SRP067352	Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts	Recently, we identified mesenchymoangioblast (MAB), as a clonal mesodermal precursor for mesenchymal and endothelial cells. Here we show, that MABs have the capacity to produce mesenchymal progenitors, which can be differentiated into pericytes or smooth muscles cells under the influence of PDGF-BB or TGFß plus sphingosylphosphorylcholine (SPC), respectively. Based on these studies we established the hierarchy of vasculogenic progenitors that provides the platform for interrogation of molecular mechanisms regulating vasculogenic cell specification and diversification from primitive posterior mesoderm. Overall design: Vasculogenic cells generated under specific culture conditions. Primary cells were used as control.	Co-expression
SRP067392	Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell tissue engineering	A goal of this project is to evaluate the integrin mRNA expression in human neural stem/progenitor cells (hNSPC) using high-throughput sequencing technologies. We found high levels of mRNA expression for the  ß1, a7, a3, a6, ß5, aV, a5, and a9 integrins. This suggests that hNSPCs may express integrin receptors that can bind fibrinogen and laminin proteins. Overall design: mRNA profiles of hNSPCs from three different passages (12, 15, and 17) were generated by deep sequencing using Illumina HiSeq 2500.	Co-expression
SRP067400	LncPRESS1 is a p53-regulated lncRNA that safeguards pluripotency by disrupting SIRT6 mediated de-acetylation of histone H3K56	Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs, highly expressed in pluripotent hESCs and repressed by p53 during differentiation, to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors. RNA-seq of hESCs depleted of lncPRESS1 revealed that lncPRESS1 controls a gene network that promotes pluripotency. Further, we found that lncPRESS1 physically interacts with SIRT6 to prevent SIRT6 chromatin localization and maintain high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a novel pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity Overall design: TP53 KD RNA-seq with and without RA, lncRNA KD RNA-seq in H9 human Embryonic Stem cells (hESCs)	Co-expression
SRP067401	Pluripotent stem cell disease modeling of GATA6 haploinsufficiency in human pancreatic development	To better understand molecular mechanisms of human pancreatic development associated with GATA6 haploinsufficiency, we performed RNA-seq analysis to characterize the biological processes affected by GATA6 heterozygous mutation. We identified 542 differential expression genes in the mutants, of which 310 were downregulated. Gene ontology analysis showed that top downregulated transcription factors were associated with developmental process. Overall design: Examination of two wild-type and two GATA6-/+ HUES8 lines at the PP1 stage using the first-generation pancreatic differentiation protocol	Co-expression
SRP067469	Effects of Freeze-Thawing and Intravenous Infusion on Mesenchymal Stromal Cell Gene Expression	Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the microenvironment that the cells encounter after administration may impact the properties of MSC. It has been demonstrated that the large majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the effect of freeze-thawing and of the mouse lung microenvironment on human adipose tissue-derived MSC. The effect of freeze-thawing on the whole genome expression profile of MSC was small and did not exceed inter-donor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells after blood exposure in vitro and after infusion to mice. Exposure for 2h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological and metabolic pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and that disease specific conditions may shape MSC after administration. Overall design: 3 groups, n=3 per group + 1 negative control	Co-expression
SRP067481	Homo sapiens Raw sequence reads	Specific drug treatment to inhibite the SMCC7721 liver cancer cell proliferation	Co-expression
SRP067492	Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells	Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation. Overall design: Human embryonic stem cells (hESCs) were differentiated to hepatocytes with SB203580(SB) and Vitamin K2 (VK2). Primary human hepatocytes (PHHs)were isolated from adult liver tissues and fetal human hepatocytes (FHHs) were isolated from aborted fetal liver. We used RNA sequencing to detail the global gene expression profile of ESCs-derived hepatocytes with the treatment of SB or VK2, untreated control (Ctrl), PHHs and FHHs to delineate the difference of these cells.	Co-expression
SRP067502	Homo sapiens Raw sequence reads	MicroRNA down-regulation and noise regulation	Co-expression
SRP067516	Homo sapiens Transcriptome or Gene expression	Tick-borne flaviviruses (TBFVs) are ss(+)RNA viruses that cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. 30—60% of people who recover from severe acute disease continue to suffer debilitating neurological sequelae due to viral persistence, neurological cell damage incurred during infection and/or host response, or a combination of these. When TBFVs infect mammalian cells in vitro, an acute phase characterized by dramatic apoptosis ensues and kills >95% of infected cells by day 5. Upon refreshing the cell growth medium, surviving cells repopulate and become persistently infected for extended periods of time. However, molecular mechanisms responsible for the initiation and maintenance of viral persistence in vivo and in vitro remain vague. We used unbiased deep sequencing of the HEK 293T cell transcriptome to determine the profiles of acutely infected cells at selected time points as well as of persistently infected cells. Many genes were significantly differentially expressed during the course of the acute phase, but 451 genes were significantly differentially expressed uniquely in persistently infected cells. Ingenuity Pathways Analysis of these genes suggested that the oncogenes AKT2 and ERBB2, which favor cell survival were up-regulated in persistently infected cells, whereas pro-apoptotic genes, such as Bad and IFN-ß1 were down-regulated. There was also an up-regulation of genes encoding antiviral cytokines, such as CCL5, TNF-a and CXCL10 during the acute phase, but these were relatively suppressed in persistently infected cells. Exogenous induction of apoptosis in persistently infected cells with chelerythrine chloride indicated that these cells were resistant to apoptosis in a dose-dependent manner. In summary, the transcriptome profiles of acutely and persistently infected HEK 293T cells are different and evasion of apoptosis is critical for the initiation of TBFV persistence. These results provide a basis for further studying the precise molecular mechanisms of TBFV persistence.	Co-expression
SRP067524	Homo sapiens Transcriptome or Gene expression	RNA-Seq of sub-types of adenoic cystic carcinoma of salivary gland	Co-expression
SRP067526	Transcriptomic analysis of human neural progenitor cells differentiation into astrocytes	In this study we isolated and cultured neural progenitor cells (NPCs) from human fetal brain collected during the gliogenic phase (second trimester) of aborted fetuses, we differentiated NPCs into astrocyte using different protocols (FBS or CNTF/BMP4) and utilized RNA sequencing to analyze transcriptomic changes underlying the differentiation process Overall design: Neural progenitor cells (NPCs) isolated from 4 different donors  (91, 103, 110 and 114 days embryos) were differentiated for 1 week using 2.5% FBS, while 3 NPCs lines (two from 103 and one from 110 days embryo) were differentiated for 1 week in the presence of CNTF/BMP4. RNA was extracted from NPCs before and after differentiation and submitted for sequencing on the Illumina HiSeq 2000 platform	Co-expression
SRP067529	Effect of mitochondria deficiency on senescence-associated gene expression	We used parkin –overexpressing MRC5 fibroblasts to investigate the role of mitochondria deficiency on senescence-associated gene expression. Overall design: RNA-seq analysis on proliferating and senescent Parkin-expressing MRC5 fibroblasts treated with CCCP (treated) or DMSO (Untreated).	Co-expression
SRP067568	Transcriptome profiling of hnRNP A2/B1 and A1 depleted cells	We used NEBNext Ultra Directional RNA Library Prep Kits to prepare RNA-seq libraries of total RNA from hnRNP A2/B1 and A1 depleted A549 cells. Pro-seq libraries were prepared from A549 cells using Illumina adapters Overall design: hnRNP A2/B1 and A1 depleted A549 cells were generated by lentiviral infections of shRNA constructs. RNAs were isolated using Trizol.	Co-expression
SRP067585	Comparative transcriptomic analysis of human and Drosophila extracellular vesicles reveals extensive conservation	Extracellular vesicles (EVs) are membrane-enclosed nanoparticles containing specific repertoires of genetic material. In mammals, EVs can mediate the horizontal transfer of various cargos and signaling molecules, notably miRNA and mRNA species. Whether this form of intercellular communication prevails in other metazoans remains unclear. Here, we report the first parallel comparative morphologic and transcriptomic characterization of EVs from Drosophila and human cellular models. Electronic microscopy revealed that Drosophila, like human cells release exosome-like EVs with diameter ranging from 30 to 200 nm, which contain complex populations of transcripts. RNA-seq identified abundant ribosomal RNA pseudogenes and retrotransposons in human and Drosophila EVs. Vault RNAs and Y RNAs abounded in human samples, whereas small nucleolar RNAs involved in pseudouridylation were most prevalent in Drosophila EVs. Numerous mRNAs were identified, largely consisting of exonic sequences displaying full-length read coverage and enriched for translation and electronic transport chain functions. By analogy with human systems, these extensive similarities suggest that EVs could also enable RNA-mediated intercellular communication in Drosophila. Overall design: We performed RNA-seq on extracellular vesicles purified from of human and Drosophila cell line cultures. S2R+ and D17 Drosophila EVs were analyzed, along with human A431 and HepG2 EVs.  No ribosomal RNA depletion or polyA selection was performed on EV samples. For comparative analyses, we also analyzed total cellular RNA from Drosophila D17 and human HepG2. Ribodepletion was performed on cellular samples.	Co-expression
SRP067630	Transcriptome profiling of Caki2 cells re-expressing Polybromo-1 (PBRM1)	PBRM1 is a component of the PBAF chromatin remodelling complex and has been observed to be deregulated in a significant proportion of patients with clear-cell Renal Cell Carcinoma (ccRCC). This study employs RNA-Seq to identify differentially expressed genes in cellular models of ccRCC by expressing PBRM1 in PBRM1-deficient Caki2 cells. Overall design: Using lentiviral mediated mechanism, stable Caki-2 cell line expressing PBRM1 was developed (Caki2-PBRM1). Empty vector inserted in Caki2 cells served as control (Caki2-Ø)	Co-expression
SRP067631	Integrative genomics identifies the molecular basis of resistance to Azacytidine therapy in Myelodysplastic Syndromes	RNA-seq of bone marrow CD34+ cells of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients to identify at the molecular pathways involved in primary resistance to AZA therapy. Overall design: RNA-seq of bone marrow CD34+ cells of MDS and CMML patients at pre-treatment and after 6 cycles of AZA treatment to identify at the molecular pathways involved in resistance to AZA therapy.	Co-expression
SRP067645	Gene Expression Signatures of Motor Neuron Populations Isolated from Sporadic ALS	We used total RNA-sequencing (RNA-seq) to analyze ALS MN-specific gene-expression signatures in laser capture microdissected motor neurons from post-mortem lumbar spinal cords. Overall design: To obtain transcriptome-wide gene expression measurements in adult spinal motor neurons (MNs), we performed laser capture microdissection (LCM) of lumbar spinal cord sections from 13 sporadic ALS patients and 9 controls, extracted total RNA, made RNA-seq libraries and sequenced the libraries on Illumina GA II platform	Co-expression
SRP067661	Distinct routes of lineage development reshape the human blood hierarchy across ontogeny	In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34+ cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult ''two-tier'' hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis. Overall design: Using SMARTseq, the expression profile of the new subsets identified in the linked study (12 samples in duplicates) were analyzed using RNA sequencing. The indicated subsets are all derived from neonatal cord blood.	Co-expression
SRP067666	DNA breaks and chromatin structural changes enhance the transcription of Autoimmune Regulator target genes [RNA-Seq]	The Autoimmune Regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T-cells by promoting the ectopic expression of tissue-specific genes in thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA-seq, we found that the inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by topoisomerase 1 (TOP1) inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of ?H2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional upregulation to co-occur with the chromatin structural changes within the genomic cluster of carcino-embryonic antigen-like cellular adhesion molecule (CEACAM) genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. Overall design: RNA-seq of 8 AIRE-Tet cell line samples belonging to 4 experimental conditions, each in duplicate	Co-expression
SRP067748	Differential RNA-seq analysis comparing APC-defective and APC-restored SW480 colorectal cancer cells	Identify genes that are differentially regulated as a consequence of restoration of full-length functional APC in a colorectal cancer cell lines. Overall design: Examine mRNA expression level changes between SW480 (APC defective) and SW480+APC (SW480 cells with restored functional APC) cells, whilst accounting for any non-specific expression changes by comparison to SW480+control vector.	Co-expression
SRP067759	Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia	Single-cell whole transcriptome analysis of  chronic myeloid leukemia stem cells, defined as Lin-CD34+CD38-. Overall design: We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 single cells from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML stem cells, including the identification of a subgroup of CML stem cells with a distinct molecular signature that selectively persisted during prolonged therapy. We performed differential gene expression and the gene set enrichment analyses of BCR-ABL+ vs BCR-ABL- single cells from either patients or normal donors, analyzed at different stages of the disease.	Co-expression
SRP067762	Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity	Doxorubicin (Adriamycin) is an anthracycline chemotherapy agent effective in treating a wide range of malignancies1 with a well-established dose-response cardiotoxic side-effect that can lead to heart failure2-4. Even at relatively low cumulative doses of 200–250 mg/m2, the risk of cardiotoxicity is estimated at 7.8% to 8.8%4,5. Doxorubicin-induced cardiotoxicity (DIC) can range from asymptomatic reductions in left ventricular ejection fraction (LVEF) to highly symptomatic heart failure6,7. At present, it is not possible to predict which patients will be affected by DIC or adequately protect patients who are at risk for suffering this devastating side-effect8. Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate individual patients’ predilection to DIC at the single cell level. hiPSC-CMs derived from breast cancer patients who suffered clinical DIC are consistently more sensitive to doxorubicin toxicity, demonstrating decreased cell viability, mitochondrial/metabolic function, calcium handling, and antioxidant pathway gene expression, along with increased reactive oxygen species (ROS) production compared to hiPSC-CMs from patients who did not experience DIC. Together, our data indicate that hiPSC-CMs are a suitable platform for identifying and verifying the genetic basis and molecular mechanisms of DIC. Overall design: Comparision of the effect of 1uM doxorubicin for 24 h on gene expression in hiPSC-CM derived from 6 patients	Co-expression
SRP067827	Recurrent rearrangements of the Myb/SANT-like DNA-binding domain containing 3 gene (MSANTD3) in salivary gland acinic cell carcinoma	By transcriptome (RNAseq) analysis of 3 human acinic cell carcimoma (AcCC) cases, we discovered two novel gene fusions, and further validated recurrent rearrangement of the MSANTD3 gene. By RNAseq of engineered MSANTD3 overexpression in rat salivary epithelial cells (compared to vector control), we identifed elevated expression of genes involved in protein synthesis. Overall design: Transcriptional profiling of human acinic cell carcinoma cases was done using FFPE specimens, by rRNA depletion, Illumina Truseq library preparation, and Illumina 75x2 sequencing.  RNAseq of rat salivary epithelial cells overexpressing MSANTD3 (vs. empty vector control) was done by Truseq mRNA library preparation and Illumina 50x1 sequencing.	Co-expression
SRP067837	mRNA expression profile of Lymphocytes	Va24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer, represent promising therapeutic target. However, reduced iNKT-cell numbers and function have been observed in many patients with cancer. To overcome this obstacle, we reprogramed human iNKT cells to pluripotency and then redifferentiated into regenerated iNKT cells in vitro through IL-7/IL-15-based optimized cytokine combination. They showed proliferation and IFN-? production in response to a-galactosylceramide, induced dendritic cell maturation and downstream activation of cancer antigen-specific cytotoxic T lymphocytes in vitro, and exhibited NKG2D- and DNAM-1-mediated natural killer celllike cytotoxicity against cancer cell lines. Their immunological features and availability in an unlimited supply from induced pluripotent stem cells offer the potential to develop effective immunotherapies against cancer. Overall design: Expression profile of the lymphocytes (n = 17) by highthrouput sequencing	Co-expression
SRP067843	HNF1 regulates critical functions of the human epididymis epithelium. [RNA-Seq]	HNF1a and HNF1ß recognize the same DNA consensus sequence in the genome, to which they bind as homodimers or heterodimers. Both factors share a high degree of homology their DNA binding and dimerization (N-terminus) regions but have a more divergent C-terminal transactivation domain. HNF1ß is essential for the generation of a functional male reproductive tract in mice and genital tract abnormalities are evident in humans with recessive mutations in HNF1ß. The functions of HNF1a and HNF1ß have been studied in epithelia from other several tissues (liver, kidney, intestine, and pancreas) but their role in the adult human epididymis epithelium (HEE) remains unexplored. We established that HNF1a/ß are expressed in caput HEE cells and are predicted to occupy cis-regulatory elements in these cells. To investigate the contribution of HNF1 in controlling gene expression in caput cells we performed siRNA-mediated depletion of HNF1a and HNF1ß together, followed by RNA-seq analysis. Three replicas of caput cells were transfected with the specific siRNAs or with a non-targeting control siRNA. RNA-seq after HNF1 depletion showed significant alterations in the expression of genes encoding ion channels and exchangers that are involved in controlling the luminal environment in the caput epididymis. Overall design: mRNA profiles from Caput HEE cells transfected with negative control (NC) or HNF1alpha and HNF1beta siRNA, in triplicate.	Co-expression
SRP067844	Single Cell RNA-seq Study of Midbrain and Dopaminergic Neuron Development in Mouse, Human, and Stem Cells	In order to get a better molecular understanding of human midbrain development, this study defines cell types of the ventral midbrain in both human and mouse as well as stem cell-derived dopaminergic neuron preparations, and reveals the temporal dynamics of key lineages across development and the adult. Overall design: Single cells according to Samples list consisting of: Human embryo ventral midbrain cells between 6 and 11 weeks of gestation, mouse ventral midbrain cells at six developmental stages between E11.5 to E18.5, Th+ neurons at P19-P27, and putative dopaminergic neurons at P28-P56 FACS-sorted from Slc6a3-Cre/tdTomato mice. Stem cells (iPSCs and ESCs) preparation at different stages of differentiation towards Th+ neurons.	Co-expression
SRP067876	Convergent evolution of microRNAs in the same clusters toward cooperative regulation of target genes	MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs that regulate the expression of target genes in many biological processes. One salient feature of miRNAs is that their genomic locations are significantly clustered in discrete loci. By surveying the evolutionary patterns of miRNA clustering in animal species, we found that conserved miRNAs are significantly enriched in clusters via duplication or de novo formation. We proposed a convergent evolution model to explain how clustering helps new miRNAs survive and develop functions related to the pre-existing miRNAs in that cluster. To support our hypothesis, we presented evidence that clustered miRNAs have cooperative repression effects on target genes in different human tissues. We further tested our model by studying the evolutionary trajectory of the miR-17~92 cluster. By transfecting individual miRNAs into human and fly cell lines and extensively profiling the transcriptome alternation with mRNA-Seq, we confirmed that clustered miRNAs cooperatively target overlapping sets of genes and regulate genes from the same biological pathways. Our experimental results also demonstrated the functional co-adaptation between new and old miRNAs in the same cluster. Our functional co-adaptation model provides new insights into the mechanism and functional significance of miRNA clustering.	Co-expression
SRP067878	High-throughput differential expression profiling of single cells using MASC-seq	Novel method using multiplex barcoded in vitro transciption for single cell profiling	Co-expression
SRP067910	Sequencing of messenger RNAs with N6-methyladenosine modifications in acute myeloid leukemia (AML) with and without forced expression of FTO	To identify potential mRNA targets of FTO whose m6A levels are affected by FTO in acute myeloid leukemia (AML) cells, we conducted m6A-seq for messenger RNAs isolated from AML cells with and without forced expression of FTO. Overall design: We retrovirally transduced MSCV-PIG-FTO (i.e., human FTO) or MSCV-PIG (i.e., CTRL/Control) into human MONOMAC-6/t(9;11) AML cells and then selected individual stable clones under selection of puromuycin (0.5ug/ml). Four stable lines including two each FTO-overexpressing lines (i.e., FTO+ 1 and FTO+ 2; or FTO_1 and FTO_2) and control lines (i.e., WT 1 and WT 2; or Ctrl_1 and Ctrl_2) were selected for genome-wide m6A-sequencing (m6A-Seq) assays. The m6A-seq procedure was performed as detailed in Dominissini's method (Dominissini D., et al. Nat Protocols. 2013; 8: 176-189.). Polyadenylated RNA was extracted using FastTrack MAG Maxi mRNA isolation kit (Life technology). RNA fragmentation Reagents (Ambion) was used to randomly fragment RNA. M6A antibody (Synaptic Systems) was applied for m6A pull down. And final library preparation was constructed by TruSeq Stranded mRNA Sample Prep Kit (Illumina). Final library was quantified by BioAnalyzer High Sensitivity DNA chip then deeply sequenced on the Illumina HiSeq 2500.	Co-expression
SRP067913	JAG1 Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium	Background: Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process is unknown Results: The objective of this study was to define the role of the Notch ligand JAG1 in regulating BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. Conclusions: These data demonstrate JAG1 mediated Notch signaling regulates differentiation of BC into secretory cells. This study demonstrates that expression of the Notch ligand JAG1 is highly enriched in basal stem/progenitor cells (BC) of the human airway epithelium and that modulation of its expression levels during differentiation of BC play an important role in regulating secretory cell differentiation with no effect on ciliated cell differentiation.  These observations have implications for developing novel targets to specifically modulate levels of secretory cells in human airway disorders. Overall design: RNA sequencing of primary (Passage 0) and immortalized BC was performed on cells once they had reached 70-80% confluence. The 8 RNA-Seq samples in this submission were all normal, nonsmoker samples without any over-expression or knock-down. The 8 RNA-Seq samples show the BCiNS1.1 cell line samples to be similar to the primary basal cell (BC) samples.	Co-expression
SRP067914	Human adipose transcriptome reveals primate-specific long intergenic noncoding RNAs that modulate adipocyte metabolic function	Through deep RNA-seq in human subcutaneous adipose bioposies and established long noncoding RNAs (lincRNAs) annotations, we identified human lincRNAs expressed in all subjects, including subsets of lincRNAs that exhibit differential expression by sex and race. Our comprehensive profiling on subcutaneous adipose lincRNA transcriptome provides great resource to advance novel understanding of genetic regulation in adipose biology. Overall design: Gluteal subcutaneous adipose from 25 healthy subjects were sequenced by Illumina HiSeq 2000 with poly-A selection.	Co-expression
SRP067922	Role of OSGIN1 in Mediating Smoking-induced Autophagy in the Human Airway Epithelium [RNA-Seq]	Enhanced autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the small airway epithelium to identify smoking up-regulated genes known to re-spond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 as significantly up-regulated by smoking in both the large and small airway epithelium (1.8-fold, p<0.01, 2.1-fold, p<10-4, respectively), an observation confirmed by an independent small airway microarray cohort, TaqMan PCR and RNAseq. Genome-wide correlation of RNAseq analysis of airway basal/progenitor cells isolated from healthy subjects (n=17) showed a direct correlation of OSGIN1 mRNA levels to multiple classic autophagy genes, including, LC3B, P62, WIPI1 and ATG13 (all rho>0.7, p<0.01). In vitro cigarette smoke extract exposure of nonsmoker primary airway basal/progenitor cells was accompanied by a dose-dependent up-regulation of OSGIN1 and autophagy induction. Lentivirus-mediated enhanced expression of OSGIN1 in human primary basal/progenitor cells induced puncta-like staining of LC3B and up-regulation of LC3B mRNA and protein and P62 mRNA expression level in a dose and time-dependent manner. OSGIN1-induction of autophagosome / amphistome / autolysosome formation was confirmed by co-localization of LC3B with P62 or CD63 (endosome marker) and LAMP1 (lysosome marker). Induction of autophagy by OSGIN1 is accompanied with heightened oxidative stress. Together, these observations support the concept that smoking-induced up-regulation of OSGIN1 is at least one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium. Overall design: Airway epithelium transcriptome analysis suggested that OSGIN, an oxidative response and cell death induction gene, was up-regulated by cigarette smoking and might be involved in autophagy regulation. In vitro study demonstrated that smoking can increase OSGIN1 expression and enhanced-expression of OSGIN1 led to autophagy, which is accompanied with heightened oxidative stress.	Co-expression
SRP067924	CDK4/6 inhibition sensitizes myeloma to lenalidomide by reducing the MEIS2 to CRBN ratio that accelerates IKZF1 and IKZF3 degradation	The RNA-seq data presented in this study include libraries from bone marrow plasma cells (BMPC), primary myeloma cells (BMMCs) from 7 patients, and myeloma cell line MM1.S and KMS12 Overall design: RNA-Seq on BMPC, BMMCs and cell line samples	Co-expression
SRP067926	FOXE3 Contributes to Peters Anomaly through Transcriptional Regulation of an Autophagy Associated Protein termed DNAJB1	FOXE3 is a lens specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, we have identified DNAJB1 as a transcriptional target of FOXE3 in a novel pathway that is crucial for development of the anterior segment of the eye. Overall design: Human Embryonic Kidney (HEK293FT) cells were transfected with the expression vector (pT-RexTM-DEST30) harboring either the wild type or the mutant (C240*) FOXE3 ORF (open reading frame). The experimental design included a total of eight biological replicates of cells expressing the wild type and eight replicates of mutant FOXE3 along with eight non-transfected controls. Cells were harvested 24-hour post-transfection and subjected to total RNA isolation for the preparation of whole transcriptome next-generation sequencing libraries. Initially, we examined the quality of transcriptome libraries on a MiSeq genome analyzer. Subsequent to confirmation of the quality, all libraries were paired-end sequenced (2 x 100 bp) using Illumina TruSeq Cluster V3 flow cell at a concentration of 13.0 pM in two separate lanes (12 bar-coded mRNA pooled libraries in each lane) on a HiSeq 2000 genome analyzer.	Co-expression
SRP067928	iPSC RNA-seq upon CRISPRn or CRISPRi manipulation	Assess the on- and off-target effects of dox-inducible CRISPR/Cas9 and CRISPRi constructs in a human iPS cell line.	Co-expression
SRP067934	p53 deficiency linked to BTG2 loss enhances metastatic potential by promoting tumor growth in primary and metastatic sites in PDX models of triple negative breast cancer	We performed differential expression analyses from RNA-seq data derived from isogenic p53 wild-type and p53-knockdown triple negative breast tumors Overall design: patient-derived isogenic human tumor lines diffring only in p53 status were implanted into mouse mammary glands. RNA-Seq was performed on 4 p53-deficient and 3 p53 wild-type tumors.	Co-expression
SRP067960	Trascriptome of thyroid cancer-induced macrophages	RNA sequencing data of macrophages after differentiation in the presence of TPC1 thyroid cancer cell line Overall design: Co-incubation in trans-well system between TPC1 cell lines and human primary macrophages	Co-expression
SRP067977	The Chromatin-Looping Factor ZNF143 Engages at Looping Promoters to Favor the Estrogen Response in Breast Cancer (RNA-seq)	Estrogen signaling in breast cancer cells relies on long-range chromatin interactions connecting distal regulatory elements bound by the estrogen receptor 1 (ESR1) to target gene promoters. This ensures stimulus and subtype-specific transcriptional responses. Expanding on the function of CTCF and the cohesin complex in breast cancer, we demonstrate that the chromatin-looping factor ZNF143 binds the promoter of most early-response estrogen target genes connected to distal regulatory elements in ESR1-positive breast cancer cells. Its chromatin occupancy is unaffected by estrogen stimulation, supporting a stable three-dimensional genomic architecture within the early response to estrogen. Its loss abrogates the estrogen-induced transcriptional response and growth of breast cancer cells. When taking into account CTCF, ZNF143 and cohesin complex subunits, we show that chromatin-looping factors are genetically altered in over 20% of ESR1-positive primary breast tumors. Furthermore, the overexpression of ZNF143, CTCF and RAD21, a cohesin complex subunit, in ESR1-positive breast tumors associates with a worse clinical outcome. Overall, our results suggest that ZNF143 is a new critical effector of the estrogen response and highlights the contribution of the chromatin looping machinery to ESR1-positive breast cancer development. Overall design: mRNA profiles of MCF-7 cells (siCtl or siZNF143) under vehicle (EtOH) or E2 (10 uM 17-beta oestradiol) stimulation	Co-expression
SRP068014	MBNL1-dependent modulation of gene expression in MDA-MB-231 breast cancer cells	To identify MBNL1-dependent changes in gene expression, MDA-MB-231 cells expressing either control or MBNL1-targeting shRNAs were transcriptomically profiled. Overall design: MDA-MB-231 cells stably expressing a control or two independent MBNL1-targeting shRNAs were sequenced in biological duplicate.	Co-expression
SRP068017	Transcriptomic analysis of human iPS cells derived from fragile X syndrome patients during neural differentiation	Fragile X syndrome (FXS) is one of the most prevalent inherited intellectual disabilities. The patients carry the expansion of over 200 CGG repeats located at the 5' untranslated region of fragile X mental retardation 1 (FMR1). As a result, the FMR1 promoter becomes hypermethylated leading to decreased or absent expression of its encoded RNA-binding protein fragile X mental retardation protein (FMRP). We previously generated human induced pluripotent stem (iPS) cells from fibroblasts of a FXS patient (FXS-iPSC) with expanded CGG-repeats at the FMR1 promoter. In the present work, we explored the transcriptional misregulation during the embryonic neurogenesis by in-vitro differentiation of FXS-iPSC into neurons through the intermediate stages. At each differentiation stage, we collected RNA and performed RNA-seq. After an integrated analysis, we found up-regulation of many genes encoding TFs for neuronal differentiation (WNT1, BMP4, POU3F4, TFAP2C, and PAX3), down-regulation of potassium channels (KCNA1, KCNC3, KCNG2, KCNIP4, KCNJ3, KCNK9, and KCNT1) and altered temporal regulation of SHANK1 and NNAT in FXS-iPSC derived neurons, indicating impaired neuronal differentiation and function in FXS patients. Furthermore, we found the cholesterol synthesis genes (e.g., SQLE, LSS, and FASN) are up-regulated during the in-vitro neuronal differentiation of FXS-iPSC, which may contribute to the obesity phenotype of FXS patients. In conclusion, we demonstrated that the FMRP deficiency in FXS patients has significant impact on the gene expression patterns during development, and also discovered many potential candidate genes for the cure of FXS symptoms such as neuronal abnormalities and obesity. Overall design: Eight samples at four different time including iPSC, iPSC aggregates, neuroepithelia aggregates, neuron.	Co-expression
SRP068023	Multiparameter functional diversity of human C2H2 zinc finger proteins [RNA-Seq]	C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2 arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. We have determined the binding sites and motifs of 119 C2H2 zinc finger proteins and the expression pattern of 80 cell lines overexpressing C2H2 zinc finger proteins in order to study the role of C2H2 zinc finger proteins in gene regulation. Overall design: We expressed GFP-tagged C2H2-ZF proteins in stable transgenic HEK293 cells. Total RNA was isolated using Trizol and sequencing libraries were constructed using TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold or TruSeq RNA Library Preparation Kit v2.	Co-expression
SRP068046	G9a-Mediated Methylation of ERa Links the PHF20/MOF Histone Acetyltransferase Complex to Hormonal Gene Expression	The euchromatin histone methyltransferase 2 (EHMT2, aka G9a) methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors.  The molecular mechanisms underlying this activation remain elusive.  Here we show that G9a functions as a bona fide coactivator of the endogenous estrogen receptor a (ERa) in breast cancer cells in a histone methylation-independent manner. G9a dimethylates ERa protein at lysine 235 both in vitro and in cells. Dimethylation of ERaK235 (ERaK235me2) is recognized by the Tudor domain of PHF20, which in turn recruits the MOF histone acetyltransferase (HAT) complex to ERa target gene promoters to deposit histone H4K16 acetylation promoting active transcription. Together, our in vitro and in vivo data establish the molecular mechanism by which G9a functions as an ERa coactivator. Along with the PHF20/MOF complex, G9a links the crosstalk between ERa methylation and histone acetylation governing the epigenetic regulation of hormonal gene expression. Overall design: G9a KD RNA-seq and PHF20 KD RNA-seq with and without E2 treatment	Co-expression
SRP068057	Transcriptional profiles of human blood dendritic cell (DC) subsets at steady state	Innate sensing of viruses by dendritic cells (DCs) is critical for the initiation of anti-viral adaptive immune responses. Virus, however, have evolved to suppress immune activation in infected cells. We now analyze the susceptibility of different populations of dendritic cells to viral infections. We find that circulating human CD1c+ DCs support infection by HIV and influenza virus. Viral infection of CD1c+ DCs is essential for virus-specific CD8+ T cell activation and cytosolic sensing of the virus. In contrast, circulating human CD141+ DCs and pDCs constitutively limit viral fusion. The small GTPase RAB15 mediates this differential viral resistance in DC subsets through selective expression in CD141+ DCs and pDCs. Therefore, dendritic cell sub-populations evolved constitutive resistance mechanisms to mitigate viral infection during induction of antiviral immune response. Overall design: Examination of transcriptional profiles in 4 DC subsets purified from 3 donors using RNASeq	Co-expression
SRP068066	Laser-capture microscopy coupled with Smart-seq2 (LCM-seq) for robust and efficient transcriptomic profiling of mouse and human tissues	Generally, when LCM is used in diverse transcriptomic analyses, several hundred, if not thousands, of cells are needed to obtain high quality of RNA-seq data. As some cellular populations are very small and tissue often in scarcity, we aimed to carefully document the lowest number of cells needed to retrieve sequencable libraries. We started with capturing 120 cells and subsequently scaled down to 50 cells, 30 cells, 10 cells, 5 cells, 2 cells and finally 1 cell. By optimizing multiple steps in the procedure, including direct lysis of cells without performing RNA isolation, we developed LCM-seq that couples LCM with Smart-seq2 for robust and efficient polyA-based RNA sequencing. We applied LCM-seq to mouse and human neuron samples, and demonstrated that LCM-seq can allow us to acquire high quality RNA-seq data from mouse and human tissues to conduct various transcriptomic studies. Overall design: Developing new sequencing technology LCM-seq to efficiently sequence mouse and human tissues	Co-expression
SRP068078	Methylomes and Transcriptomes of Human Pluripotent-to-Cardiomyocyte Differentiation [RNA-seq]	In this report, Tompkins et al describe the derivation, differentiation stage-specific purification, and genome-wide analysis of cardiomyocytes derived from hESCs. Key features of the molecular programs that define human cardiac muscle cell differentiation were described and researchers observed that cells may harbor epigenetic DNA methylation “memories” that reflect the gene activation history of important developmental genes. Overall design: For RNA-seq. Cardiomyocyte differentiation from human embryonic stem cells (H7). 11 time point pilot time series. D3 and D4 samples FACS sorted for primitive and cardiac mesoderm isolation, respectively. Data from negatives sorts (minus) included as well.	Co-expression
SRP068092	BBBomics - Human Blood Brain Barrier Transcriptomics Hub [RNA-seq]	Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available; of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain  features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs. Overall design: We have developed blood brain barriers transcriptomics landscape using RNA sequencing and micro RNA seqeuncing data obtained from replicates of hCMEC/D3 BBB cell line.	Co-expression
SRP068106	Co-regulation of splicing by Rbfox1 and hnRNP M [hnRNPM k-d+Rbfox1 RNA-Seq]	hnRNP M and Rbfox proteins are subunits of the Large Assembly of Splicing Regulators (LASR). The purpose of this study is to investigate how these two splicing factors affect each others'' role in regulating splice site choices in pre-mRNA. hnRNP M is knocked down by RNAi in Flp-In T-REx 293 cells (Invitrogen), whereas Rbfox1 is expressed inducibly under tetracycline control from construct integrated into the genome at the FRT site. Using this system, splicing and expression profiles of cells expressing and/or lacking these proteins are compared on a whole genome level by RNA-seq technology. Overall design: The experiment was performed in Flp-In T-REx 293, Rbfox2 knockout cells (clone 7), in which the Rbfox2 ORF was disrupted in the first constitutive exon (exon 3), thus these cells do not produce endogenous Rbfox protein. In addition to this, cells expressing Flag-tagged Rbfox1 under tetracycline control from a pcDNA5/FRT/TO construct inserted into the FRT site were generated. hnRNP M was knocked down to 10% of the normal levels by transient expression of two RNA hairpins targeting separate 3'' UTR regions. A non-targeting hairpin served as control. Four separate cell populations: not expressing Rbfox with normal levels fo hnRNP M; expressing Rbfox1 with normal hnRNP M levels; not expressing Rbfox, hnRNP M expression reduced by 90%; expressing Rbfox1, hnRNP M reduced by 90% were each grown independently in triplicates. Total RNA was collected from these cells and further treated with DNase I to avoid DNA contamination. Illumina TruSeq stranded mRNA kit was used to generate strand-specific libraries. These libraries were subjected to 50bp paired-end sequencing (Illumina HiSeq2000 platform). In parallel, a fraction of each cell population was lysed in RIPA buffer for protein analysis.	Co-expression
SRP068139	Coordinated control of senescence by lncRNA UCA1 and a novel CAPERa/TBX3 co-repressor	Coordination of a complex series of transcriptional, structural and signaling events culminates in cellular senescence, a crucial tumor suppressor mechanism. We have discovered a repressor complex composed of TBX3 and CAPERa which functions upstream of the RB and p53 effector pathways and is required to prevent senescence of primary cells and in mouse embryos. TBX3/ CAPERa directly binds and represses transcription and chromatin structure of genes in multiple senescence pathways and the LncRNA UCA1, which we have identified as a novel tumor suppressor. The TBX3/ CAPERa  complex is physically disrupted in oncogene induced senescence, providing a new molecular mechanism for derepression of prosenescence pathways in this system. Our results provide new insight into the oncogenic properties of TBX3, and are the first demonstration of CAPERa and UCA1 function in vivo. Overall design: mRNA Seq based gene differential expression analysis of two sample types (TBX3, Caper) relative to control and two sample types (pCDNA3.1, UCA1) relative to each other.	Co-expression
SRP068163	Expression profiling of MCF-7 cells with 10nM treatment of TCDD	The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD).  L-Type Amino Acid Transporter 1 (LAT1) is a leucine uptake transporter that is overexpressed in cancer.  The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report.  Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport.  Overlapping the TCDD-RNA-Seq dataset in this report with a published TCDD-ChIP-seq dataset identified that LAT1 was a direct TCDD/AHR gene target.  Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR.  TCDD-stimulated increases in LAT1 mRNA was also inhibited by the AHR antagonist CH-223191.  Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD.  Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD.  In MDA-MB-231 cells, which exhibit high levels of endogenous AHR activity, the levels of endogenous LAT1 mRNA and protein were reduced in response to knockdown of AHR with AHR-siRNA.  The regulation of LAT1 by AHR stimulated MDA-MB-231 proliferation.  Collectively, these findings have provided a deeper mechanistic understanding of extrinsic and intrinsic regulation of LAT1 by AHR. Overall design: Expression profiling of four replicates of MCF-7 cells treated with 10nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq	Co-expression
SRP068190	Towards therapeutic application of pronuclear transfer to prevent transmission of mitochondrial DNA disease	Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Assisted reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable women who carry mtDNA mutations to have a genetically related child with a greatly reduced risk of disease. Here we report for the first time that pronuclear transplantation (PNT) between normally fertilised human zygotes provides an effective approach to preventing transmission of mtDNA disease.  We found that the procedures previously used to perform PNT between abnormally fertilized human zygotes are highly inefficient when applied to those that undergo normal fertilization.  We have therefore developed an alternative approach based on transplanting PN shortly after completion of the second meiotic division rather than shortly before onset of the first mitosis.  This approach promotes highly efficient development to the blastocyst stage without affecting nuclear genome integrity. Furthermore, the expression profile of genes encoded by the nuclear and mitochondrial genomes was indistinguishable from unmanipulated control embryos. Importantly, levels of mtDNA transferred with the nuclear genome are below the threshold for mtDNA disease. Together these data indicate that transplantation of pronuclei early in the first cell cycle holds promise as a safe and effective approach to preventing transmission of mtDNA disease. Overall design: Single-Cell RNA-seq analysis of embryos generated by pronuclear transfer and unmanipulated control embryos The relationship between single cell samples and the embryo from which they were derived is indicated in the sample ''characteristics: sample type'' field.	Co-expression
SRP068194	The human cellular nucleic acid binding protien binds G-rich elements close to translation initiation sires and promotes translation. [RNA-Seq]	CNBP is a eukaryote-conserved nucleic-acid binding protein required in mammals for embryonic development. It contains seven CCHC-type zinc-finger domains and was suggested to act as a nucleic acid chaperone, as well as a transcription factor. Here, we identify all CNBP isoforms as cytoplasmic messenger RNA (mRNA)-binding proteins. Using Photoactivatable Ribonucleoside Enhanced Cross-linking and Immunoprecipitation, we mapped its binding sites on RNA at nucleotide-level resolution on a genome-wide scale and find that CNBP interacted with 3961 mRNAs in human cell lines, preferentially at a G-rich motif close to the AUG start codon on mature mRNAs. Loss- and gain-of-function analyses coupled with system-wide RNA and protein quantification revealed that CNBP did not affect RNA abundance, but rather promoted translation of its targets. This is consistent with an RNA chaperone function of CNBP helping to resolve secondary structures, thus promoting translation. Overall design: CNBP protein knockdown and RNA-seq	Co-expression
SRP068208	The effect of Foxc1 deficiency on undifferentiated and differentiated human primary keratinocytes	In this study, we used a RNA-sequencing (RNA-seq) approach to analyze the whole transcriptomes of human primary Keratinocytes (KC) at undifferentiated stage and differentiated stage with and without FOXC1 knockdown. Each treatment condition have 2 or 3 replicates. 10 million reads were collected. A total of 8202 genes were designated as present (RPKM>5 in at least one sample).   635 genes were differentially expressed (FDR<0.01, P<0.000774201).  FOXC1 knock-down significantly impaired keratinocytes differentiation process. Overall design: Proliferating foreskin normal human keratinocytes were seeded in 24 well-dishes and transfected with scrambled siRNA and FOXC1 siRNA duplexes. The following day, half of the wells were differentiated in vitro by increasing Ca2+ concentration in culture media from 0.06mM to 1.3 mM for 5 days. The other half wells of cells were cultured in 0.06mM CaCl2.  Both undifferentiated and differentiated cells were harvested for total RNA extraction.  RNA sequencing libraries were made using Illumina RNA sequencing library construction protocol.  RNA libraries were sequenced by 100bp reads on Illumina Hi-seq 2000.	Co-expression
SRP068229	miRNAs affected by antagomiR-17 treatment	To understand the the effect of antagomir-17 treatment on human endothelial cells derived from human umbilical cord blood (UCB) CD34+ hematopoietic stem cells, we have employed mRNA sequencing. The antagomiR-17 used in this study was purchased from Dharmacon and cell transfection was performed using Lipofectamine RNAiMAx from Life Technologies. Scramble antagomiR from Ambion was used as control. Cells were transfected with antagomiR-17 or scrambled antagomiR for 48 hours.  After 48 h, the cells were collected, RNA was isolated and RNA samples were shipped to Exiqon Services, Denmark for mRNA sequencing. All sequencing experiments (RNA integrity measurements, library preparation and next generation sequencing) were conducted at Exiqon Services, Denmark. Overall design: CD34+ endothelial cells differentiated from umbilical cord blood hematopoietic stem cells (CD34+) were treated with 50 nM antagomiR-17 (Dharmacon) or scrambled antagomiR (Ambion) using Lipofectamine RNAiMAx (Life Technologies) for 48 h.  Three replicates were used for each condition (i.e. antagomiR-17 and scramble antagomiR conditions).	Co-expression
SRP068275	HepG2 (human liver cancer cells) transcriptome with NiO nanoparticles exposure	The study aims to analysis transcriptome profiles of NiO nanoparticles (NiO NPs) on HepG2 cells. The 100, 25 and 5 ug/ml concentrations of NiO NPs were used to dose the HepG2 cells, respectively	Co-expression
SRP068278	RNA-seq expression data from FL-HSPCs after HOXA7 knockdown	HOXA7 regulates FL-HSPC self-renewal in vitro and in vivo. We profiled  FL-HSPCs after HOXA7 knockdown, to assess the gene expression programs regulated by HOXA7. Overall design: CD34+CD38-CD43+CD90+ HSPCs were infected with lentiviral shRNA vector targeting HOXA7 (sh-HOXA7). The emtpy lentiviral vector (LKO) was used as a control. Cells were expanded on op9 for 5 days and selected for puromicin resistance for 3 days, than sorted for HSPC immunophenotype.	Co-expression
SRP068279	RNA-seq expression data from EB-HSPC after AM580 treatment compated to DMSO-trated and FL-HSPCs	RA signalling regulated endothelial to hematopoietic transition and HSC generation. Overall design: EB- or FL-derived HSPC were profiled before (d0) or after (d6) 6 days of treatment with 0.2uM AM580 on OP9, and after 6 additional days of expandion of OP9 (d12) without treatment.	Co-expression
SRP068284	RNA Expression Profile of Calcified Bicuspid, Tricuspid and Normal Human Aortic Valves by RNA Sequencing [BAV]	Purpose: The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve (BAV) are unknown. The objective of this study was to identify genes differentially expressed between calcified BAV and tricuspid valves with (TAVc) and without (TAVn) calcification using RNA sequencing (RNA-Seq). Methods: Ten human calcified BAV and nine TAVc were collected from men who underwent aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured using the Illumina HiSeq 2000 system. Reads were aligned with TopHat. Cuffdiff, DESeq, edgeR, and SAMSeq were used to compare gene expression. Genes with adjusted P < 0.05 in the four methods were called differentially expressed. Pathway analysis was performed with IPA. Results: Two genes were up-regulated and none were down-regulated in BAV compared to TAVc. There were 462 genes up-regulated and 282 down-regulated in BAV compared to TAVn. Compared to TAVn, 329 genes were up- and 170 were down-regulated in TAVc. Conclusions: This is the first transcriptome study on calcified and normal aortic valves using RNA-Seq. BAV and TAVc have a highly similar expression profile. These results contribute to our molecular understanding of AS and the identification of new therapeutic targets that are urgently needed to prevent, slow the development or treat AS in patients with bicuspid and tricuspid valves. Overall design: Samples of aortic valves were collected from 10 male patients undergoing aortic valve replacement surgery. RNA sequencing was performed using the Illumina Hiseq 2000.	Co-expression
SRP068290	Homo sapiens Transcriptome or Gene expression	Transcriptomic profiling of 19 healthy, term human placentas collected from the Rhode Island Childs Health Study (RICHS).	Co-expression
SRP068292	RNA Expression Profile of Calcified Bicuspid, Tricuspid and Normal Human Aortic Valves by RNA Sequencing [TAV]	Purpose: The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve (BAV) are unknown. The objective of this study was to identify genes differentially expressed between calcified BAV and tricuspid valves with (TAVc) and without (TAVn) calcification using RNA sequencing (RNA-Seq). Methods: Ten human calcified BAV and nine TAVc were collected from men who underwent aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured using the Illumina HiSeq 2000 system. Reads were aligned with TopHat. Cuffdiff, DESeq, edgeR, and SAMSeq were used to compare gene expression. Genes with adjusted P < 0.05 in the four methods were called differentially expressed. Pathway analysis was performed with IPA. Results: Two genes were up-regulated and none were down-regulated in BAV compared to TAVc. There were 462 genes up-regulated and 282 down-regulated in BAV compared to TAVn. Compared to TAVn, 329 genes were up- and 170 were down-regulated in TAVc. Conclusions: This is the first transcriptome study on calcified and normal aortic valves using RNA-Seq. BAV and TAVc have a highly similar expression profile. These results contribute to our molecular understanding of AS and the identification of new therapeutic targets that are urgently needed to prevent, slow the development or treat AS in patients with bicuspid and tricuspid valves. Overall design: Samples of aortic valves were collected from 17 male patients undergoing aortic valve replacement surgery. RNA sequencing was performed using the Illumina Hiseq 2000.	Co-expression
SRP068304	RNA sequencing from cultured human fibroblasts	We performed RNA sequencing on scalp and dura fibroblasts on 11 donors across the lifespan	Co-expression
SRP068307	Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.	Long noncoding RNAs (lncRNAs) are non-protein coding RNAs regulating gene expression. Although for some lncRNAs a relevant role in hypoxic endothelium has been shown, the regulation and function of lncRNAs is still largely unknown in the vascular physio-pathology. Taking advantage of next-generation sequencing techniques, transcriptomic changes induced by endothelial cell exposure to hypoxia were investigated. Paired-end sequencing of polyadenylated RNA derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2 or normoxia was performed. Bioinformatics analysis identified ˜ 2000 differentially expressed genes, including 122 lncRNAs. Extensive validation was performed by both microarray and qPCR. Among the validated lncRNAs, H19, MIR210HG, MEG9, MALAT1 and MIR22HG were also induced in a mouse model of hindlimb ischemia. To test the functional relevance of lncRNAs in endothelial cells, knockdown of H19 expression was performed. H19 inhibition decreased HUVEC growth, inducing their accumulation in G1 phase of the cell cycle; accordingly, p21 (CDKN1A) expression was increased. Additionally, H19 knockdown also diminished HUVEC ability to form capillary like structures when plated on matrigel. In conclusion, a high-confidence signature of lncRNAs modulated by hypoxia in HUVEC was identified and a significant impact of H19 lncRNA was shown Overall design: Total RNA was extracted from two independent experiments with different time-points of hypoxia exposure (1% oxygen). HUVEC were exposed to 24h normoxia and 24h hypoxia or to 24h normoxia and 48h hypoxia. Each experiment was performed in duplicate.	Co-expression
SRP068318	The Histone Methyltransferases MLL1 and DOT1L Cooperate with Meningioma-1 to Induce AML [Human RNA-seq]	Purpose: To characterize transcriptional changes associated with inhibition of Dot1l in 2 inv(16) patient AML samples Methods: We sequenced mRNA from patient samples that were exposed to 5 uM EPZ004777 or DMSO control for 7  days. Results: Inhibition of Dot1l leads to gene expression changes in genes related to cell growth and cell cycle. Overall design: Examination of mRNA levels between cells treated with  5 uM EPZ004777 or DMSO control	Co-expression
SRP068373	SNHG5 siRNA  knock down in HCT116 cells	SnoRNA host gene 5 was knocked down with two different siRNAs and profiled for gene expression. Overall design: three replicates of two different siRNAs against SNHG5 and a control siRNA	Co-expression
SRP068424	Homo sapiens Raw sequence reads	Type-1 interferons are critical for inhibiting HIV and simian immunodeficiency virus. However, it is largely unknown which of the hundreds of interferon-stimulated genes (ISGs) restrict HIV replication (with the notable exceptions of APOBEC3G, MX2, and BST-2). To identify HIV restriction factors, we sequenced activated CD4+ T cell RNA from 19 humans with untreated HIV infection before and after peginterferon alpha 2b (IFN) injection. Antiretroviral therapy (ART) durably suppresses HIV-1, prevents progression to acquired immunodeficiency syndrome, and reduces mortality.  However, even with ART HIV-1 infected adults remain at higher risk of death from inflammatory disease. To understand the role of ART in altering cell-associated HIV RNA and host RNA changes within activated CD4  T cells we also sequenced activated CD4  T cell RNA from these same 19 humans after initiating ART and obtaining =12 weeks of undetectable viremia.	Co-expression
SRP068450	Targetting super enhancer associated oncogenes in esophageal squamous cell carcinoma [RNA-seq]	Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy and the major histological subtype of esophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of ESCC, few targetable genomic lesions were identified and no molecular-based therapy is available. To identify druggable candidates in this tumor, we performed high-throughput small-molecule inhibitor screening. The unbiased results led us to discover a highly potent anti-ESCC compound, THZ1, a newly developed covalent CDK7 inhibitor. Further in vitro and in vivo experiments showed that THZ1 has powerful anti-neoplastic properties against ESCC cells with minimal toxic effect on healthy tissues. Importantly, whole-transcriptome sequencing (RNA-Seq) revealed that low-dose THZ1 treatment led to selective inhibition of a number of oncogenic transcripts. Notably, further characterization of the genomic features of these THZ1-sensitive transcripts demonstrated that they were frequently associated with Super-Enhancer (SE). Moreover, SE analysis alone uncovered many lineage-specific master regulators in ESCC. Finally, integrative analysis of both THZ1-sensitive and SE-associated transcripts identified a number of novel oncogenes in the context of ESCC, such as PAK4, RUNX1, DNAJB1, SREBF2 and YAP1, with PAK4 being a potential druggable kinase. Together, our integrative molecular approaches identified a catalog of SE-associated lineage-specific master regulators and oncogenic transcripts in ESCC, which will significantly promote the understanding of ESCC biology. The preclinical results of THZ1 may help establish the therapeutic merit of targeting transcriptional regulation program for the treatment of this deadly malignancy. Overall design: RNA-seq of esophageal cell lines treated with either DMSO or THZ1 at various time points of treatment.	Co-expression
SRP068467	RNA-Seq data for KRAS wild-type(WT) and two mutant forms G12V and Q61H over-expressed samples with green fluorescent protein control samples using human mammary epithelial cells	The goal was to capture the transcriptional activity due to over-expression of KRAS gene. Over-expressions were validated using Western Blots. Illumina RNA-Seq technology was used to capture the downstream transcriptional activity. Reads were 101 base pairs long and single ended. An R open source package “Rsubread” was used to align and quantify the read using UCSC hg19 annotation. The integer-based gene counts were later normalized in TPM . Overall design: Profiles of gene expression were generated in cells derived from breast and used to generate a gene-expression signatures.	Co-expression
SRP068468	INTS8 mutations cause severe neurodevelopmental syndrome	Integrator (INT) is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. INT has at least 14 subunits, but INT germline mutations causing human disease have not been reported. We identified mutations in the Integrator Complex Subunit 8 gene (INTS8) causing a rare neurodevelopmental syndrome. In patient cells we identified significant disturbance of gene expression and RNA processing. Also, we show that injection of ints8 oligonucleotide morpholinos into zebrafish embryos leads to prominent underdevelopment of the head demonstrating the evolutionary conserved requirement of INTS8 in brain development. Overall design: RNA sequencing was carried out using RNA samples from fibroblasts from two individuals with germline bi-allelic INTS8 mutations and from two healthy individuals	Co-expression
SRP068551	Transcriptome sequencing identified hub genes for hepatocellular carcinoma   by weighted-gene co-expression analysis	To conduct clinical cancer research and study the genetic basis of hepatocellular carcinoma	Co-expression
SRP068565	A novel compound that blocks HIV-1 replication inhibits the splicing regulatory function of SRSF10	Purpose: We have identified a new compound (1C8) that inhibits HIV-1 replication and that displays very low cellular toxicity. Here, we assess the molecular mechanisms of action of 1C8. Following transcription of the HIV-1 genome, its primary transcript is processed to produce dozens of distinct mRNAs through the alternative use of splice sites. Results: 1C8 decreases the activity of SRSF10, a cellular protein that controls the selection of splice sites in HIV-1 transcripts. 1C8 decreases the phosphorylation of SRSF10, and this change is associated with alterations in the interaction of SRSF10 with HIV-1 transcripts and factors that control splice site selection. Thus, 1C8 represents a novel compound with properties that are potentially useful for treating HIV-1 infection. Overall design: Examination of RNA-seq to investigate alternative splicing changes between control and 4 different concentrations of a drug that 1C8. 4 replicates were sequenced for each condition.	Co-expression
SRP068584	A faithful in vivo model of human MLL-AF4 proB acute lymphoblastic leukemia	Transcriptome analysis by RNAseq of leukemia model promoted by MLL-Af4 or MLL-AF9 fusion proteins. We find each fusion protein promotes a specific gene signature correlating to those identified in patients Overall design: Human CD34+ hematopoietic stem and progenitor cells were transduced with retrovirus expressing MLL-Af4 or MLL-AF9. Transduced cells were transplanted into immunodeficient mice to induce lymphoid leukemia or placed in myeloid in vitro culture. CD19+ lymphoid leukemia cells (3 AF9, 6 Af4),  control health CD19+CD34+ proB cells (n=3) and 4 pairs of Af4 and AF9 CD33+CD19- myeloid culture cells were collected for RNA-seq	Co-expression
SRP068591	Gene signature in sessile serrated polyps identifies colon cancer subtype	RNA sequencing analysis of gene expression in serrated colon polyps, uninvolved colon and control colon Overall design: 86 colon RNA sequencing datasets (21 sessile serrated adenomas/polyps, 10 hyperplastic polyps, 10 adenomatous polyps, 21 uninvolved colon, 20 control colon and 4 colon cancer)	Co-expression
SRP068609	Gut microbiota and colonic gene expression:  a lignan trial in humans	Intake of foods high in dietary fiber is associated with lower risk of colorectal cancer. Gut bacteria convert constituents of plant foods, sugh as lignans and dietary fiber, to biologically active compounds that in animal models prevent the development of colon cancer. In a human dietary intervention, we will study how these biologically active compounds affect colon cell-signaling pathways important to colorectal cancer risk.	Co-expression
SRP068639	Transcriptomic Dynamics during Differentiation Process of Human Pluripotent Cells into Hepatocyte-like Cells	Examine characteristics of hESCs and hiPSCs during directed in-vitro differentiation into HLCs. Overall design: We generated HLCs from both hESCs and hiPSCs by directed in-vitro differentiation, and analyzing their transcriptome at representative time points during the differentiation using RNA sequencing.	Co-expression
SRP068677	Total RNA sequencing of HCT116 cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells II	Total RNA sequenceing method was used to compare the differential expression of genes in HCT116 cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells Overall design: Examination of total RNA expressed after cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells	Co-expression
SRP068678	Total RNA sequencing of HCT116 cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells I	Total RNA sequenceing method was used to compare the differential expression of genes in HCT116 cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells Overall design: Examination of total RNA expressed after cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells	Co-expression
SRP068700	A balance between secreted inhibitors and edge-sensing controls gastruloid self-organization	The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula.  Structurally, high-density hESCs relocalize their TGF-ß receptors to their lateral side in the center of the colony, while maintaining apical localization of receptors at the edge. This relocalization insulates central cells from apically applied ligands while maintaining response to basally presented ones. Additionally, BMP4 directly induces the expression of its own inhibitor, Noggin, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors, to predict human fate positioning in micropatterns, and potentially the human embryo. Overall design: We performed RNAseq of human embryonic stem cells cultured in micropatterned colonies at different time points after the addition of BMP4.	Co-expression
SRP068708	Spliced synthetic genes as internal controls in RNA sequencing experiments.	RNA sequencing (RNA-seq) can be used to assemble spliced isoforms, quantify expressed genes and provide a global profile of the transcriptome. However, the size and diversity of the transcriptome, the wide dynamic range in gene expression and inherent technical biases confound RNA-seq analysis. We have developed a set of spike-in RNA standards, termed ‘sequins’ (sequencing spike-ins), that represent full-length spliced mRNA isoforms. Sequins have an entirely artificial sequence with no homology to natural reference genomes, but align to gene loci encoded on an artificial in silico chromosome. The combination of multiple sequins across a range of concentrations emulates alternative splicing and differential gene expression, and provides scaling factors for normalization between samples. We demonstrate the use of sequins in RNA-seq experiments to measure sample-specific biases and determine the limits of reliable transcript assembly and quantification in accompanying human RNA samples. In addition, we have designed a complementary set of sequins that represent fusion genes arising from rearrangements of the in silico chromosome to aid in cancer diagnosis. RNA sequins provide a qualitative and quantitative reference with which to navigate the complexity of the human transcriptome. Overall design: Detailed transcriptomic analysis of two human cell lines with synthetic RNA spike-ins ('sequins'). Sequins were initially combined at equimolar concentrations (a "flat" mix) and sequenced neat (i.e. without any natural RNA added). We then prepared two staggered mixtures (Mix A & B) and sequenced them neat. Mix A was then spiked into total RNA extracted from K562 cells, while Mix B was spiked into total RNA extracted from GM12878 cells. Finally, we prepared a staggered mixture of fusion sequins and sequenced it neat.	Co-expression
SRP068721	Deep RNA sequencing of the human placental transcriptome	The goal of this study was to conduct an in-depth analysis of the human placental transcriptome. RNA was extracted from 16 placental samples using TRIzol following the manufacturer’s protocol. All samples were spiked with 96 External RNA Controls Consortium (ERCC) ExFold RNA transcripts. Ribosomal RNAs were depleted from samples using Ribo-Zero Gold and sequencing libraries were prepared using Illumina TruSeq Stranded Total RNA Sample Preparation kits. Sequencing was performed on the Illumina Hi-Seq 2500 using a 100bp paired-end protocol. Sequence adapters were trimmed using AdapterRemoval with options --trimns, --minlength 20. Trimmed RNA-Seq reads were aligned to known UCSC hg19 genes and the hg19 genome using Bowtie 2 v2.1.0 and TopHat v2.0.9 with options --library-type=fr-firststrand --mate-inner-dist -20 --mate-std-dev 180. UCSC hg19 reference genome and transcriptome was obtained through Illumina iGenomes (https://support.illumina.com/sequencing/sequencing_software/igenome.html). Aligned RNA-Seq reads were summarised using the summarizeOverlaps algorithm with the UCSC known genes hg19 GTF file using the the options overlapMode=``Union'''', ignoreStrand=FALSE, singleEnd=FALSE, fragments=TRUE to generate a table of unique read counts per gene for each sample. All samples were processed in the same way, with all sequencing libraries created in the same batch and sequenced together. Overall design: Villous tissue from 16 human placental samples were profiled by total RNA-Seq.	Co-expression
SRP068722	Time course RNA-Seq of Innate Lymphoid Cells in Early Acute HIV Infection	We apply RNA-seq to limited populations of Innate Lymphoid Cells type 2 and type 3 (ILC2s and ILC3s, respectively) in human individuals infected with acute HIV in the FRESH study. We measured the whole transcriptome of ILC2s and ILC3s in both untreated (n=2) and ART treated (n=2) individuals over the course of infection, in order to compare these populations at key points during infection, namely: viral detection, peak viremia, and weeks past peak viremia (6-7 weeks post detection). Lacking true biological replicates, HIV- patients in the same study (n=9) were used as replicates to conduct Differential Expression (DE) analysis between time points in both ILC2s and ILC3s on a patient by patient basis. In untreated patients, ILC2s and ILC3s differentially expressed genes associated with apoptosis and cell death between peak viremia and viral detection, while ART treated patients' ILC2s and ILC3s demonstrated a mitigated response. Comparing 6-7 weeks after detection with peak viremia revealed a relative decrease in genes associated in cell death in untreated patients, while ART treated patients showed varied responses where several DE genes were associated with immune response. Overall design: RNA-seq of two Innate Lymphoid Cell populations in 2 HIV+ untreated patients, 2 HIV+ ART treated patients, and 9 HIV- patients (control, replicates).	Co-expression
SRP068733	HDAC inhibitor SAHA reverses inflammatory gene expression in diabetic endothelial cells	While histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes. Overall design: Human aortic endothelial cells from a diabetic and non-diabetic individual were stimulated with DMSO (control), SAHA (2 µM, HDAC inhibitor) or C646 (10 µM, EP300 inhibitor) for 12 hours, or EP300 siRNA or non-target siRNA (control) for 4 hours, followed by 48 hours in fresh media. Study performed in triplicate.	Co-expression
SRP068760	MYOCD overexpression in HCASMs	To identify novel genes especially lncRNAs linked to vascular smooth muscle cell (VSMC) differentiation, we performed RNA sequencing of adenovirus–MYOCD transduced human coronary artery smooth muscle cells (HCASMs).  Simiilar amount of  empty Adenovirus was used as control. Overall design: Total RNA was isolated from duplicate HCASMs tranduced with ad-MYOCD or empty control virus and submitted for RNA-Sequencing at the University of Rochester Medical Center Genomics Research Center. Briefly, RNA-Sequencing was done with the polyadenylated RNA component at a depth of 20 million reads per replicate using the Illumina HISeq 2500.	Co-expression
SRP068772	Wiskott-Aldrich Syndrome-causative mutations disrupt alternative splicing and promote gene networks predisposed to hematologic malignancies	Wiskott-Aldrich syndrome (WAS) is characterized by X-linked thrombocytopenia, eczema, immunodeficiency, recurrent infections and increased risk of autoimmunity and malignancies. WAS is caused by mutations in the WAS gene, which encodes the exclusively hematopoietic WAS protein (WASp) that is classically characterized as a? actin nucleator. However, disruption of F-actin polymerization by WAS mutations can not account for many aspects of WAS pathogenesis. Ignorance of other functions of WASP precludes in-depth understanding of the pathogenic effects of mutant WASP, and therefore hampers development of effective therapy. Here we generated induced pluripotent stem cells (iPSCs) from WAS patients (WAS-iPSC) bearing different mutations and corresponding isogenic iPSCs in which the pathogenic mutations had been corrected by targeted genome editing. Hematopoietic cells differentiated from WAS-iPSCs not only recapitulated known disease phenotypes, but also revealed novel defects of WASP deficient cells. WASP co-localized with nuclear pores, nucleoli, nuclear speckles and PML bodies by immunocytochemistry and/or serial block face scanning microscopy (SBF-SEM). MudPIT (multi-dimensional protein identification technology) analysis revealed that WASP physically interacted with nuclear body components, nuclear structural proteins, chromatin modifying complexes, and many RNA-binding proteins including major components of the spliceosome. Next-generation sequencing captured a dramatic global change of alternative splicing in WAS patient cells. WAS mutation impacted splicing of multiple genes frequently mutated in myelodysplastic syndrome and other cancers. RNA sequencing showed that WAS-iPSC derived immune cells misregulated many cell cycle regulators, tumor suppressors, immune function genes and splicing factors, and activated gene networks that drive cancer development and inflammatory diseases. Together these data uncovered previously unappreciated functions of the WASP and provided a mechanistic understanding of the pathogenesis of malignancy and autoimmunity in the most severe form of WAS. These new knowledge could help develop targeted therapy for WAS in the future. Overall design: Human WAS-iPSC derived from two WAS patients (genotype: p.Phe35* and p.Leu425Profs*70, respectively) and gene corrected WAS-iPSCs (cWAS-iPSC) were differentiated into macrophages. Human cord blood progenitor cells were differentiated into macrophages as a control. Total RNAs were extracted and been analyzed by RNA-seq.	Co-expression
SRP068773	EPCR Expression Defines the Most Primitive Subset of Human HSPC and Is Required for Their In Vivo Activity	Cell purification technology combined with whole transcriptome sequencing and small molecule agonist of hematopoietic stem cell self-renewal has allowed us to identify the endothelial protein c receptor protein (EPCR) as a surface maker that defines a rare subpopulation of human cells which is highly enriched for stem cell activity in vivo. EPCR-positive cells exhibit a robust multi-lineage differentiation potential and serial reconstitution in immunocompromised mice. In culture, most if not all of the HSC activity is detected in the EPCR+ subset, arguing for the stability of this marker on the surface of cultured cells, a feature not found with more recently described markers such as CD49f. Functionally EPCR is essential for human HSC activity in vivo. Cells engineered to express low EPCR expression proliferate normally in culture but lack the ability to confer long-term reconstitution. EPCR is thus a stable marker for human HSC. Its exploitation should open new possibilities in our effort to understand the molecular bases behind HSC self-renewal. Overall design: Examining 3 cellular subsets: EPCR+, EPCRlow, EPCR- derived form CD34+CD45RA- cord blood cells after 7 day expansion in UM171	Co-expression
SRP068779	Gene expression profiles of rescue with wild type or SUMO double mutant TRIM24	Gene expression profiles of rescue with wild type or SUMO double mutant TRIM24 after shRNA mediated knockdown of TRIM24 in MCF7 cell line Overall design: Gene expression profiles of rescue with wild type TRIM24 and SUMO double mutant, 3 replicate each	Co-expression
SRP068796	Full-length single-cell RNA-seq applied to a viral human cancer: Applications to HPV expression and splicing analysis in HeLa S3 cells	In this study, we produced full-length RNA-seq data of 45 single HeLa S3 cells, 8 replicates of 10 pg total RNA and one 5 ng total RNA from HeLa S3 cell population. Using this data, we investigated the heterogeneity of HeLa S3 cells in gene expression, alternative splicing, fusion and HPV-host fusion and expression. This study provides comprehensive transcriptomic characters of HeLa S3 cells at the single cell level.	Co-expression
SRP068909	Manganese (II) Activates cGAS-STING pathway	We show that Manganese (II) is a potent type I-IFN inducing agonist, stimulating cells into an anti-viral state in the absence of infection. Mechanically, Mn2+ treatment led to a profound cGAS-STING-dependent innate immune activation, conferring cells or mice viral resistance. Overall design: THP1 cells were treated with Mn2+, VACV, IFNß or empty media (control). RNA was extracted and sequenced.	Co-expression
SRP068912	RNA Sequencing Reveals Immunosuppressive Role of Anthrax Lethal Toxin in Human Lung Epithelial and Monocytic Cells	Using RNA-seq, we report here that anthrax lethal toxin (LeTx) induces immunosuppression in human lung epithelial cell line A549 and monocytic cell line U937. Overall design: Examination of LeTx-treated A549 and U937, generated by deep sequencing on an Illumina HiSeq 2000 (101 cycles PE lane).	Co-expression
SRP068934	Total RNA sequencing of APC mutant and wt colonic organoids	We report elevated expression levels of genes involved in colon cancer in samples that carry mutations in the APC gene. Mutated skin fibroblasts were reprogrammed to iPSCs and then differentiated to colonigc organoids, where the total RNA was extracted from. Overall design: Comparison of the expression profiles of APC mutant and WT colonic organoids	Co-expression
SRP068957	Batch effects and the effective design of single-cell gene expression studies	Single cell RNA sequencing (scRNA-seq) can be used to characterize variation in gene expression levels at high resolution. However, the sources of experimental noise in scRNA-seq are not yet well understood. We investigated the technical variation associated with sample processing using the single cell Fluidigm C1 platform. To do so, we processed three C1 replicates from three human induced pluripotent stem cell (iPSC) lines. We added unique molecular identifiers (UMIs) to all samples, to account for amplification bias. We found that the major source of variation in the gene expression data was driven by genotype, but we also observed substantial variation between the technical replicates. We observed that the conversion of reads to molecules using the UMIs was impacted by both biological and technical variation, indicating that UMI counts are not an unbiased estimator of gene expression levels. Based on our results, we suggest a framework for effective scRNA-seq studies. Overall design: We collected single cell RNA-seq (scRNA-seq) data from three YRI iPSC lines using the Fluidigm C1 microfluidic system followed by sequencing. We added ERCC spike-in controls to each sample, and used 5-bp random sequence UMIs to allow for the direct quantification of mRNA molecule numbers. For each of the YRI lines, we performed three independent C1 collections; each replicate was accompanied by processing of a matching bulk sample using the same reagents. This study design allows us to estimate error and variability associated with the technical processing of the samples, independently from the biological variation across single cells of different individuals. We were also able to estimate how well scRNA-seq data can recapitulate the RNA-seq results from population bulk samples. We combined the 96 single cell samples from each C1 chip into their own master mix and sequenced across three lanes of a HiSeq 2500 (3 individuals x 3 replicates x 96 wells x 3 lanes = 2592 files). We prepared two separate library preparations for each bulk sample, combined them all into one master mix, and sequenced across four lanes (3 individuals x 3 replicates x 2 library preparations x 4 lanes = 72 files).	Co-expression
SRP068961	Targeting CREBBP/EP300 in cancer	Antiprolifereative effects of CREBBP/EP300 inhibitors were tested in human leukemia and lymphoma cell lines and the molecular mechanisms responsible for such effects were explored. Overall design: K562 cells were treated with CBP-30 (CREBBP/EP300 bromodomain inhibitor), C646 (CREBBP/EP300 HAT activity inhibitor) and JQ1 (BRD4 inhibitor) and changes in gene expression were evaluated by RNA-seq.	Co-expression
SRP068967	Ribosomal footprinting of CN34-Parental and CN34-LM1a	We used Illlumina Artseq Ribo Profile to perform ribosome footprinting on the above cell lines Overall design: We followed the manufacturer's protocol: Cells were treated with cycloheximide (0.1 mg/ml) to inhibit translation; total RNA(tt) and ribosome-protected RNA fragments (RPF) were isolated and library preped for sequencing simultaneously.	Co-expression
SRP068969	rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome	RNA structures are of crucial importance for biological function and gene regulation. Guanine (G)-rich sequences in RNA can assemble to form RNA G-quadruplex (rG4) structures; specific rG4s have been shown to regulate gene expression, and are associated with human diseases. However, no transcriptome-wide method has been reported to map rG4s, limiting our understanding of the rG4 structure and its relationship with function and regulation. Here we introduce a transcriptome-wide rG4 profiling method, rG4-Seq, in which the rG4-mediated reverse transcriptase stalling is read out by next-generation sequencing at nucleotide resolution. We apply this method to human RNA and report the first global map of rG4 structures for any organism. Our analysis identifies over 3,000 rG4s, and increases to over 11,000 upon addition of a rG4 stabilizing ligand Pyridostatin (PDS). Notably, we discover that besides canonical rG4s, many rG4s are non-canonical with novel structural features such as long-loops, bulges, and 2-quartet. We also find that rG4 formation is associated with its stability, Cytosine (C)-content, and the stability of alternative RNA structures. Our data reveals that rG4s can be found in messenger RNAs (mRNAs) and long intergenic noncoding RNAs (lincRNAs). In mRNAs, rG4s are enriched in untranslated regions, and are significantly correlated with microRNA target sites and polyadenylation signals. Remarkably, we found that majority of our in vitro identified rG4s can change the in silico predicted RNA structure to uncover alternative RNA conformation.. Futhermore, the rG4s that have analogues in many ortholog genes across different species show a preferential association with RNA processing and stability. rG4-seq is a broadly applicable method that enables the RNA G4 structurome and its biological roles to be interrogated and can be readily applied in other organisms on a transcriptome-wide scale. Overall design: 12 samples, 150 bp single-ended RNA-Seq libraries from cell extracts after performing RTS reaction in different buffers (Li, K and K+PDS rich buffer). Each of the 3 conditions has 4 libraries from independent biological replicates.	Co-expression
SRP068970	Loss of CSL unlocks a hypoxic response and enhanced tumor growth potential in breast cancer cells	Notch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1± protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a novel role for CSL in tumorigenesis and regulation of the cellular hypoxic response. Overall design: CSL +/+ and CSL -/- MDA-MB-231 were subjected to Notch activation/inhibition and xenograft experiment. Total RNA were extracted from the samples and sent to NGS. Single Cell RNA-sequencing was also performed from cells isolated from xenograft tumors.	Co-expression
SRP068976	RNA-seq of 50 paired hepatocellular carcinoma	RNA-seq of Illumina sequencing of 50 paired normal and tumor samples Overall design: RNA-seq of Illumina sequencing of 50 paired normal and tumor samples	Co-expression
SRP068977	Ribosomal footprinting of MDA-Parental and MDA-LM2	We used Illlumina Artseq Ribo Profile to perform ribosome footprinting on the above cell lines Overall design: We followed the manufacturer's protocol: Cells were treated with cycloheximide (0.1 mg/ml) to inhibit translation; total RNA(tt) and ribosome-protected RNA fragments (RPF) were isolated and library preped for sequencing simultaneously.	Co-expression
SRP069008	Ribosomal footprinting of MDA_Ctrl and MDA_Arg overexpression cell lines	We used Illlumina Artseq Ribo Profile to perform ribosome footprinting on the above cell lines Overall design: We followed the manufacturer's protocol: Cells were treated with cycloheximide (0.1 mg/ml) to inhibit translation; total RNA(tt) and ribosome-protected RNA fragments (RPF) were isolated and library preped for sequencing simultaneously.	Co-expression
SRP069011	Ribosomal footprinting of MDA_Ctrl and MDA_Glu overexpression cell lines	We used Illlumina Artseq Ribo Profile to perform ribosome footprinting on the above cell lines Overall design: We followed the manufacturer's protocol: Cells were treated with cycloheximide (0.1 mg/ml) to inhibit translation; total RNA and ribosome-protected RNA fragments were isolated and library preped for sequencing simultaneously.	Co-expression
SRP069016	Homo sapiens Transcriptome or Gene expression	Peripheral Blood Lymphocyte	Co-expression
SRP069018	A RUNX2-mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells	The goal is to identify transcripts that are regulated by RUNX2 in SAOS2 cells. Overall design: SAOS2 cells were transduced with lentiviruses expressing shLuc, shRUNX2_3 and shRUNX2_4 for 4 days followed by 2ug/ul puromycin selection to remove untransduced cells. A no-virus control was included to monitor the transduction efficiency. These control cells died after 2 days of puromycin selection. The lentivirally transduced cells were more than 80% survived, which indicates a high transduction efficiency. After four more days in puromycin, SAOS2 cells were harvested and subjected to total RNA extraction. 1ug total RNA were used to perform RNA-seq.	Co-expression
SRP069052	Negative control of CSL gene transcription by stress/DNA damage response and p53 [RNA-Seq]	CSL is a key transcription factor, mostly acting as a repressor. While known as main effector of Notch signaling, it can also play Notch-independent functions. Despite the wide interest in CSL, the mechanisms responsible for its own regulation have been little studied. We recently showed that CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts, which promote keratinocyte tumor development. We show here that levels of CSL gene transcription differ among HDF strains derived from many different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression in all tested strains is negatively regulated by stress / DNA damaging insults caused by UVA, Reactive Oxygen Species (ROS), smoke extract and doxorubicin treatment. p53, a key effector of the DNA damage response, functions as common negative regulator of CSL gene transcription, through both suppression of CSL promoter activity and, indirectly, through increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in the acute response of cells to DNA damaging cancer-threatening conditions. Overall design: RNA sequencing of 46 human foreskin fibroblasts	Co-expression
SRP069060	Arnica montana stimulates extracellular matrix gene expression in human macrophages differentiated to wound-healing phenotype.	Arnica m. effects were associated with a purported anti-inflammatory and tissue healing actions after trauma, bruises, or tissue injuries, but its cellular and molecular mechanisms are largely unknown. Here Arnica m. dilutions were tested using an in vitro model of macrophages polarized towards a “wound-healing” phenotype. The monocyte-macrophage human THP-1 cell line was cultured and differentiated with phorbol-myristate acetate and Interleukin-4, then exposed for 24 h to Arnica m. centesimal (c) dilutions 2c, 3c, 5c,9c, 15c or Control. None of these treatments affected cell viability. A total of 20 genes were differentially expressed comparing cells treated with Arnica m. 2c with those treated with Control only. Of these, 7 genes were up-regulated and 13 were down-regulated. Functional gene enrichment analysis showed that the most significantly upregulated function concerned 4 genes with a conserved site of EGF-like region (p<0.001) and three genes of proteinaceous extracellular matrix, including heparin sulphate proteoglycan 2 (HSPG2), fibrillin 2 (FBN2), and fibronectin (FN1) (p <0.01). Protein assay in supernatants confirmed a statistically significant increase of fibronectin production in Arnica m. 2c treated cells (p<0.05). Pooled extracts of cells treated with increasing dilutions of Arnica m. (3c, 5c, 15c) showed up-regulation of the same group of genes although with lower effect size. The down-regulated transcripts derive from mitochondrial genes coding for some components of electron transport chain. These findings provide new insights into the action of Arnica m. in tissue healing and repair, identifying increased fibronectin production by macrophages as a major therapeutic target. Overall design: Expression analysis of differentiated THP-1 cell line exposed at Arnica m. centesimal (c) dilution 2c, plus control non-exposed line both in 5 replicates.	Co-expression
SRP069063	Transcriptomic profiling discloses molecular and cellular events related to neuronal differentiation in SH-SY5Y cells	Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis to pinpoint pathways and cellular processes underlying neuronal differentiation of SH-SY5Y cells according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells outlined meaningful biological functions associated with changes in cell morphology including remodelling of plasma membrane and cytoskeleton, neuritogenesis. Seventy-three DEGs were assigned to Axonal Guidance Signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited the ability to elongate longer axonal process as assessed by the morphometric evaluation. Recognition of molecular events occurring in differentiated SH-SY5Y cells is necessary to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis. Overall design: Comparison of cell line SH-SY5Y differentiated and undifferentiated.	Co-expression
SRP069086	Fbxo32 mediated gene expression program underlies EMT and metastasis	The epithelial-mesenchymal transition (EMT) is a process by which cells lose their cell contacts and gain migratory and invasive properties. EMT is essential for numerous developmental processes including neural tube formation, in wound healing, organ fibrosis and cancer metastasis. Despite progress, the repertoire of factors involved in global transcriptional reprogramming underlying EMT remains unknown. Here we show that FBXO32, a member of the F-box protein family, is essential for phenotypic changes hallmark of EMT. Such dependency results from FBXO32-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we found that CTBP1, an established regulator of EMT, requires FBXO32 ubiquitination at Lysine 63 for its nuclear retention and gene regulatory function. FBXO32 is also highly amplified in a large panel of metastatic cancers and its knockdown severely impaired metastatic properties of cancer cells in vitro and in vivo. In addition, FBXO32 is also induced during neurogenesis and is essential for neuronal migration in vivo. Together, these findings uncover FBXO32-dependent gene regulatory circuitry that underlies EMT during development and disease. Overall design: For all siRNA mediated knockdown experiments, cells were seeded at same starting density and transfected with ON-TARGET plus SMART pool siRNAs (i.e. a mixture of 4 siRNA provided as a single reagent) (Dharmacon) every second day. For siRNA transfections, Lipofectamine RNAiMax (Invitrogen, 13778-150) was used according to the manufacturer's instructions. For experiments during TGF-ß-induced EMT, TGF-ß-induction performed at the same time when siRNA was added to avoid indirect effect due to loss of function of protein.	Co-expression
SRP069088	Live single-cell laser tag	No description.	Co-expression
SRP069101	The effect of Abl kinases on non-small cell carcinoma global transcriptome	To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent non-small cell carcinoma cells metastasis Overall design: Samples were analyzed by pair of either control versus ABL Kinase inhibitor GNF5, Or using scrambled shRNA versus ABL1/ABL2-specific shRNAs.	Co-expression
SRP069155	Sodium arcenite-treated HeLa cells	No description.	Co-expression
SRP069159	Homo sapiens Transcriptome or Gene expression	To test the difference between Abmsc and Fbmsc	Co-expression
SRP069177	Differential Gene Expression Time Course of Normal Human Immortalized (iPrECs) vs Tumorigenic (EMP-iPrECs) Prostate Epithelial Cells during In Vitro Prostate Epithelial Cell Differentiation	The first goal of this project was to identify differentially expressed genes associated with human prostate epithelial cells (PrEC) differentiation over a 2+ week time course that are associated with and potentially required for normal PrEC differentiation (J Cell Sci 123:266-76, 2010).  The second goal was to determine how these differentially expressed genes are changed when the same cells are transformed into tumorigenic cells (EMP-iPrECs) through overexpression of Erg, Myc, and shRNA to Pten (Cancer Res 74:3357-68, 2014).  In the iPrECs, we readily identified many genes that were up and down regulated over time during differentiation.  Genes that decreased include many cell cycle genes, and genes that increased include known differentiation markers.  The EMP cells did not differentiate as previously reported and was supported by the general lack of any major changes in gene expression over the EMP time course.  When iPrECs were compared to EMPs, there were over 2000 differentially expressed genes that did not overlap with the differentially expressed genes identified during the normal differentiation time course.  Thus, oncogenic transformation of PrECs results in major gene expression changes and abrogates the differentiation program. Overall design: Approach was to collect and isolate polyA-selected RNA from from two cell lines; normal human immortalized PrECs (iPrECs) and transformed human EMP-iPrECs, which had been subjected to an in vitro differentiation assay (J Cell Sci 123:266-76, 2010).  EMP-iPrECs were generated by stable expression of Erg, Myc and shRNA to Pten iPrECs (Cancer Res 74:3357-68, 2014).  Specifically, total RNA was isolated from the cells at specified time points during the course of iPrEC or EMP-iPrEC differentiation. Differentiation in untransformed cells results in a bilayer of epithelial cells- basal and luminal cells. The RNA isolated from the last two time points for iPrECs include only the luminal cells which were dissociated from the basal cells. The EMP-iPrECs did not form a bilayer, therefore all time points contain the whole population. Each time point for each cell line includes biological triplicates. Michigan State University Research Technology Support Facility Genomics Core	Co-expression
SRP069180	Searching for target genes of miR-508/509/506/514 in HCT116 cells	To elucidate whether miR-508/508/509/514  plays a role in colorectal cancer tumorigenesis,  RNA-seq analysis was performed to compare the gene expression profiles of miR-508/508/509/514 mimics and control microRNA transfectants. Overall design: RNA-seq was performed in HCT116 colorectal cancer cells after miR-508/508/509/514 mimics and control microRNA virus infection	Co-expression
SRP069181	A comparison of gene expression between lesional and non-lesional derived keratinocytes of Hailey-Hailey disease patients.	Purpose: The goal of this study was to compare NGS-derived keratinocytes transcriptome profiling (RNA-seq) between non lesional and lesional derived keratinocytes of hailey-Hailey disease patients. Methods: kerationocytes gene profiles of lesional and non-lesional derived keratinocytes were generated by deep sequencing, in triplicate, using Illumina HIseq2000. The sequence reads that passed quality filters were analyzed at gene level with the following methods: STAR for the alignment; HTSeq for generating raw read counts; edgeR for normalization and differential expression analysis. QRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped about 45 million sequence reads per sample to the human genome (hg19). Hierarchical clustering of gene expressions clearly showed separation between non-lesional and lesional keratinocytes. A total of 1,453 differentially expressed genes at FDR<0.05 were identified, uncovering several genes that may contribute to Hailey-Hailey manifestation function. Conclusions: Our study represents the first detailed analysis of keratinocyte gene expression profile, generated by RNA-seq technology.  We conclude that RNA-seq gene based characterization of HHD-keratinocytes would expedite genetic network analyses and permit the dissection of complex biological functions. Overall design: non-lesional and lesional  mRNA profiles of Hailey-Hailey Patients- derived kerationocytes  were generated by deep sequencing, in triplicate, using Illumina Hiseq 2500.	Co-expression
SRP069212	RNA-seq analysis of hepatocellular carcinoma with portal vein tumor thrombosis	Portal vein tumor thrombosis is a strong poor indication of HCC. Characterizing the molecular alterations of these metastatic HCCs is important for understanding the molecular mechanisms during HCC progression and metastasis. Previous genomic studies mainly focus on single molecular layer, such as gene expressions or exonic mutations. In this study, we systematically examined the copy number variation (CNV), DNA methylation, miRNA and transcriptome of matched adjacent normal tissues, primary tumors and PVTTs from 19 HCC patients. Based on the integrative multi-omics profiles, we established the molecular landscape of the metastatic HCCs and identified a set of the recurrent genomic alterations and candidate driver genes. Overall design: RNA-seq of matched adjacent normal, primary tumor and PVTT samples from HCC patients	Co-expression
SRP069217	Capturing the biology of mild versus severe disease in a pluripotent stem cell-based model of Familial Dysautonomia	Familial Dysautonomia is a genetic disease, however patietns with the same genotype present with mild or severe forms of the disease. We used the pluripotent stem cell technology to capture the differences in disease severity in vitro during neurodevelopment as well as during maintanance of the cells, showing developmental and degenerative phenotypes. RNA seq. analysis of the groups confirmed those diffferences. Overall design: Analysis of RNA from PSC-derived neural crest cells from severe FD, mild FD and healthy patients	Co-expression
SRP069228	Metformin reverses gene expression signautres in hyperglycaemics endothelial cells	Metformin is a well tolerated and often prescribed treatment for type 2 diabetes. However, the effect of metformin on gene expression in endothelial cells remains unknown. We used RNA-seq to profile gene expression in primary human aortic endothelial cells stimulated with metformin in normoglycaemic and hyperglycaemic conditions. We identified novel pathways in hyperglycaemic endothelial cells that may be involved in the development of endothelial dysfunction. Hyperglycaemic endothelial cells expressed interferon-response pathway genes such as MX1 and IFI27. Transcription factor analysis implicates the activation of STAT1 and IRF1. Co-treatment of hyperglycaemic cells with metformin prevented glucose-dependent changes in gene expression, including interferon response genes. Indeed, the effects of metformin in endothelial cells were dependent on glucose levels. In normoglycaemic cells, metformin subtly regulated changes in gene expression. In contrast, metformin was strongly associated with the reversal of gene expression changes induced by hyperglycaemia. Overall design: Human aortic endothelial cells were stimulated with DMSO (control), metformin (2 mM), D-glucose (30 mM) or metformin and  D-glucose (2 mM and 30 mM respectively) for 64 hours. Study performed in triplicate.	Co-expression
SRP069235	Gene expression in human glioblastoma specimens	We assessed global gene expression changes in 32 human glioblastoma specimens Overall design: Human mRNA profiles of 32 glioblastoma specimens, were obtained by sequencing on Illumina HiSeq 3000	Co-expression
SRP069243	Genome-wide expression profile in FH-deficient (UOK262) vs FH-competent (UOK262pFH) human cells derived from metastatsis to the mediastinum of a HLRCC patient	Comparison of the transcriptome of human kideny cancer cells either wild-type for FH or FH-deficient. The UOK262 cells were isolated from mediastinum metastasis of a HLRCC patient (Yang et al. Cancer Genetics and Cytogenetics, Volume 196, Issue 1, 1 January 2010, Pages 45–55). FH function was restored in the UOK262 by re-expressing the FH transcript from an exogenous plasmid. Overall design: Examination of gene transciption in 2 cell types.	Co-expression
SRP069264	Coupled electrophysiological recording and single-cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation	The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion are generated. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single-cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here, we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single-cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions. Overall design: Patch-Seq of 20 hESC/hiPSC-derived neurons.	Co-expression
SRP069329	Homo sapiens male germ cell transcriptome	Goal of this study is to identify the transcriptome of human male germ cell subtypes during normal spermatogenesis as a reference for subfertility.	Co-expression
SRP069333	Expression of MERTK based on Multiple Sclerosis (MS) risk haplotype	Whole transcriptome RNA-seq analysis to measure group-wise RNA expression level of the MERTK gene in 3 healthy controls (known to be homozygous non-risk haplotype at MERTK gene locus) and to compare this to the group-wise RNA expression level of the MERTK gene in 5 Multiple Sclerosis-affected (MS-affected) individuals (known to be homozygous for the MS risk haplotype at the MERTK gene locus). Overall design: We sequenced the whole transcriptome of 3 healthy control samples which were all homozygous for the MS non-risk haplotype at the MERTK gene. We also did the same RNA-seq protocol on 5 MS-affected subjects that were all homozygous for the Risk haplotype at the MERTK gene. All 8 samples were sequenced evenly across 3 lanes of an Illumina HiSeq NGS machine to remove any batch-type effects that could be caused by sequencing e.g. all cases in one lane and all controls in another lane.	Co-expression
SRP069348	HeLa cell raw sequence reads for demonstration of the DASH technique	HeLa cell culture RNASeq data was obtained to demonstrate the effectiveness of the Cas9 based DASH technique for depletion of unwanted abundant sequences.	Co-expression
SRP069359	RNA-Sequencing of HUVEC treated with Tie2 activating antibody	We analyzed genome-wide transcriptional changes induced by ABTAA+Ang2, using RNA-seq analysis of HUVECs Overall design: Examination of 3 different antibodies treated to HUVEC to analyze the effect of Tie2 activation	Co-expression
SRP069361	hMTR4 plays a central role in creating balanced nuclear RNA pools for degradation and export I	To define the in vivo targets of the human nuclear exosome, we performed stranded RNA-seq using rRNA-depleted RNAs isolated from nuclei of HeLa cells. To compare the RNA levels in each sample in an unbiased fashion, we added spike-in controls to equal amount of total nuclear RNAs. Overall design: rRNA-depleted RNAs isolated from nuclei of control, hRRP40 or hMTR4 siRNA treated HeLa cells were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP069362	hMTR4 plays a central role in creating balanced nuclear RNA pools for degradation and export II	To define the in vivo targets of the human nuclear exosome, we performed stranded RNA-seq using polyA RNAs isolated from nuclei of HeLa cells. To compare the RNA levels in each sample in an unbiased fashion, we added spike-in controls to equal amount of total nuclear RNAs. Overall design: PolyA RNAs isolated from nuclei of control, hRRP40 or hMTR4 siRNA treated HeLa cells were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.	Co-expression
SRP069723	Expression profiling by high throughput sequencing of tumors derived from human prostate epithelial cells transformed with the oncogenes N-Myc and myrAKT1.	MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Expression profiling by high throughput sequencing of experimentally generated human tumors with mixed NEPC and prostate adenocarcinoma. Overall design: Gene expression analysis of laser capture microdissected NEPC and adenocarcinoma from three independent engineered human tumors of mixed NEPC and prostate adenocarcinoma phenotype.	Co-expression
SRP069746	Human blood CD1c? dendritic cells encompass CD5-high and CD5-low subsets that differ significantly in phenotype, gene expression and functions	There are three major dendritic cell (DC) subsets in both human and mouse, plasmacytoid DCs (pDCs) and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4+  naive T cells into different subsets including Th1, Th2, Th17, Th22 and regulatory T cells (Tregs). In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported.  In the present study, we showed that human blood CD1c+ conventional DCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5high DCs expressed higher levels of cDC2-specific genes, including IRF4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5low DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with CD5low subpopulation, CD5high subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5high DCs induced naïve T-cell proliferation more potently than the CD5low DCs. Moreover, CD5high DCs induced higher levels of IL-10-, IL-22- and IL-4-producing T-cell formation, whereas CD5low DCs induced higher levels of IFN-?-producing T-cell formation. Thus, we show that human blood CD1c+ cDC2s encompass two subsets that differ significantly in phenotype, gene expression, and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance. Overall design: The mRNA profiles of two human blood CD1c+ conventional DCs (cDC2s) subpopulations, in triplicate.	Co-expression
SRP069760	RNA Sequencing Facilitates Quantitative Analysis of Transcriptomes in Human Normal and Cancerous Tissues	Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNAs that may regulate gene expression in eukaryotes. However, the regulation and function of human circRNAs remain largely unknown. Here we generate ribosomal-depleted RNA sequencing data from six normal tissues and seven cancers, and detect at least 27,000 circRNA candidates. Overall design: RNA profiles of six normal tissues and seven cancers were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP069773	RNA-seq of human fibroblasts after irradiation	Comparing gene expression level by Illumina sequencing of fibroblasts after irradiation Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 6 samples, 3 samples per group, 2 groups: 1) MRC-5 cells population doublings (PD) 16 and irradiation (20GY) and 2) HFF cells PD32 and irradiation (20GY)	Co-expression
SRP069787	Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]	TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. Overall design: RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).	Co-expression
SRP069789	Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_Stability]	TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. Overall design: RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).	Co-expression
SRP069826	Club cells surviving influenza A virus infection induce temporary non-specific anti-viral immunity	Cells respond differently to influenza virus infection after already having been infected previously. Overall design: Anlysis of cellular RNA after influenza virus infection	Co-expression
SRP069864	MOF acetyl transferase regulates transcription and respiration in mitochondria	Histone acetylation is sensitive to metabolic cues, however interplay between histone acetyl transferases and cellular metabolism remains poorly understood. Here we report the localization of a classical nuclear HAT- MOF and members of Non-Specific Lethal complex in mitochondria. MOF regulates expression of oxidative phosphorylation (OXPHOS) genes, residing in both nuclear and mitochondrial genomes, selectively in aerobically respiring cells. Furthermore, MOF/KANSL1 depletion causes impaired mitochondrial translation and reduced respiration. MOF loss is catastrophic for tissues with high-energy consumption. In mouse hearts, Mof knockout causes hypertrophic cardiomyopathy, compromised ventricular contractility/ stroke volume and ultimately leads to cardiac failure within three weeks of birth. RNA-seq analysis of the cardiomyocytes revealed deregulation of mitochondrial nutrient metabolism and OXPHOS pathways. Consistently, electron microscopy on affected tissues revealed mitochondrial deterioration with high tissue heterogeneity, commonly observed in mitochondrial diseases. Thus, we reveal a novel function of MOF in mitochondrial homeostasis and propose MOF as a sensor connecting epigenetic regulation to metabolism. Overall design: We generated mRNA-seq profile of Mof depleted HeLa cells adapted in glucose or galactose media. We also present nuclear RNA seq profile from Mof deleted cardiomyocytes.	Co-expression
SRP069884	IL-15 activates mTOR and primes stress-activated gene-expression leading to prolonged anti-tumor capacity of NK cells	Treatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor post-infusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK cell functions following cytokine withdrawal to model post-infusion performance. In contrasts to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided functional advantages. Genome-wide analysis of cytosolic and polysome-associated mRNA revealed cytokine dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced functional advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15 stimulated NK cells was also observed using a clinically applicable protocol for NK cell expansion. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK cell cancer therapy. Overall design: Freshly isolated NK cells from 6 donors were activated with IL-2 or IL-15 for 48 hours, followed by cytokine withdrawal for 24 hours, resulting in four RNA samples per donor. From each sample, both the cytosolic as well as the polysomal fraction were collected. Donor 3 contains activation and post withdrawal data from two different donors due to poor RNA-quality obtained for some samples which did not allow for processing of the complete set of 6 donors (resulting in a total of 40 samples).	Co-expression
SRP069960	RNA-seq analysis of SLIRP knockdown with 1nM DHT in LNCaP cells	The purpose of this study was to profile gene expression changes that could occur with the loss of co-repressor SLIRP. In addition, we wanted to investigate how DHT could further alter gene expression. Methods: LNCaP cells were transfected with custom nonsense control siRNA or a pool of SLIRP siRNA (HSS130109, HSS188666, HSS188667 Invitrogen, Carlsbad, CA) at 40nM for 24hrs. Cells were washed once with PBS and replaced with SFM containing EtOH or 1nM/ml DHT for another 24hrs.  Two biological replicates were collected from 2 different experiemnts for total of 4 replicates. RNA collected  was sequenced using Illumia HiSeq2000 single read 50 bp by the HTSF core at UNC and aligned and normalized by the Bioinformatics core at UNC. Results: We found a differential gene expression pattern between our control and SLIRP knockdown samples. We also identified a 176 AR gene signature with 3 subclasses and a large SLIRP gene signature (~1700). Overall design: Examination of control (NS) vs. SLIRP siRNA treated with 1nM DHT in the prostate cancer cell line LNCaP	Co-expression
SRP069968	mRNA-seq from Nutlin-3a, doxorubicin, and DMSO treated HCT116 p21-/- cells	We sequenced mRNA from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h. Overall design: Examination of mRNA levels from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h using four replicates each.	Co-expression
SRP069976	Human-Leishmania skin lesion transcriptome	The goal of this study is to simultaneously examine host and parasite gene expression programs in skin lesions of human patients infected with the intracellular parasite Leishmania. We conducted high-resolution sequencing of the transcriptomes from early and late stage cutaneous leishmaniasis biopsies using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes, helping to explain tuning of the immune response to parasite transcriptomic profiles present in the lesion microenvironment. This data provided a deeper look at the transcriptomic profile of the host response in conjunction with a novel look at the parasite transcriptome in human cutaneous lesions. These data also offer the first glimpse of Leishmania gene expression profiles specific to the cutaneous manifestation of disease in human patients. This metatranscriptomic study provides a solid framework for future functional, genomic, and clinical studies of leishmaniasis as well as intracellular pathogenesis in general.	Co-expression
SRP070059	Genetic Tagging During Human Mesoderm Differentiation Reveals Tripotent Lateral Plate Mesodermal Progenitors	Although clonal studies of lineage potential have been extensively applied to organ specific stem and progenitor cells, much less is known about the clonal origins of lineages formed from the germ layers in early embryogenesis.  We applied lentiviral tagging followed by vector integration site analysis (VISA) with high-throughput sequencing to investigate the ontogeny of the hematopoietic, endothelial and mesenchymal lineages as they emerge from human embryonic mesoderm. In contrast to studies that have used VISA to track differentiation of self-renewing stem cell clones that amplify significantly over time, we focused on a population of progenitor clones with limited self-renewal capability. Our analyses uncovered the critical influence of sampling on the interpretation of lentiviral tag sharing, particularly among complex populations with minimal clonal duplication. By applying a quantitative framework to estimate the degree of undersampling we revealed the existence of tripotent mesodermal progenitors derived from pluripotent stem cells, and the subsequent bifurcation of their differentiation into exclusively bipotent endothelial/hematopoietic or endothelial/mesenchymal progenitors. Overall design: Our goal was to analyze transcriptome changes of mesoderm commitment during human embyronic stem cells differentiation. RNA were extracted and sequenced from two populations, human embryonic stem cells (H1 line) and the human early mesodermal progenitors (hEMP) differentiated from H1.	Co-expression
SRP070060	A human mitochondrial DNA genetic bottleneck prevents mutational meltdown by purifying the early maternal germ line	Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but it is not clear how they arise and propagate in the humans. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Close scrutiny revealed the signature of selection against non-synonymous variants in the protein-coding region, tRNA gene variants, and variants in specific regions of the non-coding D-loop. In isolated single PGCs we saw a profound reduction in the cellular mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules during early germline development. Single cell deep mtDNA sequencing showed rare variants reaching higher heteroplasmy levels in later PGCs, consistent with the observed genetic bottleneck, and predicting >80% levels within isolated organelles. Genome-wide RNA-seq showed a progressive upregulation of genes involving mtDNA replication and transcription, linked to a transition from glycolytic to oxidative metabolism. The metabolic shift exposes deleterious mutations to selection at the organellar level during early germ cell development. In this way, the genetic bottleneck prevents the relentless accumulation of mtDNA mutations in the human population predicted by Muller's ratchet. Mutations escaping this mechanism will, however, show massive shifts in heteroplasmy levels within one human generation, explaining the extreme phenotypic variation seen in human pedigrees with inherited mtDNA disorders. Overall design: RNA-Seq and NGS analysis to investigate transcriptomes and mtDNA sequences of fetal hPGCs	Co-expression
SRP070081	RNA-Seq of SLNCR1 over-expression in the melanoma cell line A375	RNA-Seq was used to profile transcriptional changes induced by overexpression of the long non-coding RNA SLNCR1, as well as mutant version SLNCR1 delta conserved and SLNCR1 conserved. Overall design: The A375 melanoma cell line was transfected with pcDNA3.1 (-) expressing either full length SLNCR1, SLNCR1 delta conserved, or SLNCR1 conserved.	Co-expression
SRP070122	Cajal bodies are linked to genome conformation [RNA-Seq]	The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity. Overall design: Examination of RNA expression following depletion of Cajal bodies using siRNAs targeting TCAB1 and USPL1	Co-expression
SRP070129	A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans	A multi-subunit exosome complex is a major eukaryotic exoribonuclease that in the cytoplasm requires the SKI complex for activity. In yeast, SKI forms a heterotetramer and delivers RNA substrates directly into the exosome channel. Such cooperation requires Ski7 protein, which links the exosome and SKI complexes. However, since the human genome does not encode an orthologue of the yeast Ski7, the factor mediating SKI and exosome linkage in human cells is unknown. Proteomic analysis revealed that the human cytoplasmic exosome interacts with HBS1LV3, a protein encoded by a newly discovered short splicing isoform of HBS1L. HBS1LV3 recruits the SKI complex to the exosome. In contrast, the canonical HBS1L variant, HBS1LV1, acting as a ribosome dissociation factor, does not associate with the exosome and instead interacts with the mRNA surveillance factor PELOTA. HBS1LV3 contains a new domain of unknown structure with the short linear motif RxxxFxxxL, which is responsible for exosome binding, and may interact with the exosome core subunit RRP43 in way that resembles the association between Rrp6 RNase and Rrp43 in yeast. Depletion of HBS1LV3 and the SKI complex helicase SKI2W similarly affected the transcriptome by strongly upregulating a large number of genes. Moreover, following HBS1LV3 or SKI2W depletion the half-lives of representative upregulated mRNAs were increased, thus supporting the involvement of HBS1LV3 and SKI2W in the same mRNA degradation pathway. In contrast, HBS1LV1 depletion had little effect on transcriptome homeostasis. Our data indicate that human HBS1LV3 is the long-sought factor that links the exosome and SKI complexes to regulate cytoplasmic mRNA decay. Overall design: Examination of siRNA-mediated silencing in HEK293 cell lines. To identify transcripts that are degraded by cytoplasmic SKI/HBS1LV3/exosome supercomplexes, we used specific siRNAs to knock down HBS1LV1, HBS1LV3 or SKIV2L gene expression in (i) WT HEK293 cells and (ii) HEK293 cells rescued with siRNA insensitive protein.  Analyses were performed in triplicate.	Co-expression
SRP070148	Transcriptome profiling of human keratoconus corneas through RNA sequencing identifies collagen synthesis disruption and downregulation of core elements of TGF-ß, Hippo, and Wnt pathways	To understand better the factors contributing to keratoconus (KTCN), we used RNA sequencing to perform a transcriptome profile of human KTCN corneas. Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-ß, Hippo, and Wnt signaling pathways influencing corneal organization. We identified long noncoding RNAs (lncRNAs) and conducted a computational analysis of their potential functions, and found that lncRNAs regulated the processing and expression of the aforementioned genes. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN. Overall design: Transcription profiling of 25 KTCN and 25 non-KTCN corneas using RNA-Seq	Co-expression
SRP070430	Next Generation Sequencing Facilitates Quantitative Analysis of HCC cells transfected with NCsiRNA or CDCA8siRNA	We hypothesized if targeting of CDCA8 with small interfering (si) RNA could inhibit HCC progression. We also investigated molecular mechanism to mediate HCC cell death caused by CDCA8 silencing. To accomplish this, Huh1 and Huh7 human HCC cells were transfected with CDCA8 siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to CDCA8 knockdown, global changes in gene expression were examined using RNA sequencing. As results, siRNA silencing of CDCA8 inhibited HCC cell growth by blocking cell-cycle progression and inducing apoptosis. RNA sequencing showed that, representatively, the anti-proliferative effects were driven by a subset of molecular alterations including the upregulation of tumor suppressive ATF3 and GADD34 genes, whereas a key regulator of cell growth and invasiveness BGLAP was repressed. Subsequent Western blotting also revealed that CDCA8 silencing decreases the levels of pro-caspase 3 and PARP-1, accelerating apoptotic signaling in HCC cells. In addition, targeting CDCA8 effectively suppressed HCC tumor growth growth in a murine xenograft model. Taken together, these findings suggest that CDCA8 could be a promising molecular target for systemic therapy of HCC. Overall design: Examination of 2 different siRNA transfected cells in 2 cell lines.	Co-expression
SRP070439	Multivalent binding of PWWP2A to H2A.Z-marked transcriptional active chromatin regulates mitosis and organ development [RNA-seq]	The essential histone variant H2A.Z affects various DNA-based biological processes by so far not well understood mechanisms. Using a comprehensive label-free quantitative mass spectrometry-based approach we identified the human H2A.Z nucleosome interactome providing further insights into H2A.Z’s regulatory functions. Besides histone modification writer, eraser and reader complexes we identified PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A binds unprecedented strong to chromatin through a concerted multivalent binding mode. Two internal protein regions separately allow H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain mediates direct DNA binding. PWWP2A is found at euchromatic regions where it preferable binds to the H2A.Z-nucleosome-containing transcriptional start sites of transcribed genes. Cellular depletion of PWWP2A results in impaired proliferation caused by a mitotic delay likely due to deregulation of involved target genes. According with the strong cellular phenotype, knockdown of frog PWWP2A leads to severe developmental cranial facial defects arising from neural crest cell differentiation and migration problems. Together, this study identifies PWWP2A as an H2A.Z-specific multivalent chromatin binder and provides a novel link between H2A.Z, chromosome segregation and organ development. Overall design: RNASeq of HeLa cells treated with control or PWWP siRNA	Co-expression
SRP070442	RNA-Seq Analysis of Anacardic Acid Treated MCF7 and MDA-MB-231 Breast Cancer Cell Lines	Anacardic acid (AnAc) is a mixture of 6-alkylbenzoic acid congeners that are produced in a number of plants. Previously, we showed a specific congener AnAc 24:1n5 acts as a nuclear receptor alternate site modulator (NRAM) to inhibit breast cancer cells in an estrogen receptor (ER)-dependent manner by interfering with ER-DNA binding. AnAc 24:1n5 also inhibited the growth of a triple negative breast cancer (TNBC) cell line, through an undefined mechanism. Additional work from our labs  indicated AnAc 24:1n5 inhibits prostaglandin synthase and that inhibition is more specific to COX-2. Reports from other investigators indicate AnAc has a number of interesting potential pharmacological targets. We previously used qRT-PCR to investigate expression changes in endogenous estrogen-regulated genes, i.e., TFF1, CCND1, and CTSD in breast cancer cell lines. However, since AnAc has the capacity of effect multiple molecular targets and since we detected an ER-independent inhibition of breast cancer cell proliferation, we suspect additional unknown molecular targets are affected in breast cancer cells. Identification of such targets using RNA-seq would be quite beneficial in targeting TNBC which primarily affects premenopausal women with a predominance in women of African and Latina ancestry.  The goal of this portion of the project is to use next-generation RNA-SEQ to identify alterations in molecular target sequence levels in ER-positive and -negative breast cancer cell lines treated with AnAc. Overall design: There are two breast cancer cell lines used in this study, including MCF-7 (invasive breast ductal carcinoma; estrogen receptor positive (ER+); progesterone receptor positive (PR+); human epidermal growth factor 2 negative (HER2-)) and MDA-MB-231 (breast adenocarcinoma; triple negative – ER-; PR-; HER2-).  Each of these cell lines was treated with anacardic acid (AnActrt) with three replicates each, resulting in a total of 12 RNA samples.  One MDA-MB-231 control sample and one MDA-MB-231 AnActrt treated sample were removed after QA/QC determined they were likely contaminated samples.	Co-expression
SRP070532	miR-126 Orchestrates an Oncogenic Program in B-Cell Precursor Acute Lymphoblastic Leukemia	MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden. Overall design: Study 1: Turning off miR-126 expression from an experimental murine B-ALL in vivo; Study 2: Modulation of miR-126 expression in human cord blood stem and progenitor cell populations in vitro.	Co-expression
SRP070564	RNA-seq of HL60 cells treated with epigenetic therapy	RNA-seq was performed after HL60 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples	Co-expression
SRP070636	MLL1 is essential for the senescence-associated secretory phenotype [RNA-Seq]	Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence-associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces “SASP-like” inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression. Overall design: This study consists of a single replicate of RNA-seq from oncogene-induced senescent (or control) IMR90 cells in a MLL1 knockdown (or WT) background, for a total of four samples	Co-expression
SRP070649	Longitudinal transcriptome profiling of post-treatment Lyme disease syndrome	Most Lyme disease patients treated with appropriate antibiotics recover rapidly and completely, but a minority of patients develop persistent symptoms correlating with disseminated disease, a greater severity of illness at presentation, and delayed antibiotic therapy. When lingering or recurrent symptoms are associated with a functional decline and persist for greater than 6 months, patients are considered to meet clinical criteria for post-treatment Lyme disease syndrome (PTLDS), although the exact molecular mechanisms underlying this condition remain unknown. We performed longitudinal whole transcriptome sequencing of PTLDS patients' immune cells. No immune mechanism specific to PTLDS were uncovered to date. Overall design: Gene expression profile from peripheral mononuclear blood cells (PBMC) of PTLDS patients was undertaken. Seven Lyme disease patients were sampled at 3 time points: acute Lyme pre-treatment (V1), 3 weeks later, immediately following completion of a standard course of antibiotics (V2), and 6 months following treatment completion (V5). Total RNA was extracted from 10e7 PBMC, followed by mRNA purification, paired-end barcode library preparation and sequencing on an Illumina HiSeq 2000.	Co-expression
SRP070657	An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response [RNA-seq]	Estrogen receptor a (ERa) is an important biomarker of breast cancer severity and a common therapeutic target. Recent studies have demonstrated that in addition to its role in promoting proliferation, ERa also protects tumors against metastatic transformation. Current therapeutics antagonize ERa and interfere with both beneficial and detrimental signaling pathways stimulated by ERa. The goal of this study is to uncover the dynamics of coding and non-coding RNA (microRNA) expression in response to estrogen stimulation and identify potential therapeutic targets that more specifically inhibit ERa-stimulated growth and survival pathways without interfering with its protective features. To achieve this, we exposed MCF7 cells (an estrogen receptor positive model cell line for breast cancer) to estrogen and prepared a time course of paired mRNA and miRNA sequencing libraries at ten time points throughout the first 24 hours of the response to estrogen. From these data, we identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of paired mRNA and microRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that over-expression of miR-503 suppresses breast cancer cell proliferation. Overall, these data indicate that miR-503 acts as a potent estrogen-induced tumor suppressor microRNA that opposes cellular proliferation and has promise as a therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. Overall design: Quantification of mRNAs in MCF7 cells responding to estrogen following a period of estrogen starvation. Three independent biological replicates (30 samples: 3 replicates x 10 time points) of MCF7 cells were exposed to 10nM Estradiol for 0, 1, 2, 3, 4, 5, 6, 8, 12 , or 24 hours, and total RNA was extracted from the samples. Total RNA was used to generate paired RNA and miRNA sequencing. RNA libraries were prepared using an Illumina TruSeq stranded mRNA library preparation kit.	Co-expression
SRP070663	Homo sapiens raw sequence reads - Ethnically Diverse hiPSC	Ethnically diverse - African American, Hispanic Latino, Asian - induced pluripotent stem cell lines bioinformatics data	Co-expression
SRP070668	Effect of BB608 on Gene Expression in HNSCC Cell Line	Study to determine the genome wide effects on transcripton in FaDu cells treated with BB608, a transcription factor inhibitor Overall design: 2 samples analyzed, 3 biological replicates per sample	Co-expression
SRP070687	Next Generation Sequencing Facilitates Quantitative Analysis of colorectal cancer cells transfected with NC siRNA or RPL9 siRNA	Ribosomal protein L9 (RPL9), a component of the 60S subunit, is up-regulated in human colorectal cancer (CRC). We thus hypothesized if targeting of RPL9 with small interfering (si) RNA could inhibit CRC progression. We also investigated molecular mechanism to mediate CRC cell death caused by RPL9 silencing. HCT116 and HT29 human CRC cells were transfected with RPL9 siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to RPL9 knockdown, global changes in gene expression were examined using RNA sequencing. As a result, RPL9 silencing caused inhibition of CRC cell growth through induction of apoptotic cell death. RNA sequencing revealed that RPL9-specific knockdown led to dysregulation of 918 genes in HCT116 and 3178 genes in HT29 cells. Among those, 296 genes showed the same directional regulation (128 up- and 168 down-regulated genes), including up-regulation of tumor suppressors such as KLF6 and ATF3, and were considered as a common RPL9 knockdown signature. Western blotting proved that down-regulation of RPL9 was accompanied with the decrease in the levels of PARP-1 and pro-caspase 3, accelerating apoptotic signaling. Of importance, targeting RPL9 significantly inhibited CRC growth in a murine xenograft model. In conclusion, these results suggest that inhibition of RPL9 expression could be an attractive option for molecular targeted therapy of colorectal cancer. Overall design: Examination of 2 different siRNA transfected cells in 2 cell lines.	Co-expression
SRP070694	BASP1 modifies the Tamoxifen response	We report that WT1 transcriptional repressor protein BASP1 interacts with oestrogen receptor alpha (Era), and interaction which in enhanced in the presence of Tamoxifen. We utilised RNASeq to identify common BASP1 and ERa target genes as well as Tamoxifen responsive genes that are altered in the absence of BASP1. Overall design: Total mRNA sequencing analysis of MCF7 cells treated with either siRNA against BASP1 or negative control siRNA, with and without Tamoxifen treatment. Each experiment was performed in triplicate.	Co-expression
SRP070710	mRNA expressions in pre-treatment melanomas undergoing anti-PD-1 checkpoint inhibition therapy	PD-1 immune checkpoint blockade provides significant clinical benefits for cancer patients. However, factors influencing innate sensitivity remain incompletely catalogued. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies. Mutations in cell adhesion genes and the DNA repair gene BRCA2 were enriched in responding tumors, and a high mutational load associated with improved survival. Innately resistant tumors displayed frequent transcriptomic up-expression of genes that enriched for mesenchymal transition, cell adhesion, ECM organization, wound-healing and angiogenesis. The transcriptomes of innate resistance also enriched for signatures indicating up-regulation of these processes. Notably, MAPK-targeted therapy (MAPKi) induced similar signatures in melanoma, suggesting that a form of MAPKi resistance mediates cross-resistance to anti-PD-1 therapy. Co-enrichment of IPRIM (Innate anti-PD-1 Resistance Induced by MAPKi) signatures defined a transcriptomic subset across advanced cancers, suggesting that attenuating processes underlying these signatures may augment anti-PD1 responses. Thus, multi-factorial determinants influence anti-PD-1 patterns in melanoma. Overall design: Melanoma biopsies pre-anti-PD-1 therapy were sent for transcriptomic analysis by paired-end RNAseq analysis to find the correlates of response vs. non-response to the therapy	Co-expression
SRP070723	Comparison of HCC cell lines and primary HCCs-RNAseq data	There are concerns about whether cancer cell lines could faithfully represent the matched primary cancer cells. Comparison of the HCC cell lines and primary HCCs demonstrated that, during long-term in vitro culture, cell lines retain the genetic landscape of the matched primary HCCs. Overall design: RNAseq and WGS comparison of of 9 matched primary HCCs, early-passage PDCs and late-passage cell lines.	Co-expression
SRP070768	RNA-SEQ assay for wild type and CRISPR induced endoglin knockout human pulmonary artery smooth muscle cells (PASMC)	The goal of this study is to investigate the differential transcripted genes affected by CRISPR induced endoglin knockout in PASMC cells. Overall design: Total RNA was purified from NTC or ENG-/- PASMC cells using RNeasy Mini Kit (Qiagen, Hilden, Germany). RNA quality and concentration were assessed with Agilent Tapestation 200 (Agilent Technologies) and Qubit 2.0 (ThermoFisher Scientific).  ~250-500 ng RNA were used for library construction. The NGS libraries were constructed using the KAPA Stranded mRNA-Seq Kits (KapaBioSystems). mRNA was captured using magnetic oligo-dT beads and 1st strand cDNA was synthesized using random priming. In order to preserve strand-specificity, 2nd strand synthesis, which converts the cDNA:RNA hybrid to double-stranded cDNA (dscDNA), was marked by dUTP incorporation. cDNA framents were A-tailed by adding dAMP to the 3''-ends of the dscDNA library fragments. dsDNA Illumina TruSeq "forked”  adapters 3''-dTMP overhangs were then ligated to A-tailed library insert fragments. Each of the six libraries were ligated with a unique Truseq 6bp barcode. Library fragments were amplified using the KAPA HiFi HotStart polymerase. The strand marked with dUTP was not amplified, allowing strand-specific sequencing. Fragment length and library quality was assessed on a 2100 Bioanalyzer using the High Sensitivity DNA Kit (Agilent Technologies).  Libraries were diluted to 10nM and pooled at equimolar ratios. The pool was then diluted to 2nM and denatured in NaOH following Illumina recommendations. 10pM of denatured library pool was loaded in one HiSeq lane and flowcell was clustered on the Illumina C-bot. 5% PhiX control was spiked-in. The flowcell was sequenced on a HiSeq 2500 V4 chemistry with 50bp Single read protocol. Data was demultiplexed and Fastq files were generated using BcptoFastq 1.8.4 script provided by Illumina.	Co-expression
SRP070776	Activin A regulates human T follicular helper (Tfh) cell differentiation	To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher.  Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.	Co-expression
SRP070779	Modeling the ESR1 tyrosine 537 mutation with CRISPR-Cas9 for mechanistic studies and evaluation of therapeutic approaches for metastatic breast cancer [RNA-Seq]	Estrogen receptor-a (ERa) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERa target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERa binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen. Overall design: Hormone depleted MCF7 Luc or Y537S cells were treated with 10nM E2 or ethanol, as vehicle control, for 8 hours, with 3 replicates (2 replicates for Y537S + E2). RNA-seq was carried out using Illumina Hiseq 2500.	Co-expression
SRP070780	RNA-sequencing of metaplastic carcinoma of the breast	No description.	Co-expression
SRP070810	Dissecting stages of human kidney development and Tumorigenesis with surface markers affords simple prospective Purification of nephron stem cells	When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms'' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Overall design: Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.	Co-expression
SRP070815	24hr CA treatment vs. DMSO in HCT116 cells (from ''Identification of CDK8 and CDK19 substrates in human cells using cortistatin A and quantitative phosphoproteomics'')	Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we report here the first large-scale identification of Mediator kinase substrates in human cells (HCT116).  Among over 16,000 quantified phosphosites, we identified 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II.  Although RNA-Seq data correlated with Mediator kinase targets, CA effects on gene expression were limited and distinct from CDK8 or CDK19 knockdown.  Quantitative proteome analyses, which tracked about 7,000 proteins across six time points (0 – 24h), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation; contrary to expectations, increased turnover of Mediator kinase targets was not generally observed.  Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest cellular roles beyond transcription, including metabolism and DNA repair. Overall design: HCT116 cells were treated with either 100nM CA or DMSO in biological triplicate for each population (6 samples total). Treatment was for 24h for compound and vehicle.	Co-expression
SRP070819	Enhanced CLIP uncovers IMP protein-RNA targets in human pluripotent stem cells important for cell adhesion and survival [RNA-Seq]	Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using a recently developed enhanced UV crosslinking and immunoprecipitation (eCLIP) approach, we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad region- and binding site-level IMP1 and IMP2 show reproducible binding to a large and overlapping set of 3''UTR-enriched targets. RNA Bind-N-Seq applied to recombinant full-length IMP1 and IMP2 reveals CA-rich motifs that are enriched in eCLIP-defined binding sites. We observe that IMP1 loss in hPSCs recapitulates IMP1 phenotypes, including a reduction in cell adhesion and an increase in cell death. For cell adhesion, in hPSCs we find IMP1 maintains levels of integrin mRNA, specifically regulating RNA stability of ITGB5. Additionally, we show IMP1 can be linked to hPSC survival via direct target BCL2. Thus, transcriptome-wide binding profiles identify hPSC targets modulating well-characterized IMP1 roles. Overall design: eCLIP-seq was performed in biological replicate for IGF2BP1/IMP1 and IGF2BP2/IMP2, as well as one replicate each for IGF2BP3/IMP3, RBFOX2, and an IgG control. Each sample has a size-matched input control for analysis	Co-expression
SRP070828	Identification Of Candidate Anti-Cancer Molecular Mechanisms Of Compound Kushen Injection Using Functional Genomics	Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours.  However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion.  We have used the MCF-7 breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression.  Cells were treated with CKI for 24 and 48 hours at two concentrations (1.0 and 2.0 mg/mL), and 5-Fluorouracil (5-FU) was used to treat cells as a positive control.  Cell proliferation and apoptosis activity were measured with XTT and Caspase-3 assays respectively.  Transcriptome data of cells treated with CKI or 5-FU for 24 and 48 hours were acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion.  We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI.  Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells.  CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism.  In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.  Overall, we have comprehensively investigated the utility of transcriptome analysis with high-throughput sequencing to characterise the molecular response of cancer cells to a TCM drug, and provided a practical guideline for future molecular studies of TCM. Overall design: High-depth paired-end RNA-seq from MCF-7 cell line. Each sample contains 3 biological replicates.	Co-expression
SRP070836	Next Generation Sequencing for Quantitative Analysis of transcriptome of follicular compared to non-follicular CD8 T cells from  HIV+ Lymph nodes	The goal of the study was to characterize the molecular signatures of CD8 T cell subpopulations sorted from HIV+ lymph nodes and HIV- tonsils. We compared the transcriptome profiles of follicular and non -foliccular CD8 T cells (sorted based on the surface expression fo CCR7 and CXCR5, chemokine receptors that govern the intratissue trafficking of T cells). This is the first study addressing this question. We found several genes differentially expressed in these two CD8 T cell populations. Our pathway analysis revealed that several pathways related to costimulation/activation as well as to beta-catenin pathway were differentially expressed in these two CD8 t cell populations too. Overall design: CD8 T cell populations were sorted and whole transcriptome analysis was performed using an Illumina machine	Co-expression
SRP070840	Capicua-dependent transcriptional changes in human cancer cell lines treated with trametinib	We performed a genome-scale CRISPR screen in a KRAS-mutant pancreatic cancer cell line treated with the MEK inhibitor trametinib, and found that loss of the transcriptional repressor CIC confers resistance to MEK inhibition. We determined that CIC loss also confers resistance to MEK or BRAF inhibition in lung cancer, colorectal cancer, and melanoma cell lines with mutant RAS or BRAF. CIC is a transcriptional repressor that is phosphorylated and inhibited by the MAPK pathway. We hypothesized that inhibition of the MAPK pathway would lead to activation of CIC and repression of CIC target genes. Loss of CIC would therefore restore expression of these genes, conferring drug resistance. To identify the relevant CIC target genes that mediate trametinib resistace, we generated 4 Cas9-expressing cell lines from different lineages and with different RAS or RAF mutations, and generated control (gGFP) or CIC-knockout (gCIC) cell lines. We treated cells with DMSO or trametinib for 24 hours, and performed NRA-seq. We found that trametinib treatment reduces expression of at least one member of the PEA3 family of ETS transcription factors (ETV1, ETV4, and ETV5) in all cell lines assessed, and that loss of CIC results in maintained expression of these genes despite MEK inhibition. We further validated that ETV1, 4, and 5 expression was necessary for resistance mediated by CIC loss; and that ETV1, 4, or 5 expression was sufficient to confer trametinib resistance. Overall design: 4 Cas9-expressing human cancer cell lines (A549, CALU1, HCT116, PATU8902) were used to generate 3 isogenic cell lines with intact CIC (gGFP-1) or knocked out CIC (gCIC-1 or gCIC-2). Each of these 12 cell lines were treated with DMSO or trametinib for 24 hours (duplicates)	Co-expression
SRP070843	RNA sequencing of siSNRNP40 in breast cancer cells	To identify gene expression profile changes upon SNRNP40 depletion, RNA-sequencing was performed on breast cancer cells transfected with siRNAs targeting SNRNP40. Overall design: Libraries were generated using ScriptSeq v2 RNA-seq Library Preparation Kit (Epicentre) and run on Illumina HiSeq 2500.	Co-expression
SRP070884	Next Generation Sequencing Analysis of control and SRSF2-/- Huh7 cells Transcriptomes	We generated the SRSF2-/- Huh7 cells,and collected the cells at 2 days after transfected with siRNA. Then, we extracted RNAs and performed next generation sequencing. By comparing sequencing data from control and SRSF2 -/- samples, we profiled the alternative splicing events and gene expression regulated by SRSF2 in HCC. Overall design: Huh7 cells mRNA profiles of  control and SRSF2-/- were generated by deep sequencing, using Illumina HiSeq2000.	Co-expression
SRP070938	Restoration of mesenchymal RPE by transcription factor-mediated reprogramming	TGFbeta-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelial (RPE) differentiation after periods of sustained sub-confluent culture or repetitive passage. Inhibition of TGFbeta signaling using receptor kinase inhibitors forestalls the onset of passage-dependent EMT and can restore the capacity to differentiate to cells that previously underwent the mesenchymal switch [Radeke et al., 2015, Genome Med. 7:58]. However, even with the sustained inhibition of mesenchymal gene expression using  TGFbeta signaling inhibitors the cells eventually lose the capacity to attain a characteristic phenotype. This suggests that there are additional mechanisms at play that contributeto the prevention of RPE differentiation after protracted periods of wound stimulus and mitosis. In this study we investigate the non-TGFbeta-mediated processes that contribute to the demise of the RPE phenotype after extended periods of proliferative wound response. Using comparative transcriptomics, we show that with increasing passage there is a downregulation of RPE genes, misregulation of cell cycle genes, a decline in proliferative potential that cannot be prevented or reversed by inhibition of TGFbeta signaling using the TGFbeta receptor kinase inhibitor A-83-01. Importantly, among the RPE genes with decreased expression are several transcription factors known to be critical for RPE development. Exogenous expression of MYCN and OTX2 in conjunction with A-83-01 treatment restored the ability of passage 7 RPE  to differentiate. Taken together, these results demonstrate that the loss of capacity to differentiate as a result of chronic wound stimulus is a product of both TGFbeta pathway-dependent increases in mesenchymal gene expression and a TGFbeta pathway-independent loss of RPE programming. Overall design: PolyA+ RNA-Seq analysis of primary fetal RPE donor lines as a function of passage with and without treatment with A-83-01 or after transcription factor-mediated reprogramming were done in triplicate using cells obtained from different donors. PolyA+ RNA-Seq analysis of the adult RPE cell line ARPE-19 was carried out in triplicate using independent experimental replicates obtained on different days. In two instances the reads from duplicate sequencing runs were carried out on the same seqeuncing libraries and the sequence files were combined prior to analysis.	Co-expression
SRP070996	The genomic landscape of pediatric T-cell acute lymphoblastic leukemia reveals novel X-linked somatic mutations associated with apoptosis resistance. [RNA-Seq]	Background. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis. It represents 15% of pediatric ALL and has a threefold higher incidence among males. T-cell transformation is a multi-step process involving cooperating events leading to altered T-cell signaling, proliferation, differentiation and survival. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Results. Using an integrative approach combining genomic and transcriptomic data, we performed comprehensive molecular characterization of 30 pediatric T-ALLs. We identified common T-ALL targets and confirmed the overall poor outcome of early immature cases. We also showed that deletion of the CDKN2A locus is associated with lower risk of relapse. In addition, we identified novel T-ALL drivers including a member of the spliceosome machinery U2AF1 as well as novel X-linked tumor suppressors MED12 and USP9X, that had never been associated to T-ALL before. Interestingly, almost 60% of these events were found in early immature cases which represented only 35% of the cohort. Functional validations further demonstrated the putative role of these novel T-ALL genes in driving transformation by demonstrating the aberrant splicing provoked by U2AF1 p.R35L and the protective effect against apoptosis of MED12 and USP9X repression. Conclusions. This study highlights the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment. Overall design: Total RNA was extracted from bone marrow samples at diagnosis for patients 432, 437, 547, 693, 716, 743, 744, 748, 791 and 849 using the mirVana Isolation kit (Ambion) according to the manufacturer’s protocol. The Allprep DNA/RNA Mini kit (Qiagen) was used for relapse samples in patients 791 and 879. For patient 744, mature RNA was also purified using the Ambion''s MicroPoly(A)Purist kit (Small Scale mRNA Purification Kit P/N AM1919). Following a DNAse I treatment, total or mature RNA samples were quantified by NanoDrop ND1000 (Thermo-Fisher Scientific) and RNA quality was assessed using the Agilent 2100 Bioanalyzer (Agilent). Ribosomal ribonucleic acid (rRNA) were depleted using the Invitrogen RiboMinus Eukaryote kit (Life Technologies). cDNA libraries were prepared using the SOLiD Total RNA-seq kit (diagnosis samples) and the Illumina TruSeq Stranded Total RNA kit (relapse samples) based on manufacturer’s protocol and sequenced on the Life Technologies SOLiD 5500 System or the Illumina HiSeq 2500 System.	Co-expression
SRP071026	Homo sapiens Transcriptome or Gene expression	Viral discovery project through the generation of human serum transcriptome from target subjects.	Co-expression
SRP071088	Tricyclic Antidepressants Induce Inactivation of Hepatic Stellate Cell (HSC) Myofibroblasts	Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs. Overall design: HSCs and HSCs stimulated with TGF-beta were treated with the TCA, nortriptyline or ethanol vehicle for 48 hours. RNA-seq was performed in duplicate for each condition	Co-expression
SRP071170	Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression	IL-6 is a proinflammatory cytokine implicated in multiple autoimmune diseases. Here we show that IL-6 induced STAT3 and STAT1 phosphorylation is enhanced in CD4 and CD8 T cells from patients with T1D compared to healthy controls. Enhanced IL-6/pSTAT3 is associated with increased surface IL-6R and early clinical disease. The transcriptome of IL-6 treated CD4 T cells from T1D patients reveals upregulation of genes involved in T cell migration. The data suggest that individuals with type 1 diabetes may benefit from therapeutic targeting of the IL-6 pathway. Overall design: CD4+CD25- T cells were purified from thawed PBMC of seven subjects with type 1 diabetes. Cells were left unstimulated or were treated with 10ng/ml IL-6 for 24 hours. RNA was extracted and RNA sequencing was performed.	Co-expression
SRP071195	Differentially expressed vascular development genes for iPSC-ECs from CDI	Here we report genes upregulated for iPSC-ECs cultured in PEG hydrogels relative to control cells on tissue culture polystyrene (TCP) surfaces included adhesion, matrix remodeling, and Notch signaling pathway genes relevant to in vivo vascular development. Overall design: Comparison between differentially expressed genes in 2D versus 3D culture of iPSC-ECS	Co-expression
SRP071197	Huntingtin aggregation impairs autophagy leading to Argonaute-2 accumulation and global microRNA dysregulation	Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates resulting in alterations in autophagy. However, the consequences of impaired autophagy on neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation, as well as post-mortem material from patients with Huntington''s disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNAinduced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation, but also directly contributes to global alterations of intracellular posttranscriptional networks. Overall design: Examination of mRNA sequencing of i) lentiviral mediated overexpression of wtHTT (18Q) and mHTT (66Q) in 293T cells, ii) striatal tissue collected from AAV-wtHTT and AAV-mHTT injected mice and examination of small RNA sequencing from i) lentiviral mediated overexpression of wtHTT (18Q) and mHTT (66Q) in 293T cells and ii)  AGO2-RIP and total RNA samples obtained from AAV-wtHTT and AAV-mHTT injected mice.	Co-expression
SRP071199	Dual RNA-sequencing of host and pathogen during Plasmodium berghei infection of hepatocytes in vitro	We report the dual RNA-sequencing of host and pathogen transcriptomes during Plasmodium berghei liver-stage development in vitro. Unlike traditional transcriptomic approaches that analyze RNA reads separately from host and pathogen, a dual-approach maps the mixed reads to each annotated genome within samples of pathogen-infected host cells. This is a powerful method, as host and pathogen transcriptomes can be analyzed simultaneously. We have taken advantage of this dual-RNA sequencing approach in order to gain insight into Plasmodium liver stage development within host hepatocytes. Huh7.5.1 hepatocytes were infected in vitro with P. berghei sporozoites freshly dissected from infected Anopheles stephansi mosquitos, and cells were collected throughout liver-stage development. This included samples collected at time zero (uninfected hepatocytes and sporozoites before infection), time 24 hours post infection (when the sporozoites have transformed into trophozoites), and time 48-50 hours post infection (when the trophozoites have transformed into liver-stage schizonts). Overall design: Dual RNA-sequencing of P. berghei-GFP and human RNA in infected and uninfected Huh7.5.1 cells	Co-expression
SRP071203	Systematically characterizing dysfunctional long intergenic non-coding RNAs in multiple brain regions of major psychosis	Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed “major psychosis”. Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD. Here, we performed RNA sequencing on 82 post-mortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. We characterized lincRNA transcriptome in the three brain regions and identified 20 differentially expressed lincRNAs (DELincRNAs) in BA11 for BD, 34 and 1 in BA24 and BA9 for SZ, respectively. Our results showed that these DELincRNAs exhibited brain region-specific patterns. Applying weighted gene co-expression network analysis, we revealed that DELincRNAs together with other genes can function as modules to perform different functions in different brain regions, such as immune system development in BA24 and oligodendrocyte differentiation in BA9. Additionally, we found that DNA methylation alteration could partly explain the dysregulation of lincRNAs, some of which could function as enhancers in the pathogenesis of major psychosis. Together, we performed systematical characterization of dysfunctional lincRNAs in multiple brain regions of major psychosis, which provided a valuable resource to understand their roles in SZ and BD pathology and helped to discover novel biomarkers. Overall design: RNA sequencing of 82 brain samples including each of 19 from BA9 and BA24 and 44 from BA11. We performed RNA sequencing on three brain regions namely the BA11 (part of orbitofrontal cortex), BA24 (part of anterior cingulate) and BA9 (part of dorsolateral prefrontal cortex) from SZ and BD patients and psychiatrically normal individuals.In summary, there were 44 BA11 samples from 16 SZ, 16 BD and 12 control subjects, and 19 BA24 and 19 BA9 samples from the same subjects including 6 SZ, 7 BD and 6 controls.	Co-expression
SRP071232	Modeling the Neuropathology of Tuberous Sclerosis with Human Stem Cells Reveals a Role for Inflammation and Angiogenic Growth Factors [Cell Model]	Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Overall design: Two TSC+/- cell lines and two TSC-/- cell lines were independently generated from wild-type human embryonic stem cells by genome editting with zinc finger nucleases. Two cell lines were handled in the same way but without any known human gene editted and they are used as negative controls. Two independent biological replicates of each of the six cell lines are profiled with ribosome profiling technique.	Co-expression
SRP071235	Modeling the Neuropathology of Tuberous Sclerosis with Human Stem Cells Reveals a Role for Inflammation and Angiogenic Growth Factors [Treatment]	Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Overall design: Rapamycin, AZD-8055, and DMSO were given to two TSC+/+ cell lines and two TSC-/- cell lines after six weeks of differentiation. Cells are harvested after 3 hours treatment and are subject to ribosome profiling and RNA-seq analysis.	Co-expression
SRP071245	Effective Detection of Variation in Single Cell Transcriptome using MATQ-seq	We report here a new single-cell RNA-seq assay, Multiple Annealing and dC-Tailing based Quantitative single-cell RNA-seq (MATQ-seq), which provides the accuracy and sensitivity that enable the detection of transcriptional variations existing in single cells of the same type. We performed a systematic characterization of the technical noise using pool-and-split averaged single-cell samples and showed that the biological variations in single cells were observed with statistical significance. Overall design: 10 HEK293T single cells and 10 HEK293T pool-and-split averaged single cell samples were sequenced with MATQ-seq. We also sequenced 6 MCF10A single cells and 6MCF10A pool-and-split averaged single cell samples. To characterize the capture efficiency, we also sequenced 6 averaged one-fifth MCF10A single-cell samples with ERCC spike-in. Additional 38 HEK293T single cells (HEK293T_clone1_SC*) and 10 HEK293T pool-and-split averaged single cell samples (HEK293T_clone1_SC_average*) were sequenced with MATQ-seq.	Co-expression
SRP071331	KSHV Infection Mimics the Hypoxic Response Based on Next-Generation Sequencing [mRNA-Seq]	Purpose: Kaposi’s sarcoma associated-herpesvirus (KSHV) causes several hyperproliferative disorders, including Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. KSHV encodes for a number of microRNAs (miRNAs), and KSHV infection can affect the expression of cellular miRNAs. Hypoxia has been shown to induce KSHV reactivation, directly induce several KSHV lytic genes, and also induce the most abundant latent viral protein, LANA.  Also, several KSHV proteins can stabilize and increase the cellular levels of hypoxia-inducible factor (HIF-1a). However, the degree to which hypoxic pathways are utilized by KSHV has yet to be determined. Methods: We investigated the interplay between hypoxia and KSHV infection by comparing the 31effects of hypoxia and KSHV infection on miRNA and mRNA expression, and by examining the 32effects of hypoxia on uninfected and KSHV-infected cells. This was accomplished using next-33generation sequencing (NGS), qRT-PCR, Taqman assays, and pathway analysis. Results: NGS analysis of human mRNAs revealed striking similarities (~34%) between the transcriptomic response to hypoxia and the transcriptomic response to KSHV infection. Additionally, hsa-miR-210, a key hypoxia-inducible miRNA with pro-angiogenic and anti-apoptotic properties, was found significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Finally, KSHV infected cells differed somewhat in their response to hypoxia compared to KSHV-uninfected controls. Conclusions: These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and induces miR-210 up-regulation. The understanding of how these miRNAs, genes and pathways are regulated by HIF-1a and KSHV infection are essential to a better understanding of the biology of KSHV-associated diseases. Overall design: 6 samples analyzed. Two experimental conditions: hypoxic uninfected cells (SLK cells) and hypoxic chronically KSHV-infected cells (SLKK cells) (n=3). Two sequencing platforms: microRNA-Seq and mRNA-Seq.	Co-expression
SRP071332	Expression profiling of IL-13 stimulated PBMCs with and without an IL-13R antagonist	This experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). Overall design: The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.	Co-expression
SRP071547	Dynamic gene regulatory networks of human myeloid differentiation [RNA-seq]	We utilize gene expression and open chromatin footprinting data to build a gene regulatory network of key transcription factors that capture the cell and time-specific regulatory programs specified during human myeloid differentiation. Overall design: RNA-seq profiling of undifferentiated HL-60, differentiating macrophage, neutrophil, monocyte, and monocyte-derived macrophage cells.	Co-expression
SRP071553	RNA sequencing analysis of NGFR ablation in both p53-positive and negative non-small-cell lung cancer cell lines	We report the gene expression profiles by NGFR knockdown in H460 and H1299 cell lines and reveal that NGFR ablation activates p53 target gene expression. Overall design: We examined gene expression in two different non-small-cell lung cancer cell lines, one with wild-type p53 and the other without p53.	Co-expression
SRP071557	The Landscape of Antisense Gene Expression in Human Cancers	High throughput RNA Sequencing has revealed that the human genome is widely transcribed. However, the extent of natural antisense transcription, the molecular mechanisms by which natural antisense transcripts (NATs) might affect their cognate sense genes, and the role of NATs in cancer are less well understood. Here, we use strand-specific paired-end RNA sequencing (ssRNASeq) on a cohort of 376 cancer patients covering 9 tissue types to comprehensively characterize the landscape of antisense expression. Our results reveal that greater than 60% of annotated transcripts have measureable antisense expression and the expression of sense and antisense transcript pairs is in general positively correlated. Furthermore, by studying the expression of sense/antisense pairs across tissues we identify lineage-specific, ubiquitous and cancer-specific antisense loci. Our results raise the possibility that NATs participate in the regulation of well-known tumor suppressors... (for more see dbGaP study page.)	Co-expression
SRP071561	Homo sapiens Endometrium RNA-seq	Gene expression profiles of unexplained RM, RIF and fertile control during LH+7	Co-expression
SRP071602	A549A cells treated with 100 nM dexamethasone	RNA Seq A549A cells treated with 100 nM dexamethasone	Co-expression
SRP071637	Co-culture confrontation assays of commercially available cultured adult human dermal fibroblasts (HDFa) vs. multi-drug resistant bacteria	The overall objective of this study is to identify and characterize factors that influence virulence (including antibiotic resistance, and biofilm formation) in multidrug-resistant organisms (MDROs). This objective was accomplished through experiments focusing on the regulatory responses of both target and challenger organisms in bacterial-bacterial and bacterial-HDFa interactions likely to occur in the wound environment. Deep next-generation cDNA sequencing (RNA-Seq) was used as a tool to dissect the regulatory networks altered during these organismal-level confrontations. Challenges were MDROs versus human microbiome (commensal) organisms, MDROs versus other MDROs and MDROs versus the human host via cell culture. The research outcome may lead to novel treatment of combat wound infections in the future. This project was carried out in collaboration with the Walter Reed Army Institute of Research Multidrug-resistant Organism Repository and Surveillance Network (WRAIR MRSN), who provided isolates of highest clinical importance collected from the military health care system.	Co-expression
SRP071643	SC3-consensus clustering of single cell RNA-Seq data	We report a new unsupervised clustering tool for single cell RNA-seq data called SC3. We show that biologically relevant information can be obtained from preneoplastic cells of patients with myeloprolifertive disease. Overall design: examination of three different patients with myeloproloferative disease	Co-expression
SRP071659	Gene expression profile using RNA-seq in WC00060 or SR-0788 cells transfected with siRNA for KPC1 or control	Melanoma is a highly aggressive cancer with increasing incidence rates and a poor survival, particularly in patients with AJCC stage IV and advanced stage III. Deregulation of NF-kB is linked to different pathological states, including melanoma. To identify the involvement of NF-kB pathway regulation in melanoma progression, we manipulated NF-kB pathway activation and profiled gene expression using RNA-sequencing. Overall design: mRNA profiles of WC00060 and SR-0788 with KPC1 knockdown (siKPC1) or control (siCntl) generated by deep sequencing using Illumina HiSeq 2500.	Co-expression
SRP071660	Gene expression profile in IM-0223 cells transfected with KPC1 or control vector using RNA-seq	Melanoma is a highly aggressive cancer with increasing incidence rates and a poor survival, particularly in patients with AJCC stage IV and advanced stage III. Deregulation of NF-kB is linked to different pathological states, including melanoma. To identify the involvement of NF-kB pathway regulation in melanoma progression, we manipulated NF-kB pathway activation and profiled gene expression using RNA-sequencing. Overall design: mRNA profiles of IM-0223 cells overexpressing KPC1 (KPC1) or control (V0) generated by deep sequencing using Illumina HiSeq 2500.	Co-expression
SRP071669	HEK293 cells 100 cell RNAseq profiling  on Ion Proton	Five  libraries  from 100 HEK293 cells  each were prepared using a Smartseq based custom library preparation approach with unique molecular identifiers. One batch of 2 replicates (A) and one batch of 3 replicates (B) were prepared from different cell cultures. Libraries were sequenced on an Ion Proton Overall design: HEK293 cell  (100 cells)  5' selective RNAseq profiling, N4H4 unique molecular identifiers, 2 replicates (A) and 3 replicates (B)	Co-expression
SRP071670	Transcriptome profiling of single HEK293 cells with UMIs sequenced on Ion Torrent Proton (Run 20151215)	5' selective RNA-seq of 47 Single HEK293 cells  RNAseq profiling  with N4H4 unique molecular identifiers processed on a Fluidigm C1. Overall design: Single cell HEK293 cell 5' selective RNAseq profiling, 47 cells, unique molecular identifiers, custom library preparation.	Co-expression
SRP071671	Optimized Approaches for Generation of Integration-free iPSCs from Human Urine-derived Cells with Small Molecules and Autologous Feeder	We generated iPSCs from human urine cells (hUCs) with the aid of small molecules and autologous hUC feeders. A compound cocktail including Cyclic Pifithrin-a, a p53 inhibitor and other compounds known for benefiting reprogramming like A-83-01, CHIR99021, Thiazovivin, NaB and PD0325901 was used to aid hUC reprogramming (Plan B). Aided by this cocktail, we achieved significantly improved efficiency (170 folds more) for hUC reprogramming and iPSC generation. In addition, to enable iPSC generation in some cases that massive cell death occurred during delivering reprogramming factors, we replaced Matrigel with autologous hUCs as feeder for reprogramming and iPSC generation (Plan C). Replacing Matrigel with autologous feeder not only enhanced reprograming, but also avoided concern using animal components for human iPSC generation. These were efficient approaches to enable iPSC generation from hUCs that were otherwise difficult for reprogramming, which would be valuable for banking patient’s specific iPSCs. Overall design: We compared the transcriptome of hESCs, hiPSC, hUC by RNA-Seq. hiPSCs were generated from Plan B and Plan C. Plan B: RM at day 0~1, RM+5M at day 2~9, mTeSR1+6M at day10~17. UCs were seeded on Matrigel. Plan C: Medium was the same with Plan B, but seeded on autologous UCs as feeders before nucleofection.	Co-expression
SRP071689	Homo sapiens Transcriptome or Gene expression	We identify a lncRNA which low expresses and regulates self-renewal of bladder cancer stem cell. So we named it lncRNA-LBCS (low expresses in bladder cancer stem cell). Further study finds that lncRNA-LBCS bind to hnRNPK and PTBP1. To investigate the genes regulated by these, we knockdown lncRNA-LBCS, hnRNPK and PTBP1 by siRNA, respectively, and perform high-throughput sequence. So we identify a series of genes regulated by lncRNA-LBCS, hnRNPK and PTBP1, respectively.	Co-expression
SRP071700	Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns	Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects. Overall design: HeLa cell line was stably transfected with shRNA plasmids targeting CstF64. Total RNA was isolated from CstF64 KD cells and wild-type control cells using Trizol according to manufacturer’s protocols. Samples were deep sequenced in duplicate using the Illumina GAIIx system.	Co-expression
SRP071702	RNA-seq analysis of control and podoplanin knockdown lymphatic endothelial cells	To determine the transcriptome changes after podoplanin was knocked down in human lymphatic endothelial cells Overall design: Human lymphatic endothelial cells were transfected with control siRNA and podoplanin siRNA (N=2 for each group). After 48 hours, total RNA was isolated and processed for RNA-seq.	Co-expression
SRP071739	Changes in RNA expression in human oral cavity carcinoma cells as a result of LDB1 reduction	The study was designed to identify differential expressed genes between human oral cavity carcinoma cell lines with and without LDBI knockout Overall design: Three parental human oral cavity carcinoma cell lines were used as control, LDB1 was knocked out in the three parent cell lines to create KO cell lines.	Co-expression
SRP071758	Airway epithelial cells from smokers with and without bronchial premalignant lesions	While lung cancer is the leading cause of cancer death in the US, we have a limited understanding of the earliest molecular events preceding the onset of disease. Prior work has demonstrated that cigarette smoke creates a molecular “field of injury” throughout the airway epithelium and that there are distinct alterations in the airway transcriptome among smokers who have lung cancer. Molecular characterization of this airway “field of injury” in current and former smokers with premalignant lesions (PMLs) could provide novel insights into the earliest molecular events associated with lung carcinogenesis and identify relatively accessible biomarkers to guide lung cancer detection and early intervention. Using mRNA sequencing (mRNA-Seq), we profiled 82 cytologically normal bronchial airway epithelial cells collected during autofluorescence bronchoscopy from high-risk smokers with and without bronchial PMLs, 75 of which were used in downstream analyses. We identified 280 genes differentially expressed in the “field of injury” between subjects with (n=50)  and without (n=25) PMLs (FDR<0.002), 81 of which were up-regulated in subjects with PMLs. Oxidative phosphorylation (OXPHOS), the electron transport chain (ETC), and mitochondrial protein transport pathways were strongly enriched among these up-regulated genes (FDR<0.05). We next demonstrated that OXPHOS activation is shared between the “field” and the PMLs with increased oxygen consumption and increased staining for mitochondrial markers in biopsies of PMLs from patients as well as an animal model of lung squamous cell carcinoma (SCC) premalignancy. The 280-gene signature also has a significant concordant relationship to gene expression changes identified in PMLs adjacent to lung SCC tumors, in lung SCC tumors, and in the cytologically normal airway of individuals with lung cancer (FDR<0.05).  These findings suggest that these expression changes are reflective of early cancer-associated changes occurring throughout the respiratory tract, and that pathways such as OXPHOS may be targets for chemoprevention.  We subsequently developed an airway gene expression biomarker that predicts the presence of PMLs (AUC=0.92, n=17 samples in test set) and show that changes in the biomarker score are associated with progression and regression of PMLs in an independent cohort (AUC=0.75, n=51 samples). The biomarker results indicate that molecular alterations in the field of injury are dynamic with progression or regression of PMLs, suggesting that these changes may be leveraged to stratify high-risk smokers with progressive disease into early intervention trials and monitor disease progression or recurrence. Overall design: 82 mRNA-Seq samples from 25 smokers without PMLs, 50 smokers with PMLs, and 7 smokers with metaplasia.	Co-expression
SRP071760	Airway epithelial cells from high-risk subjects obtained via multiple bronchoscopy procedures to follow bronchial premalignant lesions as part of lung cancer screening	While lung cancer is the leading cause of cancer death in the US, we have a limited understanding of the earliest molecular events preceding the onset of disease. Prior work has demonstrated that cigarette smoke creates a molecular “field of injury” throughout the airway epithelium and that there are distinct alterations in the airway transcriptome among smokers who have lung cancer. Molecular characterization of this airway “field of injury” in current and former smokers with premalignant lesions (PMLs) could provide novel insights into the earliest molecular events associated with lung carcinogenesis and identify relatively accessible biomarkers to guide lung cancer detection and early intervention. Using mRNA sequencing (mRNA-Seq), we profiled cytologically normal bronchial airway epithelial cells collected during autofluorescence bronchoscopy from high-risk smokers (n=75) with and without bronchial PMLs. We identified 280 genes differentially expressed in the “field of injury” between subjects with (n=50)  and without (n=25) PMLs (FDR<0.002), 81 of which were up-regulated in subjects with PMLs. Oxidative phosphorylation (OXPHOS), the electron transport chain (ETC), and mitochondrial protein transport pathways were strongly enriched among these up-regulated genes (FDR<0.05). We next demonstrated that OXPHOS activation is shared between the “field” and the PMLs with increased oxygen consumption and increased staining for mitochondrial markers in biopsies of PMLs from patients as well as an animal model of lung squamous cell carcinoma (SCC) premalignancy. The 280-gene signature also has a significant concordant relationship to gene expression changes identified in PMLs adjacent to lung SCC tumors, in lung SCC tumors, and in the cytologically normal airway of individuals with lung cancer (FDR<0.05).  These findings suggest that these expression changes are reflective of early cancer-associated changes occurring throughout the respiratory tract, and that pathways such as OXPHOS may be targets for chemoprevention.  We subsequently developed an airway gene expression biomarker that predicts the presence of PMLs (AUC=0.92, n=17 samples in test set) and show that changes in the biomarker score are associated with progression and regression of PMLs in an independent cohort (AUC=0.75, n=51 samples). The biomarker results indicate that molecular alterations in the field of injury are dynamic with progression or regression of PMLs, suggesting that these changes may be leveraged to stratify high-risk smokers with progressive disease into early intervention trials and monitor disease progression or recurrence. Overall design: 51 mRNA-Seq samples from 23 subjects obtained via bronchscopy (18 subjects with 2 procedures, 5 subjects with 3 procedures).	Co-expression
SRP071806	Carcinoma-astrocyte gap junctions promote brain metastasis by cytosolic dsDNA response transfer	Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in brain metastasis. Cancer cells assemble of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Cx43 in cancer cells support brain metastatic colonization.  We employ translating ribosome affinity purification (TRAP) to isolate translating mRNA from cancer cells in mixed asrtocyte co-cultures to determine the mechanism behind this Cx43-mediated brain metastatic growth. Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells employ these channels to transfer the cytosolic dsDNA response messenger cGAMP to astrocytes, activating the cGAS-STING pathway and production of inflammatory cytokines IFNa and TNFa. As paracrine signals, these factors activate the STAT1 and NF-?B pathways in brain metastatic cells, which support tumour growth and chemoresistance. Overall design: TRAP mRNAs were isolated from MDA231-BrM2 (control or Cx43-depleted) after co-cultured with astrocytes. Gene expression profiles were generated by deep sequencing, in duplicate, using Illumina Illumina HiSeq 2000. Two independent replicates were done per condition (i.e. rep1 and rep2).	Co-expression
SRP071811	Identification of long noncoding RNAs regulated by p53	Analyize the transcriptpme regulated by p53 in 3 pairs of isogenic p53WT and p53KO colorectal cancer cell lines untreated or treated with Doxorubicin. The hypothsis of this study is that p53 can regulate the expression of subset of lncRNAs to mediate its biological functions. Overall design: Total RNA was isolated from 3 pairs of isogenic colon cancer cell lines; HCT116-p53_WT and p53_KO; RKO-p53_WT and p53_KO: and SW48-p53_WT and p53_KO. Cells were untreated or treated with Doxorubicin (DOXO) at a final concentration of 300 nM for 16 hours.	Co-expression
SRP071837	Stimulation of isolated plasmacytoid dendritic cells (pDCs) with TLR9 agonist CpG C (CpG) and TLR7 agonist imiquimod (IMQ)	The purpose of this experiment was to assess the genes upregulated when pDCs were stimulated with TLR7 agonist imiquimod and TLR9 agonist CpG C. Overall design: pDCs were isolated from six healthy donors by FACS sorting, and were stimulated with CpG and imiquimod for 18 hours, after which RNA was extracted for next generation sequencing on the Illumina HiSeq platform. Unstimulated samples were included as controls.	Co-expression
SRP071854	Parental allele specific single-cell transcriptome dynamics reveal incomplete epigenetic reprogramming in human female germ cells	In contrast to mouse, human female germ cells develop asynchronously. Germ cells transition to meiosis, erase genomic imprints, and reactivate the X chromosome. It is unknown if these events all appear asynchronously, and how they relate to each other. Here we combine exome sequencing of human fetal and maternal tissues with single-cell RNA-sequencing of five donors.  We reconstruct full parental haplotypes and quantify changes in parental allele specific expression, genome-wide. First we distinguish PGC, pre-meiotic, and meiotic transcriptional stages. Next we demonstrate that germ cells from various stages monoallelically express imprinted genes from e.g. the SNURF-SNRPN cluster and confirm it by methylation patterns.  Finally we show that ±30% of the PGCs, are still reactivating their inactive X chromosome and that this is related to transcriptional stage, and not to embryonic age. Altogether, we reveal the complexity and cell-to-cell heterogeneity of transcriptional and epigenetic remodelling in female human germ cells. Overall design: RNA sequences from human gonadal (N=73) and adrenal cells (N=35) from the mentioned fetuses 8.1-14.4wk of development (equivalent to 10.1-16.4 weeks of gestation) using SMART-seq2.	Co-expression
SRP071860	BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitment [RNA-seq]	Cancer arises from the malignant interplay between oncogenic signaling and cell specification.  Transcriptionally activated stem, growth and survival programs reshape an epigenomic identity defined by a transcriptional core regulatory circuitry.  To study and disrupt oncogenic transcription, we first created inhibitors of BET bromodomains.  Selective antagonism of oncogenic transcriptional signaling arises from bromodomain-specific activity.  Recently, we innovated a strategy to induce selective and pronounced degradation of BET coactivator proteins via phthalimide conjugation for E3 ubiquitin ligase recruitment.  Degraders of BET bromdomains (dBETs) exhibited superior efficacy to bromodomain inhibitors in cultivated leukemia cells, through unknown mechanisms.  Here, we use chemically optimized small-molecule degronimids and kinetic measures of chromatin structure and function to unveil an unrecognized, essential role for BRD4 in the control of global productive transcriptional elongation.  Rapid loss of BRD4 attenuates phosphorylation of the carboxy-terminal domain of RNA polymerase II, independent of genomewide recruitment of CDK9 to promoters, leading to a collapse of the transcriptional core regulatory circuitry.  These mechanistic studies are performed in translational models of T-cell acute lymphoblastic leukemia, a disease emblematic for transcriptional addiction, to establish a rationale for human clinical investigation. Overall design: RNA-Seq for DMSO, dBET6, or JQ1 treated MOLT4 cells and RNA-seq of primary T cells and PDX T-ALL cells with JQ1 and dBET6 treatment	Co-expression
SRP071861	BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitment [NET-seq]	Cancer arises from the malignant interplay between oncogenic signaling and cell specification.  Transcriptionally activated stem, growth and survival programs reshape an epigenomic identity defined by a transcriptional core regulatory circuitry.  To study and disrupt oncogenic transcription, we first created inhibitors of BET bromodomains.  Selective antagonism of oncogenic transcriptional signaling arises from bromodomain-specific activity.  Recently, we innovated a strategy to induce selective and pronounced degradation of BET coactivator proteins via phthalimide conjugation for E3 ubiquitin ligase recruitment.  Degraders of BET bromdomains (dBETs) exhibited superior efficacy to bromodomain inhibitors in cultivated leukemia cells, through unknown mechanisms.  Here, we use chemically optimized small-molecule degronimids and kinetic measures of chromatin structure and function to unveil an unrecognized, essential role for BRD4 in the control of global productive transcriptional elongation.  Rapid loss of BRD4 attenuates phosphorylation of the carboxy-terminal domain of RNA polymerase II, independent of genomewide recruitment of CDK9 to promoters, leading to a collapse of the transcriptional core regulatory circuitry.  These mechanistic studies are performed in translational models of T-cell acute lymphoblastic leukemia, a disease emblematic for transcriptional addiction, to establish a rationale for human clinical investigation. Overall design: NET-Seq for DMSO, dBET6, or JQ1 treated MOLT4 cells	Co-expression
SRP071876	Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels	Purpose: Exploring mechanisms defining the unique nature of vascular development and differentiation in the brain . Methods: High-resolution gene expression profiles of embryonic endothelial cells (EC) using translating ribosome affinity purification (TRAP) and single cell RNA-sequencing. RNA-sequenzing of transcription factor infected HUVEC. Results: Comparisons of different organ-, temporal- or Ctnnb1 knock out-specific vascular translatomes revealed extensive molecular changes during the unique development of the brain endothelium. We identified brain endothelial-specific transcription factors – Foxf2, Foxl2, Foxq1, Lef1, Ppard, Zfp551 and Zic3 – that are associated with the temporal maturation of the blood-brain barrier and act downstream of the Wnt/Ctnnb1 signaling pathway. Profiling individual EC revealed a remarkable heterogeneity. Nevertheless, high levels of Foxf2, Foxq1, Ppard and Zic3 were correlated with elevated expression of differentiation markers. This could be recapitulated in vitro, where expression of Foxf2 and Zic3 in HUVEC led to an induction of blood-brain barrier differentiation markers. Conclusions: Our study provides further insights into the temporal and cellular complexity of the developing embryonic brain endothelium. Our data raises many questions and provides a basis for further studies aiming to unravel cellular and molecular mechanisms that underlie vascular development and differentiation in the CNS. We anticipate that additional investigation of the identified transcription factors is likely to be a fruitful approach in understanding and manipulating the development of BBB and to engineer more advanced blood brain barrier in vitro models. Overall design: TRAP-seq profiles for E11.5 till E17.5 wild type (WT) brain EC; E14.5 and E17.5 endothelial Ctnnb1 -/- brain EC; E14.5 head, heart, kidney, limb, liver and lung WT EC in triplicate, using Illumina HiSeq 2000. Single cell RNA-sequencing of E14.5 brain EC. RNA-sequenzing of HUVEC infected with either control, Foxf2, Foxq1, ZIC3 or three transcription factors combined in triplicate.	Co-expression
SRP071929	Global transcript structure resolution of high gene density genomes through multi-platform data integration: Illumina RNA-Seq	Strand-specific Illumina RNA-Seq was used in conjunction with Pacific Biosciences Iso-Seq and deepCAGE to globally resolve transcript structures in replicating Epstein-Barr virus. Overall design: Illumina strand-specific RNA-seq of BCR-activated Akata cells at 9 time points, and GapmeR knockdown of BZLT12-22 transcripts	Co-expression
SRP071930	Global transcript structure resolution of high gene density genomes through multi-platform data integration: deepCAGE	deepCAGE was used in conjunction with Pacific Biosciences Iso-Seq and Illumina RNA-Seq to globally resolve transcript structures in replicating Epstein-Barr virus. Overall design: deepCAGE of replicating Epstein-Barr virus in Akata cells to identify transcript 5'' ends	Co-expression
SRP071939	RNA-seq analysis of growth factor response of NHEKs to antimicrobial petide LL-37 and dsRNA mimic Poly(I:C)	In this study, we analyzed how non-coding double stranded RNA (dsRNAs) act as a damage associated molecular pattern (DAMP) in the skin, and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP. Overall design: Each sample''s RNA was isolated form a single biological source of P6 NHEKs. In total there are 4 samples (non-replicates); Control (PBS treated), 1.75uM LL-37 treated, 0.1ug/ml Poly(I:C) treated, and co-treated with 1.75uM LL-37 and 0.1ug/ml Poly(I:C).	Co-expression
SRP071942	Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)	Our study shows that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI/SNF chromatin remodeling complex to sustain MYC transcription, rapid cell proliferation, and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain, which selectively suppressed the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9, which retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells conferred resistance to the anti-proliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor-resistant allele of EZH2. Our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells. Overall design: PolyA selected RNA-seq for shRNA-expressing or inhibitor-treated mouse and human leukemia cells and fibroblasts	Co-expression
SRP071965	A blood RNA signature for tuberculosis disease risk: a prospective cohort study	Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis  infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to  assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective  signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent  South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A  16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1%  (95% CI 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The  risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for  qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a  sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active  tuberculosis, opening the possibility for targeted intervention to prevent the disease. Overall design: In this prospective cohort study, we followed up healthy, South African adolescents aged 12–18 years from  the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from  study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective  signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed  active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to  multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in  samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the  independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.	Co-expression
SRP071966	CLIC5: a novel ETV6 target gene in childhood acute lymphoblastic leukemia	Background: The most common rearrangement in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL) is the t(12;21)(p13;q22) translocation resulting in the ETV6-AML1 fusion gene. A frequent concomitant event is the loss of the residual ETV6 allele suggesting a critical role for the ETV6 transcriptional repressor in the etiology of pre-B ALL. However, the precise mechanism through which loss of functional ETV6 contributes to disease pathogenesis is still unclear Results: To investigate the impact of ETV6 loss on the transcriptional network and identify new transcriptional targets of ETV6, we used whole transcriptome analysis of both pre-B leukemic cell lines and pre-B ALL patients combined with chromatin immunoprecipitation. Using this integrative approach, we identified 4 novel direct ETV6 target genes: CLIC5, BIRC7, ANGPTL2 and WBP1L. To further evaluate the role of chloride intracellular channel protein CLIC5 in leukemogenesis, we generated cell lines overexpressing CLIC5 and demonstrated an increased resistance to hydrogen peroxide-induced apoptosis. We further described the implications of CLIC5's ion channel activity in lysosomal-mediated cell death, possibly by modulating the function of transferrin receptor with which it co-localizes intracellularly. Conclusion: For the first time, we showed that loss of ETV6 leads to significant overexpression of CLIC5, which in turn leads to decreased lysosome-mediated apoptosis. Our data suggest that heightened CLIC5 activity could promote a permissive environment for oxidative-stress induced DNA damage accumulation and thereby contribute to leukemogenesis. Overall design: To identify direct targets of ETV6, we first designed an in vitro RNA-seq experiment using ETV6-/- Reh-derived clones. Cells were transduced with lentiviral constructs to express ETV6-His and ETV6?ETS_NLS-His. Total RNA was extracted from stable cell populations and RNA-seq libraries were sequenced. Expression profiles were analyzed using EdgeR. Gene expression profiles in ETV6-His cells were first compared with ETV6?ETS_NLS-His and pLENTI cells to identify repressed genes (FDR = 0.1). We then included data from the ETV6?ETS_NLS-His vs. pLENTI comparison and further considered genes whose expression remains constant (p-value = 0.05 or logFC = -0.5) which are more likely to be direct ETV6 targets. Finally, only genes that showed a specific overexpression in t(12;21)-positive childhood pre-B ALL patients were considered.	Co-expression
SRP071981	Homo sapiens Targeted loci cultured	The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome.Using 3'' RACE-Seq, we demonstrate that all novel DIS3L2 substrates areuridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperationbetween DIS3L2 and TUTases.	Co-expression
SRP072025	Knockdown of ADNP in HCT116 colon cancer cells	RNASeq data from replicates after siRNA mediated knockdown of human ADNP in HCT116 colon cancer cells Overall design: 3 biological replicates of cells treated with siADNP or siControl	Co-expression
SRP072029	Single-cell qPCR, and bulk-level transcriptomics and epigenomics of treated macrophages	In support of a study of macrophage activation, single cell qPCR, RNAseq, CAGE, and H3K27ac ChIPseq was performed on human monocyte-derived macrophages.	Co-expression
SRP072037	Homo sapiens Transcriptome or Gene expression	Human preadipocites treatment with Bisphenol A and Bisphenol S at 25uM. Samples were collected 2 and 4 days post treatment and gene expression was evaluated by RNA-Seq.	Co-expression
SRP072038	Digitalis-like compounds facilitate redifferentiation of non-medullary thyroid cancer through intracellular Ca2+, cFOS and autophagy dependent pathways	About 20-30% of patients with metastatic non-medullary thyroid cancer (TC) have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodine therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activation for redifferentiation in thyroid cancer cell lines. Five, all digitalis-like compounds, restored hNIS expression and iodine uptake in TC cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and cFOS activation. Cell proliferation was inhibited by downregulating Akt1 and by induction of autophagy and p21-dependent cell cycle arrest. All together, digitalis-like compounds could represent a promising treatment modality for patients with dedifferentiated TC. Overall design: Non-medullary TC cell lines were treated with digitalis-like compounds for 24, 48 and 72 hours. RNA was isolated and prepared for RNA sequencing by Illumina HiSeq 2000.	Co-expression
SRP072101	Direct GR binding sites potentiate clusters of TF binding across the human genome [3]	The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Overall design: Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functional analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. This dataset [3] contains the results of RNA-seq performed on A549 cells treated with DEX or EtOH for 3 hours.	Co-expression
SRP072131	NR2E3 gene networks are associated with AHR signaling pathways	In order to identify NR2E3-specific gene expression pattern in liver cancer cell line, small hairpin RNA for NR2E3 was transfected in HepG2 human liver cancer cells. Overall design: Two groups of samples are included: 1. sh control (shCT_1, shCT_2); 2. shNR2E3 (shNR2E3 KO_1 , shNR2E3 KO_2). Gene expression profiles of NR2E3 depleted cells were compared to that of shRNA controls. Experiments were performed in HepG2 cells.	Co-expression
SRP072139	Next Generation Sequencing Analysis of human embryonic stem cells derived MESP1-mTomato reporter cells	Purpose: To compare the transcriptome of MESP1-mTomato reporter cells at undifferentiated state, mesoderm differentiation day 3 mTomato+ and mTomato- cells and MESP1+ cells undergoing endothelial differentiation in 2D and 3D. Methods: total RNA from sorted MESP1+, MESP1- and hESCs (in biological duplicates) was extracted using RNeasy Plus Mini Kit (Qiagen) and treated with RNase free DNase. Libraries prepared following the instruction of TruSeqâ„¢ RNA Sample Preparation kit (Illumina) and sequenced on Illumina HiSeq 2000. Results: genes differentially expressed in MESP1-mTomato+ and mTomato- cells were identified. Conclusions: the gene expression profile of MESP1-mTomato cells indicates that they are cardiovascular progenitor cells. Overall design: Perform RNA-seq of undifferentiated hESCs,  mesoderm differentiating MESP1+, MESP1- cells, and endothelial differentiating MESP1+ cells in 2D and 3D.	Co-expression
SRP072163	Interaction between cyclooxygenase-2 and caspase-3 abolishes the cleavage of RNA-binding protein HuR and promotes drug resistance in oral squamous cell carcinoma	Here, we show that HuR cleavage is dependent on active caspase-3 in oral cancer cells treated with ionizing radiation and the chemotherapeutic drug paclitaxel.  We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of both caspase-3 and HuR, which in turn, reduced the rate of apoptosis in paclitaxel treated cells. Specific inhibition of COX-2 by celecoxib promoted apoptosis through activation of caspase-3 and cleavage of HuR in paclitaxel-resistant oral cancer cells.  In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA and promoted COX-2 expression, exhibiting enhanced tumor growth in vivo in comparison with the cleavable form of HuR.  Finally, our RNP IP and RNA transcriptome analysis of HuR under IR revealed that the HuR cleavage product-1 (HuR-CP1) associates and promotes the expression of mRNAs encoding proteins involved in apoptosis. Overall design: 4 samples: The GFP plasmid vectors containing full-length HuR, HuR-D226A, HuR-CP1 were expressed in oral cancer cells. GFP empty vector served as a control. HuR RNP IP was performed and RNA sequencing carried out.	Co-expression
SRP072176	Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer	Introduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERa) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option.   Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor).   Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach.   Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors. Overall design: 46 samples, 28 days post treatment	Co-expression
SRP072242	Idiopathic pulmonary fibrosis bronchoalveolar lavage cells RNA-seq indicates macrophage expression of pro-inflammatory M1/M2 activation concomitant with radical species metabolism inhibition	Current concepts of idiopathic pulmonary fibrosis (IPF) are that microscopic injury drives alveolar epithelial cell dysregulated activation and epithelial mesenchymal transition, ensuing fibrocyte recruitment,  fibroblast proliferation and ECM deposition. With the background that IPF is also characterized by chronic accumulation of activated alveolar macrophages (aMAC) in the lower respiratory tract, we assessed IPFaMAC gene expression to identify patterns of activation, by RNA-seq using Illumina platform. To this we evaluated a population of 7 normal smoking controls and 16  IPF smoking patients. All IPFs had abnormal lung function and bronchoalveolar lavage (BAL) showing  >80% macrophage counts and augmented spontaneous O2 radical release. RNA was extracted from whole BAL cells. Reads were mapped onto the UCSC mRNA database (GRCh37/hg19 version), and transcripts were aggregated by gene symbol, obtaining a final 19,723 unique protein-coding gene ID list, used for further analysis. Overall design: RNA-seq transcriptomics of idiopathic pulmonary fibrosis (IPF) patients vs controls: RNA samples were extracted from macrophages obtained from bronchoalveolar lavage (BAL)	Co-expression
SRP072272	Input Strategy for Improving Analysis of ChIP-exo Data and Beyond [RNA-Seq]	Several recently emerging ChIP-seq (chromatin immunoprecipitation followed by sequencing) based methods perform chemical steps on bead-bound immunoprecipitated chromatin, posing a challenge for generating similarly treated input controls required for bioinformatics and data quality analyses. Here we present a versatile method for producing technique-specific input controls for ChIP-based methods that utilize additional bead-bound processing steps. Application of this method allowed for discovery of a novel CTCF binding motif from ChIP-exo data. Overall design: HeLa cells were transfected with either a scrambled siRNA or one of two CTCF siRNAs (Thermo Fisher Scientific ? Life technologies) using Lipofectamine RNAiMAX (Thermo Fisher Scientific - Life technologies) and incubated for 24 hr.	Co-expression
SRP072275	Homo sapiens Epigenomics	Human breast cancer T47D cell line	Co-expression
SRP072282	Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma	Our goal was to identify candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma. To reach this aim, we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by mean of a silencing approach followed by an RNA-seq analysis Overall design: Comparison of the transcriptome in normal Fallopian tube secretory epithelial cells and ovarian cancer cells with and without PAX8 silencing	Co-expression
SRP072285	Homo sapiens isolate:A375 Raw sequence reads	The translation initiation factors eIF4A1 and eIF4E are members of the eIF4F cap-binding complex that is frequently upregulated in cancers. There are ongoing efforts to develop eIF4F inhibitors as cancer therapies, but the molecular mechanisms of eIF4F-driven tumor progression remain unclear. To investigate the molecular basis of these phenotypes, we performed an integrative proteomic and transcriptomic analysis in A375 melanoma cells treated with siRNAs against eIF4A1 or eIF4E for 72 hours.	Co-expression
SRP072302	Next generation sequencing facilitates quantitative analysis of changes in mRNA after knock-down of putative master regulators of the breast cancer metastasis transcriptome.	Purpose:  To identify regulatory proteins that are potential drivers of a coordinated breast cancer metastasis gene expression signatures. Methods: Knockdown of target genes in breast cancer cell lines was achieved using scramble and/or gene-specific siRNA (ON-TARGET SMARTpool, Thermo Scientific) and Lipofectamine RNAiMAX.  48h post transfection, total RNA was isolated from cell lines using the RNeasy Plus mini prep kit (Qiagen). Nucleic acid quality was determined with the Agilent 2100 Bioanalyzer. RNA Sequencing was also performed at the New York Genome Center (Manhattan, NY, USA) using a HiSeq 2500 Ultra-High-Throughput Sequencing System (Illumina, San Diego, CA, USA). Results: Raw reads in the fastq format were aligned to Human Genome HG19 using the RNA-seq STAR aligner version 2.4.0d (http://www.ncbi.nlm.nih.gov/pubmed/23104886, http://www.ncbi.nlm.nih.gov/pubmed/26334920) as recommended by user manual downloaded along with the software. STAR aligner was chosen for mapping accuracy and speed (http://www.nature.com/nmeth/journal/v10/n12/full/nmeth.2722.html).  Mapped reads for each sample were counted for each gene in annotation files in GTF format (gencode.v19.annotation.gtf available for download from GENECODE website (http://www.gencodegenes.org/releases/19.html)) using the FeatureCounts read summarization program (http://www.ncbi.nlm.nih.gov/pubmed/?term=24227677) following the user guide (http://bioinf.wehi.edu.au/subread-package/SubreadUsersGuide.pdf). Individual count files were merged to generate the raw-counts matrix by an in-house R script, normalized to account for differences in library size and the variance was stabilized by fitting the dispersion to a negative-binomial distribution as implemented in the DESeq R package (http://bioconductor.org/packages/release/bioc/html/DESeq.html)(Anders and Huber, 2010). Conclusions:  Our data suggest that targeting keystone proteins in the breast cancer metastasis transcriptome can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing a formidable cancer intervention strategy. Overall design: Examination of mRNA profiling of breast cancer cell lines after knock-down of putative master regulators of the breast cancer metastasis transcriptome	Co-expression
SRP072326	Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection	BACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assess the resulting transcriptome changes in both organisms simultaneously by using dual RNA-seq. RESULTS: Functional analysis of the time-resolved dual RNA-seq data identifies several features of pneumococcal infection. For instance, we show that the glutathione-dependent reactive oxygen detoxification pathway in epithelial cells is activated by reactive oxygen species produced by S. pneumoniae. Addition of the antioxidant resveratrol during infection abates this response. At the same time, pneumococci activate the competence regulon during co-incubation with lung epithelial cells. By comparing transcriptional changes between wild-type encapsulated and mutant unencapsulated pneumococci, we demonstrate that adherent pneumococci, but not free-floating bacteria, repress innate immune responses in epithelial cells including expression of the chemokine IL-8 and the production of antimicrobial peptides. We also show that pneumococci activate several sugar transporters in response to adherence to epithelial cells and demonstrate that this activation depends on host-derived mucins. CONCLUSIONS: We provide a dual-transcriptomics overview of early pneumococcal infection in a time-resolved manner, providing new insights into host-microbe interactions. To allow easy access to the data by the community, a web-based platform was developed ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies. Overall design: 5 time points are analysed (0, 30, 60, 120 and 240 minutes after infection). Each time point has two biological replicates except for the 240 mpi. Furthermore, each time point has two pneumococcal strains used to infect A549 cells, encapsulated and unencapsulated pneumococci. In total there are 18 samples. cellular infection model, contains rRNA-depleted total RNA from A549 epithelial cells and D39 S. pneumoniae	Co-expression
SRP072352	Toxoplasma gondii remodels the cis-regulatory landscape of infected human host cells [RNA-seq]	To study the host transcriptome of human fibroblasts after infection with T. gondii (Type I-RH). Overall design: Three bioloigcal replicates of uninfected HFFs and three biological replicates of T. gondii (Type I-RH) infected HFFs were sequenced using directional RNA-seq.	Co-expression
SRP072365	iPSCs Reveal Protective Modifiers of the BMPR2 mutation in Pulmonary Arterial Hypertension	The goal of this study is to compare transcriptome profiling (RNA-seq) in controls, unaffected BMPR2 mutation carriers and affected familial pulmonary arterial hypertension patients, to elucidate a protective feature in iPS derived endothelial cells from the mutation carriers. Overall design: mRNA profiles of iPSC-ECs from unrelated control (n=3), unaffected BMPR2 mutation carriers (n=3) and FPAH patients with BMPR2 mutation (n=5).	Co-expression
SRP072417	NextGen Consortium: GENESiPS Study: Identifying the Gene Networks of Insulin Resistance	RNA-seq transcriptome profiling of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual Overall design: Donor erythroblast or activated T-cells were reprogrammed with a Sendai viral vector coding for reprogramming factors.  IPSC lines were propagated for ~9 passages before RNA sequencing	Co-expression
SRP072454	Mapping interactions for the TNIP2 hub protein	This experiment analyzes the set of RNAs copurifying with the protein TNIP2 (amino acids 196-346) Overall design: HEK293 cells were transfected with constructs expressing either Halo tag (controls) or Halo-TNIP2 196-346. Total RNA was purified from an aliquot of the whole cell extract (Input samples). Halo-tagged proteins were purified from the remainder of the whole cell extract, and RNA subsequently purified from the Halo purified samples (Pulldown samples).	Co-expression
SRP072459	Regulation of poly(A) tail and translation during the somatic cell cycle	Poly(A) tails are critical for mRNA stability and translation. However, recent studies have challenged this view, showing that poly(A) tail length and translation efficiency are decoupled in non-embryonic cells. Using TAIL-seq and ribosome profiling, we investigate poly(A) tail dynamics and translational control in the somatic cell cycle. We find dramatic changes in poly(A) tail lengths of cell cycle regulatory genes like CDK1, TOP2A, and FBXO5, explaining their translational repression in M phase. We also find that poly(A) tail length is coupled to translation when the poly(A) tail is <20 nucleotides. However, as most genes have >20 nucleotide poly(A) tails, their translation is regulated mainly via poly(A) tail length-independent mechanisms during the cell cycle. Specifically, we find that terminal oligopyrimidine (TOP) tract-containing transcripts escape global translational suppression in M phase and are actively translated. Our quantitative and comprehensive data provide a revised view of translational control in the somatic cell cycle. Overall design: HeLa cells were synchronized at S or M phase, and subject to RNA-seq, ribosome profiling and TAIL-seq analysis.	Co-expression
SRP072492	RNA-sequencing of human pancreatic adenocarcinoma cancer tissues	RNA-seq profiling was conducted on clinically-annotated human pancreatic adenocarcinoma cancer tissues Overall design: We measured the transcriptome in 51 clinically-annotated human pancreatic adenocarcinoma cancer tissues	Co-expression
SRP072493	RNA sequencing of human pancreatic cancer cell lines	RNA-seq profiling was conducted on human pancreatic cancer cell lines Overall design: We measured the transcriptome in 14 human pancreatic cancer cell linees	Co-expression
SRP072494	Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients	Purpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.	Co-expression
SRP072501	Primary Human Trophoblast Transcriptomes	Primary human trophoblasts from term placenta, after culturing for 72 hours.	Co-expression
SRP072506	Loss of CREBBP results in gene expression repression in lymphoma cells	KD of CREBBP at lymphoma cell line, MD901, results in reduced expression Overall design: Genome-wide profiling of total RNA transcript levels in human cell line MD901 (CREBBP wild type) with shCREBBP and scramble control.	Co-expression
SRP072507	A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop	Despite initial and often dramatic responses of epidermal growth factor receptor (EGFR)-addicted lung tumors to the EGFR-specific tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, nearly all develop resistance and relapse. To explore novel mechanisms mediating acquired resistance, we employed non-small-cell lung cancer (NSCLC) cell lines bearing activating mutations in EGFR and rendered them resistant to EGFR-specific TKIs through chronic adaptation in tissue culture. In addition to previously observed resistance mechanisms including EGFR-T790M ''gate-keeper'' mutations and MET amplification, a subset of the seven chronically adapted NSCLC cell lines including HCC4006, HCC2279 and H1650 cells exhibited marked induction of fibroblast growth factor (FGF) 2 and FGF receptor 1 (FGFR1) mRNA and protein. Also, adaptation to EGFR-specific TKIs was accompanied by an epithelial to mesenchymal transition (EMT) as assessed by changes in CDH1, VIM, ZEB1 and ZEB2 expression and altered growth properties in Matrigel. In adapted cell lines exhibiting increased FGF2 and FGFR1 expression, measures of growth and signaling, but not EMT, were blocked by FGFR-specific TKIs, an FGF-ligand trap and FGFR1 silencing with RNAi. In parental HCC4006 cells, cell growth was strongly inhibited by gefitinib, although drug-resistant clones progress within 10 days. Combined treatment with gefitinib and AZD4547, an FGFR-specific TKI, prevented the outgrowth of drug-resistant clones. Thus, induction of FGF2 and FGFR1 following chronic adaptation to EGFR-specific TKIs provides a novel autocrine receptor tyrosine kinase-driven bypass pathway in a subset of lung cancer cell lines that are initially sensitive to EGFR-specific TKIs. The findings support FGFR-specific TKIs as potentially valuable additions to existing targeted therapeutic strategies with EGFR-specific TKIs to prevent or delay acquired resistance in EGFR-driven NSCLC. Overall design: Examination of mRNA levels in DMSO and gefitinib-resistant cultures of HCC4006 and HCC827. Each group has two replicates.	Co-expression
SRP072566	RNA-Seq analysis of NKX2.2 knockdown in human pancreatic islets	Aim:Transcriptional analysis of NKX2.2 knockdown versus control in human pancreatic islets Methods:Pancreatic islets from 3 human donors  were transduced with an adenovirus encoding an shRNA directed against human NKX2.2 or a scrambled shRNA control.  Total RNA was extracted.Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the human genome (Human: NCBI/build37.2)) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq. Results: Among the dysregulated genes with a p-value=0.05 are important genes for the maintenance of  beta cell function and idenity. Conclusion: Nkx2.2 is a critical regulator of beta cell function and identity Overall design: mRNA profiles of the pancreatic islets from 3 human donors transduced with Ad.sh-NKX2.2 or scramble sh-RNA control vector were generated by deep sequencing ,  using Illumina HiSeq2000.	Co-expression
SRP072573	RNA-seq Profiles in RBPJ Maintains Brain Tumor Initiating Cells through CDK9-mediated Transcriptional Elongation	Glioblastomas coopt stem cell regulatory pathways to maintain brain tumor initiating cells (BTICs), also known as cancer stem cells.  Notch signaling has been a molecular target in BTICs, but Notch antagonists have demonstrated limited efficacy in clinical trials.  RBPJ is considered a central transcriptional mediator of Notch activity. Here, we report that pharmacologic Notch inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While Notch inhibitors decreased canonical Notch gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the RBPJ promoter and treatment with a BET family bromodomain inhibitor decreased MYC and RBPJ expression.  Proteomic studies demonstrated that RBPJ binds CDK9, a component of P-TEFb (positive transcription elongation factor), to target gene promoters, enhancing transcriptional elongation.  Collectively, RBPJ links MYC and transcriptional control through CDK9, providing potential nodes of fragility for therapeutic intervention, potentially distinct from Notch. Overall design: RNA-seq of primary patient-derived GBM brain tumor initiating cells with DAPT treatment or shRBPJ treatment	Co-expression
SRP072665	Homo sapiens Transcriptome or Gene expression	To investigate the mechanisms behind requirement for arginine in human PSCs	Co-expression
SRP072687	HEK293 Heat-shock experiment	HEK293 cells were heatshocked and differentially expressed transcripts were identified Overall design: Transcriptomes of heatshocked HEK293 cells were compared to control cells. Heatshock and control samples were treated and sequenced in triplicate.	Co-expression
SRP072690	Transcriptional profiling of JEG3 cells with HLA-G ablation via deletion of Enhancer L	HLA-G is a nonclassical HLA molecule expressed specifically in the placenta. While it is known to play a central role in maternal immune tolerance during pregnancy, the mechanism underlying its tissue-specific expression remains poorly understood. To elucidate this mechanism, we used a Massively Parallel Reporter Assay (MPRA) to systematically interrogate the HLA-G locus. This uncovered Enhancer L, a novel cis-regulatory element with enhancer activity 12kb upstream of HLA-G. To verify enhancer function and specificity for HLA-G in culture, we deleted Enhancer L in JEG3 cells and performed RNA sequencing and differential expression analysis. Upon Enhancer L knockout, we observe complete ablation of HLA-G and minimal dysregulation of other genes within 2Mb, suggesting that HLA-G is the only direct cis target of Enhancer L. DNase-seq and Chromatin Conformation Capture (3C) confirm that Enhancer L is a cell type-specific enhancer that loops into the HLA-G promoter. MPRA-based saturation mutagenesis of Enhancer L identifies motifs for transcription factors of the CEBP and GATA families which are essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as a novel mechanism controlling tissue-specific HLA-G expression at the maternal-fetal interface. Overall design: RNA sequencing of JEG3 cells with CRISPR knockout of Enhancer L	Co-expression
SRP072693	Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus [RNA-Seq]	Background: Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8% of all pregnancies.  Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown.  DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero.  Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types.  The best way to avoid this confounding effect is by using purified cell types.  However, the use purified cell types in large cohort translational studies is difficult.  The amnion, the inner layer of the fetal membranes of placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta.  In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to preeclampsia or hypertension and fetuses from normal pregnancies. Results: We performed a genome-wide DNA methylation analysis, HELP-tagging, on 62 amnion samples from placentas of uncomplicated, normal pregnancies, and those with complications of preeclampsia or hypertension.  Using a regression model approach, we found 123, 85 and 99 loci with high confidence hypertension-associated, proteinuria-associated and hypertension and proteinuria-associated DNA methylation changes, respectively. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Conclusions: Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia.  We propose that amnionic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions. Overall design: Directional RNA profiles of amnion membranes were generated by deep sequencing using Illumina HiSeq2500. Twenty-nine human amnion specimens were used: 12 control and 17 preeclampsia exposed.	Co-expression
SRP072698	RNA sequencing for identifying downstream targets of miR25/93	we identify several downstream targets that are under control of miR25/93 cluster Overall design: examination of global changes in mRNAs in two different lines	Co-expression
SRP072710	A conserved abundant cytoplasmic long noncoding RNA modulates repression of mRNAs by Pumilio proteins in human cells	Thousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionary conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD - an abundant and highly conserved cytoplasmic lncRNA. Most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two Pumilio homologs in mammals. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA binding proteins, an activity which positions them at key junctions of cellular signaling pathways. Overall design: RNA-seq following perturbations of NORAD lncRNA and Pumilio proteins in U2OS cells	Co-expression
SRP072713	Homo sapiens Transcriptome or Gene expression	Despite its tremendous heterogeneity, autism is characterized by a shared core behavioral phenotype. This suggests a convergence of the pathology on specific neural substrates. We aimed to identify region-specific molecular changes by performing the largest to date meta analysis of RNA-seq data from six cortical regions of autism patients together with DNA methylation profiling of one of the regions. We identified a prominent discordant pattern of gene expression and splicing changes that suggests a hyperactivation of the prefrontal cortex and a hypoactivation of the anterior insular cortex involved in emotional responses. Moreover, we identified a link between DNA methylation, alternative splicing and gene expression changes mediated by the chromatin modifier and high autism risk factor gene CHD8. Finally, analysis of candidate gene expression in different regions of developing human cortex suggested a predominant enrichment of misregulated genes in the layers populated by radial glia cells and producing inhibitory interneurons.	Co-expression
SRP072721	The WNT targets in human embryonic stem cells-derived endoderm cultures are composed of multi-lineage genes. [Endoderm RNA-seq and ChIP-seq data sets]	We performed RNA-sequencing with human embryonic stem cell derived cultures in the presence of WNT3a or WNT antagonist DKK1 to identify WNT targets in the differentiated endoderm cells. Furthermore, we also performed ChIP-sequencing with the differentiated endoderm cells to characterize the actual genomic regions directly regulated via the WNT-activated transcription factor TCF7L2.	Co-expression
SRP072739	Homo sapiens Transcriptome or Gene expression	Transcriptome profiling of T follicular cell subsets of human tonsil	Co-expression
SRP072759	ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage [RNA-seq]	The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells	Co-expression
SRP072769	RNAseq from disomic and trisomic fibroblasts and lymphoblastoids	RNA was sequenced from individuals Disomic and Trisomic for chromosome 21 to identify consistent changes in gene expression across individuals Overall design: Cells were cultured at subconfluency and RNA harvested for sequencing	Co-expression
SRP072791	RNA expression analysis of neuroblastoma cell lines treated with epigenetic drugs	The impact of drugs inhibiting DNA methylation (5-aza-2''-deoxycytodine, DAC) and EZH2 (EPZ-6438) on the neuroblastoma transcriptome was analyzed in two neuroblastoma cell lines. Parallel analyses investigated associated changes in histone modification and DNA methylation. Overall design: The neuroblastoma cell lines Be(2)-C and IMR5-75 were treated with DAC and EPZ-6438 in combination or alone. Controls were treated with solvent (DMSO). RNA was isolated and sequenced.	Co-expression
SRP072804	MYC dependent mRNA translation shapes gene expression and cell biology	We report that MYC controls the translation of specific mRNAs in a sequence and RNA binding protein dependent manner. Specifically, using transcriptome-scale ribosome footprinting we identify 882 mRNAs whose translation depends on MYC. These mRNAs are highly significantly enriched for specific 5ÕUTR sequence motifs that bind the SRSF1/RBM42/HNRNPK complex. For example, MYC and SRFSF1/RBM42 dependent transcripts include many components of the electron transport chain and directly affect cellular respiration. Our results provide an integrated map of MYC driven gene expression programs that includes MYCÕs ability to control mRNA translation. Overall design: Human B-cell lymphoma P493 cells were treated with Tetracycline (0.1 uM) for 24 hrs followed by cycloheximide treatment for 10 minutes in triplicates. An aliquot of cells were used for total RNA preparation and remaining cells were processed for isolation of ribosome protected fragments.	Co-expression
SRP072823	RNA-sequencing of two the B-ALL cell lines, REH and 697	Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their expression and role in pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1 positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. An ETV6/RUNX1 expression signature was established, consisting of 596 lncRNAs (434 up and 162 down) using expression analysis of a series of primary patient samples. Subsequently, RNA sequencing from BCP-ALL cell lines and shRNA-mediated silencing of ETV6/RUNX1, illustrated that lnc-NKX2-3-1, lnc-TIMM21-5, lnc-ASTN1-1 and lnc-RTN4R-1 are bona fide ETV6/RUNX1 targets and could serve as novel biomarkers of this prevalent subtype of human leukemia. Overall design: RNA-sequencing data was generated  in two B-ALL cell lines REH and 697.	Co-expression
SRP072829	Transcriptome analysis of CNS leukemia	The goal of this study is to reveal the characters and therapeutic targets of CNS leukemia.	Co-expression
SRP072832	Transcriptome analysis of NKG2CBright compared to NKG2CNeg from multigravida decidua samples	In multigravidae, a specific dNK cell population characterized by NKG2CBright expression is expanded, suggesting that this reflects a population of memory dNK generated during the first pregnancy.  Purpose: To gain further insight into the transcriptome profile of the expanded memory NKG2CBright dNK population found only in multigravida decidua samples Overall design: Flow cytometry based dNK cell sorting (based on CD56 and NKG2C) was done in order to purify CD56PosCD3NegCD16NegNKG2CBright and CD56PosCD3NegCD16NegNKG2CNeg subsets.	Co-expression
SRP072835	The MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in MLLr AML	In MLL-rearranged (MLLr) leukemias the N terminal part of the MLL gene can be fused to over 60 different partner genes. Here, we investigate the genome wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and their epigenetic signatures in order to define a core set of MLLr targets. We uncover both common as well as specific MLL-AF9 and MLL-AF4 target genes, which are all marked by H3K79me2, H3K27ac, and H3K4me3. Apart from promoter binding, we also identify MLL-AF9 and MLL-AF4 binding at specific subsets of non overlapping active distal regulatory elements. Despite this differential enhancer binding MLL-AF9 and MLL-AF4 still share a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34+ and monocyte specific genes. Comparing these datasets revealed several zinc finger transcription factors as potential MLL-AF9 co-regulators. Together these results suggest that MLL-fusions collaborate with specific subsets of TFs to aberrantly regulate the RUNX1 gene program in 11q23 AMLs. Overall design: Genome-wide (ChIP-seq) binding of MLL, AF9, AF4, H3K4me3, H3K27ac, H3K79me2 and RUNX1 in THP-1 and MV4-11 AML cell lines. Expression Profiling (RNA-seq) of THP-1 and MV4-11 cell lines, as well as 5 MLL-AF9 positive patient blasts.	Co-expression
SRP072837	Therapeutic targeting of GCB- and ABC-DLBCLs by rationally designed BCL6 inhibitors	BCL6 inhibitor induces derepression of BCL6 target genes and shows a similar transcriptional program to BCL6 siRNA Overall design: Genome-wide profiling of mRNA transcript levels in human DLBCL cell line with BCL6 inhibitor and DMSO control.	Co-expression
SRP072851	Transcriptionally inactive ATF2 variant drives melanomagenesis [Seq]	Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression. Overall design: Compared silencing of ATF2SV5 in H3A cells vs. silencing of ATF2WT via Ampliseq whole transcriptome analysis on the Ion Proton	Co-expression
SRP072864	RNA-sequencing time course of Human Intestinal Epithelial Cells (HIECs) following knockdown of miR-30bcd using complementary locked nucleic acids	To gain mechanistic insight into our finding that knockdown of miR-30 in HIECs and Caco-2 cells resulted in increased SOX9 mRNA, but decreased SOX9 protein expression, we performed RNA-sequencing on LNA30bcd-treated HIECs. We found 2440 significantly increased genes and 2651 significantly decreased genes across three time points (24 hours, 48 hours, and 72 hours post-transfection) relative to mock transfected cells. The up-regulated genes are highly enriched for both predicted miR-30 targets as well as genes in the ubiquitin-proteasome pathway. Inhibition of miR-30 also led to significantly reduced IEC proliferation and an increase in markers of enterocyte differentiation. Overall design: We evaluate transcriptional changes across time following knockdown of miR-30 family members in HIECs. We include 3 replicates each of Mock and LNA30bcd treated cells at 3 time points, 24H, 48H, and 72H post-transfection.	Co-expression
SRP072865	Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells	Here, human pluripotent stem cells (hiPSCs and hESCs) were induced to differentiate to enteric neurons through neural crest specification. We sequenced mRNA samples from enteric neuronal differentiation of human pluripotent stem cells at 4 different stage to generate the gene expression profiles of these cells. Overall design: 8 samples, including undifferentiated HDF-hiPSCs/H1, freshly isolated p75+/HNK1+ hiPSC-NCSCs and H1-NCSCs, enteric neural crest precursors (hiPSC-ENCPs 1 and hiPSC-ENCPs 2) from hiPSC-NCSCs, and enteric-like neurons (hiPSC-ENs 1 and hiPSC-ENs 2) from hiPSC-NCSCs, were analyzed.	Co-expression
SRP072875	Single-nucleus RNA-seq on undifferentiated human KD3 myoblasts and differentiated myotubes and mononucleated cells.	We report the application of single-nucleus-based sequencing technology for high-throughput profiling of transcriptome in immortazalized human myoblast KD3. By obtaining over sixty billion bases of sequence from mRNA, we generated comprehensive transcriptome profiles from KD3 undifferentiated myoblast and differentiated  multi-nucleated myotube and mono-nucleated cells. We find that the data from single-nucleus RNA-seq is consistent with the transcriptome from single-cell RNA-seq.  The pri-mRNA expression characterized by single-nucleus RNA-seq can reflect the actual miRNA level in the whole cell. Overall design: Examination of transcriptome in 1 cell type in 3 differential stages.	Co-expression
SRP072880	4ß-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells	Alternative splicing is a mechanism for increasing the protein variety of a limited number of genes. Studies have shown that aberrant regulations of the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4ß-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana, and analyzed its biological effects in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of apoptotic genes (e.g., HIPK3, SMAC/DIABLO, and SURVIVIN), changes the expression level of splicing factors (e.g., hnRNP C1/C2, ASF/SF2, SRp20, and SRp55), and induces histone tail posttranslational modifications (e.g., H3K27me1, H3K27me2, H3K36me3, and H3K79me1). Pretreatment with okadaic acid to inhibit protein phosphatase-1 could partly relieve the effects of 4bHWE on the alternative splicing of HIPK3 and SMAC/DIABLO transcripts, as well as on the dephosphorylation of ASF/SF2. Genome-wide detection of alternative splicing further indicated that several other apoptosis-related genes are also regulated by 4bHWE, including APAF1, CARP-1, and RIPK1. Moreover, we extended our study to apoptosis-associated molecules, detecting an increasing level of CASPASE-3 activity and cleavage of poly ADP-ribose polymerase in 4bHWE-induced apoptosis. Furthermore, in vivo experiments showed that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease of tumor size and weight. Taken together, this study is the first to show that 4bHWE affects alternative splicing through the modulations of splicing factors, providing a novel view of the antitumor mechanism of 4bHWE. Overall design: Examination of the global genes with altered alternative splicing in 4bHWE-treated Huh-7 cells.	Co-expression
SRP072890	Next-generation sequencing analysis of transcriptom in gemcitabine resistant pancreatic cancer cells	Next-generation sequencing was applied to compare the transcriptom of 1) SW1990 human pancreatic cancer cell lines and its gemcitabine-resistant derivative established with long-term exposure in medium containing 100 nM gemcitabine; 2) TRA-1-81+ cells and TRA-1-81- cells isolated from SW1990 human pancreatic cancer cell line. Overall design: mRNA profiles were generated with SW1990 cell lines and its derivatives by deep sequencing, using Illumina-HiSeq2500.	Co-expression
SRP072894	THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors	Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signaling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. Overall design: OCI-Ly13.2 cells were treated with 500 nM THZ-1 or vehicle for 3 h or 6 h in triplicate. Total RNA was harvested from cells and used for expression profiling via RNA-seq.	Co-expression
SRP072918	ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth [RNA-Seq]	We report that H2B deubiquitinating enzymes USP22, USP27x and USP51 have both unique and overlapping target loci. Overall design: Comparing gene expression profiles of MCF7 cells stably expressing shRNA targeting either USP22, USP27X or USP51 and cells expressing non-targeting shRNA.	Co-expression
SRP072919	Merkel cell polyomavirus small T antigen promotes pro-glycolytic metabolic perturbations required for transformation	Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1). Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-?B and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-?B subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis. Overall design: Expression of MCPyV ST or GFP was induced in IMR90 fibroblasts, and triplicate RNA samples were extracted and sequenced every 8 hours for a total of 96 hours	Co-expression
SRP072920	Peripheral Blood Mononuclear Cells (PBMC) Gene Expression-Based Biomarkers in Juvenile Idiopathic Arthritis (JIA)	Aim: To discovery biomarkers in JIA base on gene expression from RNA sequencing on PBMC Method: Paired-end Ilumina sequencing to capture gene expression of PBMC from JIA individuals and healthy controls Results:sample heterogeneity makes RNA sequencing on PBMC unsuitable as a first-step method for screening biomarker candidates in JIA Overall design: RNA sequencing on PBMC of 3 independent cohorts consist of JIA patients and healthy controls	Co-expression
SRP072941	The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion	The transcription factor SRY(sex related protein-Y)-box10 (SOX10) plays a key role in the development of melanocytes and peripheral glial cells from neural crest precursors. Recently, we and other groups found SOX10 to be involved in melanoma initiation, proliferation, invasion, and survival. However, specific mediators which impart the oncogenic role of SOX10 in melanoma remain widely unknown. To identify potential target genes of SOX10, we performed RNA sequencing to analyze genome-wide expression alterations after ectopic expression of SOX10. Among nine genes differentially regulated by SOX10, only peripheral myelin protein 2 (PMP2) was found upregulated in several other melanoma cell lines. PMP2 is one of the most abundant myelin proteins in glial cells and is necessary for the formation and maintenance of the myelin sheath. We detected PMP2 expression in a subset of human melanoma cell lines while it was absent in human melanocytes and fibroblasts. Direct binding of SOX10 to the PMP2 promoter was shown by chromatin immunoprecipitation and electrophoretic shift assay. In three-dimensional spheroid assays, we found that PMP2 overexpression increased melanoma cell invasion. In conclusion, we identified PMP2 as target gene of SOX10 and propose a novel role for PMP2 in melanoma cell invasion. Overall design: RNA sequencing was performed with 1205Lu metastatic melanoma cells transiently transfected with a vector for SOX10 overexpression (pCMV6-SOX10) or a control vector (pCMV6) in three biological replicates.	Co-expression
SRP072980	Stochastic Principles Governing Alternative Splicing of RNA	The goal of the study was to analyze the principles governing the usage of alternatively spliced transcript isoform of four types of T-cells (Naïve, Central Memory, Transitional Memory and Effector Memory) between resting and activated status. However, the principles discovered in the T cells were universal and can also be applied to other cell type and tissues. Overall design: Four types of T cells were sorted and whole transcriptome analysis was performed using an Illumina machine The readme.txt contains the column headers and description for the processed data files.	Co-expression
SRP072990	Somatic PRDM2 c.4459delA mutations in colorectal cancers control histone methylation and tumor growth	Purpose: To identify the contribution of PRDM2 c.4459delA mutation to colorectal tumorigenesis Methods: We employed rAAV-mediated genome editing to correct somatic PRDM2 c.4459delA mutation in homozygously mutated cell line. Using next-generation sequencing we have compared transcriptional profile of parental and PRDM2-corrected cells. Results: RNA-seq profiling revealed that several hallmark cancer gene sets are affected by PRDM2 c.4459delA Overall design: To address if the PRDM2 wt cells were transcriptionally different at a global level compared to their parental cells that carry PRDM2 c.4459delA mutation, we performed RNA-sequencing of parental cells and three independently generated clones with corrected PRDM2.  RNA-seq profile was generated for cells grown under normal culture conditions (10% FBS) as well as reduced serum conditions (0.5% FBS).	Co-expression
SRP072999	Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge	We report expression of genes from human Caco-2 cells (subclone TC7) after inhibition of histone deacetylases by trichostatin A, upon an E. coli bacterial challenge Overall design: RNAseq on cells pretreated or not with 5 uM TSA and challenged or not for 2 hours with E. coli	Co-expression
SRP073022	Whole transcriptome sequencing identifies increased CXCR2 expression in PNH granulocytes	To clarify the selective advantage of the GPI-AP- cells in paroxysmal nocturnal hemoglobinuria (PNH)  patients, RNA-seq was applied to examine functional effects of the PIG-A mutation in human granulocytes. Overall design: RNA seq, 2 PNH patiant''s GPI-AP-  granulocyte,2 PNH patiant''s GPI-AP+  granulocyte, 3 Healthy granulocyte	Co-expression
SRP073023	Knockout of miR-221 and miR-222 reveals overlapping and specific function between paralogous miRNAs	MicroRNAs (miRNAs) regulate the expression of mRNAs through sequence-specific binding into their 3' untranslated region (UTR). The seed sequence of miRNAs is the key determinant to recognize the target sites. The paralogous miRNAs, which share the same seed sequences but differ in their 3' parts, are known to regulate largely overlapping group of miRNAs. However, there is still no study which analyzes the functional difference among paralogous miRNAs. In this study, we compared the function between paralogous miRNAs, miR-221 and miR-222. By employing nuclease-mediated genome engineering technique, we established the knockout cell lines for these miRNAs, and analyzed their difference in target regulation precisely. We found that miR-221 and miR-222 suppress the previously identified targets, CDKN1B and CDKN1C, differentially. From the transcriptome analyses, we also found that large number of different transcripts with independent functions respond exclusively only to each of miR-221 and miR-222, respectively. Therefore, the miRNAs with common seed sequences can exert dissimilar function by regulating different groups of target mRNAs. This study illustrates that more researches are required to establish the rules of target site recognition by miRNAs. Overall design: The mRNAs from each of four different cell lines (WT, 221KO, 222KO, DKO) were applied for RNA-seq.	Co-expression
SRP073033	Joint-specific DNA transcriptome signatures in rheumatoid arthritis [RNA-seq]	Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signaling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-seq. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes.  Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients. Overall design: Total RNA-seq from knee and hip joints in rheumatoid arthritis (RA)	Co-expression
SRP073040	Integrin signaling regulates YAP/TAZ to control skin homeostasis	The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. By contrast, columnar epithelia differentiate an apical domain that recruits CRB3, Merlin (also known as NF2), KIBRA (also known as WWC1) and SAV1 to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib. Overall design: mRNA profiles of control siRNA transfected and YAP1 siRNA transfected cells were generated by deep sequencing, in triplicate, using an Illumina HiSeq 2500 instrument in two human cell lines, A431 and HaCAT. Complimentary to that, mRNA profiles of cells transfected with empty vector or a  constitutively active YAP1 mutant protein (YAP-S5A) in two human cell lines, A431 and HaCAT.	Co-expression
SRP073044	Generation of Brain Region-specific Organoids using a Miniaturized Spinning Bioreactor and Modelling ZIKV Exposure	Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability and tissue heterogeneity limit accessibility and broad applications of current organoid technologies. Here we developed a miniaturized spinning bioreactor (SpinO) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and importantly, a distinct human-specific outer radial glia cell layer. We have also developed protocols to generate midbrain and hypothalamic organoids. Finally, we employed this forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed that preferential, productive ZIKA infection of cortical neural progenitors leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell layer volume that resembles microcephaly. Together, our brain region-specific organoids and SpinO provide an accessible and versatile platform for modeling human brain development and diseases, and for compound testing. Overall design: Time course of human cerebral organoid cultures.  No Zika virus infection is involved.	Co-expression
SRP073061	GEO accession GSE80098 is currently private and is scheduled to be released on Jun 01, 2016.	If GEO accession GSE80098 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP073097	Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation (RNA-Seq)	The host innate immune response is the first line of defense against pathogens and is orchestrated   by the concerted expression of genes induced by microbial stimuli. Deregulated expression of   these genes is linked to the initiation and progression of numerous diseases associated with   exacerbated inflammation. Here, we identify Topoisomerase 1 (Top1) as a critical positive   regulator of RNA polymerase II (RNAPII) transcriptional activity at pathogen-induced genes.   Notably, depletion or chemical inhibition of Top1 suppresses the host response against   replicating Influenza and Ebola viruses as well as bacterial products. As a result, therapeutic   pharmacological inhibition of Top1 protects mice from death in experimental models of   chemical- and pathogen-induced lethal inflammation. Our results indicate that Top1 inhibition   could be used as therapy against life threatening infections characterized by an acutely   exacerbated immune response. Overall design: RNA seq was performed on Ebola (Wild type and mutant) infected or uninfected THP-1 cells in the presence of DMSO or Camptothecin	Co-expression
SRP073100	Prox1 (Prosper-related homeobox  1)  transcription factor depletion effect on CGTH-W-1  cells.	Analysis of CGTH-W-1  follicular thyroid carcinoma cells transcriptome following  48 hrs siRNA-mediated depletion of PROX1. PROX1 is a homeobox transcription factor. PROX1  depletion decreases  migratory ability, motility and invasivness and induces profound cytoskeleton changes of CGTH-W-1  cells.  Results provide insight into the role of PROX1 in the thyroid cancer. Overall design: Three biological replicates for a given condition	Co-expression
SRP073102	Whole transcriptome splicing analysis in isogenic lung epithelial and adenocarcinoma cell lines with or without a recurrent splicing factor mutation, U2AF1 (S34F)	The splicing factor gene, U2AF1, is recurrently mutated in a variety of human cancers, including lung adenocarcinomas.  The most frequent U2AF1 mutant, U2AF1 p.Ser34Phe (S34F), induces specific changes in pre-mRNA splicing, but it is unclear how these splicing changes are regulated. We have used genomic editing methods to modify the U2AF1 gene locus in an immortalized human bronchial epithelial cell line (HBEC3kt) and in human lung adenocarcinoma cells with pre-existing U2AF1 alleles, creating a U2AF1 S34F allele in the endogenous locus of HBEC3kts and inactivating U2AF1 S34F alleles in two lung adenocarcinoma cell lines (H441 and HCC78). By comparing global splicing alterations in these isogenic pairs of cell lines, we have identified many splicing alterations that are associated with the U2AF1 S34F mutation. Further, by decreasing the levels of wild-type U2AF1 in the isogenic HBEC3kt cells, we show that the magnitude of mutant-associated splicing is proportional to the ratio of S34F:WT gene products. This observation suggest that wild-type U2AF1 is a negative regulator of splicing alterations induced by U2AF1 S34F. Overall design: mRNA sequencing for the indicated isogenic cell lines using Illunima HiSeq2000 or HiSeq2500, paired-end 101 bp.	Co-expression
SRP073103	HLA peptides derived from tumor antigens induced by inhibition of DNA methylation for development of drug-facilitated immunotherapy	Treatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor’s gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2''-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. Overall design: The transcriptomes, proteomes and HLA peptidomes of the U-87, T98G and LNT-229 GBM human cell lines were analyzed before and after treatment with Decitabine. Overall, the RNA-Seq transcriptome analyses resulted in the identification of above 26000 transcripts, the proteome analyses identified about 7500 proteins and the HLA class I peptidome analyses resulted in above 25000 identified HLA peptides. Two biological repetitions of the transcriptome, three of the proteome and three of the HLA peptidome were performed with each of the cell lines and treatment, resulting in highly reproducible datasets.	Co-expression
SRP073112	Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [RNA-seq]	In neuroblastoma, amplification of the oncogenic basic helix-loop-helix (bHLH) transcription factor (TF) MYCN is the defining prognosticator of high-risk disease, occurs in one-third of neuroblastoma, and drastically reduces overall survival rates1,2. As a proto-oncogene, targeted MYCN overexpression in peripheral neural crest is sufficient to initiate disease in mouse models3. In MYCN amplified neuroblastoma, elevated expression of the factor is crucial to maintain tumor stemness4,5 and is associated with increased proliferation and aberrant cell cycle progression, as these tumors lack the ability to arrest in G1 in response to irradiation6-9. MYCN down-regulation broadly reverses these oncogenic phenotypes in a variety of neuroblastoma models10-12 and recent thereapeutic strategies to indirectly target MYCN production or protein stability have reduced tumor growth in vivo13-15. These observations motivate an investigation of MYCN binding in MYCN amplified tumors as it remains fundamentally unclear how elevated levels of the factor occupy the genome and alter transcriptional programs in neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of direct MYCN perturbation in neuroblastoma. We find that at oncogenic levels, MYCN associates with E-box (CANNTG) binding motifs in an affinity dependent manner across most active cis-regulatory promoters and enhancers. MYCN shutdown globally reduces histone acetylation and transcription, consistent with prior descriptions of MYC proteins as non-linear amplifiers of gene expression. We establish that MYCN load at the promoter and proximal enhancers predicts transcriptional responsiveness to MYCN shutdown and that MYCN enhancer binding occurs prominently at the most strongly occupied and down-regulated genes, suggesting a role for these tissue specific elements in predicating MYCN responsive “target” genes. At these invaded enhancers, we identify the lineage specific bHLH TWIST1 as a key collaborator and dependency of oncogenic MYCN. These data suggest that MYCN enhancer invasion helps shape transcriptional amplification of the neuroblastoma gene expression program to promote tumorigenesis. Overall design: RNA-Seq in SHEP-21 DOX treated time course. RNA-Seq in BE2C cells	Co-expression
SRP073163	Next Generation Sequencing Compares Effects of microRNA-9 perturbation in control and SZ hiPSC NPCs	To follow-up findings that miR-9 was abundantly expressed in control NPCs, significantly down-regulated in a subset of SZ NPCs, and that miR-9 levels/activity, neural migration and diagnosis were strongly correlated, we tested the effect of manipulating miR-9 at cellular, proteomic and transcriptomic levels. Unexpectedly, proteomic- and RNAseq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients. Methods: We compared global transcription of forebrain NPCs from two control and two SZ patients with manipulated miR-9 levels by RNAseq. Results:  Although RNAseq analysis revealed large inter-individual heterogeneity, we were able to resolve several functional consistencies in the effects of our miR-9 perturbations: i) the change in miR-9 activity was consistent with the inhibitory role of miR-9, ii) the gene expression fold-change of miR-9 target genes (between each perturbation and its corresponding control, summarized by the first principal component) was correlated (r=0.95, p=3.92e-04) with miR-9 fold change and iii) the differentially expressed (DE; p <0.01) gene list resulting from miR-9 perturbation (paired t-test) was enriched for miR-9 targets (1.53-fold, p=1.2e-5). Conclusions: We integrated the miR-9 perturbation RNAseq data with our existing RNAseq datasets contrasting control and SZ hiPSC NPC expression from our cohort 1 (six controls, four patients), to ask whether there was any relationship between the “SZ NPC signature” and “miR-9 perturbation” datasets; we observed that the DE (p-value <0.01) in “SZ NPC signature” is enriched for DE (fdr<0.01) in “miR-9 perturbation” (the overall enrichment is 2.31-fold (p=9.39e-09)); there is significant correlation between DE fold-change in these two datasets (overall genes r=0.188; p<10e-50). Effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes Overall design: Biological duplicates of passage-matched NPCs from 1 control (female) and 1 SZ patient (female) were transduced with either RV-GFP or RV-miR-9-GFP; GFP-positive NPCs were purified by fluorescent activated cell sorting (FACS) and expanded for two passages. In parallel, passage-matched NPCs from 2 controls (1 male, 1 female) and 2 SZ patients (1 male, 1 female) were transiently transfected with either scrambled or miR-9 LNA probes. In both instances, miR-9 perturbation was confirmed by qPCR.	Co-expression
SRP073180	RNA-Seq Analysis of Changes in Human Myometrial Tissue mRNA Expression Upon Labour Onset and Progression in Term Pregnancy	Purpose: The cause of labour initiation has yet to be fully elucidated for human pregnancy. This has hindered attempts to find effective therapies for the prevention of preterm labour, which affects up to 10% of pregnancies in the UK and it is the most dominant cause of perinatal death (75% of all cases). The myometrium of the uterus is where contractions that characterise labour take place, and it is here where changes at the molecular level responsible for triggering labour potential originate from. We used RNA-Seq-based mRNA sequencing technology in an attempt to identify mRNA transcripts that are differentially expressed in the myometrium upon the onset of labour, by comparing the expression profiles of tissues samples that represented non-labour (TNL), early labour (TEaL, = 3 cm cervical dilation) and established labour (TEsL, > 3 cm cervical dilation) states at term (> 37 weeks gestation) pregnancy. Methods: Myometrial biopsies from women undergoing Caesarean section were collected in accordance with the Declaration of Helsinki guidelines, and with approval from the local research ethics committee for Chelsea & Westminster Hospital (London, UK; Ethics No. 10/H0801/45). Informed written consent was obtained from all women who participated. Biopsies were excised from the upper margin of the incision made in the lower segment of the uterus, immediately washed with Dulbecco's phosphate-buffered saline (Sigma) and dissected into pieces approximately measuring 2-3 mm3. For RNA study, biopsies were immersed in RNAlater (Sigma) within 6 minutes after biopsy excision from the uterus and stored at 4°c overnight, before being taken out of RNAlater solution to be frozen for long-term storage at -80°c. For CHIP study, biopsies were snap-frozen in liquid nitrogen and stored at -80°c. All specimens were categorised into four groups according to their labour stages: preterm not in labour (PTNL, n=6), term not in labour (TNL, n=8), term in early labour (TEaL, defined as cervical dilatation <3 cm, n=8) and term in established labour (TEsL, defined as cervical dilatation >3 cm, n=6). For each sample, 60-100 mg of myometrium tissue were extracted in TRIzol (Life Technologies) by mechanical homogenisation in a Precellys 24 bead-based homogeniser using 5 cycles of 5000 rpm for 20 seconds, before chloroform treatment and centrifugation at 4°c. RNA was extracted from the aqueous phase of centrifuged homogenates using the TRIzol Plus RNA Purification kit (Life Technologies) with on-column DNase treatment prior to elution, all according to manufacturer's instructions. Final RNA samples were stored at -80°c. The quantity and quality RNA was measured using a Nanodrop ND-1000 spectrophotometer (LabTech),  Qubit fluorimeter (Life Technologies) and Bioanalyser 2100 (Agilent Technologies). Preparation of cDNA libraries was carried out using the TruSeq Stranded mRNA Sample Preparation kit (Illumina), following the high-throughput sample (HT) protocol. The quantity and quality of cDNA libraries were also tested by a Qubit fluorimeter and Bioanalyser 2100. TruSeq Stranded libraries were then multiplexed and sequenced with the average of 42 million DNA fragments per sample (100 bp paired-end reads). Quality control was performed using FastQC software (version 0.11.2). RNA-Seq reads was aligned to the GRCh38 Homo sapiens reference genome downloaded from Ensembl (release 81) with HISAT version 2.0.1 using parameters of --known-splicesite-infile --dta-cufflinks --rna-strandness RF --phred33 –p 4 -q. A list of known splice sites generated from the Ensembl GTF file using an accessory python script included in the HISAT2 package was provided to --known-splicesite-infile, of which HISAT2 will make use to assist the alignment of reads spanning two or more exons. Ensembl annotated a total of 65,989 genes, which includes 20,276 protein coding genes. As one human gene usually contains multiple transcript models, we thus conducted a transcript merging procedure to produce gene level models for expression analysis. Specifically, exons labeled as 'retained_intron' were first excluded, then overlapping interval exons of each gene were merged and a final gene level model was produced in GFF format. Only uniquely mapped (i.e. reads with the tag of NH:i:1) reads were used to produce gene read counts and calculate gene expression levels. The raw read count matrix was normalised with DESeq2 (version 1.6.3). Expression level of each gene in each sample was represented as RPKM (reads per kilobase per million mapped reads). Differentially expressed genes (DEGs) between two groups of samples were identified with DESeq2 (version 1.6.3), edgeR (version 3.8.6) and Cuffdiff (version 2.2.1). For DESeq2 and edgeR, we used the normalised read count matrix as input, and for Cuffdiff, we used the alignment bam files with uniquely mapped reads as input. Raw p-values were adjusted by FDR to produce q-values, and q-value of 0.05 were chosen as the cut-off for statistical significance in DESeq2, edgeR as well as Cuffdiff. Results: 22 RNA samples from three different labour groups were sequenced and an average of 53 million reads were obtained from each sample. More than 97.34% of reads were successfully aligned to GRCh38 reference human genome and the unique concordant pair ratio was greater than 92.39%. In total, 60,593 genes were mapped with the following criteria: (1) at least one RNA-seq read assigned to a gene; (2) we only assign a read to a gene when > 90% of this read falls into the exon regions of this gene. The principal component analysis (PCA) of these 22 samples showed that TNL and TEsL samples formed two distinct clusters whereas the TEaL group featured relatively great internal differences. Nevertheless, half of the samples from TEaL group was clustered with the TNL group and the other half was more separated yet closer to two samples of TEsL group. To determine the transcripts associated with labour, three software packages (DESeq2, EdgeR and Cuffdiff) were used to perform differential expression The transcript with a q value <0.05 in at least two methods was defined as a shared differentially expressed gene (DEG). As a result, 132 and 399 genes were identified comparing TNL with TEaL and TEsL, respectively, whereas no gene was significantly differentially expressed between TEaL and TEsL groups. Due to big differences among individual samples, in this study, the expression fold change (FC) was calculated as the ratio of median reads per kilobase per million mapped reads (RPKMs) with the bigger median RPKM divided by the smaller median RPKM. In order to minimise the noise derived from genes with low expression but high FC, we further filtered gene lists according to the following rational: if the original value of any median RPKM was <1, we artificially turned it into 1 before calculating the FC. Finally, two robust gene lists with an expression FC >1.5 between two groups (TNL vs. TEaL and TNL vs. TEsL) were generated containing 70 and 232 DEGs, respectively. Conclusions: This study, for the first time,  identifies differentially expressed genes (DEGs) and pathways that are involved in the myometrial transition from non-labouring to labouring phenotype by using samples from different stages of pregnancy and labour. The DEG lists are generated by subjecting the raw data to three sofware packages (DESeq2, edgeR and Cuffdiff), which makes the yield DEGs more robust. We conclude that some early responsive genes in circadian clock and inflammation pathways are likely to account for the labour onset and no significant changes are found on the transcription level once the labour starts. Overall design: Comparisons made between no labour (TNL, n = 8), early labour (TEaL, n = 8) and established labour (TEsL, n = 6) lower segment myometrial tissue samples, which were collected during Caesarean section (CS) with informed written consent	Co-expression
SRP073185	Inhibition of DNA methylation promotes breast tumor sensitivity to netrin-1 interference [RNA-Seq]	Results provide the animal proof of concept that inhibition of DNA methylation can sensitize solid tumors to antibodies mediating tumor cell apoptosis. Overall design: RNAseq of untreated cells, or DAC treated HMLER and MDA-MB-231 cells.	Co-expression
SRP073186	Chromatin environment, transcriptional regulation and splicing distinguish lncRNAs and mRNAs [Stability]	While long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression­–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional Overall design: Examination of RNA abundance in two cell lines (K562 and Hues9) and 5 time points after actinomycin D treatment. Three replicates per time point and cell type.	Co-expression
SRP073187	Chromatin environment, transcriptional regulation and splicing distinguish lncRNAs and mRNAs [NucFrac]	While long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression­–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional Overall design: Examination of RNA abundance for cytosolic and nuclear fractions in mouse ES cells. Two replicates each.	Co-expression
SRP073189	A TGFbeta-PRMT5-MEP50 Axis Regulates Cancer Cell Invasion through Histone H3 and H4 Arginine Methylation Coupled Transcriptional Activation and Repression	We sequenced mRNA from 3 biological replicates each of A549 lung adenocarcinoma cell lines expressing shRNA against GFP (control), PRMT5, or MEP50. We then determined differential gene expression. Overall design: Transcriptome analysis of mRNA testing the role of PRMT5 and MEP50 by knockdown in A549 human lung adenocarcinoma cells	Co-expression
SRP073191	RNA-seq study reveals unique transcriptome expression in systemic lupus erythematosus patients with distinct autoantibody profile	Systemic lupus erythematosus patients exhibit remarkable heterogeneity in clinical manifestations and autoantibody repertoires. This complexity poses major barrier in diagnosis and effective treatment of SLE. To address this we studied the SLE patients in groups categorized on the basis of distinct sera autoantibodies. SLE patients were segregated into three group based on the presence of autoantibodies against i) dsDNA only ii) ENA (extractable nuclear antigens) only or iii) both. Overall design: The mRNA profiles of each SLE patient sample and controls were generated by deep sequencing, using Illumina HiSeq 2000 platform.	Co-expression
SRP073206	Transcriptome analysis in a radiosensitive and a radioresistant cell line after ionizing radiation	Differential gene expression profiling was performed in two lymphoblastoid cell lines with different radiosentivitity, one radiosensitive (RS) and another radioresistant (RR), after different post-irradiation times. A greater and a prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24 h after irradiation genes involved in DNA damage response, negative regulation of the cell cycle and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. Overall design: Sham-irradiated and irradiated (2 Gy) cell cultures of the RS and the RR cell line were incubated at 37ºC for 4 and 24 h and 14 days. After that, RNA was extracted and sequenced with QuantSeq technology	Co-expression
SRP073208	A Reproducibility-Based Computational Framework Identifies An Inducible, Enhanced Antiviral Dendritic Cell State In HIV-1 Elite Controllers (scRNA-Seq)	Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-Seq to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. We discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. We identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells (PBMCs) from healthy individuals in vitro. Overall design: Single-cell RNA-seq profiling of HIV-1-exposed cDCs and media controls from 3 elite controllers used to identify reproducible gene expression programs associated with cell-intrinsic HIV-1 immune recognition.	Co-expression
SRP073245	RNA-seq analysis reveals profound changes in transcript profiles between siCon- and siH19-transfected EVT cells	We used high throughput sequencing to analyze the transcriptional profiling of EVT. By comparing the transcriptional profiling of EVT with or without H19 knockdown, numerous genes showed significantly altered expression as a result of H19 repression. Overall design: HTR cells were transfected with either control siRNA or siH19. 48h later after transfection, total RNA was extracted for library preparation and RNA-seq analysis to compare trancript profiles between siCon and siH19 cells.	Co-expression
SRP073247	EZH2 inhibitor-mediated transcriptional profiling in prostate cancer cells [RNA-seq]	We reported here the gene expression profiles that were mediated upon the treatment of EZH2 inhibitor in two hormone-refractory prostate cancer cell lines: the sensitive, AR-positive abl cells and the insensitive, AR-null DU145 cells. Overall design: We treated both types of prostate cancer cells with two different EZH2 inhibitors (GSK126 or EPZ-6438) at final concentrations of 5 uM for 60-72 hrs, and then collected RNAs for gene expression profiling.	Co-expression
SRP073253	Transcriptomics of Kidney Cancer Samples	Transcriptomics of Kidney Cancer Samples.	Co-expression
SRP073267	Impact of RNA degradation on fusion detection by RNA-seq	Purpose: Popular methods for library preparation in RNA-seq such as Illumina TruSeq® RNA v2 kit use a poly-A pulldown strategy. Such methods can cause loss of coverage at the 5’ end of genes, impacting the ability to detect fusions when used on degraded samples. The goal of this study was to quantify the effects RNA degradation has on fusion detection when using poly-A selected mRNA and to identify the variables involved in this process Methods: Total RNA was extracted from solid tumor tissue and whole blood using the Qiagen® miRNeasy Micro and Mini kits, respectively. The KU812 cell line was purchased from Sigma-Aldrich (St. Louis, MO) and UHR (Universal Human Reference RNA) was purchased from Agilent (Santa Clara, CA). UHR is a mixture of cell lines derived from breast adenocarcinoma, hepatoblastoma, cervix adenocarcinoma, testis embryonal carcinoma, gliobastoma, melanoma, liposarcoma, histiocytic lymphoma, lymphoblastic leukemia and plasmocytoma. For Degradation experiments, two micrograms of human universal reference RNA (UHR) (Agilent Technologies, Santa Clara, CA) and 1ug of RNA extracted from KU812 cell line (purchased from ATCC) were degraded at 74oC from 1 to 11 minutes in 1 minute intervals, using the NEBNext® Magnesium RNA Fragmentation Module Kit (NEB, Ipswich, MA). RNA was then purified and concentrated with RNeasy MinElute Cleanup Kit (Qiagen, Valencia, CA). Results: In this study, we designed experiments using artificially degraded RNA from cell lines as well as naturally degraded RNA from tissue samples to quantify the effect RNA degradation has on fusion detection when using poly-A selected RNA libraries We found that both the RNA degradation level and the distance from the 3’ end of a gene, negatively impact the read coverage profile in RNA-seq. Furthermore, the median transcript coverage decreases exponentially as a function of the distance from the 3’ end and there is a linear relationship between the coverage decay rate and the RNA integrity number (RIN). Conclusions: we found that when using poly-A pulldown techniques for library preparation in RNA-seq, the fusion sensitivity is negatively impacted by both sample degradation and distance of the fusion breakpoint from the 3’ end and developed graphs that show such effect. Such graphs can be useful in assessing the fusion sensitivity of RNA-seq in both research and clinical settings Overall design: Sequencing data was generated using Hiseq 2500 with a library of 101 paired end reads in the rapid run mode	Co-expression
SRP073286	Transcriptome analysis of H9 hESC derived cerebral organoids	RNA-seq was utilized to characterize the transcriptome of human embryonic stem cells-derived 3D cerebral organoids. Briefly, H9 hESCs were differentiated into cerebral organoids using previously established methods (Lancaster, 2013). Coding and noncoding genes were analyzed in 1 month and 2 month old cerebral organoid samples. Overall design: Examination of transcriptome of hESC and cerebral organoids 1 month and 2 months old with 2 experimental replicates per group.	Co-expression
SRP073307	Evolutionary origin and functional divergence of stem cell homeobox genes in eutherian mammals	We individually examined the ability of human ARGFX, DPRX, LEUTX, and TPRX1 to regulate gene expression by ectopically expressing these proteins in fibroblasts. Overall design: Each gene along with an empty control vector were transfected individually to drive ectopic expression in human dermal fibroblasts, in triplicate.	Co-expression
SRP073318	mRNA expression of breast cancer cell lines across different densities [SCRB-Seq]	mRNA expression profiles for 3 breast cancer cell lines seeded at different density and grown for different duration Overall design: This experiment is part of a study fo the effect of cell density on drug sensitivity [1]. Cells plated at different densities in 384-well plates were harvested at the indicated times and RNA was extracted using the RNeasy mini kit (Qiagen). To ensure sufficient RNA amounts wells with low cell numbers were pooled. Some conditions have been tested in biollogical replicates grown at the same time. Libraries were prepared by the Broad Technology Labs (BTL) following the protocol for SCRB-Seq described in [2]. Transcripts were quantified by the BTL computational pipeline using Cuffquant version 2.2.1 [3].   [1] Hafner, M., Niepel, M., Chung, M., Sorger, P.K., Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs. DOI:10.1038/NMETH.3853  [2] Soumillon, M., Cacchiarelli, D., Semrau, S., van Oudenaarden, A. & Mikkelsen, T.S. Characterization of directed differentiation by high-throughput single-cell RNA-Seq http://biorxiv.org/content/early/2014/03/05/003236   [3] Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D.R., Pimentel, H., Salzberg, S.L., Rinn, J.L. & Pachter, L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks, Nat. Protoc. 7, 562-578 (2012).	Co-expression
SRP073333	Role of COP1 on MAP kinase transcriptional output in gastrointestinal stromal tumor	COP1 regulates MAP kinase dependent stability Pea3 transcription factors. We determined the role of COP1 in the regulation of MAP kianse transciptional output.  We transfected GIST882 cells with siRNA against a scrambled sequence and two sequences against COP1. We treated cells for 8 hours with vehicle or 100 nM PD0325901 in duplicate and isolated RNA for sequencing. Overall design: Examination of transcriptome in COP1 intact and COP1 loss  GIST882 GIST cells in response to MAP kinase inhibition.	Co-expression
SRP073337	Role of COP1 on MAP kinase transcriptional output in melanoma	COP1 regulates MAP kinase dependent stability Pea3 transcription factors. We determined the role of COP1 in the regulation of MAP kianse transciptional output.  We generated A375 melanoma cells with CRISPR/Cas9 mediated COP1 (gene symbol RFWD) knockout. We treated control sgEGFP and COP1 loss sgCOP1 cells with vehicle, 1 µM vemurafinib, or 5 nM trametinib for 8 hours and isolated RNA for sequencing. Overall design: Examination of transcriptome in COP1 intact and COP1 loss A375 melanoma cells in response to MAP kinase inhibition.	Co-expression
SRP073347	Homo sapiens Raw sequence reads	The goal of this project is to investigat transcriptome profiling of peripheral blood mononuclear cells by RNA-seq in patients with eosinophilic bronchitis, cough variant asthma, or classic asthma and in healthy controls.	Co-expression
SRP073382	Transcriptome profiling of the human dorsal striatum in bipolar disorder	Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We report the first transcriptome profiling by RNA-Seq of the human dorsal striatum comparing bipolar and control subjects. Differential expression analysis and functional pathway enrichment analysis were performed to identify changes in gene expression that correlate with BD status. Further co-expression and enrichment analyses were performed to identify sets of correlated genes that show association to BD. Overall design: Total RNA samples were isolated from 36 postmortem dorsal striatum subjects (18 bipolar and 18 control) and sequenced. One outlier sample was removed and 35 samples (18 bipolar and 17 control) were analyzed.	Co-expression
SRP073384	Therapeutic targeting of GCB- and ABC-DLBCL by rationally designed BCL6 inhibitor	Rationale: The BCL6 oncogene is constitutively activated by chromosomal translocations and amplification in ABC-DLBCLs, a class of DLBCLs that respond poorly to current therapies. Yet the role of BCL6 in maintaining these lymphomas has not been investigated. BCL6 mediates its effects by recruiting corepressors to an extended groove motif. Development of effective BCL6 inhibitors requires compounds exceeding the binding affinity of these corepressors. Objectives: To design small molecule inhibitors with superior potency vs. endogenous BCL6 ligands for unmet putative therapeutic needs such as targeting ABC-DLBCL. Findings: We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor with 10-fold greater potency than endogenous corepressors. The compound, called FX1, binds in such a way as to occupy an essential region of the BCL6 lateral groove. FX1 disrupts BCL6 repression complex formation, reactivates BCL6 target genes, and mimics the phenotype of mice engineered to express BCL6 with lateral groove mutations. This compound eradicated established DLBCLs xenografts at low doses. Most strikingly, FX1 suppressed ABC-DLBCL cells as well as primary human ABC-DLBCL specimens ex vivo. Conclusions: ABC-DLBCL is a BCL6 dependent disease that can be targeted by novel inhibitors able to exceed the binding affinity of natural BCL6 ligands. Overall design: gene expression profiles of DLBCL cases	Co-expression
SRP073393	PR isoform-specific ER and PR chromatin binding and gene expression observed in-vitro in breast cancer cells.	Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR dictates distinct ER and PR chromatin binding and differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Genomic analyses of the two PR isoforms, PRA and PRB, indicate that these isoforms bind distinct genomic sites and interact with different sets of co-regulators to differentially modulate gene expression as well as pro- or anti-tumorigenic phenotypes. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Of note, the two isoforms reprogrammed estrogen activity to be either pro or anti-tumorigenic. In concordance to the in-vitro observations, differential gene expression was observed in PRA and PRB-rich patient tumors and importantly, PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. This differential of better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher anti-tumor activity of combination therapies of tamoxifen with PR antagonists and modulators. Knowledge of various determinants of PR action and their interactions with estrogen signaling to differentially modulate breast cancer biology should serve as a guide to the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic.  Overall design: For in-vitro experiments, cells were grown in steroid-deprived RPMI for 48 hours to 80% confluence, before being treated for with the hormones of interest (vehicle, 10 nM estrogen, 10 nM R5020 or both estrogen +R5020). Cells were then fixed with 1% formaldehyde for 10 minutes and the crosslinking was quenched with 0.125 M glycine for 5 minutes. Fixed cells were suspended in ChIP lysis buffer (1 ml 1M Tris pH 8.0; 200 µl 5M NaCl; 1 ml 0.5M EDTA; 1 ml NP-40; 1 g SDS, 0.5 g deoxycholate) and sheared in the Diagenode Biorupter for 20 minutes (30 second cycles). 100 µl of sheared chromatin was removed as input control.  A 1:10 dilution of sheared chromatin in ChIP dilution buffer (1.7 ml 1M Tris pH 8.0; 3.3 ml 5M NaCl; 5 ml 10% NP-40; 200 µl 10% SDS; to 100 ml with H2O), 4 µg antibody and 30 µl magnetic DynaBeads were incubated in a rotator at 4oC overnight. Chromatin was immunoprecipitated overnight using anti-ER (Santa Cruz Biotechnology HC-20), anti-PR (in-house made KD68) or rabbit IgG (Santa Cruz Biotechnology SC-2027). Next, the immunoprecipitated chromatin was washed with ChIP wash buffer I (2 ml 1M Tris pH 8.0; 3 ml 5M NaCl; 400 µl 0.5M EDTA; 10 ml 10% NP-40; 1 ml 10% SDS; to 100 ml with H2O), ChIP wash buffer II (2 ml 1M Tris pH 8.0; 10 ml 5M NaCl; 400 µl 0.5M EDTA; 10 ml 10% NP-40; 1 ml 10% SDS; to 100 ml with H2O), ChIP wash buffer III (1 ml 1M Tris pH 8.0; 5 ml of 5M LiCl; 200 µl 0.5M EDTA; 10 ml 10% NP-40; 10 ml 10% deoxycholate; to 100 ml with H2O) and TE (pH 8.0). Elution was performed twice from beads by incubating them with 100 µl ChIP-elution buffer (1% SDS, 0.1 M NaHCO3) at 65oC for 15 minutes each. The eluted protein-DNA complexes were de-crosslinked overnight at 65oC in 200 µM NaCl. After de-crosslinking, the mixture was treated with proteinase K for 45 minutes followed by incubation with RNase A for 30 minutes. Finally, DNA fragments were purified using Qiagen PCR purification kit and reconstituted in 50 µl nuclear-free water. Real time PCR was performed using SYBR green.  For ChIP-seq library preparations, libraries were prepared using KapaBiosystems LTP library preparation kit (#KK8232) according to the manufacturer's protocol.	Co-expression
SRP073426	Transcriptome profile of HepG2-expressing ATP7B-H1069Q (liver hepatocellular cells) exposed to JNK or p38 Inhibitor	In order to identify the effects of JNK inhibitor or p38 Inhibitor on the transcriptome of ATP7B H1069Q-overexpressing liver cells, we performed RNAseq experiments Overall design: Transcriptome analysis of the hepatocytes overexpressing ATP7B H1069Q, compared with hepatocytes overexpressing ATP7B WT. Total RNA was extracted from HepG2 cells; RNA extracted from hepatocytes overexpressing ATP7B WT was used as control.	Co-expression
SRP073459	CDK12 regulates alternative last exon mRNA splicing and promotes invasion of a breast cancer cell line	We performed mRNA sequencing on 184-hTert and SK-BR-3 and MDA-MB-231 cell lines treated with siRNA directed to CDK12 (Cyclin dependent kinase 12) or a scrambled siRNA control. For each cell line, we generated 6 RNA-seq libraries (3 treatment replicates and 3 control replicates) to study the differential expression and the differential splicing patterns regulated by CDK12. Overall design: Examination of differential mRNA abundance and splicing patterns between the CDK12 siRNA treated samples and control samples for SK-BR-3 and 184-hTert and MDA-MB-231 cell lines.	Co-expression
SRP073460	Global transcriptome analysis in the MYCN-amplified neuroblastoma cell line IMR5-75 upon inducible MYCN-knockdown	Inducible MYCN-knockdown, followed by RNA-seq analysis in the MYCN-amplified neuroblastoma cell line IMR5-75, reveals profound time-dependent transcriptome changes. Overall design: For modulation of MYCN levels, stable neuroblastoma cell models were used where MYCN can be  downregulated via vector-based hairpin RNA induction upon addition of 1µg/ml tetracycline (IMR5-75-shMYCN. From cells treated either with tetracycline or solvent (ethanol), RNA was isolated at time points 6 hours, 12 hours and 24 hours. Experiments were done in duplicates. RNA was sequenced.	Co-expression
SRP073461	Genomic deletion of malic enzyme 2 confers collateral lethality in pancreas cancer	Comparison of malic enzyme 3 (ME3) depleted vs non-depleted xenograft tumors. ME3 is an isoform of ME2. Overall design: Sub-cutaneous tumors of nude mice injected with PATU-ishME3 (shRNA against ME3) and treated +/- Dox to knockdown ME3. 4 tumors off-dox and 2 tumors on-dox	Co-expression
SRP073483	small RNA-Seq showing transfer of bacterial outer membrane vesicle (OMV) sRNA to host airway epithelial cells	This study is the first to show transfer of regulatory bacterial sRNAs from bacterial OMVs to host cells. Overall design: Demonstration of transfer of bacterial sRNA from Pseudomonas aeruginosa OMVs to host cells in two cell types. RNA isolated from PA14 OMV exposed primary human bronchial epithelial cells or CFBE41o- bronchial epithelial cells as well as unexposed control cells was analyzed by small RNA-Seq. Primary cell exposures were performed on two donors and exposures of CFBE41o- cells were done in triplicate.	Co-expression
SRP073501	Complement protein C1q modulates macrophage molecular signaling and inflammatory responses during ingestion of atherogenic lipoproteins	C1q suppresses JAK-STAT signal transduction and activates PPAR-mediated transcription in macrophages during clearance of modified forms of LDL leading to a reduction in inflammatory response. Overall design: Human monocyte-derived macrophages (HMDM) were incubated with either oxidized (oxLDL) or acetylated low-density lipoprotein (acLDL) in the presence or absence of C1q for 3 hours. Total RNA was extracted using the Qiagen RNeasy Mini Kit. RNA libraries were constructed using the Illumina TruSeq Stranded mRNA Sample Preparation Kit. Sequences were aligned to a reference genome (hg38), RPKM and raw counts were determined using CASAVA version 1.8.2.	Co-expression
SRP073504	RNA-sequencing for EPRS shRNA Knock Down MCF7 Cell Line	Aminoacyl tRNA synthetases (ARSs) are a class of enzymes with well-conserved housekeeping functions in cellular translation. Recent evidence suggests that ARS genes may participate in a wide array of cellular processes, and may contribute to the pathology of autoimmune disease, cancer, and other diseases. Several studies have suggested a role for the glutamyl prolyl tRNA synthetase (EPRS) in breast cancers, although none has demonstrated any underlying mechanism about how EPRS contributes to carcinogenesis. In this study, we identified EPRS as upregulated in estrogen receptor positive (ER+) human breast tumors in the TCGA and METABRIC cohorts, with copy number gains in nearly 50% of samples in both datasets. EPRS expression is associated with reduced overall survival in patients with ER+ tumors in TCGA and METABRIC datasets. EPRS expression was also associated with reduced distant relapse-free survival in patients treated with adjuvant tamoxifen monotherapy for five years, and EPRS-correlated genes were highly enriched for genes predictive of a poor response to tamoxifen. We demonstrated the necessity of EPRS for proliferation of tamoxifen-resistant ER+ breast cancer, but not ER- breast cancer cells. Transcriptomic profiling showed that EPRS regulated cell cycle and estrogen response genes. Finally, we constructed a causal gene network based on over 2500 ER+ breast tumor samples to build up an EPRS-estrogen signaling pathway. EPRS and its regulated estrogenic gene network may offer a promising alternative approach to target ER+ breast cancers that are refractory to current anti-estrogens.	Co-expression
SRP073607	Divergent expression and metabolic functions of human glucuronosyltransferases through alternative splicing	Purpose: Maintenance of cellular homeostasis and xenobiotics detoxification relies on the glucuronidation pathway mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by 10 highly homologous genes. Recent evidence suggests that alternative splicing largely expands the human UGT transcriptome. Results: we establish the quantitative portrait of the UGT transcriptome in major metabolic organs and characterize cellular functions of selected alternative UGT isoforms with novel in-frame sequences. Targeted RNA sequencing uncovered that AS significantly shapes the UGT transcriptome, with variants quantitatively representing up to 35% and 60% UGT transcripts in normal and tumoral tissues respectively. Novel distinctive in-frame sequences were present in 20% alternative transcripts, which potentially encode UGT isoforms with distinct structural and functional features. Conclusions: This work exposes the important quantitative and biological significance of alternative UGT expression likely creating unparalleled protein diversity evolving from enzymes to regulators of cell metabolism. Overall design: normal and tumoral metabolic tissues by targeted RNA next-generation sequencing; Total RNA was extracted from liver, kidney, intestine and colon from multiple human donors. RNA-sequencing was conducted with a Illumina HiSeq 2500 system	Co-expression
SRP073613	Identification of mRNAs with reduced ribosomal loading upon knock-down of translation factor DAP5 from hESCs.	We have generated stable human ESCs (H9) expressing control or DAP5-targeting shRNA. Polysome profiles reveal no major changes in overall translation. PolyA+ RNA and RNA accociated with heavy polysomal fractions were purified in biological duplicates and sequenced using Illumina HiSeq 2000 instrument. We identified 122 potential mRNA targets of DAP5 translation that display reduced ribosomal loading, and hence reduced translation, in the absence of DAP5. Overall design: Total mRNA and heavy polylsomal fractions from shNT and shDAP5 expressing hESCs, each in duplicate, was deep sequenced.	Co-expression
SRP073621	The role of miR-17-92 in the miRegulatory landscape of Ewing Sarcoma (RNA-Seq)	MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3´UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing Sarcoma. miR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be the top EWS-FLI1 activated miRNA. Using a combination of AGO2 pull-down experiments by PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) and of RNAseq upon miRNA depletion by ectopic sponge expression, we aimed to identify the targetome of miR-17-92 in Ewing sarcoma. Intersecting both datasets we found an enrichment of PAR-CLIP hits for members of the miR-17-92 cluster in the 3´UTRs of genes up-regulated in response to mir-17-92 specific sponge expression. Strikingly, approximately a quarter of these genes annotate to the TGFB/BMP pathway, the majority mapping downstream of SMAD signalling. Taken together, our findings shed light on the complex miRegulatory landscape of Ewing Sarcoma pointing miR-17-92 as a key node connected to TGFB/BMP pathway Overall design: mRNA profiles of a Ewings Sarcoma cellline (clone of A673 with inducible sh EWS-FLI1 knockdown) treated with microRNA sponges and controls	Co-expression
SRP073662	Transcriptional response to the HSP70 inhibitor MAL3-101 in parental rhabdomyosarcoma cells and isogenic acquired-resistance lines.	We demonstrate that inhibition of HSP70 with MAL3-101 induces activation of the unfolded protein response, and that cells with acquired resistance upregulate a cytosolic HSP70 at the level of mRNA. Overall design: Whole transcriptome sequencing was undertaken of parental or acquired-resistance RMS13 cells treated with either DMSO or 10 micromolar MAL3-101.	Co-expression
SRP073675	RNA-Seq following PCR-based sorting reveals rare cell transcriptional signatures	Background: Rare cell subtypes can profoundly impact the course of human health and disease, yet their presence within a sample is often missed with bulk molecular analysis.  Single-cell analysis tools such as FACS, FISH-FC and single-cell barcode-based sequencing can investigate cellular heterogeneity; however, they have significant limitations that impede their ability to identify and transcriptionally characterize many rare cell subpopulations. Results: PCR-activated cell sorting (PACS) is a novel cytometry method that uses single-cell TaqMan PCR reactions performed in microfluidic droplets to identify and isolate cell subtypes with high-throughput. Here, we extend this method and demonstrate that PACS enables high-dimensional molecular profiling on TaqMan-targeted cells. Using a random priming RNA-Seq strategy, we obtained high-fidelity transcriptome measurements following PACS-sorting of prostate cancer cells from a heterogeneous population.  The sequencing data revealed prostate cancer gene expression profiles that were obscured in the unsorted populations.  Single-cell expression analysis with PACS was subsequently used to confirm a number of the differentially expressed genes identified with RNA sequencing. Conclusions: PACS requires minimal sample processing, uses readily available TaqMan assays and can isolate cell subtypes with high sensitivity.  We have now validated a method for performing next-generation sequencing on mRNA obtained from PACS isolated cells.  This capability makes PACS well suited for transcriptional profiling of rare cells from complex populations to obtain maximal biological insight into cell states and behaviors. Overall design: The PACS workflow was used to isolate a spiked-in cell subpopulation and compare its RNA profile with the hegterogeneous starting population and the individual populations.	Co-expression
SRP073683	Guided self-organization recapitulates tissue architecture in a bioengineered brain organoid model	Engineered brain organoids (enCORs) exhibit reproducible neural differentiation and forebrain regionalization. Overall design: Comparison of transcriptomes from bioengineered micropatterned enCORs and spheroids at 20 days and 60 days	Co-expression
SRP073706	FBXO10 deficiency and BTK activation upregulate BCL2 expression in mantle cell lymphoma	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to identify BTK targets by RNA-seq and high-throughput data analysis and verify these genes by quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods Methods: mino/z138 sc4/shbtk stable cell lines were generated with tet-on system vector, small hairpins were induced for 48 hours after doxycycline addition, mRNA was exacted and used for RNA sequencing. After TopHat analysis followed by Cufflinks, down/up regulated genes list was generated. qRT–PCR validation was then performed using SYBR Green assays Results: Using an optimized data analysis workflow and with a fold change =1.3 and p value <0.05, thousands of genes were changed. Altered expression of 6 genes was then confirmed with qRT–PCR, demonstrating the high qulity of the RNA-seq method. Overall design: mino/z138 sc4/shbtk stable cell lines were generated with tet-on system vector, small hairpins were induced for 48 hours after doxycycline addition, total RNA from these cells was then used for RNA-seq analysis.	Co-expression
SRP073735	Total RNA-seq of HeLa cells upon conventional or improved RNA extraction	We devised a novel improved RNA extraction method, and performed total RNA-seq to determine the effect of improved RNA extraction. Overall design: Examination of total RNAs that were derived from the same cell/TRI Reagent solution, split into two and extracted by either a conventional or improved RNA extraction method. Hokkaido System Science, Co.	Co-expression
SRP073740	Transcriptional effect of ETV1 knockdown in melanoma cells	ETV1 is amplified in a subset of melanomas. Here, we performed RNA-seq on two BRAF V600E mutant melonoma cell lines transduced with a scrambed shRNA and two individual ETV1 shRNA Overall design: Two melanoma cell lines (A375 and Colo800) were infected in duplicate with three shRNA viruses (Scrambled, ETV1sh1-B11TRCN0000013923, ETV1sh2-TRCN0000013925). Four days after infection, RNA was harvested for expression profiling.	Co-expression
SRP073743	Messenger RNA expression after MK2206/DMSO treatment of T47D cells	We performed RNA-seq in T47D cells after 24 hour treatment with the AKT inhibitor MK2206 or DMSO. We show that a group of transcripts is differentailly expressed after AKT inhibition. Overall design: Comparison of mRNA levels using RNA-seq after AKT inhibition vs vehicle	Co-expression
SRP073749	LBO D25	RNAseq data from EPCAM+ and EPCAM- population in D25 LBOs.	Co-expression
SRP073756	Homo sapiens Raw sequence reads	We compared morphological, physiological and transcriptomic features between cells cultured in the sericin-substituted medium and those in the conventional FBS-containing medium	Co-expression
SRP073767	Homo sapiens single cell RNA sequencing	The study aims to use the 10x platform to generate indexed sequencing libraries from germ line and cancer samples for single cell RNA sequencing analysis.	Co-expression
SRP073789	Gene expression profiling study by RNA-seq for identifying gene signatures associated with castration-refractory prostate cancer (CRPC) development.	The objective of this study is to identify gene signature associated with castration-refractory prostate cancer (CRPC) development. We carried out RNA-seq based transcriptome profiling using 45 prostate samples with various disease progression steps such as benign prostate hyperplasia (BPH), primary cancer of prostate (CaP), advanced CaP and CRPC. Via various statistical analyses, we identified significant gene set associated with each progression step and observed that AR was the only gene feature associated with all progression steps, indicating that AR is the crucial mediator of and has a diverse activity across the CaP progressions. Among the samples in this data set, there are 4 pairs of advanced CaP and CRPC samples, in which each pair was obtained from the same patient. Using these paired samples, we also determined differentially expressed genes between advanced CaP and CRPC, and performed comparative analysis of significant gene lists in matched sample pairs and in unpaired remained samples. By assessing expression difference between advanced CaP and CRPC groups, 309 and 182 genes were statistically significant in paired and unpaired samples, respectively (P < 0.001). When these two gene lists were compared, a total of 15 genes were common and applied to a number of downstream experimental assays. Overall design: RNA-seq data of 45 CRPC samples were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer''s protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x100 bp) using Hiseq-2000 (Illumina).	Co-expression
SRP073790	Comparative Analysis of Cas9 Activators Across Multiple Species	RNA-Seq after Cas9-gRNA transfection with different activators targeting HBG1 Overall design: we performed PolyA Selection and RNA-Seq on cells transfected with a dCas9-based transcriptional activator (VP64, VPR, SAM or Suntag) and a gRNA targeting HBG1	Co-expression
SRP073808	Homo sapiens Raw sequence reads	In vitro cultured H7 human embryonic stem cells (WiCell) and H7-derived downstream early mesoderm progenitors	Co-expression
SRP073810	RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways	To understand the nature of glucocorticoids targeting non-immune cell function, we generate RNA sequencing data from 3 human podocyte cell lines derived from 3 kidney transplant donors and identify the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells.Our results represent a significant step forward in the genome-wide characterization of the molecular effects of glucocorticoids on human podocytes. The resource generated in this study is important for understanding the targeting of non-immune cell function by glucocorticoids and also for designing more specific podocyte-targeted agents for MCN therapy. Overall design: Transcriptome profiles of human podocytes treated with vehicle and dexamethasone were generated by RNA-sequencing using Illumina HiSeq 2500	Co-expression
SRP073813	RNA-sequencing of human post-mortem brain tissues	RNA-seq profiling was conducted on clinically-annotated human post-mortem brain tissues Overall design: We measured the transcriptome in 281 clinically-annotated human post-mortem brain tissues	Co-expression
SRP073940	Safety and Efficacy of the JAK Inhibitor Tofacitinib Citrate for Alopecia Areata and Variants	The samples include RNA from scalp biopsies before treatment and at 8 weeks of treatment with Tofacitinib Citrate 5 mg BID in patients with Alopecia Areata. 32% had a SALT score of 50% or higher and 47% had clinically significant response. Overall design: Open label trial of patients with Alopecia Areata of more than 6 months in duration refractory to standard therapy. Each patient took tofacitinib citrate 5mg BID for 3 months and then stopped. Biopsies were taken pretreatment and then at 8 weeks from the scalp and submitted for RNA sequencing.	Co-expression
SRP074061	The beneficial effect of pterocarpan-rich extract from soybean leaf on metabolic syndrome in overweight and obese subjects: randomized controlled trial	We investigated the effect of pterocarpan-rich extract from soybean leaf on metabolic syndrome and elucidated anti-inflammation mechanism based on RNA-seq transcriptomic profiles in overweight and obese subjects Overall design: Total RNA of peripheral blood mononuclear cells (PBMCs) was obtained from pterocarpan-rich extract soybean leaf (PT) and biomarkers associated with lipid, glucose metabolism and inflammation was measured. Please note that raw data for the "after supplementation" samples have been lost and therefore were not provided,	Co-expression
SRP074062	Transcriptome analysis of chronic periodontitis patients'' gingival tissue	We examined the molecular and cellular mechanism for chronic periodontitis in patients'' gingival tissue by whole transcriptome sequencing. Overall design: Compare gene expression profiles between between periodontitis and healthy gingival samples using RNA-Seq (Illumina platform: Hi-Seq 2000)	Co-expression
SRP074063	Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity	Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists. Overall design: Expression profiling by high throughput sequencing	Co-expression
SRP074069	Transcriptome analysis of patient-derived xenograft models of HER2+ breast cancer brain metastases	To gain insights into tumor heterogeneity in anti-cancer drug responses of patient-derived xenograft models of HER2+ breast cancer brain metastases, we performed transcriptome gene expression profiling by Ion AmpliSeqâ„¢ Transcriptome sequencing that targets more than 20,000 human genes. Our data found that all anti-cancer drugs responders have significantly higher expression levels of AKT-mTOR-dependent signature genes as compared to the non-responders, suggesting that most HER2+ breast cancer brain metastases are depend on the AKT-mTOR pathway Overall design: Gene expression profiles of five PDX samples were generated by Ion AmpliSeq Transcriptome sequencing, in duplcate, using Ion torrent Proton machine.	Co-expression
SRP074076	Global transcriptional analysis of human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells by RNA-seq	All mammals develop from embryonic founder cells with the ability to generate all of the differentiated cells that constitute the organism. Capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. Here, we show that a chemical cocktail enables the derivation of a new stem cell type from both mice and humans, designated as extended pluripotent stem (EPS) cells. A single human or mouse EPS cell is able to contribute to both embryonic and extraembryonic lineages in inter- and intra-species chimeric mouse conceptuses respectively. Compared to known pluripotent stem cells, EPS cells show upregulation of gene modules marking embryonic cells from early preimplantation development. Further analysis shows that PARP1 inhibition is required for maintaining EPS potency. Our findings constitute a first step towards capturing authentic mammalian totipotency in vitro, and open new avenues for basic and translational research. Overall design: Total of 10 samples were analyzed, which included human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells. For human primed pluripotent stem cells, one cell line H1 was analyzed, which included two samples. For human extended pluripotent stem cells, two cell lines were analyzed, which included ES1-EPS (2 samples) and H1-EPS (2 samples). For mouse extended pluripotent stem cells, two cell lines were analyzed, which included mc6-1 (1 sample) and OG6-3 (1 sample). For mouse embryonic stem cells, two cell lines were analyzed, which included mc2i (1 sample) and OG-2i (1 sample).	Co-expression
SRP074103	Gene regulation of candidate cancer gene DIP2C	Purpose: The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized gene found mutated in breast and lung cancers. We want to understand the role of DIP2C in tumor development. Methods: We engineered human DIP2C knockout cell systems by genome editing, and then use next-generation sequencing to identify the genes affected by the loss of DIP2C. Results: Inactivation of DIP2C triggers substantial gene expression changes, cellular senescence and epithelial to mesenchymal transition in cancer cells. Overall design: To investigate if loss of DIP2C affects gene expression we performed RNA sequencing and compared gene expression levels in the DIP2C knockout cells to those in parental RKO cells.	Co-expression
SRP074114	LSD1 mediates MYCN control of epithelial-mesenchymal transition through silencing of metastatic suppressor NDRG1 gene	Neuroblastoma (NB) with MYCN amplification is a highly metastatic tumor in children, and unraveling the key players involved in MYCN-induced invasion may identify new targets for therapy. Epithelial-mesenchymal transition (EMT) plays a critical role in promoting metastasis and we have recently determined that MYCN interacts with LSD1, a histone de-methylase flavin oxidase, which has been found to promote EMT. We show here that LSD1 affects motility and invasiveness of NB cells through transcription modulation of the metastasis suppressor NDRG1, N-Myc Downstream-Regulated Gene 1. LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene and it inhibits its expression. LSD1-inhibition relieves NDRG1 repression induced by MYCN with concomitant block of motility and invasiveness of NB cells, and such effects were recapitulated by overexpressing NDRG1. Moreover, we found that low NRDG1 and high LSD1 levels in NB patients were associated with poor survival. These data suggest that LSD1 inhibition may knock down the ability of MYCN-amplified Neuroblastomas to metastasize. Our findings elucidate a mechanism of how MYCN/LSD1 control motility and invasiveness of NB cells through transcription regulation of NDRG1 expression and they suggest that pharmacological targeting of LSD1 could inhibit the NB metastatic process. Overall design: Examination of mRNA levels in SHEP Tet-21/N cells treated with TCP (tranylcypromine) and siLSD1.	Co-expression
SRP074134	ENL Links Histone Acetylation to Oncogenic Gene Expression in AML	Cancer cells are characterized by aberrant epigenetic landscapes and often exploit the chromatin machinery to activate oncogenic gene expression programs1. The recognition of modified histones by “reader” proteins constitutes a key mechanism underlying these processes; therefore targeting such pathways holds clinical promise, as exemplified by the recent development of BET bromodomain inhibitors2,3. We recently identified the YEATS domain as a novel acetyllysine-binding module4, yet its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralog AF9, is required for disease maintenance in a variety of acute myeloid leukaemias (AML). CRISPR-Cas9 mediated depletion of ENL led to anti-leukemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies in vitro and ChIP-seq analyses in leukaemia cells revealed that ENL binds to acetylated histone H3, and colocalizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemias. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced RNA polymerase II recruitment on ENL target genes, thus leading to suppression of oncogenic gene expression programs. Importantly, disruption of ENL’s functionality further sensitized leukaemia cells to BET inhibitors. Together, our study identifies ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in AML and suggests that displacement of ENL from chromatin is a promising epigenetic therapy alone or in combination with BET inhibitors for AML Overall design: iCas9-MOLM-13 or MV411 cells were transduced with sgRNA or shRNA targeting control or ENL in indicated conditions. RNA-seq was then performed to identify differentially expressed genes.	Co-expression
SRP074138	Human islets contain four distinct subtypes of ß cells	The transcriptomes of four subpopulations of beta cells isolated by FACS from five healthy human donors. Populations were defined using cell surface-labeling antibodies, avoiding the need for fixation. Overall design: There are 5 biological replicates of 4 different cell types.   Each donor yielded all 4 subtypes.	Co-expression
SRP074154	AZ1366: An inhibitor of tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition	EGFR-mut NSCLC lines show differential suceptibility to inhibition of tankyrase in the presence of EGFR inhibitors Overall design: NSCLC cells were treated in quadruplicate with gefitinib, AZ1366 (tankyrase inhibitor) or a combination thereof	Co-expression
SRP074184	Transcriptome analysis of ECFCs treated with GSK-343 and Panobinostat	Human endothelial colony-forming cells (ECFCs) represent one of the most promising sources of adult stem cells for vascular regeneration after ischemia. Yet, the molecular mechanism underlying the unique properties of these cells to repair damaged blood vessels remains unclear, and new strategies to improve their regenerative function are needed. Here, we demonstrate that ex vivo treatment of ECFCs with a combination of epigenetic drugs (i.e. the histone H3K27 demethylase inhibitor GSK-343 and the histone deacetylase inhibitor panobinostat) improves the migration of these cells and their capacity to form capillary-like networks while also increasing their resistance to serum starvation-induced apoptosis. Furthermore, the kinetic of blood flow recovery is significantly increased upon transplantation of drug-treated ECFCs in a pre-clinical model of hind-limb ischemia. Gene expression profiling by RNA-sequencing reveals that these effects are mediated through the simultaneous activation of several major pro-angiogenic signaling pathways including VEGFR, CXCR4, WNT, NOTCH and SHH. At the molecular level, we provide evidence that the two drugs work through complementary mechanisms that entail the resolving of bivalently marked genes characterized by the presence of both negative (H3K27me3) and positive (H3K4me3 and H3-Ac) histone modifications to create a transcriptionally permissive chromatin environment. Thus, ex vivo treatment with epigenetic drugs increases the vascular repair properties of ECFCs through transient activation of major pro-angiogenic signaling pathways. Overall design: ECFCs mRNA profile after treatment with GSK-343 and panobinostat epigenetic drug combiantion	Co-expression
SRP074198	Gene expression profiling of melanoma cell lines by RNASeq	Panel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines	Co-expression
SRP074202	Temporal comparison of transcriptomic alterations in human, mouse and rat primary B lymphocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)	RNA-Seq was used to analyze and compare temporal TCDD-induced gene expression changes in primary human, mouse and rat B cells. Most of the differentially expressed genes exibited species-specific expression. Cross-species comparison identified 28 orthologs commonly deregulated in all 3 species.  The study provides new insight into mechanisms of TCDD-induced suppression of B cell effector function. Overall design: Primary human, mouse, and rat mRNA profiles of primary B cells treated with either vehicle (0.02% DMSO) or 30nM TCDD for 4, 8, and 24h  were generated by sequencing.  Human B cell treatments was performed in triplicate while primary B cells from 20 mice or 6 rats were pooled.	Co-expression
SRP074235	Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor ß (ERß) Response to 5a-reductase Inhibition in Prostate Epithelial Cells	Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor (AR) driven, inflammatory disorder affecting elderly men, include 5a-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent AR ligand dihydrotestosterone (DHT). Since DHT is the precursor for estrogen receptor ß (ERß) ligands, 5AR inhibitors could potentially limit ERß activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell-adhesion protein E-cadherin by the 5AR inhibitor, dutasteride, requires both ERß and TGFß. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative-feedback loop in TGFß and ERß signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERß action through its effect on the expression of a number of steroidogenic enzymes in the ERß-ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue protective action of ERß. Overall design: Next-generation sequencing (n=3) of shRNA mediated knockdown of COX-2 or scrambled control in BPH-1 prostate epithelial cell line	Co-expression
SRP074237	mRNA expression data from human parthenogenetic haploid ESCs (hPGES), normal ESCs (H9) and human fibroblast	Here we report the derivation of human haploid ESCs from parthenogenetic haploid embryos. We used RNA-seq to compare the gene expression levels among human parthenogenetic haploid ESCs (hPGES), normal human ESCs (H9) and human forskin fibroblasts and identified that these cells  express conventional ESCs pluripotent markers and most maternally imprinted genes were  down-regulated. Overall design: To avoid the influence of diploidized cells on the expression profile, we collected samples from FACS of cells at G1/G0 stage by staining Hochest 33342. We used normal human ESCs and human fibroblast as control. Gene expression profiles of all the cell lines were analysed on illumina Hiseq 2500.	Co-expression
SRP074246	Gene expression changes upon NUSAP1 over- or under-expression in PC-3 or DU145 cells.	By transcriptome (RNA-Seq) analysis of PC-3 or DU145 prostate cancer cell lines over- or under-expressing NUSAP1, we determined genes that become differentially expressed upon expression changes of NUSAP1. Ingenuity Pathway Analysis revealed that the differentially expressed genes correlated with increased tumor progression and are involved in functions that include cancer, cellular movement, and cell morphology Overall design: Lentiviral infections were used to over- or under-express NUSAP1 or controls in triplicate in PC-3 or DU145 cell lines. Seventy-two or ninety-six hours after infection, total RNA was extracted and purified. The sequencing libraries were prepared with the TruSeq RNA Sample Preparation Kit v2 (Illumina) or TruSeq Stranded mRNA Sample Preparation Kit (Illumina) as directed by the manufacturer’s protocol.  Pooled libraries were run on a Hiseq 2000 Sequencing System (Illumina) with 101 base pair single-end reads.	Co-expression
SRP074274	Genetic ancestry and natural selection drive population differences in immune responses to pathogens in humans	Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. 12% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 569 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting eQTL. Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are central to coping with infection. Overall design: Transcriptomic profiles of 503 infected (Listeria and Salmonella) and non-infected samples at 2hr time point.	Co-expression
SRP074286	Targeting MTHFD2 in Acute Myeloid Leukemia	Purpose:  Identify new targets in acute myeloid leukemia (AML). Methods:  MOLM-14 cells were transduced with lentivirus encoding shRNAs targeting MTHFD2 (shMTHFD2 hairpin TRCN0000036553, denoted M5) and control (LacZ, shControl TRCN0000072231). RNA from 6 samples, biological duplicates (LacZ1, LacZ2; M5-1, M5-2) and a technical replicate (LacZ3, M5-3) were sequenced as 50+50 bp paired-end reads using Illumina TruSeq strand specific library. The pool of six samples was sequenced on two lanes of an Illumina HiSeq, generating 101bp paired end reads.  The software package RSEM (Li et al., 2001) was run using Bowtie (version 1.0.0) to align the reads that passed quality filters  to the hg19 GENCODE version 17 (http://www.gencodegenes.org/releases/17.html) transcriptome and to quantify transcript abundance at isoform and gene level. Results: MTHFD2 suppression induces AML differentiation. There was upregulation of well-validated myeloid differentiation genes and gene sets consistent with myeloid maturation. Conclusion: Our study supports the therapeutic targeting of MTHFD2 in AML. Overall design: mRNA profiles of  shMTHFD2 and shControl  MOLM-14 cells  were generated by deep sequencing, in triplicate, using Illumina TruSeq library.	Co-expression
SRP074291	Transcriptome analysis of MR1 reactive T cells	MHC class I-related molecule MR1 presents riboflavin-derived microbial metabolites and folate-derivatives to mucosal-associated invariant T cells, but it is unknown whether MR1 can bind alternative antigens that stimulate other T cell lineages. Here we report that human T cells displaying diverse TCR-a and ß chains recognize MR1-expressing cells in the absence of microbial ligands and respond to recombinant MR1 molecules loaded with antigens extracted from stimulatory targets. Transcriptome analysis revealed functional heterogeneity of MR1-reactive T cells (MR1T cells), which displayed differential expression of various transcription factors regulating T cell polarization, proliferation and apoptosis. Accordingly, MR1T cells displayed multiple profiles of chemokine receptor expression and secreted variable combinations of cytokines and growth factors, suggesting a diversity of immunological roles across numerous tissues. Functionally, MR1T cells were capable of inducing dendritic cell maturation and stimulating  anti-microbial responses in intestinal epithelial cells. These data demonstrate that MR1 presents endogenous antigens to a novel population of functionally diverse human T cells. Overall design: mRNA profiles of two representative MR1T cell clones in resting (not exposed to antigen) and activated (stimulated with A375-MR1 antigen target cells and activated) states	Co-expression
SRP074298	Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros	The production of definitive haematopoietic stem/progenitor cells from human pluripotent stem cells (hPSCs) remains a significant challenge. Using reporter lines to track the endothelial (SOX17) to haematopoietic (RUNX1C) transition, we found that hPSC differentiated in growth factor supplemented serum free medium generated RUNX1C+CD34+ clonogenic cells that homed to the bone marrow, but did not engraft. Compared to repopulation-competent cord blood CD34+ cells, RUNX1C+CD34+ progenitors lacked HOXA gene expression, indicating incorrect mesoderm patterning. This deficiency was ameliorated by a timed pulse of WNT activation combined with ACTIVIN antagonism. Significantly, these HOXA+ cultures now formed complex SOX17+ vessels that produced fetal liver-like haematopoietic cells, similar to the human aorta-gonad-mesonephros (AGM). Comparison of transcriptional profiles of these nascent haematopoietic stem/progenitors with cells isolated from human AGM confirmed significant similarities, consistent with the assignment of our in vitro generated cells to the definitive human haematopoietic lineage. Our findings argue that HOXA codes established early in differentiation predict cellular potential and provide correct cell patterning for the specification of definitive haematopoietic lineages from hPSCs. Overall design: mRNA profiles of 26 samples were obtained for 5 different cell populations and 2 different treatments.	Co-expression
SRP074299	A single-cell transcriptome atlas of the human pancreas	To understand organ (dys)function it is important to have a complete inventory of its cell types and the corresponding markers that unambiguously identify these cell types. This is a challenging task, in particular in human tissues, because unique cell-type markers are typically unavailable, necessitating the analysis of complex cell type mixtures. Transcriptome-wide studies on pancreatic tissue are typically done on pooled islet material. To overcome this challenge we sequenced the transcriptome of thousands of single pancreatic cells from deceased organ donors with and without type 2 diabetes (T2D) allowing in silico purification of the different cell types. We identified the major pancreatic cell types resulting in the identification of many new cell-type specific and T2D-specific markers. Additionally we observed several subpopulations within the canonical pancreatic cell types, which we validated in situ. This resource will be useful for developing a deeper understanding of pancreatic biology and diabetes mellitus. Overall design: Human cadaveric pancreata were used to extract islets of Langerhans, which were kept in culture until single-cell dispersion and FACS sorting. Single-cell transcriptomics was performed on live cells from this mixture using CEL-seq or on cells stained for CD63, CD13, TGFBR3 or CD24 and CD44. The RaceID algorithm was used to identify clusters of cells corresponding to the major pancreatic cell types and to mine for novel cell type-specific genes as well as subpopulations within the known pancreatic cell types.	Co-expression
SRP074342	FOXO1 is an oncogenic mediator in AML1-ETO leukemia	Transcriptome analysis by RNAseq of human CD34+ hematopoietic stem and progenitor cells transduced with empty vector control(MIT), AML1-ETO (AE), wildtype FOXO1 (F WT) or FOXO1 DNA binding deficient mutant (F DB). We find wildtype FOXO1 partially recapitulates gene signature of AML1-ETO Overall design: Human CD34+ hematopoietic stem and progenitor cells from three donors were transduced with retrovirus expressing MIT, AE, F WT or F DB. Transduced cells were sorted at day 5 after transduction, RNA was collected for RNAseq.	Co-expression
SRP074343	Silencing of KDM2B leads to deregulation of apoptosis related genes in GBM	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer protein that can specifically kill tumor cells while sparing healthy ones. Emerging evidences suggest that TRAIL resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at the epigenetic level is not understood. In this study, we aimed to identify novel epigenetic mechanisms regulating TRAIL response in Glioblastoma Multiforme (GBM) by a short-hairpin RNA (shRNA) screen. We employed an shRNA-mediated loss of function approach to interrogate the role of 48 genes in DNA and histone modification pathways. From this we identified KDM2B, an H3K36-specific demethylase, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity, the activation of Caspase-8, Caspase-3, Caspase-7, and cleavage of PARP. KDM2B knockdown also accelerated the apoptosis process, as revealed by live cell imaging experiments. Moreover, simultaneous knockdown of the methyltransferases responsible for generating the histone marks removed by KDM2B significantly recovered the cell death phenotype observed with KDM2B inhibition. To decipher the downstream molecular pathways regulated by KDM2B, levels of apoptosis-related genes were examined by RNA-sequencing and quantitative PCR upon KDM2B loss, which revealed de-repression of pro-apoptotic genes HRK, caspase-7, and DR4 and repression of anti-apoptotic gene Mcl-1. The apoptosis phenotype was dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. In vivo, KDM2B-silenced tumors exhibited slower growth and reduced angiogenic capacity compared to controls. Taken together, our findings suggest a novel mechanism regulating apoptotic response, where the key apoptosis components are under epigenetic control of KDM2B in GBM cells. Overall design: mRNA profiles of U87MG GBM cells transduced either by control shRNA or shRNA targeting KDM2B were generated by RNA-seq (Illumina HiSeq 2500). 2 biological replicates of shControl and shKDM2B total RNAs were barcoded individually and deep sequenced as 3 technical replicates each in 3 lanes.	Co-expression
SRP074349	Next Generation Sequencing (RNAseq) of non-small cell lung cancer	Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small cell lung cancer (NSCLC), we compared RNAseq data of 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the CTdatabase, 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase. Cluster  analysis revealed that CTA expression is histology-dependent and concurrent expression is common. Immunohistochemistry confirmed tissue specific protein expression of selected genes. Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from the Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer, was not confirmed, neither in our RNAseq-cohort nor in an independent meta-analysis of 1117 NSCLC cases. Overall design: Fresh frozen tumor tissue from 199 patients diagnosed with NSCLC and surgically treated 2006-2010 at the Uppsala University Hospital, Uppsala, Sweden and 19 paired normal lung tissues. Clinical data were retrieved from the regional lung cancer registry. Several of the new CTAs are poorly characterized Sample characteristics values represent; pTNM: decided by Hans Brunnström, pathologist in Lund Spring 2013 Stage according to pTNM: 1=1a 2=1b 3=2a 4=2b 5=3a 6=3b 7=IV Histology diagnosis spring 2013 HB: 1=squamous cell cancer 2=AC unspecified 3=Large cell/ NOS Surgery date: the date when sample arrived at Patologen UAS Age: age when surgery was performed Vital date: day of death or latest contact Dead: 0=no 1= yes Smoking history : 1=current 2=ex >1year 3=never WHO performance status: Performance status 0-4 Please note that the L608T_2122, L771T_1 data columns (in the processed data files) are associated with L608T and L771T samples, respectively.	Co-expression
SRP074369	circRNA-sequencing	circRNA sequencing for 6 samples Overall design: Examing 2 conditions, each with 3 replicates	Co-expression
SRP074415	Gene expression in BRAFV600E thyrocyte	To evaluate SASP in an in vitro model, we analyzed the gene expression profile of BRAFV600E-induced OIS thyrocytes by RNA sequencing  and detected an increase in SASP expression. Overall design: Examination of 2 different BRAFV600E-induced thyroctes, each compared with Control thyrocte.	Co-expression
SRP074418	RNASeq of 4SU labelled nascent RNA in MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946	Central to the molecular pathogenesis of MLL leukaemia is the abnormal co-optation of members of transcription complexes including disrupter of telomeric silencing 1-like (DOT1L) and bromodomain containing protein 4 (BRD4). Consequently, targeted therapies against DOT1L and BRD4 are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukaemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation we find that native BRD4 and DOT1L exist in largely separate protein complexes. Genetic disruption or small molecule inhibition of BRD4 and DOT1L shows marked synergistic activity against MLL-FP leukaemia cell lines, primary human leukaemia cells and murine leukaemia models. Mechanistically, we find a previously unrecognised functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in close proximity to superenhancers. DOT1L via H3K79me2 facilitates the deposition of histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide novel insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this poor prognostic disease. Overall design: RNASeq of 4SU labelled nascent RNA in MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946 in duplicate	Co-expression
SRP074420	RNASeq of MV4;11 cells transduced with scramble shRNA or BRD4 shRNA in combination with DMSO or SGC0946	Central to the molecular pathogenesis of MLL leukaemia is the abnormal co-optation of members of transcription complexes including disrupter of telomeric silencing 1-like (DOT1L) and bromodomain containing protein 4 (BRD4). Consequently, targeted therapies against DOT1L and BRD4 are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukaemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation we find that native BRD4 and DOT1L exist in largely separate protein complexes. Genetic disruption or small molecule inhibition of BRD4 and DOT1L shows marked synergistic activity against MLL-FP leukaemia cell lines, primary human leukaemia cells and murine leukaemia models. Mechanistically, we find a previously unrecognised functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in close proximity to superenhancers. DOT1L via H3K79me2 facilitates the deposition of histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide novel insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this poor prognostic disease. Overall design: RNASeq of MV4;11 cells transduced with scramble shRNA or BRD4 shRNA in combination with DMSO or SGC0946 in triplicate	Co-expression
SRP074426	Biased Expression of the FOXP3?3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance	This study shows for the first time that the FOXP3?3 isoform is preferentially expressed in bladder cancer and induces a more aggressive and luminal isoform is preferentially expressed in bladder cancer and induces a more aggressive and luminal regulation of cancer differentiation and the plasticity amongst cancer subtypes which can be leveraged to optimize therapeutic regimens. These findings also identify a novel molecular marker as a putative companion diagnostic to guide therapy and target to undermine chemotherapy resistance. Overall design: examination of RNA-Seq in two bladder cancer cell lines	Co-expression
SRP074429	RNA Methyltransferase METTL14 Promotes Breast Cancer Growth and Progression	We investigated the role of RNA N6-adenosine methyltransferase protein METTL14 that supports breast cancer growth and progression, and we showed METTL14 knockdown inhibited long-term survival, migration as well as invasion of breast cancer cells. Overall design: To understand the mechanism by which METTL14 may promote breast cancer growth, we performed RNA-seq analyses on METTL14 siRNA-transfected breast cancer cells (2x MDA-MB-231), comparing to cells transfected with scramble siRNAs (2 replicates). Interestingly, several genes known to be associated with oncogenic pathways were found to be significantly altered in METTL14-silenced breast cancer cells, including transforming growth factor beta1 (TGFß1), smad3, cyclin D1 and cyclin E1.	Co-expression
SRP074435	Identification of ZEB1-regulated gene expression changes in HCC827 human lung adenocarcinoma cells	We performed next-generation RNA sequencing for HCC827 human lung adenocarcinoma cells that are stably transfected with pcDNA3.1-ZEB1 or an empty pcDNA3.1 vector plasmid, in triplicate for each of the two HCC827 cell transfectants. The goal of this experiment is to identify putative downstream mediators of ZEB1 in human lung cancer cells. By successfully acquiring about 25 million reads for each sample, we identified more than 1,700 transcripts that are significantly regulated by ZEB1 (increased or decreased by ZEB1; p < 0.05). Among these genes, 87 of them are predicted direct targets for microRNA-200c, a well-established transcription target of ZEB1. Our results will be useful for further identification of genes that mediate the biological functions of ZEB1 in human lung cancer cells. Overall design: Examination of gene expression differences between HCC827 cells expressing pcDNA3.1-ZEB1 and empty pcDNA3.1 vector by next-generation RNA sequencing	Co-expression
SRP074464	RNA-seq analysis of BAP18 knockdown in prostate cancer cell line 22Rv1	BPTF associated protein of 18kDa (BAP18) has been reported as a component of MLL1-WDR5 complex. However, BAP18 is an uncharacterized protein. The detailed biological functions of BAP18 and underlying mechanisms have not been defined. Androgen receptor (AR), a member of transcription factor, plays an essential role in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) progression. Here we demonstrate that BAP18 is identified as a coactivator of AR and facilitates the recruitment of MLL1 subcomplextoAR target genes. Knockdown of BAP18 attenuates cell growth and proliferation of PCa cells. Moreover, BAP18 depletion results in inhibition of xenograft tumor growth in mice even under androgen-depletion conditions. Our data suggest that BAP18 as an epigenetic modifier regulates AR-induced transactivation and the function of BAP18 might be targeted in human PCa to promote tumor growth and progression to castration-resistance. Overall design: 22Rv1 cells carrying shBAP18 or shCtrl were cultured in hormone-free medium for 48 hours and then treated with or withoutDHT (10nM) for 24 hours prior to RNA-seq assays.	Co-expression
SRP074476	A Novel RNA Sequencing Data Analysis Method for Cell Line Authentication	We have developed a novel analysis method that can interrogate the authenticity of biological samples used for generation of transcriptome profiles in public data repositories. The method uses RNA sequencing information to reveal mutations in expressed transcripts and subsequently confirms the identity of analysed cells by comparison with publicly available cell-specific mutational profiles. Cell lines constitute key model systems widely used within cancer research, but their identity needs to be confirmed in order to minimise the influence of cell contaminations and genetic drift on the analysis. Using both public and novel data, we demonstrate the use of RNA-sequencing data analysis for cell line authentication by examining the validity of COLO205, DLD1, HCT15, HCT116, HKE3, HT29 and RKO colorectal cancer cell lines. We successfully authenticate the studied cell lines and validate previous reports indicating that DLD1 and HCT15 are synonymous. We also show that the analysed HKE3 cells harbour an unexpected KRAS-G13D mutation and confirm that this cell line is a genuine KRAS dosage mutant, rather than a true isogenic derivative of HCT116 expressing only the wild type KRAS. This authentication method could be used to revisit the numerous cell line based RNA sequencing experiments available in public data repositories, analyse new experiments where whole genome sequencing is not available, as well as facilitate comparisons of data from different experiments, platforms and laboratories. Overall design: RNA-sequencing of three colorectal cancer cell lines (HCT116, HKE3 and RKO) with either three (HCT116, RKO) or four (HKE3) replicates each.	Co-expression
SRP074481	Bladder tumor sequencing	Prospective sequencing of a patient''s bladder tumor Overall design: We obtained fresh tissue from a patient''s bladder tumor and performed whole-exome sequencing and RNA-Seq Only the RNA-Seq data is being made available through GEO. The whole exome data will be submitted to dbGaP for controlled access.	Co-expression
SRP074494	RNA-seq of hESC samples upon loss of UPF1.	Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-b and BMP signaling, which we found NMD acts through to influence definitive endoderm vs. mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages. Overall design: Examination of differential gene expression in hESCs upon loss of UPF1.	Co-expression
SRP074544	Transcriptome quantification using EXB molecular barcodes in bulk and single cell samples	The study goals are to utilize error-correcting molecular barcodes to accurately quantify transcriptomes. Conventional RNA-Seq studies with small input amounts suffer from amplification artifacts that impact downstream analyses. Random nucleotide barcodes have been used as a marker for unique molecules, but errors during PCR and sequencing negatively impact the quantification accuracy. We use error-correcting molecular barcodes to mitigate these errors and apply them to bulk mRNA and single cell transcriptomes.	Co-expression
SRP074600	MicroRNA-28 replacement for non-Hodgkin lymphoma therapy	Our studies identify the role of mIR-28 in germinal center response and its therapeutic potential for the treatment of non-Hodgkin lymphomas Overall design: The effect of miR-28 expression in the transcriptome was analyzed in Ramos Burkitt B cells by RNASeq.	Co-expression
SRP074715	Homo sapiens Primary Cell Raw sequence reads	Deep RNA sequencing of early passage primary cells and cortical (CNeuron) and dopaminergic neurons (DNeuron) derived from H1 embryonic stem cells to investigate transposable element transcription.	Co-expression
SRP074736	Transcriptional profiling reveals monocyte signature associated with JIA patient poor response to methotrexate	The mechanisms that determine the efficacy or inefficacy of methotrexate in juvenile idiopathic arthritis (JIA) are ill-defined.  The objective of this study was to identify a gene expression transcriptional signature associated with poor response to MTX in patients with JIA. RNA sequencing was used to measure gene expression in peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls. Biological differences between all JIA patients and controls were explored by constructing a signature of differentially expressed genes. Unsupervised clustering and pathway analysis was performed. Transcriptional profiles were compared to a reference gene expression database representing sorted cell populations, including B and T lymphocytes, and monocytes. A signature of 99 differentially expressed genes (Bonferroni-corrected p<0.05) capturing the biological differences between all JIA patients and controls was identified. Unsupervised clustering of samples based on this list of 99 genes produced subgroups enriched for MTX response status. Comparing this gene signature to reference signatures from sorted cell populations revealed high concordance between the expression profiles of monocytes and of MTX non-responders. CXCL8 (IL-8) was the most significantly differentially expressed gene transcript comparing all JIA patients to controls (Bonferroni-corrected p=4.12E-10). Variability in clinical response to methotrexate in JIA patients is associated with differences in gene transcripts modulated in monocytes.  These gene expression profiles may provide a basis for biomarkers predictive of treatment response. Overall design: Peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls	Co-expression
SRP074739	Ileal pouch transcriptomics reveal shared pathogenesis between pouchitis and ulcerative colitis	UC pouchitis is a potential model of UC. We prospectively examined the pouch transcriptomes of UC and familial adenomatous polyposis (FAP) IPAA patients to unveil molecular mechanisms of UC pouchitis susceptibility. Methods: Total RNA was isolated using the AllPrep DNA/RNA Mini Kit (QIAGEN, Cat No. 8020). RNA quality was evaluated using Bioanalyzer (Agilent, Santa Clara, CA). All RNA samples displayed RNA Integrity Number (RIN) >7. RNAseq including cDNA library preparation was processed at the Genomics Core Facility of University of Chicago (https://fgf.uchicago.edu/). Total RNA in the amount of 100-500µg per sample was depleted of ribosomal RNA using the Ribo-Zero kit (Epicentre, Madison, WI). The directional (first strand) cDNA libraries were prepared following the guide of TruSeq Stranded Total RNA Sample Preparation kit. Results: Unlike FAP patients, UC subjects exhibited a large set of differentially expressed genes (DEGs) between pouch and pre-pouch mucosa as early as 4 months after pouch functionalization. Functional pathway analysis of DEGs in UC pouch revealed: (1) Gain of colon-associated gene expressions and loss of ileum associated gene expressions, (2) enhanced state of immune/inflammatory response, and (3) suppressed xenobiotic, lipid, and bile acid metabolic pathways. These changes were corroborated upon reanalysis of a published larger cross-sectional study of UC and FAP patients. Moreover, >70% of DEGs mapped to published IBD and normal colonic microarray datasets displayed directional changes consistent with active UC, but not Crohn''s disease. Conclusions: UC patients exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease. The transcriptome alterations provide insights into pouchitis Overall design: Seventeen patients with UC and four patients with FAP were recruited at the University of Chicago and the Mayo Clinic Rochester. All patients underwent a total proctocolectomy with ileal pouch anal anastomosis (IPAA) as a standard of care. UC patients underwent a pouchoscopy for biopsy of the pre-pouch ileum and pouch at 4 months, 8 months, and 12 months after ileostomy closure. None of these patients had pouchitis.	Co-expression
SRP074749	Unexpected Innovative Early Diagnosis in Autism Spectrum Disorder: Premature Tooth Eruption in ADNP-Mutated Children	The discovery of activity-dependent neuroprotective protein (ADNP) regulated tooth eruption in mice and man, provides, for the first time, an early detection of tooth eruption, with full or almost full mouth of teeth at one year of age, as a potential biomarker for an intellectual disability (ID)/autism spectrum disorder (ASD) syndrome, toward improved translational medicine. Overall design: RNAseq of 4 samples, comparing three ADNP-mutated lymphoblastoid cell lines (LCLs, derived from ADNP-mutated children) with a non-mutated cell line. No replicates were performed but results were verified usign RT-PCR.	Co-expression
SRP074752	RNA-Seq of STAR-PROM Barcodes	We report the application of a massively parallel STAR-PROM assay based on the RNA-seq of 3000+ luciferase barcodes Overall design: U2OS cells are transfected with luciferase library, treated with different drugs, and RNA is collected at different time points. Barcodes are amplified by RT-PCR and sequenced.	Co-expression
SRP074795	Proteogenomic Reveals Biomarkers and Therapeutic Targets in Lymphoid Cancer	Here we find the transcriptional network regulated by ALK oncogenic activitiy in two Anaplastic Large Cell Lymphoma cell lines. Overall design: The role of ALK in regulating the transcriptome of ALK positive ALCL cell lines was studied.	Co-expression
SRP074837	MEIS2 is a novel oncogenic partner in AML1-ETO positive AML [RNA-Seq human]	MEIS2 collaborates with AML1-ETO in inducing acute myeloid leukemia in a murine bone marrow transplantation model Overall design: RNA-seq to evaluate consequence of MEIS2 Knock-down on the transcriptional profle of the t(8;21) positive Kasumi-1 cell line	Co-expression
SRP074852	DNMT and HDAC inhibitors globally induce cryptic TSSs encoded in long terminal repeats	By mapping global transcription start site (TSS) and chromatin dynamics, we observed the activation of thousands of cryptic, currently non-annotated TSSs (TINATS) following DNMTi and/or HDACi treatment. The resulting transcripts encode truncated or chimeric open reading frames that can be translated into products with predicted abnormal functions or immunogenic potential. TINAT activation after DNMTi coincided with DNA hypomethylation and gain in H3K4me3, H3K9ac, and H3K27ac histone marks. In contrast, HDACi induced only canonical TSSs in association with histone acetylation, but TINATs via a yet unknown mechanism. Nevertheless, both inhibitors convergently induced unidirectional transcription from identical sites since TINATs are encoded in solitary long-terminal repeats of the endogenous retrovirus-9 family, epigenetically repressed in virtually all normal cells. Overall design: CAGE-, ChIP-, and WGB-sequencing of NCI-H1299 EGFP-NEO reporter cells after treatment with DMSO, DAC, SB939, or DAC+SB	Co-expression
SRP074894	Mapping heterogeneity in a patient-derived melanoma culture by single-cell RNA-seq	Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy. Overall design: RNA-seq of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively.	Co-expression
SRP074904	Total RNAseq of human putamen and caudate nucleus tissues in healthy control and Bipolar Disorder individuals	A multitude of genes have been associated with bipolar disorder via SNP genotyping studies.  However, many of these associated SNPs are found within intronic or intergenic regions of the human genome.  We were interested in studying transcriptional profiles/splice variation of genes associated with bipolar disorder within the human striatum. Understanding how these associated genes are transcribed in the human brain may help to guide the development of therapeutic agents for the treatment of bipolar disorder and other neuropsychiatric illnesses. Overall design: NEBNext Ultra Directional RNAseq libraries were generated from putamen and caudate nucleus tissues from 4 healthy control individuals and 4 individuals with bipolar disorder.  These libraries were then multiplexed and run on an Illumina HiSeq platform using single read 100bp chemistries.	Co-expression
SRP075000	Analysis of chromosomal aberrations and recombination by allelic bias in RNA-Seq	Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration, and utilizes already available gene expression profiles to determine chromosomal aberrations. Overall design: RNA was extracted from different cell lines and analyzed for chromosomal stability using eSNP-Karyotyping	Co-expression
SRP075002	Convergent roles of ATF3 and CSL in chromatin control of CAF activation [RNA-seq]	Cancer associated fibroblasts (CAFs) play an important role in initiating and promoting epithelial cancers. The specific chromatin modifications involved in CAF activation remain to be elucidated. CSL, a constitutive transcriptional repressor and mediator of canonical Notch signaling, functions as a direct negative regulator of CAF effector genes and suppresses cancer/stromal cell expansion. We find that ATF3, a key stress responsive transcriptional repressor up-regulated in the acute UVA response of skin fibroblasts, is down-modulated in stromal cells of premalignant skin SCC lesions similarly to CSL. Increased ATF3 expression counteracts the consequences of compromised CSL, binding to a large set of overlapping target genes. At low basal levels, ATF3 converges with CSL in negative control of CAF activation, binding to a very small number of genomic loci that encompass mostly non-coding RNAs and pseudogenes. Silencing of ATF3 results in chromatin modifications and Pol II recruitment to many loci to which ATF3 does not bind, which are similarly affected by CSL silencing. The observed changes are of functional significance, as Bet inhibitors, which unlink activated chromatin from the basic transcription apparatus, have opposite effects of ATF3 or CSL silencing on all tested CAF effector genes. They exert a similar impact on clinically-derived CAFs both in vitro and upon topical in vivo treatment. Thus, ATF3 converges with CSL in global chromatin control of CAF activation with their loss eliciting epigenetic changes amenable to cancer and stroma-focused intervention. Overall design: Human Dermal Fibroblasts were infected with pInd-ATF3 viruses and treated for 3 days with doxyciclin at two different doses (100 and 500 ng/ml) in parallel with vehicle for 3 days, followed by RNA-Seq analysis. Human Dermal Fibroblasts were transfected with two different siRNA against ATF3 in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis (DEK32-37). Cancer Associated Fibroblasts were treated with JQ1 (500nM) or vehicle (DMSO) for 48 hours, followed by RNA-Seq analysis (DMSO_1-3, JX_1-3).	Co-expression
SRP075029	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Bulk RNA-Seq validation	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075051	microRNAs with an AAGUGC seed motif constitute an integral part of a signaling network driving NSCLC cell proliferation	miR-372-3p target identification mRNA level Overall design: Differential expression analysis 30h post transfection with miR-372-3p mimics	Co-expression
SRP075061	Transcriptome analysis in HT29 and SW480 cells depleted of Prdx2	Prdx2 is the thioredoxin-dependent peroxidase that reduces H2O2 using reducing power NADPH in the presence of thioredoxin and thioredoxin reductase. Prdx2 plays an important role in growth. factor signaling in mammlian cells. Therefore, we examined the gene expression in colon adenocarcinoma cell line HT29 after Prdx2 depletion. Prdx2 depletion resulted in a significant alteration on gene expression, including protein synthesis, metabolisms, and cell cycle. Overall design: Control-siRNA-transfected versus PRDX2-siRNA-transfected HT29 and SW480 cells	Co-expression
SRP075117	Identification of an NKX3.1-G9a-UTY regulatory network that controls prostate differentiation (Human_RWPE1_RNA-Seq)	Analysis of transcriptome of human RWPE1 cells over-expressing wild type NKX3.1 and mutant NKX3.1 (T164A). Overall design: Total RNA obtained from RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression. Engineered RWPE1 cells were harvested and processed for RNA isolation and transcriptome analysis using the MagMAX RNA isolation kit (Ambion).	Co-expression
SRP075118	Plasma cell mitochondrial pyruvate import controls the duration of humoral immunity.	RNA-sequencing was performed on human CD19- CD138+ bone marrow plasma cells. Overall design: 4 biological replicates of human CD19- CD138+ bone marrow plasma cells and 1 replicate each of naïve, IgM memory, IgG memory, and plasmablasts from peripheral blood.	Co-expression
SRP075211	Regulation of highly expressed hCINAP on translatome	hCINAP is essential for human 18S rRNA processing and ribosome assembly. hCINAP is highly expressed in human cancers and promotes cancer cell growth. To connect the role of hCINAP in ribosome biogenesis and tumor growth, genome-wide polysome profiling was performed to detect the regulation of hCINAP on ribosome assembly and translation control. The results showed taht hihgly expressed hCINAP promotes ribosome biogenesis and selectively modulates cancer-associated translatome to promote malignancy. This result provides important insights into the molecular mechanism underlying the role of hCINAP in tumorigenesis. Overall design: For the transcriptional profile, MCF7 cells transfected with control vector or GFP-hCINAP were collected and total RNA was extracted. For the polysoem profile, MCF7 cells with stably expressed GFP or GFP-hCINAP were subjected to surcose gradient fractionation. Ribosome profiles were obtained by measuring the absorbance of the sucrose gradient at a wavelength of 254 nm using a BioComp Gradient Fractionator. The fractions corresponding to subpolysome and polysome were collected and RNA was extracted. The cDNA library was generated and sequenced via Illumina HiSeqTM 2000. The clean reads were mapped to the UCSC hg19 reference genome and FPKM was assigned to calculate expression levels. The recruitment to polysome of each mRNA was calculated according to their FPKM values in the monsome and polysome.	Co-expression
SRP075227	Homo sapiens Raw sequence reads	SMMC-7721 cells were exposed to 10 µg/mL NCTD or DMSO for 24 h, and then collected for RNA isolation and sequencing.	Co-expression
SRP075236	Identification of histology-correlated intra-tumor genomic heterogeneity through stimulated Raman scattering micro-dissection sequencing	Morphologic and genetic alterations play crucial roles in tumorigenesis, and lay the foundation of diagnosis and cancer research. However, preservation of morphology with staining compromises the genetic materials. Here we propose SMD-Seq, a new approach to achieve consecutive label-free histological images construction and in situ laser micro-dissection of cancer samples for location-specific transcriptome and genome analysis. We applied SMD-Seq to unstained cryosections of human oral squamous cell carcinoma (OSCC) samples. The high quality and purity of genetic materials enabled the discovery of inter- and intra-tumor heterogeneities in both morphology and genetics. The correlative morphologic and molecular analysis of SMD-Seq is capable of dissecting the genetic variation and its effect on gene expression under shape, and provides complementary insights in cancer study.	Co-expression
SRP075248	Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neural Stem Cell Model Systems	Purpose: Use single cell RNA-seq technology on neural epithelial stem cell culture to understand the composition and transcriptome property of the model system. The culture system was then used to study ZIKV infection. Methods: Single cell RNA-seq and bioinformatic analysis on NES cells in culture and single cells from  5-6 post conception week (pcw), 16 pcw, as well as 19-20 pcw human fetal neocortex. Results: We find that NES cells are highly similar to RGCs and neural progenitor cells in terms of their gene expression profile. Both NES cells and neural stem cells/progenitors from fetal neocortex expressed canonical marker genes of proliferating and differentiating neuronal cells. Conclusions: We successfully established the NCX-NES cell culture as an experimental system for the study of neural stem cells and used it to study ZIKV infection Overall design: Single cell RNA-seq of over 1,000 cells of NCX-NES cell culture and fetal brain.  All of the cells in this dataset are non-ZIKV-infected.	Co-expression
SRP075250	Transcriptome sequencing wide functional analysis of human mesenchymal stem cells	Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs LPS. Overall design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2000(101 cycles PE lane).	Co-expression
SRP075253	Gene expression profiling study by RNA-seq for identifying genes associated with epithelial-mesenchymal transition and acquired resistance to ALK inhibitors	Treatment with ALK tyrosine kinase inhibitors often elicits profound initial antitumor responses in ALK fusion-positive patients with lung adenocarcinoma. However, patients invariably develop acquired resistance to ALK inhibitors. In this study, we aimed to identify molecular events that limit the response to ALK inhibition using genetic and epigenetic approaches. To identify novel mechanisms of acquired resistance to ALK inhibitors, we established in vitro models of acquired resistance to ceritinib using H3122 cell. For in vitro model, H3122 parental cells, ceritinib-treated resistant cells, and non-resistant cells that combinely treated with certinib and panobinostat were used for RNA-seq based gene expression profiling. Overall design: RNA-seq data of 6 samples, two H3122 parental cells, two ceritinib-treated resistant cells, and two non-resistant cells that combinely treated with certinib and panobinostat, were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer''s protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x75 bp) using NextSeq 500 platform (Illumina).	Co-expression
SRP075264	Post-transcriptional manipulation of TERC reverses molecular hallmarks of telomere disease	The telomerase RNA component (TERC) is a critical determinant of cellular self renewal. Poly(A)-specific ribonuclease (PARN) is required for post-transcriptional maturation of TERC. PARN mutations lead to incomplete 3' end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing post-transcriptional 3' oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. Inhibition of the noncanonical poly(A) polymerase PAP-associated domain–containing 5 (PAPD5) increased TERC levels in PARN-mutant patient cells. PAPD5 inhibition was also associated with increases in TERC stability, telomerase activity, and telomere elongation. Our results demonstrate that manipulating post-transcriptional regulatory pathways may be a potential strategy to reverse the molecular hallmarks of telomere disease. Overall design: mRNA sequencing of induced pluripotent stem cells and 293 cell line.	Co-expression
SRP075272	Splicing towards noncoding isoforms in colorectal carcinoma is associated with tumor hypoxia and the DNA damage response	Tumor hypoxia is associated with poor patient outcome and resistance to therapy. It is associated with a rapid decline in protein production mediated through mTOR signalling. Here we show that it also leads to widespread changes in splicing and a global shift towards the expression of noncoding isoforms, thus providing a novel and orthogonal mechanism by which cells can modulate protein expression. Overall design: Examination of mRNA levels in HCT116 cells after 0 hr, 1 hr, 2 hr and 24 hr in hypoxia. Three biological replicates each.	Co-expression
SRP075273	RNA-seq analysis of primary patient samples to characterize the CNS leukemia	We present a detailed genetic, transcriptional and physiological study of leukemic cells isolated from the CNS and bone marrows (BM) of both affected children and xenograft model of B-ALL which recapitulate the key features of CNS involvement. We reveal that leukemic cells in CNS possess distinct hypoxic signature such as proliferation suppression, decrease of mitochondrial oxidative phosphorylation and increase of glycolysis compared with leukemic cells in BM. Overall design: We compared the gene expression profiles of leukemic cells isolated from CSF and BM of primary 3 patients (ALL#6-8) with RNA-seq.	Co-expression
SRP075278	An extensive program of periodic alternative splicing linked to cell cycle progression	Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1,300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control. Overall design: By sequencing the human transcriptome through two continuous cell cycles, we identify ~1,300 genes with cell cycle-dependent AS changes.	Co-expression
SRP075289	Uridylation-mediated RNA quality control pathway in mammalian cytoplasm [RNA-Seq]	Uridylation of various cellular RNA species at the 3’ end has been generally linked to RNA degradation. Uridylated pre-miRNAs in mammals and uridylated mRNAs in fission yeast are targeted by the 3' to 5' exoribonuclease DIS3L2. In humans, DIS3L2 mutations have been associated with Perlman syndrome development and Wilms tumor susceptibility. In this work, we employ crosslinking in vivo and immunoprecipitation (CLIP) method to assess the RNA binding capacity of human DIS3L2 on a genome-wide scale. Our study uncovers a broad spectrum of uridylated RNAs in human cytoplasm, which include mature as well as aberrant forms of coding and noncoding RNAs, such as rRNAs, snRNAs, snoRNAs, tRNAs and pre-miRNAs. Most importantly, we have identified that a fraction of Pol II transcription start-site associated transcripts are exported to cytoplasm, where they are targeted by the TUT-DIS3L2 pathway. Moreover, this pathway appears to mainly target RNA regions that form stable secondary structures. Our findings imply the role of DIS3L2 and oligouridylation in general RNA quality control of most, if not all RNA classes. Overall design: RNAseq of total RNA in DIS3L2 D391N mutant (3 replicates) and empty HEK293 cells (3 replicates)	Co-expression
SRP075318	Homo sapiens Transcriptome or Gene expression	Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical testcould not provide efficient information on the causes of spermatogenesis disorder and guide the doctorhow to treat it. More effective diagnosis and treating methods could be developed if the key genesthat regulate spermatogenesis were determined. Many works have been done on animal models,while there are few works on human beings due to the limited sample resources. In current work, testistissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination ofFluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficientmethod to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screenthe change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressedgenes were clustered according to their expression patterns. Gene Ontology annotation, pathwayanalysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patternsand the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation ofspermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted.	Co-expression
SRP075319	RNA-Seq expression profiling of hepatocellular carcinoma and adjacent non-tumor liver tissues	Three pairs of hepatocellular carcinoma and adjacent non-tumor tissues were from 3 male patients suffering from stage I or II HCC with hepatitis C virus background. RNA-Seq libraries were prepared from total RNA using polyA enrichment strategy. The libraries were sequenced on Illumina HiSeq2000 instruments. Overall design: Examination of transcriptome differences between HCC and adjacent non-tumor tissue.	Co-expression
SRP075325	Improved calibration of RNA-seq expression data using whole cell spike-ins	Whole cell spike-in assay which allows to calibrate human RNAseqexpression data to a constant number of sample cells.	Co-expression
SRP075346	Homo sapiens Transcriptome or Gene expression	RNA-seq analysis of 6 WHO grade-II tumors (n=4 with the rs55705857 genotype A/G and n=2 with the genotype A/A) that were IDH1-R132H mutant, 1p/19q co-deleted and ATRX-wild-type.	Co-expression
SRP075354	Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.	RNA sequencing profiling of cumulus cells revealed that the follicles of older women have a compromised environment with hypoxic stress being the main contributor to age-related oocyte quality decay. Overall design: Twenty cumulus cells (CC) samples (from a total of 15 patients) were obtained from oocytes of either male factor or egg donor patients. RNA sequencing and bioinformatic tools were used to identify differentially expressed genes (DEGs) between CCs from seven aged and eight young patients (<35 (years old) y.o. vs >40 y.o.). Quantitative-PCR and immunoflourescent staining were used for validation.	Co-expression
SRP075376	MCF10A H-Ras RNA-Seq	Paired-end sequencing of Vector and H-Ras expressing cell lines: p53-del and WT-p53 We found that activated forms of H-Ras and PIK3CA oncogene lead to repression of p63, a p53 family member. They also lead to induction of EMT, a cancer-related process. Our results suggest that, through Ras regulation of p63, this oncogene can drive mammary epithelial cells towards greater invasive ability. Overall design: 4 samples analyzed with 3 replicates each, control samples for each H-Ras line are the Vector cell line created at the same time	Co-expression
SRP075377	RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes	Pancreatic islet cells are critical for maintaining normal blood glucose levels and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic a-, ß-, d- and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell type specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human a- and ß-cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community. Overall design: Single-cell RNA sequencing of human non-diabetic and type 2 diabetic pancreatic islet cells	Co-expression
SRP075378	Activin/Smad2-induced H3K27me3 reduction is crucial to initiate mesendoderm differentiation of ES Cells	Mesendoderm (ME) differentiation of human embryonic stem cells (hESCs) is directed by various extrinsic signals together with intrinsic epigenetic modifications.  However, the dynamics of epigenetic modifications and their regulation to initiate ME differentiation remain elusive.  In this study, we report that H3K27me3 is decreased during ME initiation, which is essential for the subsequent differentiation by collaborative effects of Activin and Wnt signaling.  Mechanistically, Activin decreases the H3K27me3 level via disruption of the SUZ12-EZH2 interaction and EZH2 degradation mediated by Smad2.  Our data suggest a two-step process of ME initiation: firstly H3K27me3-marked epigenetic priming and secondly transcription activation.  Our findings unravel a critical role of H3K27me3 priming and a direct interaction between extrinsic signals and epigenetic modifications during ME initiation. Overall design: mRNA profile of H1-hESC and treated with Activin A, Wnt3a separately or together for 6h and 24h. Together with H3K27me3 and H3K4me3 profiles of H1-hESC and treated with Activin A, wnt3a seperately or together for 2h and 6h.	Co-expression
SRP075396	Xenograft sequencing to elucidate molecular events following anti-CD44 treatment	We profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system.	Co-expression
SRP075406	Epigenetic siRNA and chemical screens identify SETD8 inhibition as a new therapeutic strategy of p53 reactivation in high-risk Neuroblastoma.	Purpose: The intergration of genetic and chemical screens identified SETD8 as a new druggable target in neuroblastoma tumor. The goal of this study is to evaluate the transcriptome profiling (RNA-seq) of Neuroblastoma cell lines after genetic and pharmacological inhibition of SETD8. Methods: mRNA profiles of NB cells after genetic and pharmacological inhibition of SETD8 were generated by deep sequencing in duplicate with Ilumina HiSeq2500 using Illumina TruSeq V4. The sequence reads were analyzed with software Trimmomatic, STAR and edgeR to determine the differetially expressed genes. qRT–PCR validation was performed using SYBR Green assays. Results:  About 60 million sequence reads per sample were mapped to the human genome (hg19).  Approximately 10% of the transcripts showed differential expression between the control and the treated samples, with a fold change =1.5 and p value <0.05. Altered expression of 12 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to SETD8 function. Conclusions: Our study identifies SETD8 as a new therapeutic target in Neuroblastoma tumor. RNA-seq transcriptome analyses and functional studies revealed that SETD8 ablation rescued the proapoptotic and cell-cycle arrest functions of p53 through reactivation of the p53 canonical pathway by decreasing p53k382me1. Overall design: mRNA profiles of Neuroblastoma cells after genetic and pharmacological inhibition of SETD8 were generated by deep sequencing in duplicate with Ilumina HiSeq2500 using Illumina TruSeq V4.	Co-expression
SRP075415	Transcriptome analysis of virus infected tissues	We report the application of RNA sequencing for transcriptome analysis of virus infected tissues, enabling the study of tissue responses to infection Overall design: Transcriptome analysis of 2 different tissues infected with two different viruses	Co-expression
SRP075430	Homo sapiens Raw sequence reads	In order to validate our method to develop immortalized cellular models of microglia, we used RNA-seq to confirm the microglial phenotype of a representative clone (C20, a clonal population), which derived from the transformation of human primary microglia (human microglia purchased cryopreserved after purification from Sciencell, Cat. #1900). Transformation was carried out with vesicular stomatitis virus G envelop simian virus 40 large T antigen viral particles (VSVG SV40), containing the pBABE-puro SV40 LT construct (Addgene, Plasmid #13970), followed by VSVG containing the human telomerase reverse transcriptase (hTERT)-neomycin (pBABE-neo-hTERT) construct (Addgene, Plasmid #1774). Immortalized cells were selected in the presence of 2 µg/mL puromycin and 600 µg/mL neomycin. Individual clonal populations, including clone C20, were allowed to grow for approximately 4 weeks prior to further testing. In addition, we also used RNA-seq to verify the capacity of these cellsto respond to an inflammatory stimulus (TNF-a).	Co-expression
SRP075449	Nuclear Surveillance of long intervening noncoding RNA	Numerous long intervening non-coding RNA (lincRNA) are generated from the mammalian genome by RNA polymerase II (Pol II) transcription.  Although multiple functions have been ascribed to lincRNA, their synthesis and turnover remain poorly characterised. Here we define systematic differences in transcription and RNA processing between protein-coding and lincRNA genes in human HeLa cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing (mNET-seq). Notably mNET-seq patterns specific for different Pol II CTD phosphorylation states reveal weak co-transcriptional splicing and poly(A) signal independent Pol II termination on lincRNA as compared to pre-mRNA. In addition, lincRNA are mostly restricted to chromatin where they are co-transcriptionally degraded by the RNA exosome. We also show that a lincRNA specific co-transcriptional RNA cleavage mechanism acts to induce premature termination. In effect functional lincRNA must escape from this targeted nuclear surveillance process. Overall design: We employed CTD phospho specific mNET-Seq with pla-B splicing inhibitor and RNA processing factors knockdown (DGCR8, Dicer1, EXOSC3 and CPSF73 proteins). mNET-seq experiments with 1% Empigen detergent treatment were performed to separate Pol II-associated complex from Pol II. We also analyzed subcellur RNA and  pA+ and pA- nucleoplasm RNA libraries for RNA processing efficiency and the turnover. There are 4  raw files come from an illumina experiment (per sample), produced in 2 lanes. They were all mapped together.	Co-expression
SRP075467	Characterisation of EZH2-deficient human embryonic stem cells [single cell RNA-seq]	Here we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null)  and EZH2+/+ (WT) human ESC	Co-expression
SRP075475	Multilineage communication regulates human liver bud self-organization from pluripotency I	Conventional 2-D differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. 3-D organoids generate complex organ-like tissues, however it is unclear how heterotypic interactions impact lineage identity. Here we use single-cell RNA-seq to reconstruct hepatocyte-like lineage progression from pluripotency in 2-D culture. We then derive 3-D liver bud (LB) organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during LB self-organization. We find that LB hepatoblasts differentiate towards hepatocyte fate, and in addition express epithelial migration signatures characteristic of organ budding. We identify hypoxia and inflammation signatures in endothelial and mesenchymal cells, which we suggest induce LB vasculogenesis. We use network analysis to predict autocrine and paracrine signaling in LBs, and show that VEGF crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals inter-lineage communication that is required for self-organization, and illuminates previously inaccessible aspects of human organ development and regeneration. Overall design: Single-cell transcriptomes from multiple time points during hepatocyte-like lineage progression from pluripotency in 2-D culture, and from 3-D liver bud (LB) organoids that self-organized after reconstituting hepatic, stromal, and endothelial interactions.	Co-expression
SRP075478	Targeting Taxane-Platin Resistant Lung Cancers with JumonjiC Lysine Demethylase Inhibitors (RNA-Seq)	Characterization of gene expression changes upon development of taxane-platin drug resistance in NSCLC cells and further, upon treatment of these resistant cells with the Jumonji KDM inhibitor, GSK-J4. Overall design: Comparison of gene expression changes between H1299 Parental cells (chemo-sensitive) and H1299 T18 cells (taxane-platin resistant), and comparison of H1299 T18: GSK-J4 treated vs. H1299 T18: DMSO control.	Co-expression
SRP075484	Epigenetic targeting of immunocheckpoint PD-L1 by BET bromodomain inhibition	Epigenetic regulators have emerged as exciting targets for cancer therapy.  Additionally, restoration of antitumor immunity by blocking the PD-L1 signaling using antibodies has proven to be beneficial in cancer therapy. Here we show that BET bromodomain inhibition suppresses PD-L1 expression and restores antitumor immunity in ovarian cancer. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription.  In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of antitumor cytotoxic T cells. Together, these data demonstrate an epigenetic approach to block PD-L1 signaling to restore antitumor immunity. Given the fact that BET inhibitors have been proven safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a novel treatment strategy for targeting PD-L1 expression. Overall design: RNA-seq for JQ1 treated and shBRD4 knockdown cells with controls	Co-expression
SRP075496	Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns.	As organisms age, cells accumulate genetic and epigenetic changes that eventually lead to impaired organ function or catastrophic failure such as cancer. Here we describe a single-cell transcriptome analysis of 2544 human pancreas cells from donors, spanning six decades of life. We find that islet cells from older donors have increased levels of disorder as measured both by noise in the transcriptome and by the number of cells which display inappropriate hormone expression, revealing a transcriptional instability associated with aging. By analyzing the spectrum of somatic mutations in single cells from previously-healthy donors, we find a specific age-dependent mutational signature characterized by C to A and C to G transversions, indicators of oxidative stress, which is absent in single cells from human brain tissue or in a tumor cell line. Cells carrying a high load of such mutations also express higher levels of stress and senescence markers, including FOS, JUN, and the cytoplasmic superoxide dismutase SOD1, markers previously linked to pancreatic diseases with substantial age-dependent risk, such as type 2 diabetes mellitus and adenocarcinoma. Thus, our single-cell approach unveils gene expression changes and somatic mutations acquired in aging human tissue, and identifies molecular pathways induced by these genetic changes that could influence human disease. Also, our results demonstrate the feasibility of using single-cell RNA-seq data from primary cells to derive meaningful insights into the genetic processes that operate on aging human tissue and to determine which molecular mechanisms are coordinated with these processes. Overall design: Examination of single cells from primary human pancreas tissue	Co-expression
SRP075535	Single cell gene expression profiling in normal HSCs and CML stem cells	CML stem cells (CMLSCs) and normal hematopoietic stem cells (HSCs) display the same set of surface markers (CD34+CD38-CD90+CD45RA-), making it infeasible to separate these two populations within the same sample. To overcome this challenge, and to minimize variations in gene expression due to individual variation, here we perform single-cell RNA-seq to compare expression profiles of CMLSCs and HSCs isolated from the same patient. We captured ~600 HSCs (CD34+CD38-CD90+CD45RA-) (~200 from each of three CML patient samples), separated them into CMLSCs (BCR-ABL+) or normal HSCs (BCR-ABL-) based on the presence of the BCR-ABL transcript, and performed paired-end deep sequencing. Typically, we obtained ~2.5 million mapped reads (>70% average mapping efficiency) and detected ~5,000 genes (transcript per million [TPM]>1) per cell. Despite the heterogeneity of the gene expression pattern, we were able to identify genes that were significantly more highly expressed in CMLSCs than in normal HSCs. Notably, among these genes are two cell surface markers, CD33 and CD47, that could potentially be used to distinguish CMLSCs from normal HSCs. We also found genes, such as PIM2, that could be targeted for CML therapy using available small molecule inhibitors. Overall design: Hematopoietic stem cell population from three chronic phase CML patients with no detectable BCR-ABL mutation.	Co-expression
SRP075555	FRY Inhibits Breast Cancer Progression and Metastasis through Activation of the Hippo/Yap Kinase Cascade	No description.	Co-expression
SRP075557	Raw sequence reads	RNA seq of three cell lines after mimics over-expression miRNA	Co-expression
SRP075564	Homo Sapiens and Mus musculus Transcriptome of Multiple Myeloma before and after LCL161 Treatment	Study the role of LCL161 in treating Multiple Myeloma in a murine and human co-clinical trial	Co-expression
SRP075565	ZBTB33 (Kaiso) Differentially Regulates Cell Cycle Through cyclin D1 and cyclin E1 in a Cell Specific Manner [RNA-seq]	The emerging correlation between aberrant DNA methylation patterns leading to transcriptional responses that promote and progress many cancers has prompted an interest in discerning the associated regulatory mechanisms. ZBTB33 (also known as Kaiso) is a specialized transcription factor that selectively recognizes mCpG-containing sites as well as a sequence-specific DNA target (termed the KBS) utilizing three Cys2His2 zinc fingers. Increasing reports link ZBTB33 overexpression and transcriptional activities with metastatic potential and poor prognosis, though the specific cellular consequences appear to be dependent on disease phenotype. There is currently little mechanistic insight into how various cellular phenotypes are then able to harness the transcriptional capabilities of ZBTB33 to differentially promote and progress the disease state. Here we have mechanistically interrogated the cell cycle responses mediated by the transcriptional activities of ZBTB33 in two different cell lines. Utilizing a series of ZBTB33 depletion and overexpression studies, we have determined that in HeLa cells ZBTB33 directly occupies the promoter regions of cyclin D1 and cyclin E1 in a KBS and methyl-specific manner, respectively, inducing increased proliferation by promoting RB1 hyper-phosphorylation, allowing for E2F transcriptional activity that coordinates an accelerated G1- to S-phase transition. Conversely, in HEK293 cells ZBTB33 indirectly regulates Cyclin E abundance resulting in reduced RB1 phosphorylation, decreased E2F activity and a decelerated transition through G1-phase. Thus, we have identified a novel mechanism by which ZBTB33 directly mediates the highly coordinated cyclin D1/cyclin E1/RB1/E2F signaling pathway controlling the passage through the G1-phase restriction point and accelerating cellular proliferation in a cancer cell line. Overall design: Determination of cellular and transcriptional consequences for ZBTB33 depletion in HeLa cells.	Co-expression
SRP075578	Regulation of DNA methylation landscape in human somatic cell reprogramming by miR-29 family (RNA-seq)	Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4 and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in iPSCs have been shown to be highly similar with embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern for using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs. Overall design: Bisulphite converted gDNAs of D551 fibroblasts transduced for 3 days with overexpression of DNMTs, TETs, TDG and OSKM or miR29a/b/c and control sponge were hybridized into Illumina Infinium HumanMethylation 450K Beadchip.	Co-expression
SRP075583	Gene expression analysis of C4-2 cells treated with ACLY inhibitor and Enzalutamide	This study examined the gene expression effects of treating androgen-deprived C4-2 prostate cancer cells with the ACLY inhibitor BMS-303141 and the AR antagonist enzalutamide. Overall design: Cells were treated with vehicle control, ACLY inhibitor alone, Enzalutamide alone, and ACLY-inhibitor and Enzalutamide combined together for 24 hours under androgen-depleted conditions (RPMI + 5% charcoal stripped serum). Biological triplicate samples were prepared.	Co-expression
SRP075592	RNA Sequencing of Induced Epithelial-Mesenchymal Transition in Human Breast Cancer Cell Lines.	Human breast cancer cell lines (MDA-MB-468; PMC42 (PMC42-ET and the epithelial PMC42-LA subline) with or without treatments (Epidermal Growth Factor or Hypoxia) inducing epithelial mesenchymal transition (EMT)	Co-expression
SRP075605	Chemical Enhancement of Direct Cardiac Reprogramming In Vitro and In Vivo	Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration.  A combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5 (GMT), can convert fibroblasts into iCMs, albeit with low efficiency in vitro. Here, we screened 5,500 compounds in primary cardiac fibroblasts and found that a combination of the transforming growth factor (TGF)-ß inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency eight-fold when added to GMT-overexpressing cardiac fibroblasts. The small-molecules also enhanced the speed and the quality of cell conversion, as we observed beating cells as early as 1 week after reprogramming compared to 6–8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared to those exposed to only GMT. Human cardiac reprogramming was similarly enhanced upon TGF-b and WNT inhibition and was achieved most efficiently with GMT plus Myocardin. Thus, TGF-ß and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration. Overall design: Examine RNA expression profile in iCMs (mouse in vitro, mouse in vivo and human in vitro)	Co-expression
SRP075608	Next Generation Sequencing Facilitates Quantitative Analysis of HIV-1 Latency in Central Memory T Cells	Purpose: Next-generation sequencing (NGS) has become a powerful microscope to study cell models of HIV.  The goals of this study is to analyze latent HIV infection in the TCM  model of HIV latency described in Martins et al 2015 and to evaluate potential markers for HIV infection. Methods: Peripheral blood mononuclear cells were collected from 4 healthy donors.  Naive CD4 T cells were isolated and utilized to generate a model of latent HIV infection.  During model generation, cells were sorted and collected for RNA extraction 10 days post infection along with their uninfected counterparts.  2 days after this, cells were activated with CD3/CD28 stimulation and collected for study for a total of 16 samples from 4 donors.  After cell collection, RNA was extracted from infected cells and their uninfected counterparts for deep sequencing by Expression Analysis. Sequence reads that passed quality filters were mapped using Tophat and counted using HTSeq.  In addition to human transcripts, we utilized 92 ERCC spikes as negative controls.  Any human gene which did not achieve at least 1 count per million reads in at least 4 samples or any ERCC that did not achieve at least 5 reads in at least 4 samples was discarded.  Differential expression for activated samples was not performed, but rather used to demonstrate upregulation of T-cell activation markers along with changing to the type and abundance of HIV transcripts produced. Results: Using an custom built data analysis pipeline, 82 million reads per sample to the human genome (build hg38) and identified 13,534 human transcripts 67 ERCC spike in transcripts, and HIV NL43 transcripts were identified with the Tophat/HTSeq workflow. Differential expression analysis was performed between uninfected and latently infected cells.  826 genes were found to be differentially expressed, 275 downregulated and 551 upregulated (FDR < 0.05) with EdgeR.  GO and Pathway analysis of differential expressed genes revealed significant dysregulation of genes involved in the p53 signaling pathway.  Subsequent studies with pifithrin demonstrated a reduction in latently infected cell during model generation. Conclusions: This study represents the first detailed analysis of HIV latency with this cell model using next generations sequencing.  These results demonstrate that the TCM model of HIV latency of Martins et al 2015 is truly reflective of HIV latency.  This study also provides a framework for which to analyze future cell models of HIV latency using next generation sequencing.  Finally, this work demonstrates that the p53 signaling pathway is a key pathway dysregulated in latency for this cell model with several genes dysregulated in HIV latency. Overall design: TCM model of HIV latency mRNA profiles of 4 donors in 4 conditions were generated by deep sequencing by Expression Analysis.	Co-expression
SRP075613	Next generation sequencing of esophageal squamous cell carcinoma (ESCC) cell line KYSE-180 single cell transcriptomes for radio-resistance analysis	Purpose: Single cell RNA-seq could observe heterogeneity of cell transcriptomes. The goals of this study are to compare the changes of  ESCC cell line KYSE-180 RNA profiles in response to different doses of radiotherapy and to analyze the radio-resistance related genes. Overall design: Methods: Cultured KYSE-180 cells accepted accumulative irradiation doses of 0 Gy, 12 Gy or 30 Gy, respectively. Single cell libraries were generated by Smart-seq 2 kit, sequenced using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the transcript expression level with TopHat followed by DESeq2/Monocle.	Co-expression
SRP075643	Transcriptome of RA-responsive and RA-resistant breast cancer cell lines	Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Several breast cancer cells respond to the antiproliferative effects of RA, but others are RA-resistant. In several cases resistance has been correlated to the amplification of the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene, but the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here we compared two human breast cancer cell lines, the MCF7 cell line, which responds to the antiproliferative action of RA and the BT474 cell line, which is RA-resistant subsequent to ERBB2 amplification in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated after RA addition. The paradigm of these proteins is the RA receptor a (RARa), which was phosphorylated in MCF7 cells but not in BT474 cells. The panel of the RA-regulated genes was also different. Overall our results indicate that ERBB2 amplification interferes with the ability of RA to activate kinases with consequences on the phosphorylation of several proteins involved in transcription and thus on gene expression. Overall design: Two human breast cancer cell lines were compared for their repertoire of genes regulated by retinoic acid (RA): the RA sensitive MCF7 cell line and the RA resistant B7474 cell line	Co-expression
SRP075645	Glutamine Deficiency Occurs in Regions of Solid Tumours and Promotes Dedifferentiation through Inhibition of Histone Demethylation	We sequenced mRNA from the core regions and the peripheral regions of  melanoma xenograft tumors Overall design: Examination of mRNA levels in samples from core and peripharal regions within the same tumor	Co-expression
SRP075651	RNA-seq analysis of human cardiosphere cells with different tubule supportive potential	RNA-seq analysis of Cardiosphere derived cells from 6 patients, three were good supporters of angiogenesis and three were poor supporters of angiogenesis Overall design: Cardiosphere derived cells were tested for their ability to support HUVEC supportive ability. 6 samples were expanded, RNA isolated and RNA-seq experiments carried out	Co-expression
SRP075704	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Mosaic-Seq of beta-globin locus (pooled infection)	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075705	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Mosaic-Seq of beta-globin locus (separate infection)	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075706	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Mosaic-Seq TNF-alpha treatment versus mock	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075707	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Mosaic-Seq of 15 SEs, 71 HSs, 241 sgRNAs	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075709	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Human/mouse mixing Drop-Seq experiments for K562 and MEFs	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells.	Co-expression
SRP075717	Homo sapiens Raw sequence reads	Post-transcriptional adenosine-to-inosine (A-to-I) RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, oncogenic activators of ADAR1 and RNA-editing dependent mechanisms governing therapy-resistant cancer stem cell (CSC) generation have not been clearly elucidated. Here we show in human blast crisis chronic myeloid leukemia that increased sensitivity to JAK2 signaling and BCR-ABL1 amplification converge on ADAR1 activation. Selective JAK2 and BCR-ABL1 inhibition prevents CSC self-renewal in a humanized BC CML mouse model commensurate with ADAR1 downregulation. While lentiviral ADAR1 induces self-renewal gene expression and impairs biogenesis of stem cell regulatory let-7 microRNAs, an editing defective lentiviral vector, ADAR1E912A, restores let -7 biogenesis. Combined RNA sequencing, qPCR and stromal co-culture data suggest that ADAR1 promotes CSC generation via let-7 pri-microRNA editing and LIN28B upregulation. Also, small molecule tool compound mediated ADAR1 antagonism impairs CSC self-renewal in stromal co-cultures and restores let-7 biogenesis. Thus, ADAR1 editase activation represents a unique therapeutic vulnerability in CSC with active JAK2 signaling	Co-expression
SRP075725	Homo sapiens Raw sequence reads	RNA-seq of NSCLC tissues and paired normal tissues	Co-expression
SRP075759	Hepatic transcriptome of pediatric hepatoblastoma.	The mechanisms underlying hepatoblastoma are not well defined.  To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing.  Hepatoblasoma was histologically confirmed.  Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children. Overall design: Hepatic mRNA profiles of normal (n=3), background (n=6), and hepatoblastoma (n=23) tissues were generated through RNAsequencing using the Illumina HiSeq2500.	Co-expression
SRP075770	Evaluation of the immunogenicity of live-attenuated influenza vaccines in nasal epithelial cells in primary differentiated human nasal epithelial cells [RNA-Seq]	The host innate immune response to influenza virus is a key determinant of pathogenic outcomes and long-term protective responses against subsequent exposures. Comparison of the transcriptional profiles obtained 24 and 36 hrs post-infection showed that the magnitude of gene expression was greater in LAIV infected cells relative to that observed in WT infected cells. Functional enrichment analysis revealed that the antiviral and inflammatory responses was largely driven by type III IFN induction in both WT and LAIV infected cells. However, the enrichment of biological pathways involved in the recruitment of mononuclear leukocytes, antigen presenting cells, and T lymphocytes was uniquely observed in LAIV infected cells. These findings indicate that cell-intrinsic type III IFN-mediated innate immune responses in the nasal epithelium are not only crucial for viral clearance and attenuation, but may also play an important role in the immunogenicity of live-attenuated vaccines Overall design: Differentiated hNECs were infected at a multiplicity of infection (MOI) of 5 50% tissue culture infectious dose per cell.  Prior to infection, cells were apically washed and the basolateral media was refreshed with 500 µl of fresh LHC Basal Medium.  The virus inoculum was added to the apical compartment and incubated for 2 hours, after which the inoculum was aspirated and the apical chamber was washed three times.  The plates were then returned to the incubator. RNA was isolated from Trizol homogenates from samples harvested at 24hpi and 36hpi.  Gene expression microarray analysis was conducted on these samples.	Co-expression
SRP075776	Analysis of polysomal enrichment and depletion of mRNA in untreated and TGF-beta treated MCF-10A and MCF7 cells	We have performed sucrose-gradient-based isolation of polysomal fractions from untreated and TGF-beta treated MCF-10A and MCF7 cells, subjected these fractions to RNA-seq, and also sequenced total mRNA from each cell line in the treated and untreated condition Overall design: Examination of two different cell types in a treated and untreated state	Co-expression
SRP075806	RNA-sequencing of human skeletal myocytes from healthy, obese, and type 2 diabetic subjects	Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). Obesity is tightly associated with T2D, making it challenging to isolate specific effects attributed to the disease alone. By using an in vitro myocyte model system we were able to isolate the inherent properties retained in myocytes originating from donor muscle precursor cells, without being confounded by varying extracellular factors present in the in vivo environment of the donor. We generated and characterized transcriptional profiles of myocytes from 24 human subjects, using a factorial design with two levels each of the factors T2D (healthy or diseased) and obesity (non-obese or obese), and determined the influence of each specific factor on genome-wide transcription. We identified a striking similarity of the transcriptional profiles associated independently with T2D or obesity. Obesity thus presents an inherent phenotype in skeletal myocytes, similar to that induced by T2D. Through bioinformatics analysis we found a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating the observed transcriptional signatures. Functional characterization of the expression profiles revealed dysregulated myogenesis and down-regulated muscle function in connection with T2D and obesity, as well as up-regulation of genes involved in inflammation and the extracellular matrix. Further on, we identified a metabolite subnetwork involved in sphingolipid metabolism and affected by transcriptional up-regulation in T2D. Collectively, these findings pinpoint transcriptional changes that are hard-wired in skeletal myocytes in connection with both obesity and T2D. Overall design: Isolated skeletal muscle precursor cells from 24 males and females (6 normal glucose tolerant, 6 obese, 6 type 2 diabetic, and 6 obese and type 2 diabetic) were differentiated in vitro and stimulated with insulin. RNA from fully differentiated myotubes sampled at 0, 0.5, 1, and 2 hours after insulin stimulation was quantified using RNA-seq (96 samples in total). The 6 base-line (0h) samples from normal glucose tolerant individuals are available under the submission GSE63887, the remaining 90 samples are contained in this submission.	Co-expression
SRP075807	E-cadherin loss induces autocrine activation of oncogenic growth factor signalling in metastatic lobular breast cancer.	Background: Despite the fact that loss of E-cadherin is causal to the development and progression of invasive lobular breast cancer (ILC), no targeted therapy is available to treat this major breast cancer subtype. This study is aimed at identifying clinically targetable pathways that are aberrantly active downstream of E-cadherin loss in ILC. Methods: Reverse-phase protein array (RPPA) analyses were performed in the context of E-cadherin loss using mouse and human breast cancer cells. A combination of mRNA sequencing, conditioned medium growth assays and CRISPR-Cas9 knock-out experiments were performed to identify and validate activation of oncogenic pathways in ILC.  Human ILC samples were employed to validate activation by immunohistochemistry on tissue micro-arrays. Finally, we assessed the effect of pathway inhibition using anoikis resistance and anchorage-dependent growth in vitro. Results: We demonstrate that E-cadherin loss leads to increased activation of FAK and PI3K/AKT signalling. Autocrine activation of growth factor receptor signalling and its downstream PI3K/AKT hub was a direct consequence of E-cadherin loss, independent of activating mutations in either PIK3CA, AKT or PTEN. Analysis of human ILC samples confirmed pathway activity, and pharmacological inhibition of AKT using AZD5363 and MK2206 resulted in robust inhibition of cell growth and survival of ILC cells in anchorage-dependent and independent conditions. Moreover, our results indicate a role for intracellular FAK in the regulation of ILC anoikis resistance. Conclusion: Our data demonstrate that E-cadherin loss evokes additional PI3K/AKT activation independent of oncogenic mutations in this pathway. We propose clinical intervention of PI3K/AKT in ILC based on functional E-cadherin inactivation, irrespective of activating pathway mutations. Overall design: Expression profiling (RNA-seq) of mouse (mILC-1, mILC-2) and human (IPH-926) invasive lobular carcinoma cell lines in adherent and suspension cell culture conditions.	Co-expression
SRP075823	Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures	Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds.  In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel with no known bioactive epitopes, Puramatrixâ„¢, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia.  Statistical analysis of next generation RNA sequencing  data  uncovered a  set  of  genes  that are  differentially  expressed  in  the  monolayer  and  matrix  hydrogel  environments.   Functional  analysis  demonstrated  that  hydrogel-upregulated  genes  can  be  grouped  into  three  broad  categories:  neuronal differentiation  and/or  neural  plasticity, response  to  neural  insult,  and  sensory  perception.  Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue Overall design: RNA sequencing of normal human astrocytes (Lonza) from 2 biological donors that were cultured for 5 days either with the peptide hydrogel Puramatrix or on tissue culture polystyrene	Co-expression
SRP075876	Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain	Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and gene regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. 74% of 35,627 demethylated regions identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development. Overall design: MethylC-seq and RNA-seq of Cerebral Organoids differentiation	Co-expression
SRP075880	Effect of SF3B1 suppression in cancer cells with different SF3B1 copy-number levels	Breast cancer cell lines containing stable dox inducible shRNAs targeting SF3B1 were profiled by RNA sequencing. We determined the effect of gene expression and splicing changes before and after knocking down SF3B1 in cell lines with normal copy number (SF3B1neutral) or partial copy loss (SF3B1loss) cell lines Overall design: RNA profiles for SF3B1 suppression were generated from 8 breast cancer cell line pairs (-/+ dox) with no techincal replicates.	Co-expression
SRP075882	Human basal-like breast cancer cell line HCC1143 treated with BET inhibitor JQ1 in combination with MEK inhibitor Trametinib or PI3K/mTOR inhibitor BEZ235	The goal of this experiment was to understand the changes in gene expression in the human basal-like breast cancer cell line HCC1143 following treatment with the MEK inhibitor Trametinib (T), PI3K/mTOR inhibitor BEZ235 (B), the BET inhibition JQ1 (JQ), Trametinib + JQ1 (TJ), or BEZ235 + JQ1(BJ), compared to a DMSO control (D). Samples were treated for 72hr and run in triplicate. Overall design: The human basal-like breast cancer cell line HCC1143 was treated for 72hr with 1uM Trametinib (T), 1uM BEZ235, 1uM JQ1 (JQ), 1uM Trametinib + 1uM JQ1 (TJ), 1uM BEZ235 + 1uM JQ1 (BJ), or a 0.05% DMSO control. Total RNA was isolated using a QIAGEN total RNA RNeasy kit, libraries were generated with a Truseq kit, and samples were run on the Nextseq500, data processing is described below.	Co-expression
SRP075911	Targeted differentiation of regional ventral neuroprogenitors and related neuronal subtypes from human pluripotent stem cells	Purpose: To find the mechanism for the differences in cell fates between the EB (embryoid body) and AD (adherent) culture conditions Methods: hESCs were cultured in different methods, and RNA-seq were generated , in triplicate, using Illumina GAIIx. The sequence reads  were analyzed  with Weighted gene correlation network analysis (WGCNA) and  Gene Ontology (GO) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: We totally found roughly 600 genes which were specifically enriched in both day 4 EB cells and day 4 EB cells treated with SB431542 and LDN193189. Meanwhile, there were around 1000 genes which showed significant higher expression in AD cells Conclusions: complex intracellular cell contexts and extracellular components work together and define the distinct differentiation potencies of the AD and EB cells upon SHH patterning. Overall design: mRNA from hESCs cultured in AD and EB conditions were analysed, in triplicate, using Illumina HiSeq 2000.	Co-expression
SRP075919	A Basal Stem Cell Signature Identifies Aggressive Prostate Cancer Phenotypes	Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Overall design: Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq	Co-expression
SRP075920	Human Cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion.	We analysed whole PolyA+ RNA from human osteosarcoma U2OS cells depleted for human Cactin or transfected with a control shRNA. Overall design: Two independent shRNAs targeting human Cactin (shCac_C and shCac_D), a control shRNA (shCtrl), a single cell line (U2OS)	Co-expression
SRP075940	Effects on siProx1 and siTie2 in HDLEC	No description.	Co-expression
SRP075958	PNET animal model: new insights	Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs. Overall design: RNA-seq of tumors from central nervous system primitive neuroectodermal tumor (CNS PNET) animal model	Co-expression
SRP075965	PHF20 readers link methylation of histone H3K4 and p53 with H4K16 acetylation	PHF20 is a core component of the lysine acetyltransferase complex MOF-NSL that produces the major epigenetic mark, H4K16ac, and is necessary for transcriptional regulation and DNA repair, however the role of PHF20 in the complex remains elusive. Here, we report on functional crosstalk between epigenetic readers of PHF20. We show that the PHF20 PHD finger recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents first example of a native PHD reader selective for this modification. Biochemical and structural analyses illuminate the molecular mechanism underlying this function and explain the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a novel PHF20-mediated link between MOF HAT, p53 and H3K4me2-dependent cellular events and suggest a model for rapid spreading of H4K16ac-encriched open chromatin. Overall design: H1792 cells were transduced with shRNAs targeting PHF20 or control non-tareting shRNAs and selected with puromycin for 4-6 days. RNA-seq was then performed to identify differentially expressed genes among different conditions.	Co-expression
SRP075966	Transcription control by the ENL YEATS domain in acute leukemia [RNA-seq]	Recurrent chromosomal translocations involving the mixed lineage leukemia gene (MLL) give rise to highly aggressive acute leukemia associated with poor clinical outcomes. The preferential involvement of chromatin-associated factors in MLL rearrangements belies a dependency on transcriptional control. To identify new targets for therapeutic development in MLL, we performed a genome-scale CRISPR-Cas9 knockout screen in MLL-AF4 leukemia.  Among validated targets, we identified the transcriptional regulator, ENL, as an unrecognized dependency particularly indispensable for proliferation. To explain the mechanistic role for ENL in leukemia pathogenesis and the dynamic role in transcription control, we pursued a chemical genetic strategy utilizing targeted protein degradation. ENL loss suppresses transcription initiation and elongation genome-wide, with pronounced effects at genes featuring disproportionate ENL load. Importantly, ENL-dependent leukemic growth was contingent upon an intact YEATS epigenomic reader domain. These findings reveal a novel dependency in acute leukemia and a first mechanistic rationale for disrupting YEATS domains in disease. Overall design: RNA-seq in MV4;11 (Cas9; ENL-FKBP(F36V); ENL -/-) cells with dTAG-13 and EPZ-5676 treatment	Co-expression
SRP075977	Transcriptome signatures of human induced pluripotent stem cell-derived cardiomyocytes classify cardiomyocyte subtype populations	We profiled the transcriptome of cardiomyocytes from hiPSCs throughout differentiation and at a single cell level to identify subpopulations. We further studied on the transcription factors NR2F2, TBX5, and HEY2 in these subpopulations. Overall design: Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have become a powerful tool for human disease modeling and therapeutic testing. However, their use remains limited by their immaturity and heterogeneity. To characterize the source of this heterogeneity, we performed bulk RNA-seq on hiPSCs undergoing differentiation into cardiomyocytes over an extended time course followed by single-cell RNA-seq at a later time point (day 30).  These analyses identified novel single-cell populations, characterized by the distinct or overlapping expression of TBX5, NR2F2, HEY2, ISL1, JARID2, and HOPX transcription factors. Analysis of RNA-seq data from hiPSC-CMs both during differentiation in vitro and from human heart tissues suggests these transcription factors underlie physiologically distinct lineages. Using CRISPR genome editing and ChIP-seq, in conjunction with patch clamp, calcium imaging, CYTOF, and single-cell Western analysis, we now demonstrate that these transcription factors play an essential role in specification of early atrial (NR2F2) and late ventricular (HEY2) cardiomyocytes. We RNA-sequenced NR2F2, TBX5, HEY2 gene edited lines as well as day 30 hiPSC-CMs overexpressing NR2F2, TBX5, and HEY2.  These new targets, sequencing data, and methods provide a platform for improved investigation of in vitro cardiac heterogeneity.	Co-expression
SRP075990	Directed differentiation of human embryonic stem cells to corneal endothelial cell-like cells: A transcriptomic analysis	The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. Human embryonic stem cells (hESCs) hold the promise of providing an abundant donor source for generating CEC cells for cell replacement therapies. Here we demonstrate that CEC-like cells can be efficiently derived from human ESCs. In addition, we performed global gene expression profiling of stem-cell-derived CEC cells, incorporating with adult CEC cells, fetal CEC cells and other human tissue type data. Our data indicate that hESC-derived CEC-like cells closely resemble human fetal CEC cells. Overall design: We analyzed a total of 44 samples. 6 samples were sequenced by our group. High-throughput RNA-seq data from human ES cell-derived CEC-like cells samples (n=4) and cultured adult CEC samples (n=2) using Illumina HiSeq 2000. 38 samples are publicly available in GEO. The entire set of processed data is linked below as supplementary file 44_samples_RPKM.txt.	Co-expression
SRP076036	Next Generation Sequencing Facilitates Quantitative Analysis of human patient derived primary Glioblastoma (GBM) cancer cell Transcriptomes	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare GBM transcriptome profiling (RNA-seq) after shRNA based knockdown of PRKAB1 and to compare gene expression by optimal high-throughput data analysis Overall design: Methods: Total RNA profiles of two GBM cells (scramble and PRKAB1 sh RNA treated) were generated by deep sequencing, in triplicate, using Illumina Hiseq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays	Co-expression
SRP076037	KSHV LANA upregulates the expression of EGFL7 proteins in BJAB cells	The objective of this study was to determine the effects of LANA on the expressions of the cellular genes. Overall design: BJAB cells were transduced with lentiviral vector expressing LANA or the control vector, total RNA was extracted for the detection of relative expression of cellular genes in LANA expressing cells.	Co-expression
SRP076073	RNA-Seq of Human pneumonias	Identification of potential key long non-coding RNAs and target genes associated with pneumonia using RNA sequencing data.	Co-expression
SRP076085	Total RNA sequencing of WT intestinal orgaonids.	We report elevated expression levels of genes involved in small intestine or colon regional identity. hESCs were differentiated to colonigc organoids, where the total RNA was extracted from. Overall design: Comparison of the expression profiles of colonic and small intestinal organoids	Co-expression
SRP076097	TLR2/1 ligand and IFN-g inducible genes in human monocyte-derived macrophages (MDMs)	Transcriptome profiles for innate and adaptive immune stimuli important for host response against mycobacteria.  Human monocyte-derived macrophages were stimulated with TLR2/1 ligand and interferon-g, stimuli present during innate and adaptive immune responses, respectively. Overall design: Human monocyte-dervided macrophages from five healthy donors were stimulated with TLR2/1L, IFN-g, or media control for 2, 6, and 24 hours.  RNA-sequencing was performed on a total of 45 samples.	Co-expression
SRP076099	Homo sapiens Transcriptome or Gene expression	RNA editing in human brain development	Co-expression
SRP076104	The DPYSL2 gene connects mTOR and schizophrenia	We report a transcriptome comparison of HEK293 cells modified at the DPYSL2 gene promoter dinucleotide repeat (chr8:26,435,510-26,435,534) by CRISPR/Cas9 to change from the common 11 repeats to the more rare 13 repeats Overall design: 11/11 repeat HEK 293 cells were modified by CRISPR/Cas 9. Cell were flow sorted by the co-transfected GFP and single cells were expanded. From those we selected 4 modified and 8 unmodified clones for RNA seq. RNA was extracted at 80% confluency	Co-expression
SRP076105	Whole-transcriptome profilings between a pair of HCA7-derived KRAS-wildtype cetuximab sensitive and resistant colon cancer cells from 3D culture	We report the results of RNA-Seq and small RNA-Seq from a pair of HCA7-derived, KRAS wildtype CC and CC-CR cultured in 3D. A total of 361 genes showed more than a two-fold change in expression (false-discovery rate [FDR] - adjusted p<0.01) between CC-CR and CC; there were 141 transcripts upregulated and 220 transcripts downregulated in CC-CR compared to CC. Small RNA-Seq detected 7 miRNAs upregulated and 24 miRNAs downregulated in CC-CR cells compared to CC cells (fold change>2, FDR<0.01). Differential expression analysis revealed several novel candidates that may contribute to cetuximab resistance. The whole-transcriptome profilings using cetuximab resistance model from 3D culture provide novel candidates for cetuximab resistance and further functional studies might open the door to a novel understanding of how non-mutational mechanisms mediate cetuximab resistance. Overall design: mRNA and small-RNA profiles of cetuximab sensitive CC and resistant CC-CR from 3D culture were generated by deep sequencing, in triplicate, using Illumina NextSeq 500 sequencer.	Co-expression
SRP076139	ATAC-seq data from 3 cancer cell lines and RNA-seq data from 1 cancer cell line	RNA-seq and ATAC-seq data to understand how gene regulation and chromatin accessibility correlates with function enrichment in CRISPR screen for melanoma drug resistance	Co-expression
SRP076162	L1CAM dependent transcriptional programs in brain metastatic cells	L1CAM dependent gene expression programs in vitro and ex vivo were analyzed by translating ribosome affinity purification and sequencing (TRAP-Seq). Overall design: EGFP-Rpl10a+, shControl or shL1CAM expressing H2030-BrM cancer cells were seeded to organotypic brain slice, cultured for 48h, and processed through the TRAP protocol. Cells under regular tissue culture (0h) were collected as pre-vascular cooption controls.	Co-expression
SRP076175	BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire [mRNA-Seq]	We examined context specific function of BRD4 in promoting lineage specific gene expression and show that BRD4 is essential for osteoblast differentiation. Overall design: We performed  mRNA sequencing from hFOB cells (undifferentiated and differentiated for 5 days into osteoblastic lineage) following BRD4 inhibition by JQ1 or siRNA mediated depletion.  The mRNA-Seq includes namely 7 conditions: undifferentiated hFOBs treated with DMSO or non-targeting control siRNA (siCNTR), differentiated hFOBs with DMSO or siCNTR treatments; differentiated hFOBs treated with JQ1 or two siRNAs against BRD4 (#3 & #4). The libraries were performed in triplicates.	Co-expression
SRP076176	Quantitative profiling of the UGT transcriptome in human drug metabolizing tissues [Total RNA]	Purpose: Maintenance of cellular homeostasis and xenobiotics detoxification relies on the glucuronidation pathway mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by 10 highly homologous genes. Recent evidence suggests that alternative splicing largely expands the human UGT transcriptome. Results: we establish the quantitative portrait of the UGT transcriptome in major metabolic organs. RNA sequencing uncovered that AS significantly shapes the UGT transcriptome, with variants quantitatively representing up to 35% and 60% UGT transcripts in normal and tumoral tissues respectively. Novel distinctive in-frame sequences were present in 20% alternative transcripts, which potentially encode UGT isoforms with distinct structural and functional features. Conclusions: This work exposes the important quantitative and biological significance of alternative UGT expression likely creating unparalleled protein diversity evolving from enzymes to regulators of cell metabolism. Overall design: Total RNA was extracted from liver, kidney, intestine and colon from multiple human donors. RNA-sequencing was conducted with a Illumina HiSeq 2500 system	Co-expression
SRP076210	Nuclear Actin Regulates Inducible Transcription by Enhancing RNA Polymerase II Clustering	Nuclear actin dynamics regulate enhanced RNA polymerase II clustering on specific genes upon serum stimulation, thus establishing the serum-induced transcriptional program. Overall design: We sequenced the transcriptomes of U2OS cells overexpressing actin mutant G13R and those expressing GFP as control, at both normal-growth and serum-stimulation conditions.	Co-expression
SRP076222	Adaptation of the Kinome Promotes Resistance to BET Bromodomain Inhibitors in Ovarian Cancer	Small molecule BET bromodomain inhibitors (BETi) are actively being pursued in clinical trials for the treatment of a variety of cancers, however, the mechanisms of resistance to targeted BET protein inhibitors remain poorly understood. Using a novel mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BET inhibitor treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi, JQ1. Through application of Multiplexed Inhibitor Beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BET inhibitor therapy. Overall design: RNAseq was employed to identify changes in kinase RNA expression following short term (48h) or chronic (JQ1R) JQ1 treatment in three different ovarian cancer cell lines.	Co-expression
SRP076224	Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs	The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL_short RNA from the ferritin mRNA 5'' UTR. Importantly, DIS3L2 contributes to surveillance of pre-snRNAs during their cytoplasmic maturation. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3'' RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis. Overall design: To investigate DIS3L2 functions genome-wide, total RNA samples were collected from model cell lines producing either WT or mut DIS3L2 three days after induction with doxycycline. The RNA samples were rRNA-depleted before preparation of strand-specific total RNA libraries according to the standard TruSeq (Illumina) protocol. TruSeq library preparation favours RNA molecules longer than 200 nt, and shorter transcripts are suboptimal for sequencing via this protocol. Thus, to obtain information about potential DIS3L2 RNA substrates with lengths between 20 and 220 nt, another RNA-Seq was carried out in parallel (with size selection through gel purification). The stable inducible HEK293 cell lines producing DIS3L2 variants were obtained using “pAL_01” and “pAL_02” plasmid constructs and the Flp-In™ T-REx™ system according to the manufacturer’s guidelines. “pAL_01” and “pAL_02” plasmids are vectors for co-expression of recoded C-terminal FLAG-tagged DIS3L2 [wild type (WT) variant or its catalytic mutant counterpart (mut), respectively] and sh-miRNAs directed against endogenous DIS3L2 mRNA.	Co-expression
SRP076235	RNA-Seq data for AKT, BAD, ERBB2, IGF1R, RAF1 and KRAS(G12V) overexpressed samples with twelve green fluorescent protein control samples using human mammary epithelial cells	The goal was to capture the transcriptional activity due to over-expression of AKT, BAD, ERBB2, IGF1R, RAF1 and KRAS(G12V) genes .Overexpressions were validated using Western Blots. Illumina RNA-Seq technology was used to capture the downstream transcriptional activity. Reads were 101 base pairs long and single ended. An R open source package “Rsubread” was used to align and quantify the read using UCSC hg19 annotation. The integer-based gene counts were later normalized in TPM . Overall design: Profiles of gene expression, downstream of  AKT, BAD, ERBB2, IGF1R, RAF1 and KRAS(G12V) over-expression, were generated in cells derived from breast and used to generate a gene-expression signatures.	Co-expression
SRP076260	Epigenomic remodeling of the PAX8 cistrome in high grade serous ovarian cancer [RNA-Seq]	We report mapping of the PAX8 cistrome in three high grade serous ovarian cancer cell lines (KURAMOCHI, OVSAHO, and JHOS4) compared to three benign immortalized fallopian tube cell lines (FT33, FT194, and FT246). We identified a highly conserved PAX8 binding pattern common across benign fallopian tube cell lines that was distinct from the unique PAX8 binding patterns seen in each cancer cell line. Overall design: Comparison of benign and malignant Mullerian cell lines with and without PAX8 knockdown. For each cell line, three distinct siRNAs targeting PAX8 plus a pool of all three siRNAs were examined and compared to both a non-transfected control as well as a control transfected with a non-targeting siRNA.	Co-expression
SRP076270	Comparison of human brain and spinal cord neural stem cells (NSCs)	Regional identity of several kind of human neural stem cells were assessed by RNA-Seq Overall design: We compared whole transcriptome of human fetal spinal cord, fetal brain, fetal spinal cord derived NSCs, H9-derived NSCs, H9-derived spinal cord NSCs, and UCSF4-derived spinal cord NSCs	Co-expression
SRP076277	Identification of Tissue-Specific Protein-Coding and Noncoding Transcripts across 14 Human Tissues Using RNA-seq	Many diseases and adverse drug reactions exhibit tissue specificity. To better understand the tissue-specific expression characteristics of transcripts in different human tissues, we deeply sequenced RNA samples from 14 different human tissues. After filtering many lowly expressed transcripts, 24,729 protein-coding transcripts and 1,653 noncoding transcripts were identified. By analyzing highly expressed tissue-specific protein-coding transcripts (TSCTs) and noncoding transcripts (TSNTs), we found that testis expressed the highest numbers of TSCTs and TSNTs. Brain, monocytes, ovary, and heart expressed more TSCTs than the rest tissues, whereas brain, placenta, heart, and monocytes expressed more TSNTs than other tissues. Co-expression network constructed based on the TSCTs and TSNTs showed that each hub TSNT was co-expressed with several TSCTs, allowing functional annotation of TSNTs. Important biological processes and KEGG pathways highly related to the specific functions or diseases of each tissue were enriched with the corresponding TSCTs. These TSCTs and TSNTs may participate in the tissue-specific physiological or pathological processes. Our study provided a unique data set and systematic analysis of expression characteristics and functions of both TSCTs and TSNTs based on 14 distinct human tissues, and could facilitate future investigation of the mechanisms behind tissue-specific diseases and adverse drug reactions. Overall design: Identification of Tissue-Specific Transcripts across 14 Human Tissues Using RNA-seq	Co-expression
SRP076297	Genes that mediate leptomeningeal metastasis from breast and lung solid tumor primaries	Little is understood about the gene expression changes that underlie cancer spread to the cerebrospinal fluid, or leptomeningeal metastasis. Using four cancer cell line models, we empolyed iterative in vivo selection to generate subpopulations of these cell lines able to access the leptomeningeal space and grow once there. We compared the gene expression profile of the terminally selected cells or "Lep" cells with that of the parental or "Par" cells, as well as that of an intermediate stage of in vivo selection or "Int" cells. Analyses for brain parenchymal metastatic derivatives or "BrM" cells were included for comparison. Overall design: Four different models were employed: Two human breast cancer cell lines, MDA-MB-231 and HCC1954 as well as one human lung cancer cell line, PC9 and a mouse non-small cell lung cancer cell line, Lewis lung carcinoma. Three technical replicates of each Par cell line, two or three biological replicates and two technical replicates of each of the Int and Lep cells were all subjected to analysis.	Co-expression
SRP076307	Single cell RNA-seq of human pancreatic endocrine cells from Juvenile, adult control and type 2 diabetic donors.	We successfully sequenced and annotated more than 400 cells from child, adult control, type 1 diabetes and type 2 diabetes donors. We detect donor-type specific transcript variation. We also report that cells from child donors have less defined gene signature. Cells from type 2 diabetes donors resemble juvenile cells in gene expression. Overall design: Cells from three adult controls (56, 74, 92), one donor with type 1 diabetes (91), two donors with type 2 diabetes (75, 143), and two child donors (40, 72) were sequenced. Numbers in parathesis indicates number of cells sequenced.	Co-expression
SRP076334	Identification of rare, dormant and therapy resistant stem cells in acute lymphoblastic leukemia	Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD). Therapeutically adverse characteristics were reversible, as resistant, dormant cells became sensitive to treatment and started proliferating when dissociated from the in vivo environment. Our data suggest that ALL patients might profit from therapeutic strategies that release MRD cells from the niche. Overall design: Gene expression profiles from two PDX ALL Samples (ALL-199 & ALL-265) were generated for either dormant (LRC) vs. dividing (non-LRC) cells or drug treated vs. non-treated cells. For single cell analysis one mouse were analyzed for each condition.	Co-expression
SRP076388	Homo sapiens Transcriptome or Gene expression	Altered Histone H3 Acetylation Plays the Driving Force in the Transition of Urinary Bladder Cells from a Reversible State to an Irreversible Malignant Transformation Induced by MMAIII Exposure: A Time-Series Analysis	Co-expression
SRP076426	The rectal mucosal transcriptome of men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) compared with men who have never engaged in anal intercourse (controls)	We report differences in mRNA gene expression in rectal biopsies from MSM compared to controls and for MSM timed with episodes of CRAI. Overall design: Rectal biopsies were obtained from MSM at two study timepoints: 1. after who abstaining from CRAI for >72 hours and 2.after engaing in CRAI within the last 24 hours.  Rectal biopsies were also obtained from men who never engaged in AI.	Co-expression
SRP076434	mRNA-Seq of human severe pneumonia	Identification of potential key genes associated with pneumonia using RNA sequencing data.	Co-expression
SRP076437	Raw sequence reads	HLA-I positive and negative subpopulations isolated from human clear cell sarcoma xenografts	Co-expression
SRP076454	The different gene expression profile of knockdown LRP5/6 or knockdown ß-catenin in hepG2 cell line through RNA-Seq	LRP5/6 receptor is an important receptor for the activation of ß-catenin. Therefore, the downregulation of LRP5/6 can lead to the degradation of ß-catenin. We sequenced mRNA from hepG2 cell after knocking down LRP5/6 or ß-catenin separately by siRNA for 48hour. The different expression profile of mRNA was studied in two groups. Overall design: Examination of mRNA levels in hepG2 cell by knocking down LRP5/6 or ß-catenin for 48hour using siRNA.	Co-expression
SRP076456	Aberrant transcriptional networks in neurogenesis of Paroxysmal Kinesigenic Dyskinesia-induced pluripotent stem cell lines though neural induction method of dual inhibition of SMAD signaling	Paroxysmal kinesigenic dyskinesia (PKD) is an episodic movement disorder with autosomal-dominant inheritance and marked variability in clinical manifestations.Proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD, but the molecular mechanism underlying the pathogenesis of PKD still remains a mystery. The phenotypes and transcriptional patterns of the PKD disease need further clarification. Here, we report the generation and neural differentiation of iPSC lines from two familial PKD patients with c.487C>T (p. Gln163X) and c.573dupT (p. Gly192Trpfs*8) PRRT2 mutations, respectively. Notably, an extremely lower efficiency in neural conversion from PKD-iPSCs than control-iPSCs is observed by using the iPSC-neural differentiation protocol that relies on the dual inhibition of SMAD signaling. Moreover, we show the high expression level of PRRT2 throughout the human brain and the expression pattern of PRRT2 in other human tissues for the first time. To gain molecular insight into the development of the disease, we conduct global gene expression profiling of PKD cells at four different stages of neural induction and identify altered gene expression patterns, which peculiarly reflect dysregulated neural transcriptome signatures and a differentiation tendency to mesodermal development, in comparison to control-iPSCs. Additionally, functional and signaling pathway analyses indicate significantly different cell fate determination between PKD-iPSCs and controls-iPSCs. Together, the establishment of PKD-specific in vitro models and the illustration of transcriptome features in PKD cells would certainly help us with better understanding of the defects in neural conversion as well as further investigations in the pathogenesis of the PKD disease. Overall design: RNA-Seq of 16 cell samples derived from different neural differentiation stages of PKD-iPSCs and 7 cell samples from that of normal iPSCs	Co-expression
SRP076462	The ß-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner	In pediatric glioma cell lines, treatment with ICG-001 had no inhibitory effect on canonical Wnt-target genes but induced significant up regulation of various known ß-catenin target genes in both cell lines and top 20 GO-annotations of down-regulated genes by ICG-001  were associated with biosynthetic and metabolic processes and cell cycle division processes. Overall design: Pediatric cell lines were treated with ICG-001 or DMSO for 48h	Co-expression
SRP076475	Gene expression by high-throughput sequencing of T47D-MTVL human breast cancer cells upon H1.4 knock-down and multiple H1 variants	Gene expression of T47D-MTVL human breast cancer cells expressing Dox-inducible shRNAs against histone H1.4 (120sh) or multiple H1 variants (225sh) Overall design: Stable breast cancer-derived cell lines expressing an shRNA against one of each of the histone H1 isoforms in response to doxycycline (Dox) were grown for six days in the presence or absence of Doxicycline, RNA extracted and high-thorughput sequenced. Cell lines used: inducible shRNA against H1.4 or multiple H1 variants and random shRNA-expression vector.	Co-expression
SRP076490	Homo sapiens Transcriptome or Gene expression	Gingival mRNA profiles of young and old human gingiva were generated by deep sequencing using HiSeq 2000 sequencing system (Illumina)	Co-expression
SRP076496	Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription [RNA-Seq]	gene expression data from 3 pairs of cancer associated fibroblasts and normal fibroblasts from the same individual Overall design: mRNA seq data from 3 normal and 3 cancer associated fibroblast cell lines	Co-expression
SRP076513	Next Generation Sequencing Analysis of control and DEHP exposure HepG2 cell Transcriptomes	we treated the HepG2 cells with low concentration or control solvent for a long time. Then we extracted the RNAs and performed the next generation sequencing. By comparing sequcing data from control and DEHP treated samples, we profiled the gene expression regulated by low concentration exposure. Overall design: HepG2 cells mRNA profiles of Control and DEHP treated samples were generated by deep sequencing, using ABI Ion Proton.	Co-expression
SRP076519	Next Generation Sequencing of liver and subcutaneous fat tissues obtained from obese subjects	Patients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese  subjects undergoing bariatric surgery and then used for the mRNA expression analyses. Overall design: mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500.	Co-expression
SRP076532	Transcriptome analysis of human monocytes 6h after stimulation with pathogens/vitamins	Human monocytes were infected with three different pathogens. Furthermore, some of the samples were additionally treated with either vitamin A or D. The goal of the study is to identify different gene regulatory patterns, e.g. to figure out the impact of the vitamin treatment upon pathogenic stimulus.	Co-expression
SRP076553	Differential gene expression of human melanoma cells [RNA-seq]	We report the gene expression comparison of human A375 melanoma cells with GDF6 and BMP pathway modulation. These comparisons were used to determine the gene signature regulated by GDF6. Overall design: Examination of gene expression in one cell type +/- GDF6 knockdown as well as +/- downstream pathway reactivation.	Co-expression
SRP076581	RNA-seq of PDX	Transcriptome sequencing of patient-derived xenografts of lung carcinomas.	Co-expression
SRP076599	Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [RNA-seq]	Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown. Results:  Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients. Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity. Overall design: RNA-seq of 8 samples of peripheral blood derived mononuclear cells from CD patients having T/T or C/C genotype for rs6716753 SNP, with and without LPS treatment. 4 samples from healthy individuals with and without LPS treatment. RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours: siRNA mediated knockdown of SP140 versus controls. RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours for each condition: siRNA mediated knockdown of SP140 versus controls.	Co-expression
SRP076616	MHC Transcriptomic landscape at haplotype-specific resolution	To explore the effect of human MHC haplotype on gene expression phenotype across the MHC, we examine the MHC transcriptomic landscape at the haplotype-specific resolution for three prominent MHC haplotypes (A2-B46-DR9, A33-B58-DR3 and A1-B8-DR3) derived from the RNA-sequencing of MHC-homozygous B-LCLs. We demonstrate that MHC-wide gene expression pattern is dictated by the underlying MHC haplotype and identify 37 differentially expressed genes among the haplotypes. Overall design: Comparing gene expression patterns between multiple MHC haplotypes in B-LCLs. A total of 16 libraries were prepared with two libraries generated per cell line.	Co-expression
SRP076627	CD4+ T Cells Gene Expression-Based Biomarkers in Juvenile Idiopathic Arthritis (JIA)	Aim: To discovery biomarkers in JIA base on gene expression from RNA sequencing on CD4+ T Cells Method: Paired-end Ilumina sequencing to capture gene expression of CD4+ T cells from JIA individuals with active disease and patients in clinical remission on medication. Overall design: RNA sequencing on CD4+T cells consist of JIA patients	Co-expression
SRP076677	Pericyte-like cells generated from human pluripotent stem cells support hematopoietic stem and progenitors ex vivo	Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSC), the capacity of such cells to support hematopoiesis has not been reported. Here we have demonstrated that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, PDGFRß), a subset of cells defined as CD146++CD140alow supported functional HSPC ex vivo while CD146­-CD140a+ cells drove differentiation. The CD146++ subset expressed genes associated with the HSPC niche and high levels of the Wnt inhibitors. HSPC support was contact-dependent and was mediated in part through JAG1 expression. Molecular profiling revealed remarkable transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of diverse pools of mesenchymal populations from hPSC opens potential avenues to model their developmental and functional differences and to improve cell-based therapeutics from hPSC. Overall design: Our goal was to analyze and compare transcriptome of human pluripoten stem cell-derived mesenchyme (CD146++ and CD146-) with primary human lipoaspirate tissue-derived pericyte (CD146+) and CD146- mesenchymal populations.	Co-expression
SRP076678	Single cell transcriptome of human myometrial and cervical tissue during pregnancy	No description.	Co-expression
SRP076711	RNA sequencing reveals levamisole target genes PTPRZ1 and MDK and their links to interferon pathway in human podocytes	To investigate the mechanisms underlying levamisole''s efficacy in disease, we performed RNA sequencing using 3 human podocyte cell lines aiming to generate transcriptome profiles of podocyte in response to levamisole. Overall design: Transcriptome profiles of human podocytes treated with levamisole were generated by RNA-sequencing using Illumina HiSeq 2500	Co-expression
SRP076712	Transcriptomic profiling of human coronary artery endothelial cells under laminar shear stress (LS), oscillatory shear stress (OS) and static culture (ST)	Aim: To survey the alteration of endothelial transcriptome under different types of shear stress and find novel shear stress-sensitive protein-coding genes as well as non-coding RNAs as potential therapeutic targets for the treatment of atherosclerosis Method: After exposed to LS, OS and ST for 24 hours (n=4, respectively), ECs were harvested by scraping, and RNA was isolated and purified. Double-stranded cDNA was generated from 100 to 150 ng of total qualified RNA using selective priming and prepared for the final library. Quantitative PCR (qPCR) was performed to quantify the library using a KAPA kit for Illumina sequencing platforms. Twelve samples were then clustered on the cBot and sequenced on a 50-cycle single end on a HiSeq 2000 to generate 50 bp paired-end reads, using TruSeq SBS v3 reagents according to manufacturer's protocols. RNA-seq fastq files were aligned to the human genome primary assembly (GRCh38) using the Subread package. Read counts on each gene were determined by featureCounts function in the Subread package using GeneCode human GTF file version 23 (http://www.gencodegenes.org/). Differential expression analysis between endothelial cells under different types of shear stress were performed using the limma package with the voom transformation. P values were adjusted by default Benjamini-Hochberg procedure. Results: RNA-seq data provided a broad view of endothelial transcriptome under shear stress. We mapped about 70 million reads and discovered over 16,000 genes that are well-expressed in human coronary artery endothelial cells. RNA-seq results were consistent with previously reported DNA microarray data and we also confirmed the expression of genes that are previously reported and novel genes with qRT–PCR results. Comparing the endothelial transcriptomes under different types of shear stress, we found that there are approximately 50% genes that are differentially expressed in ECs under ST vs. LS and OS vs. LS while 10% under ST vs. OS. Conclusion: RNA-seq data provide a framework for investigating endothelial transcriptome under shear stress. We found that endothelial cells under LS condition profoundly differs from those under either ST or OS conditions. The profiling also reveals a large amount of novel shear sensitive genes and lncRNAs that are not reported before. It provides the community with potential targets for anti-atherosclerosis drug development considering the determinant role of shear stress in the distribution of atherosclerotic lesions in the arterial tree. Overall design: Human coronary artery endothelial transcriptomic profiles under LS, OS and ST were generated by RNA-sequencing, in quadruplicate, using Illumina HiSeq 2000	Co-expression
SRP076716	Three different in vivo models of synovial sarcoma (xenograft: Fuji; PDX: CTG-0331 and CTG-0771) treated with or without the indicated dose of the EZH2 inhibitor, tazemetostat	The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output.  The enzymes that catalyze these activities are often contained within multiprotein complexes in nature.  Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis.  An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers.  Here we show that preclinical models of synovial sarcoma - a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein - display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2.  Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro.  Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3.  These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers. Overall design: Three different in vivo models of synovial sarcoma (xenograft: Fuji; PDX: CTG-0331 and CTG-0771) treated with or without the indicated dose of the EZH2 inhibitor, tazemetostat	Co-expression
SRP076717	Genome-wide analysis of human iPS cell-derived hepatocyte-like cells induced by methoxamine treatment.	Analysis of whole gene expression during differentiation from hiPS cells into hepatocyte-like cells. The hypothesis tested in the present study was that the hepatocyte-like cells induced with adrenergic receptor agonists were identical to those induced with conventional growth factors (hepatocyte growth factor and oncostatin M). Results provide the important information of the differentiation mechanisms from hepatoblasts into hepatocytes. Overall design: Total RNA obtained from undifferentiated hiPS cells, hiPS cell-derived hepatoblast-like and hepatocyte-like cells. The hiPS cells were induced to differentiate into hepatoblast-like cells, then the cells were treated with methoxamine or growth factors (hepatocyte growth factor and oncostatin M) to induce the differentiation into hepatocyte-like cells.	Co-expression
SRP076719	Multiple Origins of Virus Persistence during Natural Control of HIV Infection	Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity. Overall design: Fluorescence-activated cell sorting (FACS) was used to sort subsets of CD4 T cells from blood (peripheral blood mononuclear cells; PBMC) and lymph node from a cohort of HIV-infected people with natural control of the virus (termed HIV controllers). Subsets of CD4 T cells that were sorted are as follows:  from blood, (1) naïve (N), (2) central memory (CM), (3) transitional memory (TM), and (4) effector memory (EM); from lymph node, (1) naïve (N), (2) non-germinal center T-follicular helpers (nGC), (3) germinal center T-follicular helpers (Tfh), (4) effector memory (EM), and (5) other central memory-like subsets (CMPD1lo57lo, CMPD1lo57hi, and/or CMPD1lo).  Total RNA and total DNA were extracted from these sorted subsets in separate fractions using RNAzol RT and DNAzol.  Total cellular DNA was used for HIV quantification and sequence analysis as describe in the publication. Total RNA used for mRNA library construction by oligo-dT purification (Dynabeads), random fragmentation by heating in the presence of Magnesium (in form of 5x first-strand buffer, LifeTech), reverse transcription (SuperScript III), and then second-strand synthesis, end repair, a-tailing, and adaptor ligation using NEBNext enzyme master mixes and oligonucleotides.  Libraries were sequenced on an Illumina HiSeq2000. Please note that each ''source name'' value represent individual who havs HIV infection with natural control of the virus.	Co-expression
SRP076722	RNA sequencing of human fibroblasts after SUPT4H1 siRNA treatment	Asses the transcriptome-wide changes associated with depletion of transcription elongation factor, SUPT4H1, in human fibroblasts. An expanded hexanucleotide repeat in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics (e.g., antisense oligonucleotides) are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor, Spt4, selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Inhibition of SUPT4H1, the human ortholog of Spt4, similarly decreased production of sense and antisense RNA foci as well as DPR proteins in c9ALS patient fibroblasts and neurons from patient-derived induced pluripotent stem cells, consistent with our finding that cerebellar DPR protein levels correlate with SUPT4H1 expression in c9FTD/ALS patients. Therapeutic targeting of a single factor to eliminate pathological features of c9FTD/ALS offers advantages over approaches that require targeting sense and antisense repeats separately. Overall design: 2 independent fibroblast lines: 2 replicate non-targeting siRNA treatments and 2 replicate SUPT4H1 siRNA treatments per line. Grouping by treatment for differential expression analysis (4 control siRNA samples and 4 SUPT4H1 siRNA samples)	Co-expression
SRP076732	Transcriptome analysis of human lung epithelial cells	Human lung epithelial subpopulations (alveolar type 2, basal and airway luminal cells) freshly dissociated from human lung were isolated by FACS. RNA-seq gene expression profiling was used to determine gene signature from each population. Overall design: Cells were isolated from the small airway (SA) and large airway (LA) of 3 human lungs	Co-expression
SRP076757	Homo sapiens Transcriptome or Gene expression	We sequenced mRNA from 6 human thyroid primary cultures (3 FOXE1 siRNA treated and 3 nontarget siRNA treated) derived from the fresh thyroid tissues of 3 individuals to generate the differentiated gene expression profiles caused by knock-down of the FOXE1 gene.	Co-expression
SRP076773	Homo sapiens Transcriptome or Gene expression	The goal of this project is to identify the differentially expressed genes in systemic lupus erythematosus patients when compared with healthy controls.	Co-expression
SRP076780	Human Single Cells - Local lung hypoxia determines epithelial fate decisions during alveolar regeneration	Single human lung epithelial cell transcriptomes, isolated and processed via Fluidigm C1 Overall design: Flow sorted cells from digested human lungs were captured on the Fluidigm C1 chip.	Co-expression
SRP076790	Transcriptome-wide analysis to determine miR-200a targets in melanoma cell lines	Three metastatic melanoma cell lines (BD-0548-ME, DP-0574-ME and WP-0614-ME) were transfected with miR precursors; we used hsa-miR negative control (NC) or hsa-miR-200a-3p precursors (miR-200a). The objective of this experiment was to determine miR-200a tagerts in melanoma cell lines. We selected low -miR-200a expression cells and then we overexpresed miR-200a or NC. Finally, we compared metastatic melanoma cells overexpressing miR-200a (miR-200a) to the same cell line but overexpressing negative control miR (NC). mRNA profiles were generated by deep sequencing using Illumina HiSeq 2500. Overall design: Total RNA extrated from melanoma cell lines	Co-expression
SRP076801	Genome-wide expression screening discloses long noncoding RNAs involved in thyroid carcinogenesis	Context: Long non-coding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. Objective: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. Overall design: We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters.	Co-expression
SRP076805	Parvovirus B19 NS1 protein induces cell cycle arrest at G2 phase	We construct two stable UT7/Epo-S1 cell lines which could be inducible expressing B19 NS1 and NS1 TAD2 domain mutation proteins. After treated with or without doxycycline induction, we extract the total RNA for RNA-seq analysis. Overall design: UT7/Epo-S1 cells were transduced by lentiviruses inducible expressing NS1 or NS1mTAD2. Two days post-transduction, puromycin was added at a concentration of 0.5 µg/ml, then cells were cultured in presence of puromycin for 3 to 4 passages to select the lentivirus transduced cells.  UT7/Epo-S1 cells stably expressing NS1 (NS1-S1) and NS1mTAD2 (NS1mTAD2-S1) were cultured under similar conditions as normal S1 cells except for the addition of 5 mg/ml doxycycline (Dox) for inducing the expression of NS1 and NS1mTAD2 proteins, respectively. Total RNA of the two cell lines treated with or without Dox were extracted and for further RNA-seq analysis.	Co-expression
SRP076812	Gene profiling of human adult and pediatric liver cancer cells	In an effort to comprehend some of the molecular differences between two cancers that originate in the same tissue, adult HCC and pediatric HB, we profiled four HCC and four HB cell lines using RNA sequencing. We identified an enhanced sugar uptake and usage in HB tumors compared to adult HCC, and two different metabolic subtypes of HB. We identified an enhanced sugar uptake and usage in HB tumors compared to adult HCC, and two different metabolic subtypes of HB. In particular, we showed that embryonal HB cell lines largely rely on glycolysis and express higher level of GLUT3, together with HK1, PFKP and LDHB coding for enzyme of glycolysis. On the contrary, fetal tumors express genes involved in gluconeogenesis, and as notable exception they express HK2, which is often over-expressed in adult solid tumors. Importantly, we found that the different utilization of HK isoforms renders the two HB subtypes sensitive to specific glycolysis inhibitors. Overall design: HCC and HB gene profiles were generated by deep sequencing, in duplicates, using Illumina HiSeq 2500.	Co-expression
SRP076815	FTO Regulates Activation of Rho GTPases Signaling as N6-methyladenosine RNA Demethylase and an Rhotekin Partner Protein	Reversible RNA modification of N6-methyladenosine (m6A) plays a critical role in post-transcriptional gene regulation1-13. Although the fat mass and obesity-associated protein (FTO) has been previously shown to function as an m6A demethylase in nuclear RNA1,14, its exact function in disease pathogenesis remains a mystery. Here, we demonstrate that FTO suppresses the activation of Rho GTPase signaling via both its demethylation activity and specific interaction with Rho effector, Rhotekin (RTKN)15. The knockdown of FTO activates RhoA and RhoC, induces stress fibres, and accelerates cell migration. Endogenous RTKN is highly expressed in certain cancer and cancer-derived cell lines16,17 with overexpression of RTKN leading to moderate activation of Rho18. We further found that overexpression of RTKN blocks nuclear import of FTO and traps FTO in the cytoplasm to mediate m6A demethylation of cytosolic mRNA, thereby changing gene expression by preventing m6A-dependent mRNA decay and translation. Our results illustrate how FTO represses Rho activation through m6A demethylation and direct interaction with RTKN, and shed new light on FTO-dependent post-transcriptional gene regulation in RTKN overexpressed cancers, which may provide a new direction for developing anti-cancer therapies. Overall design: RNA-seq in HeLa cells	Co-expression
SRP076842	RNA-seq in HepG2 and IMR90 cells	Expression analysis in HepG2 and IMR90 cells in presence of Fluc siRNA or sPom121 or Nup98 siRNA Overall design: Transfect siRNA - extract RNA 72 hrs post transfection	Co-expression
SRP076845	Transcriptome changes due to nuclear penetration of cancer extracellular vesicles	Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication in autocrine or paracrine manner. We report that cancer-derived EV biomaterials reach nuclei of human melanoma and breast carcinoma cells and multipotent mesenchymal stromal cells  (MSCs) through Rab7+ late endosome subdomains that penetrate into nuclear envelope invaginations. MSCs were exposed to cancer Evs in the presence or absence of drugs that block nucler import or export through the nuclear pores. Depletion of CD9 or inhibition of importin ß1, two EV-associated molecules, abrogated the nuclear localization of EV-derived biomaterials and EV-induced early changes in MSC transcriptome notably in genes involved in inflammation. Also inhibition of nuclear export by leptomycin B inhibited early changes in MSC transcriptome. This novel cellular pathway may become a cancer therapeutic target. Overall design: mRNA-Seq Human mesenchymal stromal cells alone or exposed to cancer Evs in the presence or absence of uptake modulators	Co-expression
SRP076848	Gene expression profiling of papillary thyroid cancer from central and invasive regions	We analyzed the gene expression profile of papillary thyroid cancer from central and invasive regions. Overall design: Examination of 3 different papillary thyroid cancer groups and analysis of each group between central and invasive regions.	Co-expression
SRP076864	Genome-wide Transcriptome Analysis of CD36 Overexpression in HepG2.2.15 Cells to Explore Its Regulation Role of Metabolism and HBV Life Cycle	To understand the molecular basis underlying the response to increasing CD36 overexpression in HepG2.2.15 cell, we performed genome-wide sequencing of the mRNAs from HepG2.2.15-CD36OE cell and HepG2.2.15-vector cell using the RNA-seq technology to detect its differential transcriptomic profile. Overall design: To better understand the molecular changes in the response of the CD36 overexpression in HepG2.2.15 cell, three cDNA libraries from HepG2.2.15-vector cell (Vector-1, Vector-2, Vector-3) and HepG2.2.15-CD36 overexpression cell (CD36OE-1, CD36OE-2, CD36OE-3) were constructed, respectively. After ensuring quality control, Ion ProtonTM Sequencer was used for sequencing the cDNA libraries.	Co-expression
SRP076871	Transcriptome profiling of self-renewing hESCs and multipotent mesoderm progenitor cells as a function of substrate stiffness	We performed RNA-sequencing on human embryonic stem cell samples grown on soft (400Pa) and stiff (60kPa) hydrogels under self-renewal and differentiation conditions Overall design: Whole-transcriptome RNA sequencing in the conditions described	Co-expression
SRP076879	JQ1 +/- Vemurafenib in BRAF mutant melanoma (A375)	The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Overall design: 16 samples analyzed from 8 mice (each mouse was bearing two tumors, one on each flank) in 4 treatment groups (control, vemurafenib alone, JQ1 alone, JQ1+vemurafenib)	Co-expression
SRP076884	Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade	Prostate cancer (PCa) is the most common malignancy among western men and the second leading-cause of cancer related deaths. For men who develop metastatic, castration-resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. Deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid catabolism to fuel PCa growth. In fact, the CPT1A isoform is abundant in PCa, especially in those with high-grade tumors. Since lipid oxidation is stimulated by androgens, we have evaluated the synergistic effects of combining CPT1A inhibition and anti-androgen therapy. Mechanistically, we have found that decreased CPT1A expression is associated with decreased AKT content and activation, likely driven by a breakdown of membrane phospholipids and activation of the INPP5K phosphatase. This results in increased AR content and increased sensitivity to the anti-androgen enzalutamide. To better understand the clinical implications of this findings, we have evaluated fat oxidation inhibitors (etomoxir, ranolazine and perhexiline) in combination with enzalutamide in PCa cell models. We have observed a robust inhibitory effect of the combinations, including in enzalutamide-resistant cells and mouse TRAMPC1 cells, a more neuroendocrine PCa model. Lastly, using a xenograft mouse model, we have observed decreased tumor growth with a systemic combination treatment of enzalutamide and ranolazine. In conclusion, our results show that improved anti-cancer efficacy can be achieved by co-targeting the AR axis and fat oxidation via CPT1A, which may have clinical implications, especially in the mCRPC setting. Overall design: Prostate cancer LNCaP cells with two different shRNAs for CPT1A were compared to non-targetting  shRNA controls.	Co-expression
SRP076885	RNA-seq characterization of downstream effects of upregulating SMN2 via down-regulating PRC2 or blocking the PRC2:SMN-AS1 interaction with a mixmer oligonucleotide	To determine how targeting the disruption of PRC2:SMN-AS1 interactions might affect PRC2 targets globally, we performed RNA-sequencing after transfection of a PRC2:SMN-AS1 targeting mixmer oligo, RN-0005, an antisense gapmer oligonucleotide targeting SUZ12, a subunit of the PRC2 complex, or mock in SMA fibroblasts. Via RT-qPCR, treatment with either the mixmer oligo or the SUZ12 gapmer for 2 and 3 days results in significant increases of SMN mRNA levels compared to transfection control samples. We sequenced total RNA from 12 GM09677 fibroblast samples split into two day or three day treatments (6 samples each). Within each set of six samples, there were 2 mock control replicates, 2 mixmer replicates, and 2 SUZ12kd-gapmer replicates. By controlling for time and looking at the two treatments versus mock samples, we identified the genes that change when knocking down PRC2 systemically with a gapmer versus more specifically blocking PRC2 activity with a mixmer oligo targeting the SMN2-AS1 lncRNA. Overall design: Mock, RN-0005 mixmer, and the SUZ12-KD gapmer treated SMA fibroblasts were sequenced. For each of the treatments, there were two time points with each time point having two replicates for a total number of 4 samples per condition. Gene expression differences were identified for the contrasts of RN-0005 vs. mock and SUZ12-KD vs. mock after fitting to a linear model blocking for time.	Co-expression
SRP076902	Dysregulated immune system networks in war veterans with PTSD	Purpose: RNA-Seq analysis can help identify large set of differentially expressed genes at a time. We performed RNA-Seq analysis to identify differentially expressed genes in the PBMCs of war veterans suffering from PTSD. Methods: Total RNA from PBMCs from PTSD +ve and -ve individuals were used for RNA-Seq analysis. Results: We obtained, on average, ~60 millions reads per sample. More than 70% of the reads were mapped to human genome. Functional analysis of the differentially expressed genes (362) revealed dysregulation in immune system network. Conclusions: Our present study provides further proof that immune system related genes and pathways are dysregulated in PTSD PBMCs. Overall design: RNA-Seq was performed with RNA from 5 each control and PTSD individuals. PBMCs collected within one hour of blood draw were used for RNA isolation. 1 ug of total RNA was used for library synthesis and sequenced in a HighSeq 2000 illumina instrument at Tufts University.	Co-expression
SRP076912	Field cancerized fibroblasts in primary culture, P2	Fibroblasts cultured from human breast cancer and adjacent normal tissues at 1cm and 5cm from the margin. Overall design: 3 patient sets of fibroblasts from tumor, and patient matched adjacent normal at 1cm and 5cm from tumor.	Co-expression
SRP076943	RNA-seq analysis to identify the genes regulated by p53-SET interplay	To identify the genes regulated by SET in a p53-dependent manner, the endogenous SET was depleted by siRNA in control or p53 knockout U2OS cells. Total RNA from each sample was extracted and the whole profile of gene expression was analyzed by RNA-seq analysis. Overall design: U2OS cells were transfected with control CRISPR/Cas9 construct or SET-specific targeting CRISPR/Cas9 construct. After selection and clone identification, we got a pair of cell lines: 1) control cell line which expresses p53 as normal; 2) p53 knockout cell line which is completely loss of p53 expression. Next, control siRNA or SET-specific siRNA was transfected into these cell lines for 96 hours. Total RNA was extracted for further RNA-seq analysis.	Co-expression
SRP076944	RNA-seq transcriptome analysis of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin	We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells. Overall design: Analysis of differentially expressed genes between epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin, biological replicates (n=7) (healthy skin donors).	Co-expression
SRP076951	Modeling human brain evolution using induced pluripotent stem cells: comparative analysis of neuronal development in humans and chimpanzees	Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species. Overall design: PolyA RNA-Seq profiling of neural progenitor cells (NPCs) and neurons differentiated from human and chimpanzee iPSCs.	Co-expression
SRP076978	iPSCs-NCSCs raw sequence reads	Analysis of the effects of LIPUS on iPSCs-NCSCs	Co-expression
SRP076982	Transcriptome analysis for anatomically separate psoriatic plaques highlight individualized expression patterns	To evaluate the transcriptomes of lesional skin from different body parts of the same individual.  Specifically, we conducted a transcriptomic study to investigate expression variability for diseased samples taken from different anatomic regions of same patient, and to compare the variability to between individuals variability. Overall design: 5 psoriasis patients, each with 4 psoriatic and 1 uninvolved skin biopsies. Totally 25 RNA-seq experiments conducted.	Co-expression
SRP076983	Aneuploidy triggers an immune response	Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells.  We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation. Overall design: Assay the transcriptional impact of aneuploidy by comparing the transcriptomes Euploid control RPE-1 cells in Aneuploid cycling RPE-1 cells and Aneuploid arrested RPE-1 cells using RNA-Seq.	Co-expression
SRP076988	Loss of Function Mutations in ETS2 Repressor Factor (ERF) Reveal a Balance Between Positive and Negative ETS Factors Controlling Prostate Oncogenesis [22PC RNA-seq]	Half of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4.  Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11.  Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions.  ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG.  Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites.  Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. Overall design: CWR22Pc cells  were infected with shNT or shERF and selected with antibiotics.  Subsequently, cells were treated with 1nM DHT  x 16hrs, or vehicle, in charcoal-stripped media.  Subsequently RNA was extracted and RNA-seq performed.  For each condition, 3 sets of equal numbers of cells were plated and then processed independently.	Co-expression
SRP076991	Loss of Function Mutations in ETS2 Repressor Factor (ERF) Reveal a Balance Between Positive and Negative ETS Factors Controlling Prostate Oncogenesis [VCaP RNA-Seq]	Half of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4.  Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11.  Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions.  ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG.  Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites.  Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. Overall design: VCaP cells were infected with lentivirus 1:  Tet-inducible shERG,  followed by lentivirus 2:  shERF or shNT, and selected with two different antibiotics.  Subsequently, cells were treated with 100ng/mL doxycycline vs vehicle, 1nM DHT x 16h vs vehicle, or both vs vehicle.  For each condition, 3 sets of equal numbers of cells were plated and then processed independently.	Co-expression
SRP077046	A functional genomics predictive network model identifies regulators of inflammatory bowel disease: Mount Sinai Hospital (MSH) Population Specimen Collection and Profiling of Inflammatory Bowel Disease	This study focuses on inflammatory bowel disease gene expression profiling. Surgical specimens from 134 patients undergoing bowel resection for inflammatory bowel disease (IBD) and non IBD controls at Mount Sinai Medical Center were collected as the source of tissue.  Control samples (CLs) were harvested from normal non inflamed bowel located more than 10 cm away from the tumor from patients undergoing bowel resection for sporadic colon cancer. Ulcerative colitis (UC) and Crohn’s (CD) patient samples were all isolated from areas containing moderate to severe inflammation. The diagnostic pathology report for each specimen was provided by the Mount Sinai Hospital Pathology Department.  Patients with UC and patients with CD shared common medications including corticosteroids, infliximab, azathioprine, and mesalamine. Overall design: Surgical specimens from 134 patients undergoing bowel resection for inflammatory bowel disease (IBD) and non IBD controls at Mount Sinai Medical Center were collected as the source of tissue. Control samples (CLs) were harvested from normal non inflamed bowel located more than 10 cm away from the tumor from patients undergoing bowel resection for sporadic colon cancer. Ulcerative colitis (UC) and Crohn’s (CD) patient samples were all isolated from areas containing moderate to severe inflammation. The diagnostic pathology report for each specimen was provided by the Mount Sinai Hospital Pathology Department. Patients with UC and patients with CD shared common medications including corticosteroids, infliximab, azathioprine, and mesalamine. The samples were collected fresh and the tissue was further processed for isolation. A representative 0.5 cm tissue fragment was isolated from the collected surgical specimen samples, flash frozen and stored at -80C. Tissue was homogenized in Trizol following the manufacturer''s protocol (Life Technologies) and RNA extraction was performed. RIN scores >7 were used for Poly A RNA-seq.	Co-expression
SRP077058	Propargite, an environmental chemical, interacts with GWAS identified diabetes genes to impact human pancreatic ß-cell death [propargite treatment]	This paper describes the first time a high-content environmental chemicals screen using pancreatic ß-like cells derived from human pluripotent stem cells (hPSCs), and discovered that a commonly used pesticide, propargite, induces pancreatic ß-cell DNA damage and necrosis. More interestingly, we found out the genetic background of ß-like cells affects their response to propargite-induced toxicity, based on isogenic hPSC platform, including for variants GWAS identified associated with T1D, since isogenic GSTT1-/- and PTPN2-/- pancreatic ß-like cells are hypersensitive to propargite-induced ß-cell death both in vitro and in vivo. In summary, our study identified an environmental chemical that contributes to the loss of ß-cells and provides an innovative platform for using hPSC-derived cells to explore gene-environment interactions that impact diabetes disease progression. Overall design: RNA-seq was used to compare the gene expression in DMSO, DMSO+GSH, Propargite and Propargite+GSH  treated  hESC derived INS-GFP+ cells.	Co-expression
SRP077068	ILF2 Regulates RNA Splicing of DNA Damage Response Genes to Confer Poor Prognosis in 1q21-Amplified Multiple Myeloma	To understand whether ILF2 is required to ensure the alternative splicing and processing of specific pre-mRNAs in Multiple Myeloma (MM), both in physiological and DNA damage conditions, we performed RNA sequencing (RNA-Seq) analysis of untreated or melphalan-treated ILF2-depleted JJN3 cells. Non-silencing or ILF2 shRNA transduced JJN3 cells were treated with melphalan for 10 hours. Overall design: Total RNA from untreated or melphalan-treated JJN3 cells transduced with a non-silencing or ILF2 shRNA (two independent replicates per condition) were isolated with the RNeasy Mini kit (Qiagen). Libraries were constructed using the Ovation RNA-Seq System V2 (Nugen) according to the manufacturer's instructions. Transcriptomic RNA-Seq was performed on the Illumina HiSeq 2000 platform using the standard paired-end protocol. In total, 60-160 million 76-bp reads were generated per sample. An initial sequence-level quality assessment was performed using FastQC (version 0.10.1, Simon Andrews). The RNA-Seq reads were then mapped to the reference human genome (GRCh37) using Tophat2, allowing a maximum of two mismatches per 76-bp sequencing end. Differential splicing was assessed by multivariate analysis of transcript splicing (MATS) using an FDR<0.05. Pathway enrichment analysis was performed with Pathway Studio.	Co-expression
SRP077072	Identification and validation of differentially expressed transcripts by RNA-Sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis	BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether RNA-Seq could be used to identify IPF expression profiles from archived Formalin-Fixed Paraffin-Embedded (FFPE) lung fibrotic tissue. RESULTS: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues (median archived time 6 years) and performed 50 bp paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. Cufflinks calculated FPKM values (Fragments per Kilobase of exon per Million) and identified differentially expressed genes between the IPF and control samples. Here we show that RNA-Seq data obtained from FFPE lung tissues is comparable to microarray data obtained from IPF fresh frozen tissues. Pathway enrichment and network analysis confirmed numerous IPF relevant genes and pathways. CONCLUSION: Our results demonstrate that transcriptomic analysis of RNA obtained from archived FFPE lung tissues is feasible. Therefore FFPE IPF lungs can be used as a valid and reliable source for transcriptomic profiling in IPF Overall design: RNA-Seq was performed on mRNA isolated from 6 IPF and 5 control lung FFPE tissues by using Illumina HiSeq 2000	Co-expression
SRP077080	Homo sapiens Transcriptome or Gene expression	Chemoresistance and metastasis remain major challenges for the treatment of epithelial ovarian cancer (EOC). It has been proposed that identification of cancer stem cells (CSCs) through biomarkers might provide new insights into EOC development and personalized chemotherapy. In the efforts to find biomarkes for EOC CSCs, we identified CDC50A, a subunit of P4-ATPases, through mass spectrum-based analysis of differentially expressed membrane proteins. The CDC50A+ EOC cells displayed self-renewal, differentiation and chemo-resistance properties of CSCs both in vitro and in vivo, and possessed molecular profile consistent with their stemness. Downregulation of CDC50A inhibited the ability of ovarian CSCs to self-renew.The CDC50A+ cells also exhibited mesenchymal phenotype and were increased in metastatic tumors. Furthermore, in retrospective analysis, CDC50A expression in tumor tissues is associated with clinicchemoresistance, PFS and OS of EOC patients. Thus, CDC50A is a marker for EOC CSCs and may serve as a novel therapeutic target.	Co-expression
SRP077230	PAX3-FOXO1 requires BRD4 to drive oncogene addiction in RMS cells [RNA-seq]	The fusion transcription factor PAX3-FOXO1 drives oncogenesis in a subset of rhabdomyosarcomas, however the mechanisms by which it remodels chromatin are unknown.  We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing super enhancers (SEs), in collaboration with master transcription factors MYOG, MYOD and MYCN.  This myogenic SE circuitry is consistent across cell lines and primary tumors. Deregulation of PAX3-FOXO1 itself occurs by translocation-induced chromatin loops bringing the PAX3 promoter under the control of FOXO1 enhancers.   Protein targets induced by, or bound to, PAX3-FOXO1 occupied SEs, were selectively sensitive to small molecule inhibition. PAX3-FOXO1 co-binds BRD4 at SEs, and BET bromodomains are required for PAX3-FOXO1-dependent transcription and cancer cell growth. Overall design: RNA-seq in FP-RMS cells exposed to either DMSO or JQ1 treatment, and RNA-seq of fibroblast cells stably transduced with either empty vector or PAX3-FOXO1 vector.	Co-expression
SRP077283	RNA-seq of naive and primed ES cells	Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. Overall design: RNA-seq of 4 naive ES samples in 4i/LA, 3 naive ES samples in 5i/LA, 2 transgene-dependant naive ES cell samples, and 5 primed ES cell samples (in hESM)	Co-expression
SRP077288	The FAM46C gene encodes a non-canonical poly(A) polymerase and acts as an onco-suppressor in multiple myeloma	FAM46C is one of the most frequently mutated genes in multiple myeloma (MM) and encodes a protein of unknown function. Using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active cytoplasmic non-canonical poly(A) polymerase, which enhances mRNA stability and gene expression. Moreover, we also found that the reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induced cell death. This is, to our knowledge, the first report that directly associates cytoplasmic poly(A) polymerase with carcinogenesis. Furthermore, our data suggest that the human genome encodes at least eleven non-canonical poly(A) polymerases with four FAM46 family members. Since FAM46 proteins are differentially expressed during development, these proteins may positively regulate transcript stability and translational rate in a tissue-specific manner. Overall design: The H929 and SKMM1 MM cells were transduced with lentiviruses carrying FAM46CWTGFP (WT) or FAM46CD90A,D92AGFP (catalitic mutant). 72h after transgene delivery total RNA was extracted and RNA-seq libraries were prepared.	Co-expression
SRP077320	Propargite, an environmental chemical, interacts with GWAS identified diabetes genes to impact human pancreatic ß-cell death [PTPN2 knockout]	This paper describes the first time a high-content environmental chemicals screen using pancreatic ß-like cells derived from human pluripotent stem cells (hPSCs), and discovered that a commonly used pesticide, propargite, induces pancreatic ß-cell DNA damage and necrosis. More interestingly, we found out the genetic background of ß-like cells affects their response to propargite-induced toxicity, based on isogenic hPSC platform, including for variants GWAS identified associated with T1D, since isogenic GSTT1-/- and PTPN2-/- pancreatic ß-like cells are hypersensitive to propargite-induced ß-cell death both in vitro and in vivo. In summary, our study identified an environmental chemical that contributes to the loss of ß-cells and provides an innovative platform for using hPSC-derived cells to explore gene-environment interactions that impact diabetes disease progression. Overall design: RNA-seq was used to compare the gene expression for two wildtype hESC (PTPN2+/+-1 and PTPN2+/+-2) and two PTPN2 knockout hESC (PTPN2-/--1 and PTPN2-/--2) derived INS-GFP+ cells.	Co-expression
SRP077355	JUNB is a critical AP1 component for SMAD2/3 binding after TGFß stimulation [RNA-seq]	We performed SMAD2/3 ChIP-seq analysis in MCF10A MII cells. To validate whether the changes in SMAD2/3 binding to the genome indeed resulted in changes in target gene expression, we performed RNA-seq transcriptome analysis after short and long periods of TGFß stimulation (0, 1.5h and 16h) in MII cells. In addition, we revealed that JUNB is a critical AP1 component for SMAD2/3 binding after TGFß stimulation. To assess the significance of JUNB for TGFß-SMAD-target genes on a genome-wide scale, we also performed RNA-seq transcriptome analysis in JUNB-knock-downed MII cells. Overall design: RNA-seq analysis in MCF10A MII cells with TGFß stimulation and/or JUNB knock down	Co-expression
SRP077469	T cells from paroxysmal nocturnal hemoglobinuria patients show an altered TNFR signaling pathway	In order to identify aberrant molecular mechanisms involved in immune targeting of HSCs in bone marrow, RNA-seq was applied to examine the transcriptome of T cell subsets from PNH patients and healthy controls. Overall design: RNA seq , 3 PNH patient's T cell subsets (CD4Naive, CD4Memory,CD8Naive, CD8Memory), 3 Healthy T cell subsets (CD4Naive,CD4Memory, CD8Naive, CD8memory)	Co-expression
SRP077504	Differentially expressed genes during pancreatic bud differentiation in cellular aggregates	Analysis of pathways altered by aggregation culture during differentiation from pancreatic progenitor cells into pancreatic bud cells. The hypothesis tested in the present study was that the high-cell density culture induces specific signals to facilitate the differentiation into pancreatic bud cells. Results provide the differentially regulated pathways between the low-cell density cultures and the high-cell density cultures. Overall design: Total RNA obtained from human ES cell-derived pancreatic progenitor cells subjected to differentiate into pancreatic bud cells. The pancreatic progenitor cells were cultured at the low-cell density or in the cellular aggregates. Samples were obtained 0, 1, 2, 3 and 4 days after culturing.	Co-expression
SRP077529	IFN-alpha response in human Type 2 Innate Lymphoid Cells (ILC2s)	Human Type 2 Innate Lymphoid Cells (ILC2s) cultured 9 hours with IFN-alpha (10 ng/mL) in the presence of IL-2, IL-7 and IL-33 (50ng/mL).	Co-expression
SRP077553	Transcriptome profile and gene expression in the human placenta	In this study, we performed a NGS analysis to identify transcriptome landscape of the human placenta during uncomplicated single and twin pregnancy, to establish a pattern of normal placental genes expression for further comprehensive analyses. Additionall aim of these studies was to identify the differentially expressed transcripts of genes in single and twin pregnancy that may participate in human pregnancy.	Co-expression
SRP077565	RHBDF2 in Stromal Fibroblasts Mediates TGF-b Signal and Enhances Cancer Cell Invasion via Intercellular Cross-Talk	Cancer-associated fibroblasts (CAFs) existing in tumor stroma play a crucial role in tumor progression. Here, we show that stromal fibroblasts near cancer cells are likely to display up-regulated RHBDF2 expression caused by chronic stimulation from pro-inflammatory cytokines. RHBDF2 promotes both the cleavage of type I transforming growth factor (TGF)-b receptor, through tumor necrosis factor a converting enzyme activation, and the motility of CAFs upon stimulation with TGF-b1. High-motility CAFs can consequently assist cancer cell invasion. Furthermore, the expression profiles of these cytokines are significantly associated with poor prognosis in gastric cancer (GC) patients. These findings highlight the underlying mechanism whereby cancer cells take advantage of CAFs to acquire invasiveness. Overall design: 11 matched normal and cancer fibroblast cell lines from diffused type gastric cancer and normal samples	Co-expression
SRP077567	Gene Expression Profiling Of TTLL12 Knocked Down Cell With Sendai Virus Treatment	Upon virus infection, RIG-I-like receptors in host cells recognize viral RNA and activate type I interferon expression. To investigate the role of protein methylation in the anti-viral signaling pathway, we screened all the SET domain containing proteins and identified TTLL12 as a negative regulator of RIG-I signaling pathway. TTLL12 contains SET and TTL domains, which are predicted to have lysine methyltransferase and tubulin tyrosine ligase activities, respectively. Exogenous expression of TTLL12 represses IFN-ß expression induced by SeV. TTLL12 deficiency by RNA interference and CRISPR-gRNA techniques increases the induced IFN-ß expression and inhibits virus replication in the cell. Gene expression profiling also indicated that TTLL12 specifically inhibits the expression of the downstream genes of innate immunity pathways. Cell fractionation and fluorescent staining indicated that TTLL12 is localized in the cytosol. The study of various mutants suggested TTLL12's ability to repress RIG-I pathway is probably not dependent on protein modifications. Instead, TTLL12 directly interacts with VISA, TBK1 and IKKe, and inhibits the interactions of VISA with other signaling proteins. Taken together, our findings demonstrate TTLL12 as a negative regulator of RNA-virus-induced type I IFNs expression through inhibition of the interaction of VISA with other proteins. Overall design: TTLL12 was knocked down by siRNA in HCT116 and the gene expression profile was studied by RNA sequencing	Co-expression
SRP077593	Identification of a unique gene expression signature in mercury and 2,3,7,8-tetrachlorodibenzo-p-dioxin co-exposed cells	Mercury (Hg) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are major environmental contaminants that commonly co-occur in the environment. Both Hg and TCDD are associated with a number of human diseases including cancers. While the individual toxicological effects of Hg and TCDD have been extensively investigated, studies on co-exposure are limited to a few genes and pathways. Therefore, a significant knowledge gap exists in the understanding of the deleterious effects of co-exposure to Hg and TCDD. Due to the prevalence of Hg and TCDD co-contamination in the environment and the major human health hazards they pose, it is important to obtain a fuller understanding of genome-wide effects of Hg and TCDD co-exposure. In this study, by performing a comprehensive transcriptomic analysis of human bronchial epithelial cells (BEAS-2B) exposed to Hg and TCDD individually and in combination, we have uncovered a subset of genes with altered expression only in the co-exposed cells. We also identified the additive as well as antagonistic effects of Hg and TCDD on gene expression. Moreover, we found that co-exposure impacted several biological and disease processes not affected by Hg or TCDD individually. Our studies show that the consequences of Hg and TCDD co-exposure on the transcriptional program and biological processes could be substantially different from single exposures, thus providing new insights into the co-exposure-specific pathogenic processes. Overall design: Methods: we performed a comprehensive analysis of the transcriptomes of cells exposed to Hg or TCDD individually and in combination. RNA Seq gene expression comparison done in replicates.	Co-expression
SRP077595	Anti-Inflammatory Effects of Budesonide in Human Fetal Lung	Rationale. Lung inflammation in premature infants contributes to development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without apparent adverse effects as occur with systemic dexamethasone therapy. Objectives. To determine effects of budesonide on differential genes expression in human fetal lung Overall design: Methods. We prepared RNA from 3 samples of human fetal lung at 23 weeks gestation before (preculture, PC) and after 4 days culture as explants with (Bud) or without (Way) budesonide (30 nM) and performed RNAseq on the 9 samples.	Co-expression
SRP077606	Lens Epithelial Cells treated by miR-184 Raw sequence reads	Transcriptome-wide investigation of mRNA and circular RNA in miR-184 and mutant miR-184(r.57c>u) treatment human lens epithelial cells	Co-expression
SRP077668	Using AmpliSeq we have performed quantitative analysis of 20,803 genes in Negative control precursor-miR (NC-Pre-miR) and pre-miR-17 transfected Rheumatoid arthritis Synovial Fibroblasts (RASFs)	Purpose: The goals of this study are to determine the effect of microRNA-17 overexpression on 20,803 human genes in RASFs using Ion ProtonTM System platform. Human RASFs from two RA patients were transfected with pre-miR-17 or NC-pre-miR for 48 h and total RNA was prepared using miRNeasy kit (Qiagen). Total RNA integrity was checked using an Agilent Technologies 2100 Bio analyzer (Santa Clara, CA). 10 ng of high quality RNA was used to make cDNA for amplification with the Ion AmpliSeq Transcriptome Human Gene Expression kit (ThermoFisher Scientific).  The cDNA was subjected to 12 cycles of amplification with panel primers and barcoded with adapters as recommended.  Resulting sequencing libraries were quantified by qPCR using SYBR FAST master mix from KapaBiosystems (Wilmington, MA).  Sets of eight libraries were balanced, pooled and sequencing beads produced on an Ion Chef.  Sequencing was performed on an Ion P1 semi-conductor sequencing chip using an Ion Proton™ System (ThermoFisher Scientific, Grand Island, NY). Data was collected and primary analysis performed using Torrent Suite software version 5.0.3. Reads were mapped to the panel and expression values determined. R Software version R-3.2.3 was used to generate heatmap. Among the panel of 20,803 genes, the expression of 15,067 genes as shown in the representative heat map was observed in pre-miR-17 and NC-pre-miR transfected RASFs. A total of 664 significantly modulated genes (301 upregulated and 363 downregulated) using Student ‘t’ test were further utilized for the IPA analysis. The result of IPA predicted the protein ubiquitin pathway as a major canonical pathway affected by the differentially regulated genes. Interestingly, IPA analysis generated an interactome that showed connectivity among various ubiquitin ligases, NF-?B family, AP-1/cJun, 20S and 26S proteasome system. Conclusion: Our results clearly shows the major pathways affected by miR-17 overexpression in RASFs were Protein ubiquitination related. Overall design: mRNA profiles of pre-miR-17 and NC-pre-miR transfected RASFs were generated by AmpliSeq, in duplicate, using Ion Proton™ System.	Co-expression
SRP077680	Human Lens Epithelial Cells treated by m-miR-184 Raw sequence reads	To fund the relations between HLE treated by miR-184/m-miR-184	Co-expression
SRP077681	Human Lens Epithelial Cells treated by NC Raw sequence reads	Human Lens Epithelial Cells treated by NC	Co-expression
SRP077683	The effect of ADAM12 knockdown on gene expression in SUM159PT breast cancer cells	The goal of the study was to assess a possible contribution of ADAM12 to the cancer stem cell phenotype of triple negative breast cancer cells. ADAM12 was knocked down in SUM159PT cells using a doxycycline-inducible shRNA system. shADAM12 or shControl cells were incubated with or without 1 µg/ml doxycycline for 4 days, followed by RNA sequencing.	Co-expression
SRP077708	Transcriptome of Celiac Disease	The aim of this study is to analyze the transcriptome of epithelial (CD326+ enriched) and immune (CD45+ enriched) fraction in Celiac Disease and controls to find differentially expressed genes.	Co-expression
SRP077713	mRNA-seq analysis of HCT116 cells following gene overexpression of IDO1 with or without Indole treatment	To investigate the effect of indole on protection against colon injury and the role of IDO1 expression, we examined the effect of indole on hIDO1-overexpressing and empty vector control HCT116 cells by global gene expression profiling. Overall design: Examination of mRNA levels from hIDO1-overexpressing and control HCT116 cell lines treated with 1mM indole or DMF for 24 hours using two replicates each.	Co-expression
SRP077728	Transcriptome response of human oral epithelial cells treated with TNF and IL-17 and infected with Candida albicans	Human oral epithelial cells were either treated with TNF and IL-17 (or left untreated) and then subject to in vitro infection with Candida albicans.	Co-expression
SRP077731	RNA-seq data sets from in vitro infection of A549 cells with either Mucoralean fungi.	A549 airway epithelial cells were subject to in vitro infection with fungal pathogens (either Rhizopus delemar, Rhizopus oryzae or Mucor ciricinelloides) for 6 or 16 hours and then subject to RNA-seq analysis of both the host and fungal transriptomes.	Co-expression
SRP077751	Transcriptomic profile of human non-alcoholic steatohepatitis	Gene expression profile of 91 human subjects at various stages of non-alcoholic steatohepatitis.	Co-expression
SRP077846	Next-generation sequencing of lncRNAs regulated by oxygen in MCF-7 cells	To identify the oxygen-responsive lncRNAs, next-generation sequencing was performed. Cells were harvested under normoxia (O2), hypoxia (N2) and re-oxygenation (Re-O2) conditions. Each condition was done in triplicate	Co-expression
SRP077872	Zone dependent distinctive gene expression profile of the normal human liver tissue	The regulatory mechanisms that shapes the hepatic zonation is not well understood. In addition, the concept and significance of of hepatic zonation is well established in rodens, however, its relavence to human liver biology remain elusive. We conducted a comprehensive transcriptome analysis of each zonation within normal human liver vis Laser Capture Microdissection approach. Here,  we report a poly A RNA sequencing data of the individual zone of liver tissue as well as the whole liver of the corresponding subjects. Overall design: The RNA samples were collected from each zone within hepatic lobule by a Laser Captured Microdissection approach. This study examined the gene expression profile in each zone of the normal human liver.	Co-expression
SRP077885	Modulation of ESRP2 and MBNL2 in normal kidney and clear cell renal cell carcinoma cell lines for analysis of stability programs	While analyzing mRNA expression profiles of clear cell renal cell carcinoma (ccRCC) tumors, we found that the mRNAs that are bound at their 3'' UTRs by muscleblind-like splicing regulator 2 (Mbnl2) and epithelial splicing regulatory protein 2 (ESRP2) are up-regulated in tumor compared to patient-matched normal tissues. Given that MBNL2 increases the stability of its targets and ESRP2 destabilizes its targets, we predicted that, in ccRCC tumors, MBNL2 activity increases, while ESRP2 activity decreases. To investigate the effect of each of these two RNA-binding proteins (RBPs) on the transcriptome of the cell, we used shRNA to knockdown MBNL2 in two different cell line models of ccRCC (786-O and A-498), and also to knockdown ESRP2 in normal primary renal proximal tubule epithelial cells (PRPTEC). RNA-seq revealed that MBNL2 knockdown partially reverses the ccRCC-associated transcriptome in ccRCC cell lines, whereas ESRP2 knockdown shifts the transcriptome of PRPTEC toward that of ccRCC. Overall design: Two independent shRNAs were used for each protein in each cell line. Each cell line was also infected by a control shRNA in two replicates. The transcriptome after infection with MBNL2- or ESRP2-specific shRNA was compared to the transcriptome after infection with control shRNA.	Co-expression
SRP077915	Reprogrammed neurons from adult dermal fibroblasts of patients with Huntington's disease	Reprogrammed neurons from adult dermal fibroblasts of patients with Huntington's disease Overall design: De-identified human adult dermal fibroblasts from patients with Huntington's disease or age- and gender-matched healthy controls were obtained from the Coriell Institute for Medical Research Biorepository. These fibroblast samples were transduced with lentivirus to express the brain enriched microRNAs, miR-9/9* and miR-124 and striatal-enriched transcription factors BCL11B (Also known as CTIP2), DLX1, DLX2, and MYT1L to directly convert fibroblasts into striatal neurons as previously established (Victor et al., Neuron 2014; Richner et al., Nat. Prot. 2015). Total mRNA from reprogrammed neurons and non-converted fibroblasts was collected and prepared for RNA-seq analysis 32 days after viral transduction.	Co-expression
SRP077918	BCL6-centric reorganization of the genome during B cell affinity maturation	During the humoral immune response mature B-cells undergo a dramatic change in phenotype to enable antibody affinity maturation in germinal centers (GCs).  Here, we observe for the first time that these phenotypic changes are accompanied by large-scale reorganization of the genomic architecture that encodes the GCB-cell transcriptional program.  The coordinate expression of genes that specify the GCB-cell phenotype – most prominently, BCL6 – is achieved through a non-random, multilayered, chromatin reorganization process involving i) increased promoter connectivity, ii) formation of higher-order enhancer networks, iii) 5’ to 3’ gene looping, and iv) merging of gene neighborhoods that share active epigenetic marks.  These cell-specific events are closely linked to binding of GC transcription factors and the structural proteins CTCF and cohesin.  The gene encoding the GC master regulator, BCL6, is an anchor point for the formation of GC-specific gene and enhancer loops on chromosome 3. Furthermore, through CRISPR-mediated knockout we demonstrate that a putative locus control region upstream of Bcl6 is required for GCB-cell formation in mice. Thus, architectural reorganization of phenotype-driving gene sets, including assembly of cell type-specific promoter and enhancer networks, may be key to controlling tissue-specific gene expression programs. Overall design: We performed replicate HiC experiments in primary human mature naïve B cells and germinal center B cells purified from tonsils of healthy individuals to examine three-dimensional organization of the B cell genome. We performed RNAseq to measure gene expression in the same specimens.	Co-expression
SRP077921	RNA sequencing of patient derived cell lines in pancreatic cancer	Gene expression levels of pancreatic cell lines Overall design: RNA was extracted from cell lines and subjected to 50bp paired-end RNA sequencing	Co-expression
SRP077930	Transcriptome profiling of ER+ breast cancer primary tumor and its tumorsphere derivative	We profiled RNA expression in the ER+ primary tumor and the matching tumorspheres. The objective was to find genes differentially expressed between the tumorspheres and bulk tumor. Overall design: 12 pairs of matching ER+ bulk tumor and its tumorspheres	Co-expression
SRP077969	Post-transcriptional 3'UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments	Here, using genome wide analysis, we demonstrate that canonical mRNA is processed post-transcriptionally through an alternative cleavage and polyadenylation mechanism. As a result of this process, the downstream cleavage fragment of the 3'UTR remains uncapped and stable This finding indicates that different parts of gene mRNA are separate and independent, by re-annotating the human transcriptome using this model, we provide a new overview of the function and impact of microRNA (miRNA) Our results shed new light on the mammalian transcriptome and show that what were considered as 3'UTRs are in fact autonomous RNA fragments. Overall design: Examination of mRNA levels and cleavage across transcripts in U2OS and 293 cell types (3 replicates each)	Co-expression
SRP077970	Definition of human cardiac progenitor cell plasma membrane signature: comparative genomic and proteomics analysis with human mesenchymal stem cells	Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the proteome fraction associable to specific CPC functions by comparison with human mesenchymal stem cells (MSC), the reference population for cell therapy. Label-free proteomics analysis identified 526 proteins expressed differentially in CPC. Quantitative iTRAQ analysis confirmed differential expression of a substantial proportion of these proteins expressed specifically in CPC relative to MSC. Systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment is comprised by 1595 proteins including a minimal signature of 167 proteins expressed preferentially in CPC. Of these core CPC functions, we selected a panel of 15 predicted cell surface markers and validated high differential expression of CDH5, CD200 and F11R in CPC. Overall design: RNA was isolated from CPC (CPC1 (H1), CPC2 (H3), CPC3 (H4)), MSC (MSC1 (19), MSC2 (33)), MSC3 (45) and HDF (FB1, FB2, FB3) as described (Moscoso et al., 2013).  For RNAseq library production, total RNA (1 µg) was used with the TruSeq RNA Sample Preparation v2 Kit (Illumina) to construct index-tagged cDNA libraries. Libraries were sequenced (single-end mode, 75 bp length) on the Genome Analyzer IIx following the standard RNA sequencing protocol, with the TruSeq SBS Kit v5.  Fastq files containing reads for each library were extracted and demultiplexed using the Casava v1.8.2 pipeline	Co-expression
SRP077975	Host blood trancriptional profiles during Mycobacterium tuberculosis infection.	We report a pilot investigation for poly-A RNAs differentially expressed during Mycobacterium tuberculosis infection. Participation in this investigation from March 2010 to July 2013 was voluntary, only subjects that were >18 years old and that informed written consent were considered eligible.  The recruitment of tuberculosis (TB) patients was done at public hospitals in Rio de Janeiro, Brazil. The diagnostic criteria for active pulmonary tuberculosis was at least one AFB (acid-fast bacilli) -positive sputum sample for M. tuberculosis and/or positive sputum culture and/or compatible clinical evolution for pulmonary TB and less than 15 days of anti-TB treatment and was in accordance with those of the Brazilian Ministry of Health. Blood was collected from recent close contacts (rCt) and active tuberculosis (TB) index cases (n=6). Latent TB infection (LTBI) was accessed by both tuberculin skin test (TST, cut-off = 5mm) and in house interferon-gamma release assays (IGRA, cut-off = 100 pg/ml), therefore, 12 rCt were classified as uninfected controls and 16 with LTBI.  Subsequently, the sequencing was performed following the standard protocols on Illumina HiSeq® 2500 Sequencing System (Illumina, San Diego, CA) running 100 bp paired-end reads (PE100) and generating approximately 30 million reads passing filter for each sample to produce the mRNA reads. Mining these RNAseq data, highly prominent modulation of DOCK9, EPHA4, and NPC2 mRNA expression was observed in the TB samples, indicating that they might have a role in TB pathogenesis. These differential modulations upon M. Tuberculosis infection were further validated by additional evidences in larger cohorts from different geographical areas. Overall design: We collected blood samples from the recent close contacts (rCt) at the recruitment and monitored them for 1-year. All TB participants were treatment-naïve. An infection mRNA signature was derived from whole blood RNA sequencing data by comparing TB and uninfected rCt. We selected the 3 most prominent genes, by area under the ROC curve analysis, for additional validations. Some of the LTBI participants also showed the mRNA infection profile.	Co-expression
SRP077979	Regulators of cellular heterogeneity in basal-like breast cancer influence symmetric versus asymmetric division rates (Expression profiles)	Differentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect the mechanisms controlling intratumoral heterogeneity within basal-like breast cancers. We show that cancer cells can transition between a differentiation state related to that of normal luminal progenitors and a state closer to that of mature luminal cells, and that this occurs through asymmetric cell divisions. The Polycomb factor EZH2 and the Notch pathway act to increase the rates of symmetric divisions that produce progenitor-like cells, while the FOXA1 transcription factor promotes asymmetric divisions that reduce the numbers of such cells. Through functional screening, we identified a group of regulators that control cancer cell differentiation state and the relative proportions of tumor cell subpopulations. Our findings highlight the regulation of asymmetric cell divisions as a mechanism controlling intratumoral heterogeneity, and identify molecular pathways that control breast cancer cellular composition. Overall design: Expression profiles of three cell subpopulations – K18+, K18+K14+ and K18+Vim+ – sorted from the breast cancer cell lines HCC70 and MDA-MB-468	Co-expression
SRP077998	Next Generation Sequencing Facilitates Quantitative Analysis of Human Primary and Pluripotent Stem Cell-Derived Epicardial Cell Transcriptomes	Next-generation sequencing (NGS) has significantly advanced the elucidation of developmental signaling mechanisms that are important for different cell lineage formation from human pluripotent stem cells (hPSCs). We report here the application of RNA-sequencing technology for transcriptome profile of human primary and hPSC-derived epicardial cell, and compare to those of other cell lineages including hPSCs, mesoderm, cardiomcyotyes. Eight epicaridal cell samples from four different hPSC lines and four different donors were performed in IIIumina HiSeq2500. The resulting sequence reads (about 20 million reads per sample) were mapped to human genome (hg19) using HISAT, and the RefSeq transcript levels (RPKMs) were quantified using the python script rpkmforgenes.py. Our RNA-seq data confirmed the stable expression of key epicardial cell markers including WT1, TBX18, TCF21, ALDH1A2 and ZO1, and the gene set enrichment analysis (GSEA) showed enrichment in extracellular matrix related pathways and keratinocyte (epithelial) differentiation. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to epicardial function. This study represents the first detailed analysis of epicardial transcriptomes generated by RNA-seq technology, providing insight into the mechanisms underlying the differentiation of hPSCs into epicardial cells. Overall design: Epicardial transcriptome profiles of 8 different samples from 4 hPSC lines and donors were generated by RNA-seq technology using IIIumina HiSeq2500	Co-expression
SRP078006	Profiling in vivo Bone Lesion and ex vivo Bone-In-Culture Array Samples by Next-Generation Sequencing	Based on RNA-seq, we performed transcriptomic profiling to examine the similarities or differences between BICA (bone-in-culture array) and IVBL (in vivo bone lesion). CIBERSORT analysis reveals that the major local cellular components are comparable between BICA and IVBL, but differ dramatically in orthotopic tumors. Principle component analysis of human RNAs indicated that the transcriptomic profiles of cancer cells in BICA are more closely mimicking IVBL, as compared to cancer cells in 2D and in orthotopic tumors. These results provide transcriptome-wide evidence supporting BICA as a platform to mimic bone microenvironment. Overall design: 2D culture cells, orthotopic tumors, BICA samples and bone lesions, all developed by MCF-7, are subject to NGS and then analyzed.	Co-expression
SRP078053	The NFkB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells	The epithelial-mesenchymal transition (EMT) is a multistep dedifferentiation program important in tissue repair. Here, we examined the role of the transcriptional regulator NFkB in EMT of human primary small airway epithelial cells (hSAECs). Surprisingly, transforming growth factor ß (TGFß) activated NFkB/RELA proto-oncogene, NFkB subunit (RELA) translocation within 1 day of stimulation, yet induction of its downstream gene regulatory network occurred only after 3 days. A time course of TGFß-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFß stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified Wnt, cadherin, and NFkB signaling as the most prominent TGFß-inducible pathways. By comparison, RELA controlled expression of 3,138 overlapping genes mapping to Wnt, cadherin, and chemokine signaling pathways. Conducting upstream regulator analysis, we found that RELA controls six clusters of upstream transcription factors, many of which overlapped with a transcription factor topology map of EMT developed earlier. RELA triggered expression of three key EMT pathways: (1) the Wnt/ß-catenin morphogen pathway, (2) the JUN transcription factor, and (3) the Snail family transcriptional repressor 1 (SNAI1). RELA binding to target genes was confirmed by ChIP. Experiments independently validating Wnt dependence on RELA were performed by silencing RELA via genome editing and indicated that TGFß-induced WNT5B expression and downstream activation of the Wnt target AXIN2 are RELA-dependent. We conclude that RELA is a master transcriptional regulator of EMT upstream of Wnt morphogen, JUN, SNAI1-ZEB1, and interleukin-6 autocrine loops. Overall design: RNA-seq transcriptome profiling of TGF-Beta stimulated RelA wildtype and knock-down cells	Co-expression
SRP078060	Regulators of cellular heterogeneity in basal-like breast cancer influence symmetric versus asymmetric division rates (shRNA targeting)	Differentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect the mechanisms controlling intratumoral heterogeneity within basal-like breast cancers. We show that cancer cells can transition between a differentiation state related to that of normal luminal progenitors and a state closer to that of mature luminal cells, and that this occurs through asymmetric cell divisions. The Polycomb factor EZH2 and the Notch pathway act to increase the rates of symmetric divisions that produce progenitor-like cells, while the FOXA1 transcription factor promotes asymmetric divisions that reduce the numbers of such cells. Through functional screening, we identified a group of regulators that control cancer cell differentiation state and the relative proportions of tumor cell subpopulations. Our findings highlight the regulation of asymmetric cell divisions as a mechanism controlling intratumoral heterogeneity, and identify molecular pathways that control breast cancer cellular composition. Overall design: Expression profiles of HCC70 cells expressing shRNAs targeting regulatory factors that influence basal-like cancer cell population composition	Co-expression
SRP078071	Tpl-2 small molecule project	Tpl-2 is a serine/threonine kinase that has been studied extensively in monocytes. Tpl-2 is believed to phosphorylate MEK1/2, which is upstream of ERK1/2, and regulates inflammatory gene expression in response to TLR and IL-1b receptor signaling. In the course of performing proof-of-concept studies using a small molecule inhibitor (SMI) of Tpl-2, we were surprised to see the inhibitor affect cytokine production in human neutrophils. Unlike human monocytes, which respond at least some degree to both Tpl-2 and MEK inhibitors, neutrophils showed a disconnect between Tpl-2 and MEK. A panel of genes in this cell type can be fully blocked by a Tpl-2 SMI, and yet show no response to a MEK SMI, suggesting Tpl-2 mediates its effect through substrates other than MEK. Overall design: The goal of this study is to compare the gene expression profiles of LPS-treated human neutrophils treated with vehicle, Tpl-2 SMI, or MEK SMI, in order to shed light on the MEK-independent arm of the Tpl-2 response. Purified neutrophils from 5 healthy donors were split into 4 groups: Unstimulated neutrophils, vehicle treated for 6.5 hrs; Neutrophils pretreated 30 min with vehicle, then stimulated 6 hrs with 10 ng/ml LPS; Neutrophils pretreated 30 min with G-432, then stimulated 6 hrs with 10 ng/ml LPS; and Neutrophils pretreated 30 min with G-573, then stimulated 6 hrs with 10 ng/ml LPS. This yields a total of 20 samples (5 donors x 4 conditions).	Co-expression
SRP078073	L-MYC Expression Maintains Self Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells	These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in brain tumors, TBI and other CNS diseases Overall design: Comparison of early and late passages of human NSC008, LM-NSC008 and LM-NSC008 Differentiated cells in culture	Co-expression
SRP078083	Single cell RNA-seq analysis of a squamous cell carcinoma of urinary bladder	We use single cell RNA-seq method to analysis the transcriptional heterogeneity in squamous cell carcinoma of urinary bladder. The single cell sequencing approach is based on the method of single-cell tagged reverse transcription (STRT).	Co-expression
SRP078114	Homo sapiens Tell''s lab	Apurinic/apyrimidinic endonuclease 1 (APE1) is one of the most important enzyme in the DNA base excision repair (BER) pathway. Besides providing a crucial role in the maintenance of genome stability, APE1 acts as a redox-coactivator by regulating the expression of genes involved in tumor progression. Due to its important role in many physiological and pathological processes, including tumorigenesis, aging, angiogenesis, and oxidative stress signaling, APE1 is an emerging target for combination therapy of cancers through the use of DNA-repair or redox inhibitors. However, its causal involvement in the tumorigenic process and in chemoresistance remains to be elucidated. Recent findings have unraveled the novel role of APE1 in RNA metabolism; although the mechanisms and the functional significance remains largely unknown. To identify novel APE1-bound RNAs, we performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in HeLa cells clones expressing an ectopic FLAG tagged wild type APE1 protein. APE1-bound RNA were purified using an anti-FLAG antibody. Experiments were performed in triplicates and to further reduce potential false positives, a negative control of resin lacking the proper antibody was introduced.	Co-expression
SRP078126	Changes in human endometrial gland transcriptome over the window of implantation	Human endometrial glands from early, mid and late secretory phases were captured using laser microdissection, and analyzed to characterize the gene expression changes during the window of implantation. Overall design: Laser-captured endometrial glands were analyzed for gene expression changes over time during the window of implantation	Co-expression
SRP078132	3'READS+, a sensitive and accurate method for 3' end sequencing of polyadenylated RNA	Sequencing of the 3' end of poly(A)+ RNA identifies cleavage and polyadenylation sites (pAs) and measures transcript expression. We previously developed a method, 3' region extraction and deep sequencing (3'READS), to address mispriming issues that often plague 3' end sequencing. Here we report a new version, named 3'READS+, which has vastly improved accuracy and sensitivity. Using a special locked nucleic acid oligo to capture poly(A)+ RNA and to remove bulk of the poly(A) tail, 3'READS+ generates RNA fragments with an optimal number of terminal As that balance data quality and detection of genuine pAs. With improved RNA ligation steps for efficiency, the method shows much higher sensitivity (over two orders of magnitude) compared to the previous version. Using 3'READS+, we have uncovered a sizable fraction of previously overlooked pAs located next to or within a stretch of adenylate residues in human genes, and more accurately assessed the frequency of alternative cleavage and polyadenylation (APA) in HeLa cells (~50%). 3'READS+ will be a useful tool to accurately study APA and to analyze gene expression by 3' end counting, especially when the amount of input total RNA is limited. Overall design: Nine 3''READS+ libraries were made with different amounts (100 ng, 200 ng, 400 ng, 1000 ng, 5000 ng, 15000 ng) of input Hela RNA.	Co-expression
SRP078134	Identification of a nuclear exosome decay pathway for processed transcripts	The   RNA   exosome   is   fundamental   for   the   degradation   of   RNA   in eukaryotic  nuclei.  Substrate  targeting   is  facilitated  by  its  co-factor Mtr4p/hMTR4,  which  links  to RNA-binding  protein  adaptors. One  such activity  is  the  human  Nuclear  EXosome  Targeting  (NEXT)  complex, composed  of  hMTR4,  the  Zn-finger  protein  ZCCHC8  and  the  RNA-binding  factor  RBM7.  NEXT  primarily  targets  early  and  unprocessed transcripts, demanding   a   rationale   for   how   the   nuclear exosome recognizes processed  RNAs. Here, we describe the  PolyA tail eXosome Targeting  (PAXT)  connection, comprising  the  hitherto  uncharacterized ZFC3H1 Zn-knuckle  protein  as  a  central  link  between  hMTR4  and  the nuclear  polyA  binding  protein  PABPN1.  Individual  depletion  of  ZFC3H1 and  PABPN1  results  in  the  accumulation  of  common  transcripts,  that are   generally   both   longer   and   more   3'polyadenylated   than   NEXT substrates. Importantly, ZFC3H1/PABPN1  and  ZCCHC8/RBM7  contact hMTR4  in  a  mutually  exclusive  manner,  revealing  that  the  exosome targets nuclear transcripts of different maturation status by substituting its hMTR4-associating adaptors. Overall design: RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control), RRP40, RBM7, ZCCHC8, PABPN1 and ZFC3H1. Both total and BrU RNA (one hour labeling) were collected for each condition in triplicates. The spike-in sequences used in the samples can be provided upon request.	Co-expression
SRP078148	Single-nucleotide-resolution mapping of HBV promoters using CAGE	We provide a comprehensive map of transcription start sites (TSSs) for HBV at single nucleotide resolution using CAGE. Overall design: Expression profiles using CAGE for HepG2.2.15 (3 replicates), primary human hepatocytes (3 replicates),  HepAD38 (2 replicates) and mouse liver tranduced with AAV-HBV (3 replicates)	Co-expression
SRP078152	Ebolavirus species associated with differential pathogenicity induce distinct host responses in human macrophages	Highly pathogenic Zaire ebolavirus (EBOV) infection is associated with a dysregulated immune response and high levels of cytokines and chemokines are observed in fatal human cases. . In stark contrast Reston ebolavirus (RESTV) might be non-pathogenic for humans yet the underlying mechanisms determining pathogenicity for different Ebola viruses are not understood. In this study we investigate antiviral immune responses in EBOV- and RESTV- infected primary human monocyte-derived macrophages (MDM). We provide evidence that increased pathogenicity of the highly pathogenic EBOV is associated with a strong activation of host responses from infected MDM. The observed cytokine response after EBOV infection is strikingly similar to LPS-mediated immune signatures however EBOV caused significant induction of the interferon response in addition. In contrast we show that the low pathogenic RESTV fails to elicit significant immune responses in infected MDM. These results demonstrate a correlation of pathogenicity and excessive MDM activation for different Ebola virus species. Interaction of the viral glycoprotein (GP) with Toll-like receptor 4 (TLR4) leading to activation of NF_B signaling is responsible for this effect rather than differences in replication or blocking of immune signaling. We demonstrate that inhibition of TLR4 is able to abolish EBOV-GP mediated NF_B activation which might offer the possibility to develop targeted treatments for EBOV limiting the extreme immune response that seems to be detrimental to the host. Overall design: RNA was isolated from primary cultured human macrophages (n=3 donors) that were either mock-infected, infected with Ebola virus (Kikwit-95) or Reston virus (Pennsylvania), or treated with lipopolysaccharide (LPS).	Co-expression
SRP078156	OSCC genome and transcriptiome sequencing	Integrated genome and transcriptome analyses for oral squamous cell carcinoma in the Taiwanese population	Co-expression
SRP078166	Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation (RNA-Seq)	We screened for small molecules that reactivated latent HIV-1 and identified benzotriazoles as latency-reducing agents. Here, we characterize the effects of HODHBt on gene expression in cultured T cells from three donors by polyA RNA-Seq and on STAT5A occupancy of the HIV-1 LTR promoter by ChIP-Seq. These and other results demonstrate that benzotriazoles block SUMOylation of phosphorylated STAT5, prolonging its transcriptional activity. Overall design: 1 micogram of total RNA from 4.6, 8.3, or 13 million cells (3 donors) per treatment	Co-expression
SRP078169	RNA-seq analysis of activated plasmacytoid dendritic cell subsets after viral infection	Hematopoiesis generates cell diversity through evolutionarily-determined differentiation programs defined at steady-state conditions. Here, we show that peripheral innate immune activation can generate cell diversity and functional specialization during the activation process. We found that activation of steady state human plasmacytoid pre-dendritic cells (pDCs) with a single microbial stimulus induced their differentiation into three phenotypically, morphologically, and functionally distinct subsets, in the absence of cell division: P1 (PD-L1+CD80-), P2 (PD-L1+CD80+) and P3 (PD-L1-CD80+). Different stimuli induced variable proportions of the subsets, suggesting that steady state pDC are multipotent. P1-pDCs display a plasmacytoid morphology and strong specialization on IFN production, whereas P3-pDCs adopt a dendritic morphology and adaptive immune functions. P2-pDCs have an intermediate functional profile. We found that a P1-pDC phenotype is present in human autoimmune diseases associated to type I IFN production as lupus and psoriasis, supporting their pathophysiological relevance. We propose that peripheral innate activation represents a differentiation mechanism to generate subsets diversity and functional complementarity in human pDCs. Overall design: 15 samples: medium (control condition), ex-vivo, P1, P2 and P3, each from 3 healthy donors. Ex-vivo plasmacytoid dendritic cells from the blood of healthy human donors were treated for 24h with influenza virus. Treated cells were sorted as P1, P2, and P3 subsets depending on surface markers: P1 (PD-L1+CD80-), P2 (PD-L1+CD80+) and P3 (PD-L1-CD80+). Non-treated control cells correspond to  pDCs  kept in medium.	Co-expression
SRP078214	BET inhibitors suppress BZLF1 expression [MutuI RNA-seq]	Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV life cycle: expression of the immediate-early gene BZLF1 and lytic genome replication. This represents a novel mode of action for antiviral drugs that may increase efficacy and decrease emergence of resistance. The RNA-seq data below show that the first block by JQ1 occurs before transcription of any EBV lytic genes (see wigs of EBV transcriptomes). A subset of the same RNA-seq data (three replicates each of Mutu+vehicle was compared to Mutu+JQ1) was examined for changes in the human transcriptome, and those results are presented in the spreadsheet "Differential_Expression_GEO" Overall design: RNA-seq from MutuI pretreated with JQ1 or vehicle, treated with antibody or vehicle, experiment performed in triplicate	Co-expression
SRP078234	Left-right asymmetry of maturation rates in human embryonic neural development	Left-right asymmetry is a fundamental organizing feature of the human brain, and neuro-psychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks post conception, the majority of human foetuses move their right arms more than their left arms, but because nerve fibre tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role. Here we have used gene expression profiling in 18 human embryos to show that the left side of the human spinal cord, between four and eight weeks post conception, matures slightly faster than the right side, even though both sides transition from transcriptional profiles associated with cell division and proliferation at earlier stages, to later neuronal differentiation and function. The hindbrain showed a left-right mirrored pattern compared to the spinal cord. Overall design: RNA was extracted from left and right spinal cord and left and right hindbrain from 18 human embryos ranging in age from Carnegie stage 13 to Carnegie stage 23. For library preparation, Illumina TruSeq RNA-kits (Illumina, San Diego, CA, USA) were used according to the manufacturer’s instructions. The library was sequenced using Illumina HiSeq(TM) 2000 at BGI, yielding paired reads of 90bp. The clean reads were aligned to the reference sequence GRCh37 (hg19) with SOAPaligner/SOAP2 v2.21 and Tophat (v2.08).	Co-expression
SRP078245	Integrated Systems Biology Analysis of KSHV Latent Infection Reveals Viral Induction and Reliance on Peroxisome Mediated Lipid Metabolism	Kaposi’s Sarcoma herpesvirus (KSHV), an oncogenic virus, modulates host cell signaling and metabolism to maintain latent infection. To unravel the underlying cellular mechanisms modulated by KSHV, we identified changes in the host proteome, phosphoproteome and transcriptome landscape upon KSHV infection of endothelial cells. A Steiner Forest algorithm was used to integrate proteomic, phosphoproteomic and transcriptomic data with transcriptome based predicted transcription factor activity to identify cellular networks altered by latent KSHV. Overall design: RNA was isolated from hTert-immortalized microvascular endothelial (TIME) cells either infected with KSHV or mock-infected in 3 biological replicates	Co-expression
SRP078261	BET inhibitors suppress lytic DNA replication [Akata-Zta RNA-seq]	Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV life cycle: expression of the immediate-early gene BZLF1 and lytic genome replication. This represents a novel mode of action for antiviral drugs that may increase efficacy and decrease emergence of resistance. The RNA-seq data below show that the second block causes a decrease in expression of late but not early lytic genes. Overall design: (A) RNA-seq from Akata-Zta pretreated with JQ1 or vehicle, then treated with doxycycline or vehicle, experiment performed in triplicate. (B) RNA-seq from Akata-Zta pretreated with I-BET, then treated with doxycycline or vehicle, experiment performed in triplicate.	Co-expression
SRP078268	Transcriptomics changes in liver metastatic biopsies of colorectal carcinoma between pre-treated and acquired resistance to Cetuximab [mRNA]	Two patients who were newly diagnosed and pathologically confirmed metastatic colorectal cancer were screened for eligibility between August 2011 and December 2013 in Affiliated Hospital, Academy of Military Medical Sciences. They were treated with Cetuximab in combination with FOLFOX regimen and obtained continuous partial responses in more than six months. CT scans of liver lesions were performed every two to eight weeks. The four biopsies were evaluated by two pathologists and were confirmed that the tumor purities were greater than 50%. Each biopsy was subjected to high-throughput RNA and small RNA sequencing to obtain expression profiles of genes and miRNAs. Overall design: The mRNA profiling of 4 liver metastatic biopsies of colorectal carcinoma from 2 patients with matched-pairs design of pre-treated and acquired resistance to Cetuximab.	Co-expression
SRP078309	Genome-wide analysis of Dengue virus 2 infected cells	The goal of this study was to compare the transcriptional profile (RNA-seq) of Dengue virus 2 and mock infected cells at 24 and 36 hours post infection. Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses.  Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. Overall design: A549 cells where infected with Dengue virus 2 or mock and after 24 and 36 hours post infection mRNA was purified. Then the transcriptional profile of these cells was analyzed using RNA-seq.	Co-expression
SRP078311	Homo sapiens isolate:Hela Transcriptome or Gene expression	To Identify new factors of GR-mediated mRNA decay.	Co-expression
SRP078314	Identification of transcriptomic drivers of squamous cell carcinoma development through a preneoplastic intermediate [human RNA-Seq]	Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in the U.S. annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). In order to identify potential targets for molecularly targeted chemoprevention, we performed integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar UV-driven Hairless mouse model. We identified the major transcriptional drivers of this sequence showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this UV-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. Overall design: We sought to identify important genetic events that drive squamous cell carcinoma development through combined analysis of next generation sequencing of matched patient samples with a UV-driven mouse model to identify key pathways.	Co-expression
SRP078315	Homo sapiens isolate:H9 HESCs (WA09) Transcriptome or Gene expression	Dengue virus (DENV) infection causes profound changes in the host cells and these changes underlie the immune response-based viral clearance and pathogenesis. There are several major cell/tissue types relevant for DENV pathogenesis in vivo, including immune cells, liver, and vascular endothelial cells. We applied a directed differentiation system that produces hepatocyte-like cells (HLCs) from pluripotent stem cells to investigate various aspects of DENV- hepatic cells interaction. Human embryonic stem cells were resistant to DENV infection while progeny hepatic cells were permissive. The transition to DENV permissiveness coincided with the upregulation of entry factors for the virus. Infection of HLCs by DENV was self-limiting due to the activation of the interferon (IFN) pathways, which protected by-stander cells from infection but failed to induce the same level of interferon-induced genes (ISGs) expression in the infected cells due to the subversion of IFN signaling by DENV. Innate immunity also protected the infected cells from virus-induced apoptosis. Furthermore, DENV infection activated the NF-?B pathway, increased production of reactive oxidative species (ROS), and led to production of inflammatory cytokines which may contribute to the cytokine storm implicated in dengue hemorrhagic fever (DHF). Finally, DENV infection of HLCs resulted several in vitro phenotypes that may have relevance for acute liver failure and vascular permeability during DHF. These include the disruption of adherens junctions and the downregulation of many liver specific genes such as albumin (ALB) and coagulation factor V (F5).	Co-expression
SRP078317	Impact of laminin a1 chain on colorectal cancer progression	Expression analysis of control HT29 or Laminin a1 expressing HT29 xenografts in nude mice Overall design: RNA from 3 independents subcutaneous tumors per group were analyzed.	Co-expression
SRP078374	Total RNA sequencing of INS-GFP+ cells differentiated from HES3 hESCs treated with DMSO or H1152	To systematically examine the cellular identity of INS+ cells derived after H1152 treatment, INSw/GFP HES3 hESCs were differentiated to a pancreatic progenitor population and treated with 10 µM H1152 for 8 days in sphere culture. The INS-GFP+ cells of H1152 or DMSO treated spheres were purified by cell sorting and transcripts profiled using RNA-seq. Overall design: The INS-GFP+ cells of H1152 or DMSO treated spheres were purified by cell sorting and transcripts profiled using RNA-seq. Rat insulin promoter driven ZsGreen-sorted beta cells from human islets were also assayed.	Co-expression
SRP078414	Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells [BAA]	We report the response of Caco-2 cells to infection by C. concisus strains or exposure to C. concisuszonula occludens toxin Overall design: Identification of differential transcript expression following C. concisus infection or exposure to zonula occludens toxin. BAA dataset.	Co-expression
SRP078416	Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells [Toxin]	We report the response of Caco-2 cells to infection by C. concisus strains or exposure to C. concisuszonula occludens toxin Overall design: Identification of differential transcript expression following C. concisus infection or exposure to zonula occludens toxin. Toxin dataset.	Co-expression
SRP078417	Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells [UNSWCD]	We report the response of Caco-2 cells to infection by C. concisus strains or exposure to C. concisuszonula occludens toxin Overall design: Identification of differential transcript expression following C. concisus infection or exposure to zonula occludens toxin. UNSWCD dataset.	Co-expression
SRP078419	Whole transcriptome analysis of lung squamouse cell carcinoma	Discovery of novel diagnostic and/or prognostic biomarkers of lung squamous cell carcinoma based on a whole transcriptome analysis using RNA sequencing (RNA-seq). Transcriptomic profiles of 12 available samples, out of 87 recruited patients with lung squamous cell carcinoma (SCC) were generated using Ion Proton system. Overall design: Tumoral mRNA profiles of 12 patients with lung SCC were generated by deep sequencing, using Ion Proton system.	Co-expression
SRP078437	Read-through transcription as a general mechanism mediating methylation and silencing of intragenic CGIs [CAP-Seq]	The human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of a-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the a-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands. Overall design: CapSeq was performed on day 7 in vitro differentiated EBs containing the human gene sequence of RHBDF1 with (RHBDF1+P; chr16:47,861-63,210, hg18) or without  (RHBDF1-P; chr16:47,911-60,819, hg18) its promoter in the a recombination mediated cassette exchange (RMCE) system established within the mouse a-globin locus (Lynch et al., 2012, DOI: 10.1038/emboj.2011.399 ) to map transcription initiation sites within the transgene. Please note that the Cap-seq methods captures the 5' end of any short RNA that was Capped, capturing both coding and non-coding RNA.	Co-expression
SRP078441	RNA-seq of primary patient AML samples	The goals of this study are to compare transcriptome profiling (RNA-seq) of patients BM with or without ASXL2 mutations. Overall design: Patient bone marrow mRNA profiles with or without ASXL1/2 mutations were generated by deep sequencing	Co-expression
SRP078442	RNA-seq of ASXL2 shRNA KD in SKNO-1 cells	The goals of this study are to compare transcriptome profiling (RNA-seq) of Asxl2 knockdowned SKNO-1 cells to control SKNO-1 cells. We found substantial number of genes are differentially expressed in Asxl2 knockdowned cells. Overall design: SKNO-1 mRNA profiles of ASXL2 knockdowned and control cells were generated by deep sequencing, two differrent shRNA for ASXL2, in triplicate.	Co-expression
SRP078450	Transcriptional response to hepatitis C virus infection and interferon alpha treatment in the human liver	Hepatitis C virus (HCV) is widely used to investigate host-virus interactions and cellular responses to infection have been extensively studied in vitro. In human liver, interferon (IFN) stimulated gene expression can mask direct transcriptional responses to virus infection. To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV-infected patients lacking an activated endogenous IFN system. We show that the expression changes observed in these patients predominantly reflect immune cell infiltrates rather than changes in cell-intrinsic metabolic pathways. We also investigate the transcriptomes of patients with endogenous IFN activation, which paradoxically cannot eradicate viral infection. We find that most IFN-stimulated genes (ISGs) are induced by both the endogenous IFN system and by recombinant IFN therapy, but with significantly higher induction levels in the latter. We conclude that the innate host immune response in chronic hepatitis C is too weak to clear the virus. Overall design: In this study, we aimed to disentangle the direct and indirect effects of HCV infection on cellular transcriptional profiles, by performing a detailed characterization of the gene expression changes associated with HCV infection, endogenous IFN system activation and pegIFNa treatment in the human liver. With this objective, we generated and analyzed high-throughput transcriptome sequencing profiles from liver biopsies derived from different categories of HCV-infected and non-infected patients, prior to and during treatment. First, to unveil HCV-induced cell-autonomous effects and to separate them from IFN-induced changes in the transcriptome, we selected liver biopsies from patients with chronic hepatitis C (CHC) without hepatic ISG induction, and compared them with un-infected control biopsies. Second, we examined the transcriptomic changes associated with the endogenous activation of the IFN system. Finally, we analyzed the gene expression changes resulting from pegIFNa/ribavirin treatment, by comparing transcriptome data from liver biopsies obtained before treatment and at different time points during the first week of therapy.	Co-expression
SRP078484	RNA-sequencing based transcriptome-wide expression profiling of Cynomolgus monkey and human IPSCs in vitro differentiated into endothelial cells	We report a macaque in vitro endothelial cell system using induced pluripotent stem cells (IPSCs) from Cynomolgus monkey (Macaca fascicularis). Based on a protocol adapted for human IPSCs we directly differentiated macaque IPSCs into endothelial cells under chemically defined conditions. The resulting endothelial cells can be enriched using magnetic cell sorting and display endothelial marker expression and function. RNA sequencing revealed that the differentiation process closely resembled vasculogenesis. Moreover, we show that endothelial cells derived from macaque and human IPSCs are highly similar regarding gene expression patterns and key endothelial functions such as inflammatory responses. These data demonstrate the power of IPSC differentiation technology to generate defined cell types such as endothelial cells as translational in vitro model to compare cell type specific responses across species. For more detail see also: Eva C Thoma, Tobias Heckel, David Keller, Nicolas Giroud, Brian Leonard, Klaus Christensen, Adrian Roth, Cristina Bertinetti-Lapatki, Martin Graf, Christoph Patsch. "Establishment of a translational endothelial cell model using directed differentiation of induced pluripotent stem cells from Cynomolgus monkey" (under submission) Overall design: mRNA expression profiles of Cynomolgus monkey and human IPSC and in vitro differentiated IPSC-derived endothelial cells measured by deep RNA-sequencing on an Illumina HiSeq2500 instrument	Co-expression
SRP078495	Network-based, cross-cohort discovery of transcriptional mechanisms presiding over maintenance of high-risk neuroblastoma subtype state	Network-based analysis of neuroblastoma samples from two large cohorts identified master regulator proteins controlling the transcriptional state of three high-risk molecular subtypes. In particular, a TEAD4-MYCN positive feedback loop emerged as the core regulatory motif of a small protein module presiding over implementation and stability of the subtype associated with MYCN amplification. Specifically, MYCN transcriptionally activates TEAD4, which in turn activates MYCN both transcriptionally and post-translationally. The resulting MYCN-TEAD4 positive feedback loop plays a critical role in maintaining aberrant activity of a 10-protein regulatory module that causally regulates the transcriptional state of this subtype. Consistently, loss of TEAD4 activity induces core module activity collapse and abrogates neuroblastoma cell viability in vitro and in vivo, thus suggesting novel therapeutic strategies for this important childhood cancer. Overall design: Study of the transcriptional control by TEAD4 and MYCN positive feedback loop using RNA-seq profiles of TEAD4, WWTR1 and MYCN shRNA knockdowns in neuroblastoma BE2 cells. ChIP-Seq analysis using TEAD4 antibody in BE2 cells.	Co-expression
SRP078500	ARID1A-mutated ovarian cancers depend on HDAC6 activity	ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers.   ARID1A and TP53 mutations are typically mutually exclusive.  Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers.  Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors.  This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumors.  The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A.  HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells.  HDAC6 directly deacetylated the Lysine 120 residue of p53, a pro-apoptotic post-translational modification.   Thus, ARID1A mutation inactivates p53' apoptotic function by upregulating HDAC6.  These results indicate that pharmacological inhibition of HDAC6 is a novel therapeutic strategy involving ARID1A-mutation Overall design: RNA-seq transcription profiling of samples with altered HDAC6 activity	Co-expression
SRP078505	Phenotype-driven precision oncology in patient-derived tumor models predict therapeutic response in squamous cell carcinoma	Comparison of single-cell transcriptomic profiles of cell lines obtained from the primary and metastatic tumor from a single patient. Overall design: Analysis of single-cell transcriptomic profiles of cell lines derived from the primary squamous cell carcinoma tumor and a metastatic lymph node tumor isolated from a single patient.	Co-expression
SRP078515	Genomic and molecular characterization of the Physical Sciences - Oncology Network Bioresource Core Facility (PBCF) cell lines - mRNA sequencing	Cell lines provided by Physical Sciences-Oncology Network Bioresource Core Facility (PBCF) originate from the same lot number and passage number of ATCC seed stock. 39 of these cell lines were analyzed by ACGT using mRNA sequencing as described here, as well as using Exome sequencing and miRNA sequencing. mRNA sequencing made use of libraries prepared using the TruSeq Stranded RNA Sample Preparation Kit, and bar-coded with individual tags. Library preparation performed using a semi-automated 96-well plate method, with washing and clean-up/concentration steps performed on the Beckman Coulter Biomek NX platform and with ZR-96 DNA Clean &amp; ConcentratorTM-5 plates, respectively. Appropriate quality control analysis performed at every step, and the libraries quantified via qPCR with the Kapa kit and/or the Agilent 2100 Bioanalyzer. Indexed libraries prepared as equimolar pools and loaded onto MiSeqTM flow cell to generate paired-end 2x50 bp reads. The resulting information used to perform library evaluation and pooling adjustments for the HiSeq2000 dual flow cell loading. Pooled and validated libraries run on HiSeq2000 (2x100 paired end runs) in order to generate at least 30,000,000 paired-end reads per sample library. HG19/Build37 was the human reference assembly.	Co-expression
SRP078524	TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling	We created two cell lines derived from Ovcar8 by stably transfecting with an eGFP-firefly luciferase fusion protein and either an additional copy of the gene TWIST1 or an shRNA against TWIST1, under the control of the CMV promoter. RNA sequencing was used to look for differential expression of genes that may impact cisplatin resistance in epithelial ovarian cancer. Overall design: RNA-seq for differential expression between two cell lines differing in expression of gene of interest. Run as biological replicates and technical triplicates.	Co-expression
SRP078536	Analysis  of active enhancers and direct androgen receptor target genes in VCaP prostate cancer cells	Androgen receptor (AR) is typically overexpressed in castration-resistant prostate cancer (CRPC). CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs). This study analyzed direct transcription programs of the AR, the prevalence of AR enhancers and the transcriptional regulators involved in the regulation of at the enhancer regions. The analysis utilized global nuclear run-on sequencing (GRO-seq). The GRO-seq data were integrated with the ARB and VCaP cell-specific transcription factor-binding data. Androgen in 30 min activated and repressed transcription of a large number of genes including novel AR targets IGF-1 receptor and EGF receptor. GRO-seq analysis also revealed that only a fraction of the ARBs resides at functional enhancers. Activation of AR bound enhancers was most potent at the sites that also bound PIAS1, ERG and HDAC3. Our genome-wide data provide new insights how AR can directly control growth-signaling pathways in CPRC cells. Overall design: ChIP-seq samples were collected from cells treated with vehicle (ethanol, EtOH) or 10 nM R1881 (synthetic androgen methyltrienolone). IgG sample was collected from EtOH- and R1881-treated cells and used as background control. Biological duplicate samples of the AR (R1881-treated) and CTCF (vehicle- and R1881-treated) ChIP-seq samples were analyzed by using Illumina HiSeq 2000 platform 1.9. Single IgG and H3K9me3 (R1881-treated) samples were analyzed with the same platform. GRO-seq was used to determine androgen-induced changes in nascent transcription in VCaP and LNCaP cells.	Co-expression
SRP078541	Whole blood RNA sequencing in idiopathic pneumonia syndrome reveals a unique transcriptomic profile compared to ARDS	The acute respiratory distress syndrome (ARDS) is a highly lethal syndrome characterized by hypoxemia and bilateral lung infiltrates in response to an inciting event such as sepsis. Allogeneic bone marrow transplantation (BMT) is a life-saving treatment for patients with hematologic malignancies that can be complicated by ARDS. We sought to identify blood gene expression signatures that distinguish whether ARDS in BMT may be a distinct pathobiologic entity from ARDS in non-BMT patients. RNA-Seq was used to measure whole blood transcript expression differences between 26 patients meeting the Berlin definition of ARDS: 8 patients without BMT and 5 BMT patients with ARDS from the Brigham and Women's Registry of Critical Illness (RoCI), as well as 7 non-BMT patients with sepsis and 6 BMT patients with sepsis. RNA was globin cleared using the Ambion GLOBINclear kit prior to preparation of poly(A)-selected RNA-Seq libraries with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 75 base pair paired-end reads, which were aligned to the hg38 reference genome using STAR. Differential expression analysis was performed using DESeq2. Overall design: mRNA profiles obtained via RNA-Seq for whole blood samples from ARDS patients with and without BMT	Co-expression
SRP078560	Transcriptomic profile of circulating memory T cells can differentiate between latent tuberculosis individuals and healthy controls	Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 and CD8 T cells isolated from individuals with latent tuberculosis, as well as from tuberculosis negative healthy controls. Overall, we found specific gene signatures in each cell subset that could successfully discriminate between individuals with latent tuberculosis and healthy controls. Overall design: RNA-sequencing of sorted memory CD4 and CD8 T cells from cryopreserved PBMC of 10 subjects with latent tuberculosis infection and 10 tuberculosis negative healthy controls	Co-expression
SRP078574	Generating STAT3/5 resistant human breast cancer cell lines (MDA-MB-231 & T47D) using chronic treatment with SH-4-54	MDA-MB-231 and T47D human breast cancer cells were chronically treated with the novel STAT3/5 inhibitor SH-4-54 for 60 and 30 days, respectively. Surviving treatment-resistant individual clones were isolated and characterized for their phosphorylated STAT3 and phosphorylated STAT5 status. 3 biological replicates of mRNA from a representative resistant clone derived from both MDA-MB-231 and T47D cells, in parallel with mRNA from their respective wild-type counterparts, was subjected to NextGeneration Sequencing to analyze changes in gene expression between untreated and resistant cells.	Co-expression
SRP078585	Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases	Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3' end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here we show that the nuclear canonical (PAPalpha and PAPgamma) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN, and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues. Overall design: 3''READS of siStar-PAP, siPAPa, siPAP? and siCtrl samples in HEK293 cells	Co-expression
SRP078597	A Druggable TCF4- and BRD4-dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm (RNA-Seq)	Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi''s) induce BPDCN apoptosis, which was attributable to disruption of the TCF4-dependent transcriptional network and loss of BPDCN-specific super-enhancers. BETi''s retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy. Overall design: We performed RNA sequencing (RNA-Seq) on the 6 FFPE BPDCN biopsies for which the FFPE RNA was not excessively degraded. Because only one PHN and none of the primary AML cases passed the RNA QC for library generation, we embedded BPDCN cell lines (Cal-1 and Gen2.2) and AML cell lines (HL-60, MOLM-14 and SKM-1) in paraffin blocks after formalin fixation, and used the FFPE RNA-Seq from these cell lines as a compare/contrast control.	Co-expression
SRP078618	Transcriptomic Differences Associated with TSC2 Gene Expression Loss in Lymphangioleiomyomatosis [human cells]	Pulmonary Lymphangioleiomyomatosis (LAM), a rare lung disease that affects predominantly women, is characterized by proliferation of smooth muscle-like cells in the lungs, destruction of lung tissue, upregulation of VEGF-D, and growth of lymphatic vessels inducing a loss of pulmonary function. TSC2 gene mutations that render TSC2 inactive are a common finding associated with LAM. To better understand the function of the TSC2 gene in LAM , we sought to characterize differences in the transcriptome of cells where TSC2 is inactivated. RNA-Seq was used to measure transcript expression differences between a human TSC2-null angiolipoma cell line derived from an individual with LAM, and the same cell line with re-expressed TSC2 to serve as a control. The Illumina TruSeq method was used to prepare poly(A)-selected stranded RNA-Seq libraries, and 100bp paired-end reads were generated with an Illumina Hi-Seq 2500 instrument in high output mode. RNA-Seq data was analyzed using kallisto (http://pachterlab.github.io/kallisto/) and R. Overall design: Transcriptomic profiles obtained via RNA-Seq for human TSC2-null angiolipoma cell line derived from an individual with LAM; the same cell line with TSC2 re-expressed served as a control; cells were treated with Rapamycin, STAT3, or left untreated.	Co-expression
SRP078872	Expression patterns in chronic thromboembolic pulmonary hypertension	We sequenced RNA from pulmonary arteries from CTEPH, IPAH or healthy, failed donors Overall design: Expression pattern in human pulmonary arteries during CTEPH or IPAH, using healthy failed donors as control	Co-expression
SRP078912	RNAseq from disomic and trisomic T cells and monocytes	RNA was sequenced from Disomic and Trisomic individuals for chromosome 21 to identify consistent changes in gene expression across individuals Overall design: Cells were cultured at subconfluency and RNA harvested for sequencing	Co-expression
SRP078920	RNAS-Seq of Bupivacaine treatment of human neuroblastoma cells	Identification of potential key genes associated with Bupivacaine treatment using RNA sequencing data.	Co-expression
SRP078925	Discovery of Novel Determinants of Endothelial Lineage: Insights from Chimeric Heterokaryons	Our study provides a systematic and mechanistic approach for identifying key regulators in directed differentiation of pluripotent stem cells to a variety of somatic cell lineages. Overall design: RNA-Seq data were generated for mouse ESC and human endothelial cells: separate, co-cultered and fused samples have been analyzed	Co-expression
SRP078931	Integrated analyses identify phenotype specific BMP4 signaling in breast cancer [RNA-seq]	Bone morphogenetic protein 4 (BMP4) plays an important role in cancer pathogenesis. In breast cancer, it reduces proliferation and increases migration in a cell line-dependent manner. To characterize the transcriptional mediators of these phenotypes, we performed RNA-seq and DNase-seq analyses after BMP4 treatment in MDA-MB-231 and T-47D breast cancer cells that respond to BMP4 with enhanced migration and decreased cell growth, respectively. Overall design: We characterized mRNA levels from BMP4 treated and non-treated MDA-MB-231 and T-47D cells using RNA-seq	Co-expression
SRP078938	Global gene expression profiles of cardiac progenitors differentiated from human pluripotent stem cells in 3D culture under simulated microgravity	Methods: RNA-seq libraries were prepared using the Illumina TruSeq RNA kit and the TrueSeq method was employed for mRNA enrichment. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq1000 system. Reads were mapped on the Human Genome Reference and normalized expression table was generated. Results: Among differentially expressed genes, 53 of them were up-regulated and 75 were down-regulated. Conclusions: Data demonstrate increased expression of genes associated with growth, development, and pro-survival in cardiac progenitors cultured under simulated microgravity compared with those cultured under standard gravity. Overall design: RNA-sequencing analysis was performed to compare global gene expression profiles of cells at differentiation day 8 under simulated microgravity vs. standard gravity.	Co-expression
SRP078976	Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response (UPR) pathway	We examined the transcriptional changes modulated by KDM1A inhibitor NCD-38 by performing global transcriptome analysis. Glioma Stem Cells (GSC10) were treated with either vehicle or NCD-38 for 24 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that NCD-38 modulated several genes that are involved in unfolded protein response, endoplasmic reticulum stress pathway and NRF-2 mediated oxidative stress response. Overall design: Total RNA was isolated from the GSC10 cells that were treated with vehicle or NCD-38 for 24 hours. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.	Co-expression
SRP078982	CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair	BACKGROUND: Deletion of the chromatin remodeler CHD1 is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability [1-3]. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear. DESIGN: To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 WT and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss. RESULTS: We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vivo, ex vivo and in a patient with metastatic PCa. Mechanistically, CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair. CONCLUSIONS: Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ and suggest that CHD1 loss may contribute to genomic instability seen in this subset of PCa patients. Overall design: In total, 11 murine samples and 9 human samples were analyzed. For each genotype, there are 3 to 6 replicates.	Co-expression
SRP078984	Massively-parallel functional characterization of MAPK1 missense mutants	Genome-directed oncology has the potential to revolutionize patient treatment, but is limited by an abundance of rare, uncharacterized and therapeutically uninformative somatic variants. To accelerate characterization of the “long tail” of rare somatic variants, we quantified the activity and drug responsiveness of virtually all possible (99.84%) missense variants in the Ser/Thr kinase MAPK1/ERK2. We identified recurrent and rare hypermorphic and loss-of-function alleles, revealing that variant activity is uncorrelated with mutational frequency. Somatic ERK2 variants displayed variable responses to RAF-, MEK- and ERK-directed therapies, potentially informing clinical treatment strategies for patients whose tumors harbor these alterations. A subset of recurrent and rare somatic variants co-localized on ERK2 protein-protein interfaces, yet engendered contrasting phenotypes based on their specific sub-domain localization. The approach presented here represents an allele-characterization framework that compliments existing computational efforts and supports current and future somatic variant discovery efforts, advancing the promise of genome-guided treatment strategies. Overall design: Examination of the transcriptional output (mRNA)  for a set of ERK2 Alleles under both trametinib drug treatment and DMSO controls. All experimental conditions were done in duplicates and sequenced in quadruplicates. Thus, each biological sample (48 total) was sequenced in 4 different lanes, resulting in total of 192 sequenced samples	Co-expression
SRP078990	Transcriptomic changes mediated by ß-amyloid in human aortic endothelial cells (HAOEC)	We found that ß-amyloid accumulation is modulated in HAOEC cells by overexpression or blocking of lncRNA BACE1-AS, which in turn regulates both BACE1 mRNA and protein expression. BACE1 is key-enzyme in the synthesis of ß-amyloid from Amyloid Precursor Protein (APP). The transcriptomic changes mediated by 400nM  ß-amyloid was investigated in HAOEC cells. Overall design: HAOEC cells stimulated or not with 400nM ß-amyloid	Co-expression
SRP079002	Enriched retinal ganglion cells derived from human embryonic stem cells (RNA-seq)	We performed the whole transcriptome analysis in human H9 ES cells and in retinal ganglion cells (RGC) derived from H9 ES cells. Overall design: RNA-seq in H9 human ESCs and RGC derived from H9 ESCs	Co-expression
SRP079004	Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation	Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. Comprehensive transcriptome analysis was employed to validate the capacity of three prioritized compounds to remodel the ER proteostasis environment, and to assess the prefential activation of ATF6 transcriptional targets relative to targets of the IRE1/XBP1s and PERK arms of the UPR. Overall design: HEK293T-Rex and HEK293-DAX cells were treated for 6 hr with vehicle (DMSO), 1 µM Tg, 10 mM TMP (in HEK293DAX), or 10 µM 132, 147 or 263 in biological triplicate at 37 °C	Co-expression
SRP079058	Single-Cell RNAseq analysis of diffuse neoplastic infiltrating cells at the migrating front of human glioblastoma	We used single-cell RNAseq to investigate the heterogeneity of glioblastoma tumors and assess differential expression between cells within and in proximity of the tumor. Overall design: Examination of cell types in human primary glioblastoma samples.	Co-expression
SRP079166	Engineered human pluripotent stem cell-derived intestinal tissues with a functional enteric nervous system	The enteric nervous system (ENS) of the gastrointestinal (GI) tract controls many diverse functions including motility and epithelial permeability. Perturbations in ENS development or function are common, yet a human model to study ENS-intestinal biology is lacking. We have used a tissue engineering approach with pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining PSC-derived neural crest cells (NCCs) with developing human intestinal organoids (HIOs). When cultured alone, NCCs had full differentiation potential in vitro, however when recombined with HIOs they differentiated into neurons and glial cells. NCC-derived ENS neurons self-assembled within the developing intestinal mesenchyme and exhibited neuronal activity as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, formed interstitial cells of Cajal, and had an electro-mechanical coupling that regulated waves of propagating contraction. This is the first demonstration of a human PSC-derived intestinal tissue with a functional ENS. Overall design: We examined 4 conditions (3 replicates per condition) of HIO in vitro that include mRNA profiles of HIO (Control); HIO with NCCs (HIOs+ENS); HIO with PHOX2B-/+ NCCs (HIO+ENS_Phox2b_Het); HIO with PHOX2B-/- NCCs (HIO+ENS_Phox2b_Homo). Samples were sequenced using Illumina TruSeq RNA sample prep kit.	Co-expression
SRP079175	Effect of BCL11B overexpression on transcriptome of T-cell acute lymphoblastic leukemia (T-ALL) cells	To investigate the effects of BCL11B on T-cell differentiation, we  performed gain of function studies in cells with a T-lineage differentiation arrest, namely T-ALL cells. Gene expression profiling by RNA-Seq demonstrated that BCL11B overexpression induced transcriptional changes consistent with T-cell differentiation as early as 72 hours after transduction, indicating a rapid regulatory effect of BCL11B on the T-lineage transcriptional program and supporting an important role for BCL11B in human T-cell differentiation. Overall design: T-ALL cells were transduced with a BCL11B-GFP expression vector (overexpressing cells) or an empty GFP vector (control cells). GFP+ cells were isolated by fluorescence activation cell sorting (FACS) at 72 hours post transduction and analyzed by RNA-Seq to determine the effect of BCL11B on the transcriptome of T-ALL cells.	Co-expression
SRP079189	Dysregulated synaptic gene expression and axonal neuropathology in a human iPSC-based model of familial Parkinson''s disease	We generated de novo induced pluripotent stem cells (iPSCs) from two Parkinson’s Disease patients (PD) harboring the p.A53T mutation. iPSC-derived mutant neurons displayed disease-relevant phenotypes at basal conditions, including protein aggregation, compromised neuritic outgrowth and contorted axons with swollen varicosities containing aSyn and tau. We have performed RNA Sequencing (RNA-Seq) of neurons from PD patient and control samples. RNA sequencing has also been performed to neurons derived from HUES samples subjected to the same differentiation protocol as reference. Overall design: We have performed RNA Sequencing (RNA-Seq) in neurons PD and control samples (two clones from each individual), along with HUES-derived neurons.	Co-expression
SRP079213	Innate to adaptive: Human IFN-gamma producing CD4+ T cells can derive directly from CXCL8-producing recent thymic emigrants.	An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this ''innate-like'' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells' peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that 'innate like' CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells Overall design: Examination of RNA-Seq count data from 96 single cells	Co-expression
SRP079214	RNAseq to profile IFNg response in human primary monocytes	We did transcriptome profiling for monocytes treated with or without IFNg to characterize IFNg response. Overall design: Human primary monocytes were cultured for 24 hours with or without IFNg, harversted and prepared for RNA for RNAseq.	Co-expression
SRP079223	Reprogramming of human stem cells towards a rejuvenated and transformation-resisting state by recoding a single nucleotide	Premature senescence-associated functional decay and neoplastic transformation of transplanted human stem cells or their derivatives represent two major roadblocks for regenerative medicine. Cellular senescence acts as a major mechanism antagonizing neoplastic transformation, and stem cells evading senescence are prone to oncogenic transformation. So far it is unknown whether there is any genetic code, rewriting of which can simultaneously brake cellular senescence and oncogenic transformation programs. Here, we identify a single nucleotide in human genome(target on the transcription factor NRF2) as a candidate code, switch of which blocks both senescence and transformation pathways. Genetic modification stabilizes the wild type human mesenchymal stem cells (hMSCs) at a “sustainably younger” state. More importantly, the same genetic manipulation endows hMSCs with the ability of counteracting oncogenic transformation. Our study thus provides the first proof-of-concept of genetic enhancement of human stem cells, a strategy holding potential to generate superior and safer stem cell materials for cell replacement therapy. Overall design: RNA-seq of MSCs-NRF2 +/+_EP, MSCs-NRF2 AG/AG_EP, MSCs-NRF2 +/+_LP, MSCs-NRF2 AG/AG_LP, TMSCs-NRF2 +/+ and TMSCs-NRF2 AG/AG.	Co-expression
SRP079226	Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant mRNA signatures	Tumor-infiltrating macrophages, NK cells, CD8+ and CD4+ T cells sorted from clear cell renal cell carcinoma patient specimens. Overall design: 4 macrophage samples (CD45+CD3-CD56-CD14+), 2 CD16+ NK cell samples (CD45+CD3-CD56+CD16+), 5 CD8+ T cell samples (CD45+CD3+CD8+), 3 CD4+ T cell samples (CD45+CD3+CD4+), and one non-immune cell sample (CD45-).	Co-expression
SRP079257	Experimental validation of candidate regulators of KRAS transcriptional components.	We sequenced mRNA from HCC44 and YAPC cell lines stably expressing Cas9, and infecting with indicated gRNAs against regulators of KRAS transcriptional components. Overall design: KRAS mutant cell lines HCC44 and YAPC stably expressing with Cas9 were infected with three independent gRNAs targeting indicated genes or controls (GFP, RFP, random gRNAs) and harvested 8 days after infection.	Co-expression
SRP079342	RNA-seq of Human neural progenitor cells exposed to lead (Pb) reveals transcriptome dynamics, splicing alterations and Pb disease risk associations	We use time series RNA-seq to conduct a genome-wide survey of the temporal transcriptome response of human embryonic stem (ES) cell-derived neural progenitor cells (NPCs) exposed to lead. Overall design: NPCs were derived from human embryonic stem cells (hESCs) with a modified protocol from a previously reported protocol (Chambers et al. 2009) (Methods). We used lead acetate to treat NPCs at two different concentrations, 3 µM and 30 µM.	Co-expression
SRP079357	Artemisinins target GABA receptor signaling to induce alpha to beta cell transdifferentiation	Type 1 diabetes is characterized by the destruction of pancreatic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, overexpression of the master regulatory transcription factor Pax4 or loss of its counterplayer Arx are sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx and induce beta-cell characteristics in alpha cells. We show that the protein gephyrin is the mammalian target of these antimalaria drugs. Finally, we demonstrate that gephyrin-mediated enhancement of GABAA receptor signaling is the mechanism of action of these molecules in pancreatic transdifferentiation. Our results indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells. Overall design: Transcriptional dissection of Artemether treated, human pancreatic islets of one donor using single-cell RNA-seq	Co-expression
SRP079381	Long non-coding RNA TYKRIL controls pericyte function and survival in the cardiovascular and central nervous system through regulation of p53 activity and PDGFRß expression	Vessel maturation is dependent on platelet derived growth factor (PDGF), which signals via tyrosine kinase receptors and facilitates recruitment of pericytes. Long noncoding RNAs (lncRNAs) regulate endothelial and smooth muscle cell properties, but their role in pericyte function is unclear. Using RNA sequencing, we identify the hypoxia induced lncRNA “Tyrosine kinase receptor inducing lncRNA” (TYKRIL) as a species conserved lncRNA which regulates pericyte function by controlling PDGF receptor beta (PDGFRß) expression in vitro, in vivo and in human disease. TYKRIL preferentially binds to the N-terminus of p53, thereby acting as a p53 decoy molecule that prevents the interaction with its co-activator p300, which augments the expression of the known p53 target PDGFRß. In summary, our results identify TYKRIL as a key regulator of pericyte function by acting as a previously unknown modulator of p53 activity which may enable to develop novel therapeutic concepts in PDGFRß and p53 dependent disease states. Overall design: To identify the hypoxia regulated transcriptome in human pericytes, cells were exposed towards 24 hours of hypoxia (1%O2, 5% CO2, humidified atmosphere). Normoxic controls were kept at 20% O2, 5% CO2, humidified atmosphere. Hypoxia was performed in 3 independent experiments. Total, ribosomal depleted RNA was analyzed by RNA deep sequencing following hypoxia. To investigate the impact of the long noncoding RNA TYKRIL on the pericyte transcriptome, TYKRIL was silenced by LNA GapmeRs, controls were treated with scramble LNA GapmeR control. TYKRIL was silenced in 3 independent experiments and total, ribosomal depleted RNA was subsequently analyzed via RNA deep sequencing.	Co-expression
SRP079672	Integrative analysis of DNA methylation and expression during EPC differentiation_mRNA-Seq	Analysis of DNA methylation and gene expression changes during regulated endothelial progenitor cells (EPCs) to outgrowth endothelial cells (OECs). Results provide information of DNA methylation and gene expression pattern during cord-blood derived EPCs differentiation. Taken together, we discovered specific set of genes regulated by hyper- and hypo-methylation during differentiation. Overall design: mRNA and MeDIP seq using total RNA and genomic DNA isolated from cord blood-derived EPCs and OECs.	Co-expression
SRP079684	Single-cell profiling of non small cell lung cancer associated B-cells.	Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking.  Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited.    Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC).    Results:  Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers.  The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC.  There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster.  Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10.    Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.   Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking.  Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited.    Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC).    Results:  Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers.  The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC.  There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster.  Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10.    Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Overall design: Single-cell comparison of normal and tumor infiltrated B-cells.	Co-expression
SRP079700	Glucose inhibits cardiac maturation through nucleotide biosynthesis	In summary, we discovered (1) that glucose dose-dependently inhibits cardiac maturation in vitro and in vivo, (2) that the maturation-inhibitory effect is dependent on nucleotide biosynthesis via the PPP, (3) that the developing heart accomplishes glucose deprivation condition by limiting the glucose uptake at late gestational stages during normal embryogenesis, and (4) that perturbation of the glucose deprivation in gestational diabetes affects natural cardiomyocyte maturation and potentially contributes to congenital heart disease. Overall design: Three different samples, three replicates each	Co-expression
SRP079701	The global transcriptome analysis in the time course of hESC-derived cardiac differentiation	We analyzed the global transcriptome signature over the time course of the cardiac differentiation from hESC by RNA-seq. We characterized the genome-wide transcriptome profile of 5 distinct stages; undifferentiated hESC (day 0), mesodermal precursor stage (hMP, day 2), cardiac progenitor stage (hCP, day 5), immature cardiomyocyte (hCM14) and hESC-CMS differentiated for 14 additional days (hCM28). While the stem cell signature decreases over the five stages, the signatures associated with heart and smooth muscle development increase, indicating the efficient cardiac differentiation of our protocol. Overall design: Five different temporal samples, two replicates for only first four samples day 0 through day 15	Co-expression
SRP079726	hCLE/RTRAF-HSPC117-DDX1-FAM98B: A new cap-binding complex that activates mRNA translation	hCLE/C14orf166/RTRAF, DDX1 and HSPC117 are components of cytoplasmic mRNA-transporting granules kinesin-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117 and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of eIF4E; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest a positive role of hCLE complex modulating mRNA translation. Overall design: Standard RNA-seq protocol was applied for comparing two sample types (HEK293T cells transfected with hCLE-TAP plasmid or empty TAP) with two biological replicates each. More than 20 million single-end, strand-specific 50 nt reads were generated for each sample.	Co-expression
SRP079838	Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules	Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offer a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report human adult astrocytes could also be converted into neuronal cells by a different set with fewer small molecules. These induced neuronal cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed the gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. When transplanted into postnatal mouse brains, these induced neuronal cells could survive in vivo. Altogether, our study provides a new strategy to directly generate transgene-free neurons from human adult astrocytes by small molecules. Overall design: In this data set, we include RNA-Seq data of human astrocytes treated with small molecules (Valproic acid, Chir99021, Repsox, forskolin, i-Bet151 and ISX9) for 0, 2, and 30 days, as well as neurons derived from human embryonic stem cells	Co-expression
SRP079850	Identification of mesothelial-to-mesenchymal gene signature in ascitic fluid-isolated mesothelial cells through RNA-sequencing	RNA-sequencing analysis was carried out on ascetic fluid-isolated mesothelial cells from ovarian cancer patients compared to control human peritoneal mesothelial cells to identify a mesothelial-mesenchymal gene signature. Overall design: Three control human peritoneal mesothelial cell samples isolated from omentum obtained from non-oncologic patients undergoing abdominal surgery and three ascitic fluid-isolated mesothelial cell samples obtained from the peritoneal effucsions of stage III/IV ovarian serous carcinoma patients	Co-expression
SRP079879	CELL TYPE-SPECIFIC EFFECTS OF IBTK ON GENE EXPRESSION AND RNA SPLICING	The IBTK gene encodes the major protein isoform IBtka, that was recently characterized as substrate receptor of Cul3-dependent E3 ligase, regulating ubiquitination coupled to proteasomal degradation of Pdcd4, an inhibitor of translation.In this study, we have investigated the role of IBTK in the regulation of the human wide genome expression. In particular, we have performed High Throughput Deep RNA-Sequencing to analyze the transcriptome of epithelial (HeLa) and erythroleukemic (K562) cell lines, with or without IBTK RNA interference.	Co-expression
SRP079899	Inhibition of TGFßRI as a therapy for GATA4 deficient lung cancers [patient samples]	GATA4 is frequently epigenetically silenced in lung cancers. However, the impact of GATA4 inactivation on tumorigenesis and related therapeutic strategy remain to be determined. Through the genome-wide screening of tumor suppressing transcription factors, we demonstrate that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vitro. Interestingly, ectopic GATA4 expression resulted in cellular senescence. Mechanistically, GATA4 up-regulates multiple miRNAs (miRNA-32, miRNA-301b, miR-320a, and miR-590) targeting TGFB2 mRNA and causes ensuing downregulation of WNT7B level to induce senescence. TGFBRI inhibitor synergizes with MEK1/2 inhibitor to promote lung cancer regression in Kras G12D/GATA4-/- mouse models. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGFB2 level and is significantly associated with poor prognosis. Overall design: Compare the mRNA profiles in adenocarcinoma and adjacent tissues  by Illumina suquencing.	Co-expression
SRP079914	RNA sequencing of MDA-MB231 and U2OS cancer cell lines exposed to the alkylating agent methyl methanesufonate (MMS) and classical chemotherapeutics	Understanding the mechanisms by which cells respond to chemotherapeutics is key to identifying means to improve therapy effiicacy while reducing systemic toxicity of these widely used classes of drugs. While determining the role of NRF2-GSH and ER stress in cells exposed to alkylating compounds such as methyl-methanesulfonate (MMS), we asked if these pathways could also be a general cell damage response relevant to other clinically used chemotherapeutics or if it is an alkylation specific response. With this intent, we performed RNA sequencing of MDA-MB231 breast cancer and U2OS osteosarcoma cells lines treated for 8 hours with a topoisomerase II inhibitor etoposide (20 µM), the antimitotic beta-tubulin-interacting drug paclitaxel (0.2 µM), doxorubicin (1 µM) and compared to MMS (40 µg/mL) treated cells. Doses represent IC50 level after 72 hours exposure. We observed that even though non-alkylating drugs, especially etoposide, caused an increase in the mRNA expression of some NRF2 and ER stress signaling markers, the number and magnitude of upregulation of genes markers in either pathway was more pronounced in alkylation treatments compared to other drugs. This indicates that alterations in NRF2 and ER stress pathways could be more likely associated with differential sensitivity to alkylating chemotherapies. Overall design: MDA-MB231 breast cancer and U2OS osteosarcoma cells lines were treated with the 72 h IC50  dose of etoposide (20 µM), paclitaxel (0.2 µM),  doxorubicin (1 µM) or  MMS (40 µg/mL) for 8 h, and RNA was extracted and analyzed.	Co-expression
SRP079916	Ebola virus glycoprotein variant with increased infectivity for human cells dominated the 2013-2016 outbreak	The unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation. Overall design: We generated stocks of lentiviral vector bearing one the following three M-EBOV GPs: founder, A82V, and A82V/T230A. These viral stocks were used to challenge MDDCs from two healthy, anonymous human donors. Stimulated MDDCs were harvested at 1, 2, 4, and 6 hours after viral addition. Gene expression in M-EBOV GP challenged MDDCs was compared to a unstimulated control.	Co-expression
SRP079954	ZSCAN5B and its primate-specific paralogs bind RNA polymerase III genes and extra-TFIIIC (ETC) sites to modulate mitotic progression [SiRNA RNA-Seq data set]	Particularly in the context of differentiation and development, the importance of three-dimensional chromatin architecture to gene regulatory mechanisms is becoming increasingly clear.  The most ancient known mechanism of chromatin organization involves TFIIIC, a transcription factor (TF) that recruits RNA polymerase III (Pol III) for transcription of tRNA and other types of non-coding RNA genes. From yeast to mammals, TFIIIC binds to tRNA genes (tDNAs) and scattered “extra-TFIIIC” (ETC) loci and serves to tether these loci together as anchors of chromatin loops. TFIIIC activities are modulated by MAF, MYC, and other TF proteins that are still unidentified.  Here we identify the ZSCAN5 TF family - including mammalian ZSCAN5B and its primate-specific paralogs - as proteins that occupy mammalian Pol III promoters and ETC sites.  We show that ZSCAN5B binds with high specificity to a conserved subset of tDNA loci and other Pol III genes in human and mouse and that primate-specific ZSCAN5A and ZSCAN5D also bind Pol III genes, although ZSCAN5D preferentially localizes to MIR SINE- and LINE2-associated ETC sites. ZSCAN5 genes are expressed in proliferating cell populations and are cell-cycle regulated, and gene expression data suggested that they might cooperate to regulate basic cellular functions including mitotic progression. Consistent with this predicted role, ZSCAN5A knockdown led to increasing numbers of cells in mitotic cells and aneuploidy in cultured cells. Together these data implicate ZSCAN5 genes in regulation of Pol III gene transcription and nearby Pol II genes, ultimately influencing cell cycle progression and differentiation in a variety of tissues. Overall design: Human HEK 293 cells were treated with siRNA designed to knock down RNA from ZSCAN5A or ZSCAN5B genes respectively, or a scrambled negative control siRNA. Gene expression was compared between knocked down samples and control samples to determine differentially expressed genes.	Co-expression
SRP079968	Gene expression profiling of drug-tolerant persister BT474 breast cancer cells derived from lapatinib treatment	Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant “persister” cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets. Overall design: 3 biological replicates of BT474 persister cells, two biological replicates of BT474 parental cells	Co-expression
SRP079972	The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network	Background and Aims: The LIM protein AJUBA participates in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription, yet its roles in tumor development and progression are poorly defined. The aim is to determine the role of AJUBA in colorectal tumorigenesis. Methods:  We performed data mining in Oncomine databases and immunohistochemistry (IHC) assays on 67 paired colorectal cancer (CRC) samples; we manipulated the AJUBA expression in SW-1116 and Caco-2 cells using specific shRNA and overexpression plasmids and performed assays for cell viability, cell cycle and apoptosis; we performed RNA-seq and qRT-PCR assays to identify genes regulated by AJUBA; we performed western blot, co-immunoprecipitation assays to study the interaction of AJUBA and JAK/STAT; Results: We discovered that AJUBA is highly expressed in CRC and promotes CRC cell growth in culture and in xenograted mice via an inhibition of apoptosis by repression of the IFIT2 gene. AJUBA specifically binds the FERM domain of JAK1 to dissociate JAK1 from the IFN? recepter, resulted in inhibition of STAT1 phosporylation and concomitantly its nuclear translocation.  Clinically, the level of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and pSTAT1. Conclusion: Ajuba functions as a specific suppressor of the Interferon-activated JAK1/STAT1 signaling to promote colorectal cancer development via an inhibition of Interferon induced apoptosis. Overall design: RNA-seq assays to identify genes regulated by AJUBA in SW-1116 cancer cell lines. SW-1116-AJUBA OE and SW-1116-Vector cells were used for sequencing.	Co-expression
SRP079984	Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B-cells	RNA-Seq of EBV-positive B-lymphoblastoid cell line MP1 and EBV-positive Burkitt’s lymphoma cell line Raji	Co-expression
SRP080002	RNA-Seq of retinal tissue from a Human Eye	We report RNA-Seq experiments of retinal tissue from Homo Sapiens Overall design: Examine retinal tissue from human	Co-expression
SRP080020	Homo sapiens Transcriptome or Gene expression	explore human	Co-expression
SRP080054	Homo sapiens strain:HeLa Raw sequence reads	Compare m1A levels in the 16S (large) mitochondrial ribosomal RNA in TRMT61B knockdown cells and control.	Co-expression
SRP080099	TC32 Ewing''s Sarcoma Transcriptome	Ewing sarcoma is a bone and soft-tissue sarcoma that depends on the continued activity of the EWS-FLI1 transcription factor, which is formed by the t(11;22)(q24;q12) chromosomal translocation. This translocation leads to the fusion of the binding domain of the ETS family member FLI1 to the transactivation domain of EWSR1 and the loss of negative regulatory domains. The result is a constitutively active transcription factor that both drives and suppresses the expression of more than 500 genes. We also show that the second-generation trabectedin analog lurbinectedin (PM01183) caused the same nuclear redistribution of EWS-FLI1, leading to a loss of binding of EWS-FLI1 at target sequences and elimination of EWS-FLI1 activity at the promoter, mRNA, and protein levels of expression. In order to show that these effects are not restricted to these selected targets, we evaluated the effect of treatment on the gene signature of EWS-FLI1 using RNA sequencing.	Co-expression
SRP080110	Genetic and transcriptional analysis of human host response to healthy gut microbiota	Study of host-microbiota interactions in humans is largely limited to identifying associations between microbial communities and host phenotypes. While these studies have generated important insight on the link between the microbiota and human disease, assessing cause and effect relationships has been challenging. Here, we have developed a novel approach to directly investigate the transcriptional changes induced by live microbial communities on human colonic epithelial cells.	Co-expression
SRP080113	N6-methyladenosine (m6A) sequencing of messenger RNAs in acute myeloid leukemia (AML) cells with and without knockdown of FTO	To identify potential mRNA targets of FTO whose m6A levels are influenced in acute myeloid leukemia (AML) cells, we conducted m6A-seq for mRNA isolated from MA9.3ITD cells with and without knockdown of FTO Overall design: We lentivirally transduced pLKO.1-shFTO (i.e., shFTO) or pLKO.1 empty vertor (i.e., shNS) into human MA9.3ITD (human CD34+ hematopoietic stem/progenetor cells stably infected by MLL-AF9 and FLT3-ITD) AML cells and then selected positively infected cells under selection of puromuycin (0.5ug/ml). Two stable lines including one FTO-knockdown cell line (i.e., shFTO) and one control line (i.e., shNS) were selected for genome-wide m6A-sequencing (m6A-Seq) assays. The m6A-seq procedure was performed as detailed in Dominissini's method (Dominissini D., et al. Nat Protocols. 2013; 8: 176-189.). Polyadenylated RNA was extracted using FastTrack MAG Maxi mRNA isolation kit (Life technology). RNA fragmentation Reagents (Ambion) was used to randomly fragment RNA. M6A antibody (Synaptic Systems) was applied for m6A pull down. And final library preparation was constructed by TruSeq Stranded mRNA Sample Prep Kit (Illumina). Final library was quantified by BioAnalyzer High Sensitivity DNA chip then deeply sequenced on the Illumina HiSeq 2500.	Co-expression
SRP080114	Homo sapiens Transcriptome or Gene expression	Use traditional whole transcriptome profiling, and single cell whole transcriptome profiling to understand human pre-implantation development, undifferentiated human embryonic stem cells and differentiated human embryonic stem cells.	Co-expression
SRP080272	Homo sapiens Transcriptome or Gene expression	Transcriptomic signature of two types of osteosarcoma cells - one which are sensitive and one which are resistant to cisplatin	Co-expression
SRP080292	AKR1C3-mediated adipose androgen generation fuels an adverse metabolic phenotype in polycystic ovary syndrome (PCOS)	RNA-seq samples used to support a study into understanding of the association between androgens and adipose tissue Overall design: Pairwise comparison of patients with and without PCOS and patients with PCOS and with PCOS on an oral hormone (DHEA)	Co-expression
SRP080321	53BP1 integrates DNA repair and p53-dependent cell fate decisions via distinct mechanisms	The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair,  was  first  identified  as  a  p53-interacting  protein  over  two  decades  ago,  however  its direct  contributions  to  p53-dependent  cellular  activities  remain  undefined.  Here,  we  reveal 53BP1 stimulates  genome-wide  p53-dependent  gene  transactivation  and repression  events  in response  to  ionizing  radiation  (IR)  and  synthetic  p53  activation. 53BP1-dependent  p53 modulation requires  both auto-oligomerization and tandem-BRCT domain  mediated bivalent interactions  with  p53  and  the  ubiquitin-specific  protease  USP28.  Loss  of  these  activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate  53BP1-USP28  cooperation  to  be  essential  for  normal  p53-promoter  element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides  a mechanistic  explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to  be  distinct  and  separable  from  53BP1’s  regulation  of  DNA  double-strand  break  repair pathway choice. Overall design: We evaluated the transcriptional profiles of two 53BP1? cell lines and included a positive (WT) and a negative (p53?) controls. These cell lines were treated with Nutlin-3, ionising radiation or mock treated. Three independent replicates were included for each independent condition generating a total of 36 samples.	Co-expression
SRP080352	Inhibition of TGFßRI as a therapy for GATA4 deficient lung cancers [RNA-seq]	GATA4 is frequently epigenetically silenced in lung cancers. However, the impact of GATA4 inactivation on tumorigenesis and related therapeutic strategy remain to be determined. Through the genome-wide screening of tumor suppressing transcription factors, we demonstrate that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vitro. Interestingly, ectopic GATA4 expression resulted in cellular senescence. Mechanistically, GATA4 up-regulates multiple miRNAs (miRNA-32, miRNA-301b, miR-320a, and miR-590) targeting TGFB2 mRNA and causes ensuing downregulation of WNT7B level to induce senescence. TGFBRI inhibitor synergizes with MEK1/2 inhibitor to promote lung cancer regression in Kras G12D/GATA4-/- mouse models. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGFB2 level and is significantly associated with poor prognosis. Overall design: Compare the mRNA profiles in dox and vehicle  induced A549i cell by Illumina sequencing	Co-expression
SRP080360	mRNA sequencing in acute myeloid leukemia (AML) cells with and without knockdown of FTO	To identify the expression of mRNAs after knockdown of FTO, we performed RNA-Seq in MA9.3ITD cells with or without knockdown of FTO. Overall design: We lentivirally transduced pLKO.1-shFTO (i.e., shFTO) or pLKO.1 empty vertor (i.e., shNS) into human MA9.3ITD (human CD34+ hematopoietic stem/progenetor cells stably infected by MLL-AF9 and FLT3-ITD) AML cells and then selected positively infected cells under selection of puromuycin (0.5ug/ml). The knockdown efficiency was confirmed by qPCR and western. Two stable lines including one FTO-knockdown cell line (i.e., shFTO) and one control line (i.e., shNS) were selected for RNA-Seq. Polyadenylated RNA was extracted using FastTrack MAG Maxi mRNA isolation kit (Life technology). RNA fragmentation Reagents (Ambion) was used to randomly fragment RNA. And final library preparation was constructed by TruSeq Stranded mRNA Sample Prep Kit (Illumina). Final library was quantified by BioAnalyzer High Sensitivity DNA chip then deeply sequenced on the Illumina HiSeq 2500.	Co-expression
SRP080367	CRISPRi-based genome-scale identification of functional long non-coding RNA loci in human cells	The human genome produces thousands of long non-coding RNAs (lncRNAs) – transcripts >200 nucleotides long that do not encode proteins. While critical roles in normal biology and disease have been revealed for a subset of lncRNAs, the function of the vast majority remains untested. Here, we developed a CRISPR interference (CRISPRi) platform targeting 16,401 lncRNA loci in 7 diverse cell lines including 6 transformed cell lines and human induced pluripotent stem cells (iPSCs). Large-scale screening identified 499 lncRNA loci required for robust cellular growth, of which 89% showed growth modifying function exclusively in one cell type. We further found that lncRNA knockdown can perturb complex transcriptional networks in a cell type-specific manner. These data underscore the functional importance and cell type-specificity of many lncRNAs. Overall design: 96 RNA-seq samples; 16 ChIP-seq samples	Co-expression
SRP080734	Epigenetic silencing of the tumor suppressor RASSF4 favors multiple myeloma progression	RAS is frequently mutated in multiple myeloma (MM) leading to aberrant signaling. Next to their classical oncogenic effects, RAS proteins also mediate anti-tumor effects through the Ras-Association Domain Family (RASSF) proteins. Currently, no data about the role of RASSF proteins in MM disease is available. Here we report that RASSF4 is downregulated during MM progression, correlating with a bad prognosis. Epigenetic modulating agents significantly increased RASSF4 expression, indicating that the RASSF4 downregulation is due to epigenetic silencing. Forced RASSF4 expression induced a G2-phase arrest and caspase-3 mediated apoptosis in human MM cell lines, strongly reduced viability of primary CD138+ MM cells and significantly reduced in vivo tumor growth. Moreover, we demonstrated RASSF4-MST1 binding and the involvement of the downstream signaling pathways JNK/Jun, p38 and p53. RASSF4 overexpression sensitized MM cells to the proteasome inhibitor bortezomib, the specific MEK1/2 inhibitor trametinib and the ROS inducer Prima-1Met. Consequently, combining trametinib with histone deacetylase inhibitors (HDACi) revealed very strong synergistic anti-MM activity. In conclusion, our study identified RASSF4 as a new potent tumor suppressor in MM that is epigenetically silenced during MM progression and provides the basis for novel therapeutic strategies enhancing RASSF4 expression (using HDACi) in combination with MEK/ERK inhibitors and bortezomib. Overall design: Paired-end RNA sequencing analysis of the RASSF4 transduced cell lines cultured for 5 days in the presence of doxycycline	Co-expression
SRP080737	Homo sapiens Genome sequencing	FS vs Normal joint	Co-expression
SRP080745	Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis	Purpose: To determine whether and how pleural macrophages change in phenotype, transcription and function in patients with tuberculous pleuritis following anti-TB antibiotic treatment. Overall design: Purifiy pleural macrophages from TB patients before and after antibiotics treatment --------------- identities of antibiotics not provided	Co-expression
SRP080757	Genome-wide mRNA sequencing of Panc-1 cells with or without fused IL-35 gene up-regulated	To screen out the downstream genes of IL-35 Overall design: The two subunits of IL-35, EBI3 and P35, were fused together and transfected into Panc-1 cell via lentivirus. The sequence of the fused gene is identical to that of a commercial IL-35-overexpessed plasmid (InvivoGEN, pORF9-hIL35elasti). An empty vector was used as the control. The two cell lines were subjected to a genome-wide RNA sequencing.	Co-expression
SRP080789	Control of gene expression in senescence through transcriptional read-through of convergent protein-coding genes [RNA-Seq PROLIF-SEN]	Antisense RNAs are non-coding RNAs, which can regulate their corresponding sense RNAs and are generally produced from specific promoters. By genome-wide approaches and in depth analyses at specific loci in human cells undergoing senescence, we uncover a family of antisense RNAs produced by transcriptional read-through at convergent protein-coding genes. Importantly, these antisense RNAs, that we named STARTs, repress the expression of their corresponding sense RNAs. We found that the elongation rate of RNA pol II is limited downstream of the TTS at START loci in proliferative cells. This allows transcription termination to occur before the RNA pol II reaches the convergent genes, thus preventing antisense RNA production and interference with the expression of the convergent genes. In proliferative cells, STARTs are repressed by the histone variant H2A.Z, whose local occupancy decreases in senescence. Our results thus uncover a novel mechanism of gene expression regulation, relying on the control of the expression of read-through antisense transcripts at convergent genes and underline the functional importance of the epigenetic control of RNA pol II elongation rate at intergenic regions. Overall design: Strand-specific RNA-seq datasets in proliferative cells and in Raf1-induced senescent cells (2 replicates).	Co-expression
SRP080794	CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions [RNA-seq]	In our work we used high-throughput sequencing methods to get insight in the role of CTCF in ER-mediated gene regulation in luminal breast cancer cells. After assessing genome-wide binding of CTCF, ER, FOXA1 and Lamin B in MCF7 cells treated with estrogen for different time points, we could correlate the interaction to the chromatin with estrogen-induced de novo transcription (from GRO-seq data) and loop formation (from ChIA-PET, Fullwood et al., 2009). We observed that CTCF binding correlates with ER-mediated transcription and its depletion can affect ER-ER loop formation and subsequently gene expression. Overall design: RNA-seq in MCF7 cells transfected with siRNA targeting CTCF (siCTCF) or control (siNT) and treated for 0h or 3h with 100 nM Estrogen.	Co-expression
SRP080797	Integrator orchestrates RAS/ERK1/2 signaling transcriptional programs	We investigated the occupancy of RNA PolII and INTS11 during the stimulation of EGF and compared with drug treated condition using inhibitors against MAPK pathway and Integrator. Additionally, we examined transcription by sequencing the chromatin-bound fraction of RNA. Overall design: We employed several cel lines in our experiment, including HELA, KRAS mutant lung cancer cell line A549 and BRAF mutatant melanoma cell line A375.  The conditons we  checked including EGF stimulation, MAPK pathway inhibition using BRAF, MEK or ERK inhibitiors, targeting INTS11 with RNAi or integrator inhibitor.  We used RNA sequencing to measure the expression profile and CHIP sequencing to detect INTS11 and RNA PolII recruitment on chromatin.	Co-expression
SRP080811	Integrative classification of human coding and non-coding genes based on RNA metabolism profiles	The pervasive transcription of the human genome results in a heterogeneous mix of coding and long non-coding RNAs (lncRNAs). Only a small fraction of lncRNAs possess demonstrated regulatory functions, making it difficult to distinguish functional lncRNAs from non-functional transcriptional byproducts. This has resulted in numerous competing incoherent annotations of human lncRNA. To address these challenges, we quantitatively examined transcription, splicing, degradation, localization and translation for coding and non-coding human genes. Annotated lncRNAs had lower synthesis and higher degradation rates than mRNAs. We discovered mechanistic differences explaining the slower splicing of lncRNAs. We grouped genes into coherent classes by performing annotation-agnostic unsupervised classification of RNA metabolism profiles. These classes contained both mRNAs and lncRNAs to varying degrees; they exhibited distinct relationships between steps of RNA metabolism, evolutionary patterns, and sensitivity to cellular RNA regulatory pathways. Our classification provides a functionally coherent alternative to genomic context-driven annotations of lncRNAs. Overall design: HEK293 cells were labeled with 4-thiouridine for 0, 7.5, 15, 30, 45, and 60 minutes were collected in triplicate and strand-specifically paired-end sequenced on a HiSeq2500. Please note that the ''readme.txt'' contains detailed description of the ''ST*.txt'' processed data file content and data processing steps.	Co-expression
SRP080813	Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia	Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known how mutant NPM1 (NPM1mut) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1mut AML. Using a CRISPR-Cas9 genome editing domain screen, we show NPM1mut AML to be exceptionally dependent on the menin binding site in MLL1. Pharmacological small-molecule inhibition of the menin-MLL protein interaction had profound anti-leukemic activity in human and murine models of NPM1mut AML in vitro and in vivo. Combined pharmacological inhibition of menin-MLL and DOT1L resulted in dramatic suppression of HOX and FLT3 expression, induction of differentiation, and superior activity against NPM1mut leukemia. Together, MLL1 and DOT1L are chromatin regulators that control HOX, MEIS1 and FLT3 expression and are therapeutic targets in NPM1mut AML. Combinatorial small-molecule inhibition has synergistic on target activity and constitutes a novel therapeutic concept for this common AML subtype. Overall design: RNA sequencing data of the human AML cell lines OCI-AML2 and OCI-AML3 comparing EPZ004777 [10µM] drug treatment versus DMSO vehicle control; experiments performed in biological triplicates.	Co-expression
SRP080824	INO80 is required for oncogenic transcription and tumor growth in non-small cell lung cancer [RNA-seq]	Epigenetic regulators are attractive targets for the development of new cancer therapies. Among them, the ATP-dependent chromatin remodeling complexes control the chromatin architecture and play important roles in gene regulation. They are often found to be mutated and de-regulated in cancers, but how they influence the cancer gene expression program during cancer initiation and progression is not fully understood. Here we show that the INO80 chromatin remodeling complex is required for oncogenic transcription and tumor growth in non-small cell lung cancer (NSCLC). Ino80, the SWI/SNF ATPase in the complex, is highly expressed in NSCLC cells compared to normal lung epithelia cells. Further, its expression, as well as that of another subunit Ino80b, negatively correlates with disease prognosis in lung cancer patients. Functionally, Ino80 silencing inhibits NSCLC cell proliferation and anchorage-independent growth in vitro and tumor formation in mouse xenografts. It occupies enhancer regions near lung cancer-associated genes, and its occupancy correlates with increased genome accessibility and enhanced expression of downstream genes. Together, our study defines a critical role of INO80 in promoting oncogenic transcription and NSCLC tumorigenesis, and reveals a potential treatment strategy for inhibiting the cancer transcription network by targeting the INO80 chromatin remodeling complex. Overall design: Human lung cancer cell line A549 cells were infected with shNT or shIno80, and total RNA was extracted 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, A549 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.	Co-expression
SRP080859	RNA-seq reveals changes in the astrocyte transcriptome following Borrelia burgdorferi infection	mRNA profiles of astrocytes infected with Borrelia burdorferi for 24 hours, 48 hours, and 24 hour  uninfected controls  were generated by deep sequencing, in triplicate, using Illumina HiSeq. Overall design: mRNA profiles of astrocytes infected with Borrelia burdorferi for 24 hours, 48 hours, and 24 hour  uninfected controls  were generated by deep sequencing, in triplicate, using Illumina HiSeq.	Co-expression
SRP080879	Homo sapiens strain:Peripheral Blood | isolate:SA-Beta-beta-Galactosidase-CD34-Positive Raw sequence reads	Senescent and Active-HSPCs were isolated from three healthy individuals (ages 34, 50 and 52 years). Total RNA was purified from FACS-isolated cells from each population using the Zymo Research Quick-RNA MicroPrep following manufacturer's protocol. Quality and purity of the RNA was determined in Agilent Bioanalyzer analysis using the RNA 6000 Pico kit. A total of 5 ng of RNA was used for library generation. Library generation was performed using the Nugen Ovation RNA-Seq System V2. Sequencing was done using an Illumina HiSeq 2500 with 75 base pair, paired-end reads. Six samples were multiplexed into one HiSeq 2500 lane.	Co-expression
SRP080882	MEK inhibition rewires enhancer landscapes in RAS-driven Rhabdomyosarcoma to unlock a myogenic differentation block	Trametinib-treated rhabdomyosarcoma cells undergo transcriptional reprogramming akin to myogenic differentiation.   This reprogramming is induced by loss of ERK-mediated inhibition of MYOG expression.  Restoration of MYOG allows establishment of super-enhancers at genes expressed by terminally differentiated myotubes.  Our findings demonstrate that aberrant MAP kinase activity blocks differentiation in rhabdomyosarcoma and highlight trametinib as a potential therapeutic for RAS-mutated rhabdomyosarcoma. Overall design: RNA-seq in 2 FN-RMS cell lines exposed to either DMSO or Trametinib treatment for various concentrations and timepoints, and siRNA against MEK1 or scramble.	Co-expression
SRP080883	inDrop single cell RNA-seq of hematopoietic cells derived from human pluripotent stem cells	We performed morphogen-directed differentiation of human PSCs into HE followed by combinatorial screening of 26 candidate HSC-specifying TFs for the potential to promote hematopoietic engraftment in irradiated immune deficient murine hosts. We recovered seven TFs (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, SPI1) that together were sufficient to convert HE into hematopoietic stem and progenitor cells (HSPCs) that engraft primary and secondary murine recipients Overall design: Examination of  expression pattern in hematopoietic cells.	Co-expression
SRP080924	Transcriptome sequencing of K-562 cells	We analyzed the global effect of c-Myb knockdown by sequencing the transcriptomes of K-562 cells transfected with control siRNA and si2992 (MYB knockdown), as well as K-562 cells stably expressing TY-tagged wild type c-Myb and c-Myb D152V transfected with si2992 Overall design: Cells were tranfected with siRNA and 24 hours after total RNA was extracted. Three individual experiments were performed. Libraries were prepared and 125-bp paired-end reads were obtained using an Illumina HiSeq 2500 sequencer	Co-expression
SRP080943	TT-seq captures simultaneous activation of eRNAs and promoters during T cell activation	Jurkat T cells were activated with PMA and ionomycin. Total and Labeled fragmented RNA was extracted every 5 minutes during a time course up to 15min after activation. Biological duplicates of all samples were sequenced on a HiSeq 1500 Overall design: Jurkat T cells were activated with PMA and ionomycin. Total and Labeled fragmented RNA was extracted every 5 minutes during a time course up to 15min after activation. Biological duplicates of all samples were sequenced on a HiSeq 1500	Co-expression
SRP080962	Hepatic differentiation of liver organoids	We analyzed gene expression profiles of self-organizing, multi-cellular, 3D liver organoids derived by co-culture of induced Pluripotent Stem Cell and stromal progenitors. We report the RNA-seq results of liver organoid at day0, day2, day4, day6 of co-culture. We also report RNA-seq results of constituent of the liver organoid, which are human iPSC at hepatic specification stage, human Mesenchymal stem cells derived from bone marrow, human umbilical vein endothelial cell. As controls, we also report RNS-seq results of un-differentiated human iPSC, human iPSC at definitive endoderm stage, human liver tissue, and primary cultured human hepatocytes isolated from unused donor livers. Overall design: mRNA profiles of  liver organoids and their constituents were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.	Co-expression
SRP080966	DHX9 suppresses spurious RNA processing defects originating from the Alu invasion of the human genome [RNA-Seq]	Transposable elements increase genetic diversity thus making them an important part of evolution and gene regulation in all organisms that carry these sequences. Bulk of our nascent transcriptome is comprised of transposable elements that have the propensity to form strong secondary structures. It is essential to resolve such strong secondary structures to maintain normal cellular function. Here, we show that the major nuclear RNA helicase DHX9/RHA interacts and remodels embedded Alu retrotransposable elements in the human transcriptome and B1 retrotransposable elements in the mouse transcriptome. To understand the effect of loss of DHX9 in human transcriptome we performed knockdown of DHX9 in HEK293 cells using two different siRNAs, followed by polyA-plus and polyA minus RNA extraction and sequencing. Overall design: We perfomed knockdown of human RNA heliase-A (also known as DHX9 ) in HEK293 cells using 2 different siRNAs, followed by polyA-plus and polyA-minus RNA sequencing. siRNAs used: control: silencer select siRNA control #2 (https://www.thermofisher.com/order/catalog/product/4390846) DHX9 KD_1: s4019 (http://www.ncbi.nlm.nih.gov/probe/16735410) chr1: 182860161-182860180 (hg38) DHX9 KD_2: s4020 (http://www.ncbi.nlm.nih.gov/probe/16735422) chr1: 182858158-182858177 (hg38) siRNA were used at a final concentration of 5nM, transfected to HEK293 cells with RNAiMAX. Total RNA was isolated 3d after transfection. For polyA(+) samples, TruSeq library prep protocol was used (starting with ~1µg total RNA) For polyA(-) samples, we depleted polyA(+) RNA from total RNA with oligo-dT(+) beads, twice. The rest was first ribodepleted with RiboZero kit, which then went through the TruSeq protocol. Sequencing parameters : 150x2 bp reads, full run of the NextSeq500 machine.	Co-expression
SRP080991	A single-cell transcriptome atlas of the human pancreas [CEL-seq2]	To understand organ function it is important to have an inventory of the cell types present in the tissue and of the corresponding markers that identify them. This is a particularly challenging task for human tissues like the pancreas, since reliable markers are limited.  Transcriptome-wide studies are typically done on pooled islets of Langerhans, which obscures contributions from rare cell types and/or potential subpopulations. To overcome this challenge, we developed an automated single-cell sequencing platform to sequence the transcriptome of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors, a subpopulation of REG3A-positive acinar cells, and cell surface markers that allow sorting of live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus. Overall design: Islets of Langerhans were extracted from human cadaveric pancreata and kept in culture until single-cell dispersion and FACS sorting. Single-cell transcriptomics was performed on live cells from this mixture using an automated version of CEL-seq2 on live, FACS sorted cells. The StemID algorithm was used to identify clusters of cells corresponding to the major pancreatic cell types and to mine for novel cell type-specific genes as well as subpopulations within the known pancreatic cell types.	Co-expression
SRP081022	MicroRNAs underlie genome-wide transcriptome and translatome regulation in asthma as revealed by Frac-seq (RNA-Seq)	Transcription and translation correlate poorly, as mRNA undergoes multiple regulatory steps such as alternative splicing and microRNA regulation that determine its translationability into protein. Measures of transcriptional mRNA levels may therefore misrepresent cellular activation. To test this hypothesis employing human physiological mRNA levels, we analyzed cytoplasmic and polyribosome-bound mRNA expression (Frac-seq) combined with microRNA profiling by small RNA-seq in bronchoepithelial cells from healthy and severe asthma (SA) donors, SA being a chronic inflammatory airways disease, poorly understood at the molecular level. We found 275 genes bound to polyribosomes differentially between healthy and severe asthma, of which only 11.64% overlapped with differentially expressed cytoplasmic mRNAs (226 genes). We found 335 alternatively spliced mRNA isoforms differentially bound to polyribosomes of which only ~8% were revealed by cytoplasmic mRNA analysis. Approximately two thirds of differentially expressed isoforms could not be found at the gene level in both cytoplasmic and polyribosome bound fractions, demonstrating the disruption of splicing in asthma. Only the analysis of differentially expressed isoforms bound to polyribosomes revealed disease-related pathways overlooked in total mRNA. We detected a network of 21 microRNAs differentially expressed, with 8 microRNAs accounting for more than 80% targeting observed in both cytoplasmic and polyribosome bound mRNA isoforms. Importantly, microRNAs target distinct cytoplasmic and polyribosome bound mRNAs. Hence this work, integrating deep-sequencing, subcellular fractionation and microRNA profiling, demonstrates the disruption of post-transcriptional regulatory processes as the main disease causing molecular mechanism in asthma, something that cannot be dissected employing more classic transcriptomics approaches alone. Overall design: We performed cytoplasmic and polyribosome bound RNA-seq of bronchial epithelial cells from healthy controls and severe asthmatic patients. Small RNA-seq was also performed	Co-expression
SRP081057	Homo sapiens Raw sequence reads	Effects of chronic hypoxia in pulmonary arterial smooth muscle cells.	Co-expression
SRP081073	Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells	We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4+ T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs. Novel enhancer-associated lncRNAs transcribed from the IFNG locus bind the transcription factor NF-?B and enhance binding of NF-?B to the IFNG genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one IFNG enhancer-associated lncRNA abrogates IFNG expression by memory T cells, indicating these lncRNAs have biologic function. Overall design: We extracted RNA from CD4+ naïve, central memory, and effector memory cell populations in healthy control subjects to assess expression levels of protein-coding and non-coding genes.	Co-expression
SRP081074	CD133+ vs. CD133- cells in GBML8, a primary glioblastoma tumorsphere culture	CD133+ and CD133- cells were FACS islated from GBML8 cells to find gene signatures upregulated in cancer stem cells Overall design: After surface immuno staining, CD133+ and CD133- cells were FACS isolated and subjected to RNA isolation. Experiment represent averaged data of 2 independent FACS isolations.	Co-expression
SRP081083	Discovering the miR-26a/targetome in prostate cancer cells	In this work, we showed that the re-expression of miR-26a in DU-145 prostate cancer cells restored the tumor suppressor activity of miR-26a. To discover the genes and pathways elicited by miR-26a re-expression, we used the miRNA pull out assay to capture and the Next Generation Sequencing to identify the miR-26a targets. Data showed that: i) miR-26a captured both non-coding and coding RNAs; ii) 46% of transcripts were putative miR-26a targets according to target prediction algorithms; iii) 21 pathways were significantly enriched and the “Pathway in Cancer” was among those comprising the largest number of genes, including BIRC5 that we experimentally validated. Accordingly, the detection of cell proliferation-related events showed that miR-26a exerted its tumor suppressor activity at several levels, by decreasing the survival, impairing the migration of tumor cells and by inducing both apoptosis and cell cycle block. In conclusion, we showed that the collection of miR-26a interacting transcripts (miR-26a/targetome) represented a fruitful platform to decipher the miR-26a-dependent gene expression networks. In perspective the availability of miRNA-specific and tumor-specific targetomes will allow the discovery of new druggable tumor genes and pathways. Overall design: The miRNA pull out assay was performed modifying the protocol described by Orom et al. {Methods 43, 162-165, doi:S1046-2023(07)00097-7}. DU-145 were seeded into the wells of a 6-well at the density of 1.5 x105. After 24 hours from seeding, cells were transfected using lipofectamine (Thermo Fisher) with 60nM of either miR-26a duplex (ds-miR-26aCT) or a mix of 3' biotin-tagged miR-26a 7tU (nucleotide 7 was a thiouridine) and miR-26a 17tU duplexes (ds-miR-26aBIO). The day after transfection, the cells were washed with PBS and irradiated with UV (365nm, 2J/cm2), using the Bio-Link crosslinking (BLX) (Ambrose Lourmat) with appropriate UV lamps, to induce cross-linking of tU nucleotides to RNA. Total RNA was extracted adding directly on adherent cells TRIzol reagent (Thermo Fisher) and following the instructions provided by the manufacturer. After DNAse treatment, 15 µg of RNA was incubated for 4 hrs at 4°C with 100 µl of streptavidin-conjugated beads (200 µl of Streptavidin Sepharose high performance, GE Healthcare) previously suspended in PO buffer (1M Tris pH8, 5M NaCl, 1M MgCl2, NP40 50 µl in 100 ml buffer). After 2 washes with PO buffer and 2 washes with DEPC-treated water, the RNA complexed with beads was recovered by adding 1 ml Trizol directly on the beads and then following the TRIzol RNA extraction protocol. We performed two biological replicates obtaining two miR-26aCT (control) and two miR-26aBIO (miR-26a) pull out samples. The RNA isolated after the miRNA pullout procedure from both miR-26aCT and miR-26aBIO samples was used for the construction of the cDNA libraries using the TruSeq Stranded Total RNA Sample Preparation kit (Illumina) according to the manufacturer's suggestions. cDNA libraries were sequenced by HiSeq2000 (Illumina) in single-reads mode (50bp) by IGA Technology Service, Udine, Italy, obtaining about 20 million of reads for each samples.	Co-expression
SRP081103	Genome-wide transcriptomic analysis of cardiomyocyte differentiation from human embryonic stem cells and iPS cells (RNA-seq)	In this study, time-course transcriptome profiling of caidiomyocyte differentiation derived from human hESCs and hiPSCs was investigated. Two hiPSC lines (C15 and C20) and two hESC lines (H1 and H9) were differentiated to caidiomyocytes. The cells were collected for RNA-seq analysis at day0(undifferentiated cells) day2 (mesoderm), day4 (cardiac mesoderm) and day30 (cardiomyocytes) using Illumina HiSeq 2000 sequencer. Overall design: Two hiPSC lines (C15 and C20) and two hESC lines (H1 and H9) were grown in 12-well plates with  Essential 8 medium (Thermo Fisher Scientific). The cardiomyocyte differentiation was initiated using a monolayer differentiation method with PSC Cardiomyocyte Differentiation kit (Thermo Fisher Scientific). At day 0, 2, 4 and 30 during the differentiation period (before the medium-change on that day), cells were collected using Accutase (Thermo Fisher Scientific), and then store in -80C till RNA isolation. For each cell line and each time-point, cells from two independent differentiation wells were used as two biological replicates. RNA-seq libriries were sequenced by a HiSeq 2000 sequencer (Illumina) with 2 X 101 cycles. RNA-seq fastq data were aligned with Tophat (version 2.0.9) to GRCh39/hg19 Homo sapiens reference genome from the UCSC Genome Browser. Cuffdiff of the Cufflinks software (version 2.2.1) and GRCh39/hg19 Homo sapiens gtf file from UCSC Genome Browser were used to estimate abundances of transcripts and generate their FPKM values. Table of FPKM values of all samples were created using cummeRbund package in R.	Co-expression
SRP081127	Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs	We performed N6-methyladenosine (m6A) immunoprecipitation of ribosome-depleted RNA to identify m6A-circRNAs Overall design: Total RNA was isolated from human embryonic stem cells (hESCs) and HeLa cells. Total RNA was depleted of ribosomal RNA and libraries were prepared for sequenceing before and after m6A immunoprecipitation (RIP).	Co-expression
SRP081151	Homo sapiens Transcriptome or Gene expression	RNA-seq analysis to study the effect of SMAD7 in Acute Lymphoblastic Leukaemia.	Co-expression
SRP081160	Depicting early human development and germ cell origin with porcine embryos	Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate in early postimplantation embryos. Since early human embryos cannot be investigated directly, we extended our recent in vitro model for hPGC fate, alongside direct analysis of early porcine embryos, which develop in a highly similar manner.  Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak epiblast in response to WNT and BMP-pSMAD signalling, followed by sequential induction of SOX17–BLIMP1 expression. This is reminiscent of our observations for the human in vitro counterpart. Mechanistic analysis in the culture model for hPGC specification and gastrulation shows that a balanced SOX17-BLIMP1 gene dosage is critical and sufficient for PGC specification; SOX17 subsequently induces definitive endoderm during gastrulation. We demonstrate that porcine embryos when combined with a tractable human model system can provide insights on early human development and mechanisms of early cell fate decisions. Overall design: RNA-Seq analysis to investigate transcriptomes of hESCs and hPGCs induced from hESCs with cytokines or with overexpression of SOX17 and BLIMP1	Co-expression
SRP081174	Ets homologous factor has critical roles in epithelial dysfunction in airway disease [RNA-seq]	Ets homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor. Using EHF ChIP-seq and RNA-seq after EHF depletion, we show its targets in HBE cells are enriched for genes involved in degradation of misfolded proteins, inflammation, and wound repair. Overall design: mRNA profiles from primary human bronchial epithelial cells treated with negative control (NC) or EHF siRNA, in quintuplicate.	Co-expression
SRP081182	human fatty tissue Transcriptome	understand the funcation of fatty	Co-expression
SRP081183	Homo sapiens Transcriptome or Gene expression	humman Transcriptome	Co-expression
SRP081184	Homo sapiens Transcriptome or Gene expression	a	Co-expression
SRP081185	Homo sapiens Transcriptome or Gene expression	human	Co-expression
SRP081186	human gene Transcriptome	human gene Transcriptome analysis	Co-expression
SRP081188	Homo sapiens Transcriptome or Gene expression	human Transcriptomehuman Transcriptomehuman Transcriptomehuman Transcriptomehuman Transcriptome	Co-expression
SRP081211	Transcriptome of iPSC-derived Cerebral Organoids with Heterozygous Knockout in CHD8	CHD8 (chromodomain helicase DNA binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is the most commonly mutated gene in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities, and affects cancer cell proliferation. To better understanding the molecular links between CHD8 functions and ASD, we have applied the CRISPR/Cas9 technology to knockout (KO) one copy of CHD8 in induced pluripotent stem cells (iPSCs) and build cerebral organoids, a model for the developing telencephalon. RNA-seq was carried out on KO organoids (CHD8+/-) and isogenic controls (CHD8+/+). Differentially expressed genes (DEGs) revealed an enrichment of genes involved in neurogenesis, forebrain development, Wnt/ß-catenin signaling and axonal guidance. The SZ and bipolar disorder (BD) candidate gene TCF4 was significantly upregulated. Our CHD8 KO DEGs were significantly overlapped with those found in a transcriptome analysis using cerebral organoids derived from a family with idiopathic ASD and another transcriptome study using iPS cell-derived neurons from patients with BD, a condition characterized in a subgroup of patients by dysregulated WNT/ß-catenin signaling. Overall, the findings show that distinct ASD, SZ and BD candidate genes converge on common molecular targets - an important consideration for developing novel therapeutics in genetically heterogeneous complex traits. Overall design: iPSCs derived from a healthy subject were transduced with CRISPR/Cas9 vectors with  single guide RNA sequences to target the N-terminal of CHD8 protein to generate truncated mutations. The CHD8+/- iPSC lines were used to generate cerebral organoids for RNA-seq analysis, together with samples prepared from the parental clones, for a total of 6 samples (two biological replicates of wild-type (WT) and 4 biological replicates of CHD8+/-).	Co-expression
SRP081236	Transcriptome analysis identifies the dysregulation of ultraviolet target genes in human skin cancers	In this study, we performed RNA-Seq studies to generate a transcriptomic cohort containing UV-responsive genes in human skin cells exposed to different UVR conditions. We then performed rigorous bioinformatics analysis to define a UV gene expression signature that is conserved among cells from different donors. We further demonstrated that the UV signature genes are significantly enriched in genes dysregulated in human skin squamous cell carcinomas. Overall design: UV-responsive genes were identified by characterzing the differentially expressed genes between UV-irradiated human keratinocytes and non-irradiated control keratinocytes.	Co-expression
SRP081249	ADAR1 controls apoptosis of stressed cells by inhibiting Staufen-mediated mRNA decay	Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA).  The p150 isoform suppresses the dsRNA sensing mechanism that activates the interferon induction mediated by the MDA5-MAVS signaling.  In contrast, the biological function of the p110 isoform localized in the nucleus remains largely unknown. Here we show that stress-activated phosphorylation of ADAR1p110 by MKK6/p38 MAP kinases promotes its binding to Exportin-5 and nuclear export to the cytoplasm.  Once translocated to the cytoplasmic, ADAR1p110 suppresses apoptosis of stressed cells by protecting many anti-apoptotic gene transcripts that contain 3'UTR dsRNA structures such as those consisting of inverted Alu repeats.  ADAR1p110 competitively inhibits binding of Staufen1 to the 3'UTR dsRNAs and antagonizes the Staufen1-mediated mRNA decay mechanism.  Our studies revealed a new stress response mechanism regulated by MAP kinases, in which ADAR1p110 translocates to the cytoplasm and regulates a class of mRNAs required for survival of stressed cells. Overall design: Examination of transcription changes due to ADAR1 and double ADAR1/STAU1 knockdown using RNA-seq	Co-expression
SRP081264	Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells	Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-homeodomain transcription factor DUX4 in skeletal muscle cells. Many different cell culture models have been developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human muscle cells. Although results generated using each model are generally consistent, differences have also been reported, making it unclear which model(s) faithfully recapitulate DUX4 and FSHD biology. In this study, we systematically compared RNA-seq data generated from three different models of FSHD—lentiviral-based DUX4 expression in myoblasts, doxycycline-inducible DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4—and show that the DUX4-associated gene expression signatures of each dataset are highly correlated (Pearson's correlation coefficient, r ~ 0.75-0.85). The few robust differences were attributable to different states of cell differentiation and other differences in experimental design. Our study describes a model system for inducible DUX4 expression that enables reproducible and synchronized experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expression. Overall design: We performed a systematic comparison of DUX4-regulated changes in the transcriptome in our inducible codon-altered DUX4 expression system (iDUX4), the endogenous DUX4 expression system (enDUX4), and cells transduced with lentivirus constitutively expressing DUX4 (vDUX4). The specific datasets used in this comparison are as follows: iDUX4 represents a new dataset generated from the MB135 immortalized human myoblasts with the doxycycline inducible codon-altered DUX4 (iDUX4), performed in biological triplicate fourteen hours after DUX4 induction in growth media, with uninduced cells as a control; enDUX4 represents the published dataset of differentiated FSHD myocytes that do or do not express endogenous DUX4, as determined using a DUX4-responsive fluorescent reporter and flow sorting (9); vDUX4 represents a published dataset wherein two different myoblast cell lines (MB135 and 54-1) were transduced with a lentiviral construct that drives constitutive DUX4 expression via the PGK promoter and maintained in growth media for 24 hours (MB135) or 36 hours (54-1) prior to harvesting RNA.	Co-expression
SRP081272	Epigenomic Profiling of Primary Gastric Adenocarcinoma Reveals Super-enhancer Heterogeneity [RNA-seq]	Regulatory elements in cancer remain poorly characterized in primary solid tumors. Here we applied microscale histone modification profiling to delineate the landscape of somatic promoters and super-enhancers in primary gastric adenocarcinoma, analyzing 94 epigenomic  profiles of primary tumors, normal tissues, and cell lines Overall design: Total RNA extracted from gastric cell lines, tumors and matched gastric non-malignant (normal) tissues was sequenced.	Co-expression
SRP081284	Cell responses to dysregulated VZV-induced cell-cell fusion	The highly conserved herpesvirus glycoprotein complex, gB/gH-gL, mediates membrane fusion during virion entry and cell-cell fusion.  Varicella-zoster virus (VZV) characteristically forms multi-nucleated cells, or syncytia, during the infection of human tissues but little is known about this process.  The cytoplasmic domain of VZV gB (gBcyt) has been implicated in cell-cell fusion regulation because a gB[Y881F] substitution causes hyperfusion.  The gBcyt regulation is necessary for VZV pathogenesis as the hyperfusogenic mutant gB[Y881F] is severely attenuated in human skin xenografts.  In this study, gBcyt regulated fusion was investigated by comparing melanoma cells infected with wild type-like VZV or hyperfusogenic mutants.  The gB[Y881F] mutant exhibited dramatically accelerated syncytia formation in melanoma cells caused by fusion of infected cells with many uninfected cells, increased cytoskeleton reorganization and rapid displacement of nuclei to dense central structures when compared to pOka using live cell confocal microscopy.  VZV and human transcriptomes were concurrently investigated using RNA-seq to identify viral and cellular responses induced when the gBcyt regulation was disrupted by the gB[Y881F] substitution.  The expression of four vital VZV genes, ORF61 and glycoproteins, gC, gE and gI, was significantly reduced at 36 hours post infection for the hyperfusogenic mutants.  Importantly, hierarchical clustering demonstrated an association of differential gene expression with dysregulated gBcyt-mediated fusion.  A subset of Ras GTPase genes linked to membrane remodeling were upregulated in cells infected with the hyperfusogenic mutants.  These data implicate the gBcyt in the regulation gB fusion function that, if unmodulated, triggers cellular processes leading to hyperfusion that attenuates VZV infection. Overall design: Biological duplicates from 3 time points (12, 24 and 36 hours post infection) of uninfected MeWo cells or MeWo cells infected with varicella-zoster virus strain pOka or mutants gB[Y881F], gB[Y920F] or gB[Y881/920F]	Co-expression
SRP081287	RNA-sequencing of milk cells extracted from pre-partum secretions and longitudinally from mature human milk across the first year of lactation	Changes in mammary cell behavior mediating normal breast development during pregnancy and lactation are poorly understood due to limited availability of breast biopsies during this time. Human milk contains a hierarchy of cells including stem cells, mature milk producing cells (lactocytes) and myoepithelial cells. Here we non-invasively sampled the total epithelial cell population of the lactating mammary gland from mature HM collected from healthy mother/infant dyads during the first year postpartum, and explored temporal changes in the mammary cell transcriptome using RNA sequencing. Comparisons were done with mammary secretions from late pregnancy from the same women and with purchased resting mammary tissue. Distinct gene signatures were found for the different mammary developmental stages examined. Cell adhesion pathways were differentially regulated between the resting gland and pregnancy, whereas immune cell signaling and morphogenesis/cancer pathways differed between lactation and pregnancy or the resting gland, respectively. The transcriptome of lactation remained consistent in the first year postpartum in these successfully lactating women. The gene signatures characteristic of HM cells confirmed lactation genes previously reported in animal models and the HM fat globule. This study identifies key genes and molecular pathways undergoing controlled regulation as the mammary gland transitions from a quiescent into a functional organ, providing experimental targets for the molecular investigation of mammary gland pathologies. Overall design: The human milk cell transcriptome was generated from cells extracted from pre-partum samples and mature milk at months 1, 3, 6 and 12 of lactation.	Co-expression
SRP081348	Homo sapiens Genome sequencing	Identification of potential key genes associated with Astragalus auxiliary treatment of liver cirrhosis using RNA sequencing data.	Co-expression
SRP081445	HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue Destructive Phenotype	While the survival rate of HIV-infected individuals has dramatically improved with the development of highly active anti-retroviral therapy, HIV-infected individuals have an increased risk for chronic disorders, including the development of COPD, manifesting as emphysema. The mechanisms of HIV-associated emphysema are not understood. Based on the knowledge that human airway basal cells (BC) function as stem/progenitor cells capable of differentiation into specialized ciliated and secretory cells during natural turnover and repair in response to injury, we hypothesized that HIV interacts with, and consequently induces pathologic programming of the BC that contributes to the development of emphysema. Overall design: Studies were designed to assess: (1) if HIV binds to, infects and/or replicates in BC; (2) identify which BC receptor(s) are responsible for HIV capture; and (3) the reprogramming of BC biology upon HIV exposure. Infectious HIVNL4-3 was used for all studies. Soluble heparan sulfate and heparinase III were used to prevent HIV/BC interactions. BC phenotypes after HIV exposure were assessed by TaqMan quantitative PCR, ELISA, phospho-MAPK array, protease array, cell invasion assay, and zymography.	Co-expression
SRP081473	Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer	Anti-androgen therapies including the new androgen receptor (AR) antagonist MDV3100 are the first therapeutic approach in treating prostate cancer (PCa). However, tumors frequently become castration resistant through multiple mechanisms including alternative expression of AR splice variants. To identify new inhibitors which block both full-length AR (AR-FL) and constitutively-active truncated AR splice variants (AR-Vs), a library of natural compounds was screened for molecules that could inhibit AR-driven transcription in PCa cells expressing AR-FL or AR-Vs. We identified the small-molecule Ailanthone (AIL) as a potent inhibitor of both AR-FL and AR-Vs. AIL down-regulates both AR itself and its target genes in PCa cell lines as well as orthotopic animal tumors. Moreover,AIL directly binds to the co-chaperone protein p23 and prevents AR’s interaction with HSP90, which results in the disruption of the AR-chaperone complex followed by Ubiquitin/proteasome-mediated degradation of AR as well as other p23 clients including AKT and Cdk4. Meanwhile, overexpression of p23 dose-dependently rescued AIL-mediated cell proliferation inhibition, suggesting that p23 might be a critical target of AIL. Furthermore, treatment of MDV3100-resistant 22RV1 xenografts with AIL reduced tumor volume by 77.5% (2 mg/kg/day AIL, intraperitoneal) and 79.2% (5 mg/kg/day AIL, oral) compared with the control group.  Finally, AIL possesses favorable drug-like properties such as good bioavailability (25.7% F), high solubility, lack of CYP inhibition, and low hepatotoxicity, although signs of gastrointestinal toxicity were observed at high doses. In conclusion, AIL overcomes MDV3100 resistance in castration resistant prostate cancer (CRPC) with excellent absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, thus suggesting that AIL is a potential candidate for the clinical treatment of CRPC. Overall design: Retinal mRNA profiles of LNCaP cells treated with or without AIL in the absence or presence of AR1-651 were generated by deep sequencing using Illumina HiSeq2000	Co-expression
SRP081477	Single Cell Transcriptome Conservation in Cryopreserved Cells and Tissues	Sample preservation method that maintains transcripts in viable single cells and so allows to disconnect time and place of sampling from subsequent processing steps. Overall design: Single cell transcriptomes from 1,486 fresh and conserved cells from human blood, ovarian and lung tumor xenografts, mouse colon tissue, and human, mouse and canine cell cultures.	Co-expression
SRP081515	Expression profile of LNCaP/AR cells with or without HNF4G expression grown for long term in charcoal stripped-serum (CSS) media	To study the underlying mechanism of androgen independent growth we performed transcriptome analysis of LNCaP/AR-Vec and LNCaP/AR-HNF4G at day 9 of growth in CSS and LNCaP/AR-HNF4G at 32 days of growth in CSS to identify the HNF4G transcriptome, as well as determinants of castration-resistant growth Overall design: RNA-seq	Co-expression
SRP081517	Expression profile of HNF1A knockdown and overexpression in 22RV1 and LNCaP cells respectively	To determine genes regulated by HNF1A in 22Rv1, we performed siRNA  mediated knockdown of HNF1A using pooled siHNF1A (L-008215-00-0005 5 nmol) and pooled siSCR purchased from Dharmacon.  RNA was harvested 3 days after transfection and gene expression profiling was performed. Similarly to determine genes regulated by HNF1A in LNCaP, we performed retroviral transduction of  LNCaP cells in duplicate for HNF1A  and empty vector control expression. cDNA for HNF1A in RC211201 vector (origene) was subcloned  into a murine stem cell virus (MSCV)-based retroviral vector with hygromycin selection marker (Addgene). After 3 days of transduction, cells were selected for four days in hygromycin and later on RNA was harvested for gene expression profiling. Overall design: RNA profiles were generated by deep sequencing using Illumina HiSeq.	Co-expression
SRP081577	TCF21 and Aryl-hydrocarbon receptor gene cooperate to activate a pro-atherosclerotic gene expression program	Genome-wide association studies (GWAS) for coronary artery disease (CAD, also termed coronary heart disease, CHD) have discovered and validated 48 loci genome-wide and recent 1000-Genomes based meta-analyses have discovered additional 8 loci with significant association, however, true follow-up studies on the mechanisms of association are still scarce. Here we analyze the relationship of two transcription factors, TCF21, one of the lead GWAS candidate genes for coronary artery disease and AHR, aryl hydrocarbon receptor, which previously was not implicated as fundamental for the atherosclerotic process. We show that both the predicted and in-vivo ChIP-Seq binding sites for TCF and AHR colocalize in the human genome with over 400 predicted sites and 119 ChIP-Seq sites directly overlapping. TCF and AHR-ARNT predicted binding sites longitudinal phasing was observed near the transcription start sites, outlining the position of +1 nucleosome. AHR-ARNT matrix was highly enriched in both TCF21 ChIP-Seq peaks and ATAC-Seq open chromatin regions in human coronary artery smooth muscle cells (HCASMC), implicating the role of AHR in this important cell type for vascular biology. Co-expression modules of TCF21 and AHR showed high degree of connectivity. Separation of rotationally phased and unphased predicted binding sites for TCF and AHR resolved the roles of direct and indirect TCF-AHR interactions, and implicated as highly-modulated various inflammatory, interleukin and cytokine related processes, while ChIP-Seq co-localization of TCF21 and AHR/ARNT emphasized the role of calcium related processes. We performed TCF21 overexpression analysis in human coronary artery smooth muscle cells (HCASMC) and obtained GO ontologies that recapitulate in vivo pathophysiology of the atherosclerotic vessel wall, and a set of chronic inflammatory ontologies was established with the colocalization of TCF21 and AHR ChIP-Seq sites as well as with the binomial testing of GWAS SNP overrepresentation. We experimentally confirmed that TCF21 binds to and regulates AHR gene expression in HCASMC, as well as to elements near AHR downstream genes, such as CYP1A1, using reporter assays. The functional relevance of AHR pathway in HCASMC is confirmed using AHR ligands TCDD and oxidized LDL. Finally, we show that AHR is elevated in atherosclerotic arteries using laser capture microdissection in mice in vivo and in human ex vivo. In conclusion, we extend GWAS results to functional assays and show that TCF21 and AHR functional connectivity provides a novel mechanism for diseased coronary vessel wall biology. Overall design: [RNA-Seq] HCASMC: TCF21 overexpression and control. The ChIP-Seq data are submitted under GSE61369 and the ATAC-Seq data are submitted under GSE72696.	Co-expression
SRP081599	DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk [RNA-seq]	We generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes	Co-expression
SRP081605	Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (whole blood RNA-seq)	Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab. This work is part of the Immune Tolerance Network AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes); data are also available through the ITN TrialShare portal: https://www.itntrialshare.org/project/Studies/ITN027AIDB/Study%20Data/begin.view?. Overall design: We performed bulk RNA-seq on 190 whole blood samples from visit months 0 (R: 14, NR: 16: C: 15, total: 45), 6 (R: 16, NR: 17, C: 15, total: 48), 12 (R: 13, NR: 14, C: 16, total: 43), and 24 (R: 17, NR: 20, C: 17, total: 54).	Co-expression
SRP081644	An automatec microwell platform for large-scale single cell RNA-seq.	We report an automated microwell array platform for single cell RNA-seq with significantly improved performance over previous implementations. We demonstrate cell capture efficiencies of >50%, compatibility with commercially available barcoded mRNA capture beads, and parallel expression profiling from thousands of individual cells. We apply our system to comprehensively assess heterogeneity in gene expression of patient-derived glioma neurospheres and uncover subpopulations similar to those observed in human glioma tissue. Overall design: Performed single cell RNA-seq on thousands of cells from three cell lines.	Co-expression
SRP081654	Molecular, Phenotypic, and Sample-associated Data to Describe Pluripotent Stem Cell Lines and Derivatives	The use of induced pluripotent stem cells (iPSC) derived from independent patients and sources holds considerable promise to improve the understanding of development and disease. However, optimized use of iPSC depends on our ability to develop methods to efficiently qualify cell lines and protocols, monitor genetic stability, and evaluate self-renewal and differentiation potential. To accomplish these goals, 57 stem cell lines from 10 laboratories were differentiated to 7 different states, resulting in 248 analyzed samples. Cell lines were differentiated and characterized at a central laboratory using standardized cell culture methodologies, protocols, and metadata descriptors. Stem cell and derived differentiated lines were characterized using RNA-seq, miRNA-seq, copy number arrays, DNA methylation arrays, flow cytometry, and molecular histology. All materials, including raw data, metadata, analysis and processing code, and methodological and provenance documentation are publicly available for re-use and interactive exploration at https://www.synapse.org/pcbc. The goal is to provide data that can improve our ability to robustly and reproducibly use human pluripotent stem cells to understand development and disease.	Co-expression
SRP082150	Cancer Associated Fibroblasts are defined by a core set of epigenome changes that contribute to the tumor phenotype [RNA-seq]	Cancer Associated Fibroblasts (CAFs) play an active role in tumourigenesis. It is unknown how the permanent phenotypic changes in CAFs are encoded at the molecular level. Here we use whole genome sequencing and microarray analysis to interrogate the epigenome, transcriptome and genome of patient-matched CAF and non-malignant prostate fibroblast (NPF) cells. Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics, transcriptomics and genetics in human cancer associated fibroblasts (CAFs) and non-malignant prostate fibroblasts (NPFs)	Co-expression
SRP082152	Gene expression profiles in response to proanthocyanidins in pancreatic cancer cells	Proanthocyanidins (PAs) that are naturally occurring compounds have shown the potential chemopreventive ef?cacy against various forms of cancers in different tumor models. To elucidate the responsible molecular mechanisms involved in antitumor therapeutic effects of PAs, the transcriptome changes of pancreatic cancer cells exposure to PAs at 3, 12 and 24h were investigated in this study. Through two biological replicate sequencing, 966, 3543 and 4944 differentially expressed genes in response to PAs exposure were detected at 3, 12 and 24h, respectively. GO and KEGG analysis showed that cell cycle checkpoints and DNA repair modulations or inhibition were the mainly mechanisms in PAs anti-cancer. Overall, this study provided novel insights into not only the first integrated overview on global gene expression in pancreatic cancer cells post PAs exposure, but also the underlying mechanisms of anti-cancer effects of PAs for chemotherapy. Overall design: Transcriptome change of PANC-1 cells post Proanthocyanidins (20 µg/ml) exposure at 3, 12 and 24h  were investigated. A biological replicate sequencing was carried out.	Co-expression
SRP082197	The Genomic Landscape of Atypical Fibroxanthoma	In this study, we used exome sequencing and RNA sequencing to describe the genomic landscape of Atypical Fibroxanthoma (AFX). Using exome sequencing data, we identified several genes commonly mutated in our samples such as CSMD3, COL11A1, and FAT1. We also identified deletions in chr9p and chr13q in the AFX tumors. Using our RNA-sequencing data, we identified 8591 differentially expressed genes, of which 3524 genes had at least a 2 log fold change between AFX tumors and normal keratinocytes. We also identified several pathways that are dysregulated in AFX, such as epithelial to mesenchymal transition and tumor-associated macrophage response. Overall design: Eight atypical fibroxanthoma samples were collected during Mohs surgery and wide local excision. The samples were snap frozen and embedded in Tissue-Tek. Laser capture microdissection was used to isolate the tumor and normal keratinocytes. Exome sequence libraries were prepared with the Nimblegen SeqCap EZ Exome 3.0 capture kit. The RNA samples were reversed transcriped using the Nugen''s Ovation RNA-Seq system-kit and prepared using Nugen''s Ovation Ultralow kit. 101bp paired-end sequencing was performed on an Illumina HiSeq 2500 for the exome and RNA-Seq libraries. The normal keratinocytes were used as controls in this study when compared to the tumor. RNA-seq data in this Series.	Co-expression
SRP082208	RNA-seq of naive and primed ES cells (NHSM)	Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. Overall design: RNA-seq of 3 naive ES samples in NHSM (Gafni et al.) and 3 primed ES cell samples (in hESM)	Co-expression
SRP082225	Evolution of an lncRNA leads to a primate specific modulation of alternative splicing	We performed the poly(A)-seq of 293T,Hela,THP-1 and N2a cell treated with si5S-OT,shPTBP1 or siU2AF65 Overall design: There are 18 samples without replicates and 5 of them are control.	Co-expression
SRP082227	Physiologic expression of Sf3b1K700E causes impaired erythropoieses, aberrant splicing, and sensitivity to pharmacologic spliceosome modulation	Over 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knock-in mouse model of the most common SF3B1 mutation, Sf3b1K700E. Sf3b1K700E mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1K700E myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3' splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1K700E to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills Sf3b1K700E-expressing cells. Thus, Sf3b1K700E expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS. Overall design: 15 samples, including 6 mouse and 9 human samples with varying SF3B1 status	Co-expression
SRP082274	Next generation sequencing of IL-10 stimulated (M2c) macrophages	Alternatively activated “M2” macrophages are commonly believed to function at late stages of wound healing, behaving in an anti-inflammatory manner to mediate the resolution of the pro-inflammatory response caused by “M1” macrophages. However, the differences between two main subtypes of M2 macrophages, namely interleukin-4 (IL4)-stimulated “M2a” macrophages and IL10-stimulated “M2c” macrophages, are not well understood. M2a macrophages are characterized by the secretion of anti-inflammatory cytokines and the stabilization of angiogenesis. However, the role and temporal profile of M2c macrophages in wound healing are not known. Therefore, we performed next generation sequencing (RNAseq) to identify biological functions and gene expression signatures of M2c macrophages compared to M1 and M2a macrophages plus an unactivated control (M0). Following validation by Nanostring, 18 genes were found to be upregulated by M2c macrophages compared to the other phenotypes (using an adjusted p-value cutoff of 0.05 and fold change of 1.5). Many of these genes are associated with angiogenesis and matrix remodeling, including CD163, TIMP1, SERPINA1, VCAN, and MMP8. Analysis of the macrophage-conditioned media for secretion of matrix-remodeling proteins showed that M2c macrophages secreted higher levels of MMP7, MMP8, and TIMP1 compared to the other phenotypes. Surprisingly, temporal gene expression analysis of a publicly available microarray data set of human wound healing showed that M2c-related genes were upregulated at early times after injury, similar to M1-related genes, while M2a-related genes appeared later or were downregulated. While further studies are required to confirm the timing and role of M2c macrophages in vivo, these results suggest M2c macrophages function at early stages of wound healing. Identification of markers of the M2c phenotype will allow more detailed investigations into the role of M2c macrophages in vivo.	Co-expression
SRP082310	Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation	We profiled the transcriptional changes in N/TERT-1 immortalized keratinocytes after doxycylin induction of gain-of-function mutants of the inflammasome sensor protein  NLRP1. Overall design: Stable N-TERT/1 cell lines were generated using lentiviral transduction. Experimental group includes doxycline-treated N/TERT cells expressing NLRP1 mutants A54T, M77T and A66V. Control group includes doxyclin-treated vector-transduced N/TERT cells and two NLRP1 mutant-transduced cell lines that were not treated with doxycycline. All cells were harvested three days after induction. Total RNA was isolated using Trizol reagent.	Co-expression
SRP082314	Hematopoietic Stem/Progenitor Cell Expansion Without Differentiation is Achieved in Zwitterionic Hydrogels	We report the application of Zwitterionic Hydrogel to enable differention-free expansion of human hematopoietic stem/progenitor cells (HSPC) derived from cord blood. Overall design: To have an advanced insight on the activity of HSPC in  zwitterionic matrix, we conducted mRNA deep-sequencing in HSPC before and after culture	Co-expression
SRP082319	Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells [Bulk RNA-Seq]	Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for the clinical application of hPSCs. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrated that the directed switching of defined ECMs robustly yields highly purified (>95%) endothelial progenitor cells (PSC-EPCs) from hPSCs in integrin-laminin axis and rho signaling pathway-dependent manner. Overall design: RNA-sequencing was conducted to identify the genes that were differentially expressed among differential conditions to induce the differentiation to the endothelial lineages.	Co-expression
SRP082321	Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells [Single Cell RNA-Seq]	Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for the clinical application of hPSCs. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrated that the directed switching of defined ECMs robustly yields highly purified (>95%) endothelial progenitor cells (PSC-EPCs) from hPSCs in integrin-laminin axis and rho signaling pathway-dependent manner. Overall design: Single cell RNA-sequencing was conducted to describe transcriptional dynamics from pluripotent stem cells toward the endothelial lineages.	Co-expression
SRP082374	Molecular characterization of human osteoblast-derived extracellular vesicle mRNA using next-generation sequencing	In this study, we present the comparative transcriptome analysis of human osteoblasts and their corresponding EVs using next-generation sequencing. We demonstrate that osteoblast-EVs are specifically depleted of cellular mRNAs that encode proteins involved in basic cellular activities, such as cytoskeletal functions, cell survival and apoptosis. In contrast, EVs are significantly enriched with 254 mRNAs that are associated with protein translation and RNA processing. Moreover, mRNAs enriched in EVs encode proteins important for communication with the surrounding cells, in particular with osteoclasts, adipocytes and hematopoietic stem cells. Strikingly, EVs are particularly enriched with RAB13 mRNA, which is linked to vesicular trafficking. The latter suggests that EVs may affect vesicle production in target cells. These findings provide the foundation for understanding the molecular mechanism and function of EV-mediated interactions between osteoblasts and the surrounding bone microenvironment. Overall design: Simian virus 40-immortalized human osteoblast cells (SV-HFO cells) were cultured for fourteen days and EV isolated. Total and EV RNA was isolated using TRIzol reagent, and mRNA/miRNA-Seq was performed as described.	Co-expression
SRP082399	The effect on p53-induced gene transactivation by NEAT1 knockdown.	To explore the effect of NEAT1 on gene transactivation induced by p53, we evaluated the changes in gene expression by RNA-seq in NEAT1 knockdown or control U2OS cells. Overall design: Osteosarcoma U2OS cells were transfected with siRNA targeting NEAT1 or negative control siRNA and then treated with nutlin-3a which activates endogenous p53. The change of p53-induced gene transactivation was analyzed.	Co-expression
SRP082406	Efficient derivation of microglia-like cells from human pluripotent stem cells	Microglia-like cells and neural cells were generated from several hES and hIPS lines. As subset was characterized by RNA seq and compared to expression profiles of published primary and induced samples. ABSTRACT: Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages which have been recognized to play a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and Adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts and resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines, and find that pMGLs derived from MeCP2 mutant hES cells are smaller than their isogenic controls. We further describe a culture platform to study integration and live behavior of pMGLs in organotypic 3D-cultures. This modular differentiation system allows the study of microglia in highly defined conditions, as they mature in response to developmentally relevant cues, and provides a framework to study the long-term interaction of microglia residing in a tissue-like environment. Overall design: Individual donors/genetic backgrounds. Dataset inlcudes 4 differentiated neural progenitor biological replicates (NPC1-4), 2 primary fetal microglia samples as reference, 5 induced microglia samples grown in basal medium (pMGL1-5), 3 induced microglia samples grown in neural conditioned medium (pMGL1-3+NCM)	Co-expression
SRP082415	Transcriptome analysis of alternative splicing events in WT and P-KO H9 cells	We have used RNA-seq to explore alternative splicing events in WT and P-KO H9 cells Overall design: RNA-seq for wild type (WT) and SPA paternal KO (P-KO) H9 cells	Co-expression
SRP082419	A-to-I RNA editing and somatic mutations have a similar magnitude of contribution to proteomic diversity in cancer	Through the proteogenomic approach, we identified several adenosine-to-inosine RNA editing sites with mass spectrometry evidence. For the enzymes, ADAR1 and ADAR2, are responsible for A-to-I RNA editing, we perturbed the expression levels of the two genes to further validate those RNA editing sites in three cell lines, including Hs578T, SLR23 and SLR25.	Co-expression
SRP082423	Transcriptional changes induced by Brd4 inhibitor, AZD5153, in cancer cell lines	We sequenced mRNA from 12 human cancer cell lines treated with DMSO or AZD5153 for 24h to determine compound mechanism of action Overall design: Measured mRNA levels in cell lines treated with either AZD5153 or DMSO for 24h	Co-expression
SRP082426	Novel gene expression profile of women with intrinsic skin youthfulness by transcriptome sequencing	Our study is an unbiased, whole transcriptome search for genes associate with intrinsic skin youthfulness in healthy volunteers that is controlled for co-variates. We identify novel candidate skin youthfulness genes and detail why they are highly worthy of future study. Of particular interest are PHLDA1, a follicle stem cell marker, and HAS2-AS1, a non-coding gene.  We demonstrate that immunologic gene sets are the most significantly altered in skin youthfulness,suggesting the immune system plays an important role in skin youthfulness, a finding that has notpreviously been recognized. Overall design: Identify genes associated with intrinsic skin youthfulness in healthy volunteers  from sun protected skin.	Co-expression
SRP082443	Global loss of epigenetic and transcriptional fidility defines a subclass of cancer with immunotherapy resistance	We report that some cancers have extensive loss of epigenetic and transcriptional fidelity, characterized widespread spurious transcription and mRNA processing defects (Loss of transcriptional fidelity: LTF+). LTF impairs transcriptional elongation and imposes a highly specific molecular phenotype where pathways regulated by long genes, such as those involved in inflammatory response are consistently impaired in LTF+ tumors. Accordingly LTF blunts inflammatory response and confers resistance to immune mediated anti-tumor attack, and correlates with poor response to immunotherapeutic drugs in renal cell carcinoma and melanoma patients. We show that genetic or chemical perturbation of gene body histone methylation or of transcriptional elongation can recapitulate LTF-like phenotype, imposing resistance to immune-mediated anti-tumor mechanisms in-vitro and in-vivo. Overall design: Using single end RNAseq we examine the gene expression profile of 6 cell lines	Co-expression
SRP082444	Stress-dependent change in the levels of RNAs	Investigation of a change in the levels of RNAs upon stress conditions	Co-expression
SRP082460	Genome-wide transcriptomic profiling of cardiomyocyte differentiation from human ES cells and iPS cells under exposure to sublethal of isotretinoin (RNA-seq)	In this study, isotretinoin (INN)-induced alternations in transcriptome during caidiomyocyte differentiation derived from human hESCs and hiPSCs were investigated. H1-hESC and C15-hiPSC were differentiated to caidiomyocytes under exposure to sublethal level of INN, and cells were collected at day 0 (undifferentiated cellsl) day 2 (mesoderm) and day 6 (cardiac progenitors) for genome-wide transcriptomic profiling by RNA-seq. Overall design: H1-hESC and C15-hiPSC were grown in 12-well plates with Essential 8 medium (Thermo Fisher Scientific), and the cardiomyocyte differentiation was initiated using a monolayer differentiation method with PSC Cardiomyocyte Differentiation kit (Thermo Fisher Scientific) under exposure to 25nM of isotretinoin (INN). At day 0, 2 and 6 during the differentiation period (before the medium-change on that day), and cells were collected using Accutase (Thermo Fisher Scientific), and then store in -80C till RNA isolation. For each cell line and each time-point, cells from two independent differentiation wells were used as two biological replicates. RNA-seq libriries were constructed using ScriptSeqâ„¢ v2 RNA-Seq Library Preparation kit (Epicentre Biotechnologies), and then sequenced by a HiSeq 4000 sequencer (Illumina) with 2 X 101 cycles. RNA-seq fastq data were aligned with Tophat (version 2.0.9) to GRCh39/hg19 Homo sapiens reference genome from the UCSC Genome Browser. The human gene symbols and their raw counts were calculated using HTSeq (version 0.6.1p1) package in Python with GRCh39/hg19 Homo sapiens gtf file. Differential gene-expression analysis was performed using edgeR package in R, and the normalization was performed using a trimmed mean of M-values (TMM) method.	Co-expression
SRP082503	Molecular analysis of renal cell carcinoma with unclassfied histology [gene expression]	Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell RCC (nccRCC) that have no standard therapy. The oncogenic drivers in these tumors are unknown. We performed a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, Single Nucleotide Polymorphism array, fluorescence in-situ hybridization, immunohistochemistry, and cell-based assays. We identified recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%), and MTOR (8%). Integrated analysis revealed distinct molecular subsets, including a subset of 26% uRCC characterized by NF2-loss, dysregulated Hippo-YAP pathway and worse survival. Overall design: Analysis of RNA from uRCC with or without NF2-loss	Co-expression
SRP082518	Gene expression profile of TGFbeta treated human coronary smooth muscle cell (HCASM)	TGFbeta induces VSMC gene expression in human coronary artery smooth muscle cell (HCASM) Overall design: Subconfluent human coronary artery smooth muscle cells (HCASM) were starved overnight followed by TGFbeta treatment for 24 hours. RNA was then extracted for deep-sequencing.	Co-expression
SRP082522	Single-cell alternative splicing analysis with Expedition reveals splicing dynamics during neuron differentiation	Alternative splicing (AS) generates isoform diversity critical for cellular identity and homeostasis, yet characterization of this diversity in single cells remains limited. We developed Expedition, a computational framework to categorize and visualize the heterogeneity of AS from single-cell transcriptomes. Expedition consists of (i) outrigger, a de novo splice graph transversal algorithm to detect AS from single cell RNA-seq; (ii) anchor, a Bayesian approach to assign splicing modalities and (iii) bonvoyage, using non-negative matrix factorization to visualize modality changes. By applying Expedition to single iPSCs undergoing neuron differentiation, we discover that 25% of AS exons exhibit bimodality and are flanked by longer and more conserved introns harboring distinct cis-regulatory motifs. Bimodal exons are highly dynamic during cellular transitions, preserve translatability, enriched in recently emerged genes and have conserved AS in mammals. Applying Expedition (http://github.com/YeoLab/Expedition) in single cells redefines our estimates and understanding of AS in evolution and biology. Overall design: Analysis of alternative splicing changes across motor neuron differentiation	Co-expression
SRP082529	Single cell RNA-seq data of human hESCs to evaluate SCnorm: robust normalization of single-cell rna-seq data	Normalization of RNA-sequencing data is essential for accurate downstream inference, but the assumptions upon which most methods are based do not hold in the single-cell setting. Consequently, applying existing normalization methods to single-cell RNA-seq data introduces artifacts that bias downstream analyses. To address this, we introduce SCnorm for accurate and efficient normalization of scRNA-seq data. Overall design: Total 183 single cells (92 H1 cells, 91 H9 cells), sequenced twice, were used to evaluate SCnorm in normalizing single cell RNA-seq experiments. Total 48 bulk H1 samples were used to compare bulk and single cell properties. For single-cell RNA-seq, the identical single-cell indexed and fragmented cDNA were pooled at 96 cells per lane or at 24 cells per lane to test the effects of sequencing depth, resulting in approximately 1 million and 4 million mapped reads per cell in the two pooling groups, respectively.	Co-expression
SRP082564	Mouse Dux is myotoxic and shares partial functional homology with its human paralog DUX4	We report the RNA-seq experiments performed in human myoblasts transfected with human DUX4 and mouse Dux. Overall design: Comparison of genes up- and down-regulated by DUX4 and Dux in human myoblasts to identify pathways similiarly regulated by both transcription factors.	Co-expression
SRP082567	Large-Scale Atlas of Mutant IDH1-Dependent Chromatin State Reprogramming, Reversibility, and Persistence [RNA-seq]	Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations drive the development of gliomas and other human malignancies.  Significant efforts are already underway to attempt to target mutant IDH in clinical trials.  However, how mutation of IDH leads to tumorigenesis is poorly understood. Mutant IDH1 promotes epigenetic changes that promote tumorigenesis but the scale of these changes throughout the epigenome and the reversibility of these changes are unknown.  Here, using both human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant IDH1-induced epigenomic reprogramming.  We characterize the changes in the histone code landscape, DNA methylome, chromatin state, and transcriptional reprogramming that occur following IDH1 mutation and characterize the kinetics and reversibility of these alterations over time.  We discover coordinate changes in the localization and intensity of multiple histone marks and chromatin states throughout the genome.  These alterations result in systematic chromatin states changes, which result in widespread gene expression changes involving oncogenic pathways.  Specifically,  mutant IDH1 drives alterations in differentiation state and establishes a CD24+ population that features enhanced self-renewal and other stem-like properties.  Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations.  Together, these observations provide unprecedented molecular portraits of mutant IDH1-dependent epigenomic reprogramming at high resolution.  These findings have significant implications for our understanding the mechanisms underlying mutant IDH function and for optimizing therapeutic approaches to targeting IDH mutant tumors. Overall design: RNA-sequencing of inducible IDH1 R132H astrocyte and tumorsphere models	Co-expression
SRP082580	Bi-allelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney	Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples.  PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion.  Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. To identify transcriptional targets of the Hippo pathway in kidney we performed PTPN14 knockdown followed by RNA-seq in 2 kidney cancer cell lines (CAKI-1 and A-704) and a normal kidney epithelial cell line (HK-2).  PTPN14 siRNAs were first functionally validated in a MCF-7 TEAD reporter luciferase stable cell line. Both siRNAs showed comparable knockdown efficiency and significantly increased luciferase reporter activity. In 2 of the kidney cell lines PTPN14 knockdown increased cell proliferation compared to non-target controls. While we observed excellent correlation between genes dysregulated by either PTPN14 or LATS1 knockdown within each cell line (HK2, CAKI-1 and A704), the overlap across the 3 cell lines was only 23 genes. Further, these 23 genes did not show concordant differential expression in MTSCC tumors. Overall, these results illustrate the marked tissue specificity of Hippo pathway targets.Finally, taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. Overall design: Cell lines (CAKI-1, HK2 or A704) were either transfected with 2 independent siRNAs or non-target controls.  Forty eight hours post transcription total RNA was isolated and subjected to RNA-seq analysis	Co-expression
SRP082676	RNA sequencing of skeletal muscle of myotonic dystrophic (DM1) patients	Introduction: Myotonic dystrophy of type 1 (DM1), the most common dystrophy in adults, is an autosomal dominant inherited disease, affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as myotonia, muscle weakness, muscle loss and atrophy. The disease is caused by the mutation of the DMPK "Dystrophia Myotonica Protein Kinase" gene. The mutation correspond to an abnormally large expansion of CTG tri-nucleotides repeats located in the 3''-untranslated region of this gene. Expanded CTG repeats are normally transcribed, but accumulates in RNA aggregates that sequester RNA-binding proteins such as the splicing regulator MBNL1. Consequently, due to MBNL1 sequestration, DM1 is characterized by aberrant splicing of a wide number of mRNA, which are themselves responsible for the symptoms observed in the disease. Purpose: To determine as much as possible novel splicing misregulations taking place in DM1 skeletal muscle, we performed a paired-end RNA sequencing (RNA-seq) using muscles samples of normal individuals (CTRL, n=3) versus muscles of DM1 patients (DM1, n=3). The data was analyzed by a bioinformatical software, called MISO, in order to map the alternative splicing changes between normal and DM1 muscle. The aim of this study was to get a broad and precise view of the splicing changes occurring in DM1 muscle. Overall design: PolyA RNA extracted from skeletal muscle biopsies originating from normal individuals (CTRL, n=3) or patients suffering of myotonic dystrophy type I (DM1, n=3), were analyzed by massive paired-end RNA sequencing.	Co-expression
SRP082679	MLL-AF4 binds directly to a BCL-2 specific enhancer and impacts H3K27 acetylation	Survival rates for children diagnosed with acute lymphoblastic leukemia (ALL) have drastically improved, but those carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in ALL is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we showed that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. We went on to show that MLL leukemias are particularly sensitive to treatment with the BCL-2 inhibitor venetoclax which synergizes with both standard chemotherapeutic agents as well as DOT1L inhibitors. Altered expression of other BCL-2 family members is a major cause of resistance to ventoclax, so here we perform a detalied analysis of MLL-AF4 regulation of the entire BCL-2 family. By measuring nascent RNA production, we find that of all the BCL-2 family genes, MLL-AF4 directly controls the transcription of both BCL-2 and MCL-1, but only BCL-2 shows a significant loss of steady state RNA levels. Interestingly however, both MCL-1 and BCL-XL protein levels are dependent on MLL-AF4 activity through an unknown and likely indirect mechanism. Finally, we analyze MLL-AF4 regulation of the BCL-2 gene in greater detail and using Capture C we identify a major BCL-2 specific enhancer consisting of two clusters of H3K27Ac. Loss of MLL-AF4 activity results in a reduction of H2K27Ac levels at the major BCL-2 enhancer, revealing a novel regulatory dependence on MLL-AF4 function at BCL-2. Overall design: Examination of MLL-AF4-mediated regulation at BCL2-family genes using nascent RNA-seq to observe gene expression changes following siRNA-mediated knockdown and treatment with the DOT1L inhibitor EPZ-5676. We also investigated changes in histone mark occupancy at the BCL2 promoter and enhancer following siRNA-mediated knockdown of MLL-AF4	Co-expression
SRP082682	Empirical assessment of analysis workflows for differential expression analysis using RNA-Seq	Background: RNA-Seq is supplanting microarrays as the preferred method of transcriptome-wide identification of differentially expressed genes. However, RNA-Seq analysis is still rapidly evolving, with a large number of tools available for each of the three major processing steps: read alignment, expression modeling, and statistical determination of differentially expressed genes. Although some studies have benchmarked these tools against gold standard gene expression sets, few have evaluated their performance in concert with one another. Additionally, there is a general lack of testing of such tools on real-world, biologically relevant datasets, which often possess qualities not reflected in tightly controlled reference RNA samples or synthetic datasetsResults: Here we evaluate ten combinatorial implementations of several of the most commonly used analysis tools (RSEM, TopHat2, STAR, htseq, Cufflinks, DESeq2, edgeR, EBseq, and Cuffdiff) for their impact on differential gene expression analysis by RNA-Seq. A test dataset was generated from highly purified human classical and nonclassical monocyte subsets from a clinical cohort, allowing us to evaluate analysis workflow performance using four previously published microarray and BeadChip analyses of the same cell populations as reference datasets. We find that the choice of methodologies leads to wide variation in number of genes called significant, as well as precision and recall. In general, recall is correlated with the number of significant genes identified, whereas precision is inversely correlated with both recall and the number of significant genes identified. Additionally, we report that the choice of statistical analysis approach and read aligner exhibited stronger impacts on recall, precision, and F1 score than the choice of software for expression modeling.Conclusions: There is wide variation in the performance of RNA-Seq workflows to identify differentially expressed genes. Different workflows lead to a precision/recall tradeoff, and the ultimate choice of workflow should take into consideration how the results will be used in subsequent applications. Our analyses highlight the performance characteristics of these workflows, and the data generated in this study could also serve as a useful resource for future development of software for RNA-Seq analysis.	Co-expression
SRP082685	Binding to SMN2 pre-mRNA-Protein complex elicits specificity for small molecule splicing modifiers	Small molecule splicing modifiers have been extensively described which target the generic splicing machinery and thus have low target specificity. We have identified potent splicing modifiers with unprecedented high selectively, correcting the splicing deficit of the SMN2 (survival motor neuron 2) gene in Spinal Muscular Atrophy (SMA). Here we show that they directly bind to two sites of the SMN2 pre-mRNA, thereby stabilizing a novel ribonucleoprotein (RNP) complex in the SMN2 gene that is critical for the high target specificity of these small molecules over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work may have wide-ranging consequences for further research to identify small molecules that target splicing correction of specific genes by interacting with tertiary RNA structures. Overall design: mRNA profiling of type I SMA fibroblasts treated with NVS-SM1	Co-expression
SRP082692	iPSC-Derived Cholangiocytes	Human iPS cells were differentiated to cholangiocyte-like cells thorugh five phases of endodermal differentiation. Overall design: Human iPSC were generated by forced expression of the Yamanaka pluripotency factors. We then pursued a stepwise differentiation strategy toward iDCs, using precise temporal exposure to key biliary morphogens, and we characterized the cells,  using a variety of morphologic, molecular, cell biologic, functional, and in vivo approaches.	Co-expression
SRP082964	Human Osteosarcoma Transcriptome	Osteosarcoma (OS) is one of the most aggressive bone malignancy. Sub-optimal therapy has irretrievably compromised chances of survival of OS patients for years. Also lack of extensive research on this rare disease has hindered its therapeutic development. Cisplatin (CDDP) is an integral part of current treatment regime for OS. However, despite the proven benefits of CDDP, acquisition of resistance impedes therapy. Also, the molecular effects post CDDP insult in OS cells is poorly understood. Hence, we characterized molecular alterations associated with CDDP-exposure and resistance in OS cells. Resistance to CDDP in OS cells was developed and deep sequencing of mRNA was performed. It depicted an altered transcriptomic signature of resistant cells with enrichment of pathways regulating proliferation. Overall, a significant up-regulation of coding-RNAs and down-regulation of non-coding-RNAs were obtained. Further, analysis of immediate effect of CDDP-shock showed an increase in autophagy and JNK signaling, acting as a pro-survival strategy. Regulatory connections between MAPK signaling and autophagy favoring survival under CDDP-shock was elucidated. Taken together, this is the first study portraying not only global transcriptomic alterations in resistant OS cells but also showing key molecular changes associated with CDDP-insult in OS cells. Our results can be better utilized for future therapeutic benefit. Overall design: We analyzed 5 samples, each being the representative of stages in the acquisition of chemoresistance. Control was the parental HOS cell line with which other comparisons are/will be made in future.	Co-expression
SRP082973	Mandatory Role of HMGA1 in Human Airway Epithelial Normal Differentiation and Post-injury Regeneration	Background: High mobility group AT-hook1 (HMGA1) is essential for airway basal cell mucociliary differentiation, barrier integrity and wound repair.  HMGA1 expression suppresses the abnormal basal cell differentiation to squamous, inflammatory and epithelial-mesenchymal transition phenotype commonly observed in association with cigarette smoking and chronic obstructive pulmonary disease (COPD). Results: HMGA1 knockdown experiments indicate that when HMGA1 expression is suppressed, the airway basal cells cannot normally differentiate into a mucociliary epithelium, form an intact barrier, and repair following injury. Instead, airway basal cell differentiation was skewed to an abnormal squamous EMT-like phenotype associated with airway remodeling in COPD. This study demonstrates that HMGA1 plays a key role in normal airway differentiation, regeneration of the normal airway epithelium following injury, and suppression of expression of genes related to squamous metaplasia, EMT and inflammation. Overall design: [RNA-seq] Non-smoker large airway epithelium cells, large airway basal cells, small airway epithelial cells, small airway basal cells.  Smoker large airway basal cells, COPD smoker large airway basal cells,.	Co-expression
SRP083013	RNA-Seq analysis of 4N and 2N RPE1 cells following polyploid induction via cytokinesis failure or Aurora kinase inhibition [tpo3]	Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells.  This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression.  Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology.  Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53.  Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21.  Rare proliferating tetraploid cells can emerge from acute polyploid populations.  Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2.  Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53.  These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis. Overall design: Three biological replicates of cells treated with either Aurora inhibitor (ZM447439), CytochalasinD, or untreated are FACS sorted into 2N or 4N populations and assessed for gene expression differences via RNA Seq for a total of 18 samples.	Co-expression
SRP083014	RNA-Seq analysis of 4N and 2N RPE1 cells following polyploid induction via cytokinesis failure by siRNA knockdown of Anillin [tpo8]	Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells.  This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression.  Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology.  Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53.  Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21.  Rare proliferating tetraploid cells can emerge from acute polyploid populations.  Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2.  Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53.  These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis. Overall design: Three biological replicates of cells treated with siRNA against Anillin or a non-targeting control are FACS sorted into 2N or 4N populations and assessed for gene expression differences via RNA Seq for a total of 12 samples.	Co-expression
SRP083126	Homo sapiens Transcriptome or Gene expression	Gene expression of Human THP-1 cells infected by cytomegalovirus	Co-expression
SRP083129	LINC00520 is Induced by Src, STAT3, and PI3K and Plays a Functional Role in Breast Cancer	Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNA-mediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer. Overall design: Transcriptome profiling of MCF10A-Src transformation and LINC00520 over expression	Co-expression
SRP083134	Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal- Niche Interactions	Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here, we performed single-cell RNA-seq analysis of over 2000 FGCs and their gonadal niche cells in female and male human embryos spanning several developmental stages. We found that the female FGCs undergo four distinct sequential phases characterized by mitosis, retinoic acid signaling, meiotic prophase, and oogenesis. Male FGCs develop through stages of migration, mitosis and cell cycle arrest. Individual embryos of both sexes simultaneously contain several subpopulations, highlighting the asynchronous and heterogeneous nature of FGC development. Moreover, we observed reciprocal signaling interactions between FGCs and their gonadal niche cells, including activation of BMP and Notch signaling pathways. Our work provides key insights into crucial features of human FGCs during their highly ordered mitotic, meiotic, and gametogenetic processes in vivo. Overall design: Here we performed single cell RNA-seq analysis for 2,167 individual PGCs as well as their gonadal niche cells, covering the developmental stages from 4 to 26 weeks after gestation in both female and male human embryos	Co-expression
SRP083135	RNA-seq of KD, rescues of NMD factors, and UPF1-flag CLIP-seq in HeLa cells.	This study aims at confidently identifying endogenous nonsense mediated decay (NMD) targets. To achieve this purpose, we performed KD of a few NMD factors in HeLa cells. Additionally, we performed rescue experiments for each factor, expressing an RNAi-resistant version of the gene from a plasmid. To determine transcripts bound by UPF1 in HeLa cells, A construct with a C-terminally flag tagged version of UPF1 was expressed. In order to avoid competition with endogenous UPF1, a KD was performed. Overall design: KD and rescue of three NMD factors (UPF1, SMG6, SMG7), plus a combined SMG6 and SMG7 KD, with individual rescues. 2 biological replicates of UPF1-flag CLIP-seq were carried out.	Co-expression
SRP083137	Targeting the Creatine Kinase Pathway in EVI1-Positive Acute Myeloid Leukemia	Purpose: Identify new targets in EVI1-Positive Acute Myeloid Leukemia Methods: Treatment with cyclocreatine  of EVI1-driven AML cell lines TF-1,  UT-7 and UCSD-AML1. Cyclocreatine was purchased from Sigma-Aldrich (Sigma). TF-1, UT-7 and UCSD-AML1 cells were treated in quadruplicate with either vehicle or 3 mM cyclocreatine for 24 hours. Total RNA was extracted and profiled by RNA sequencing (HiSeq, Illumina) at BioMicroCenter from Massachusetts Institute of Technology (Cambridge, MA, USA). Results: Alteration of arginine-creatine metabolism by the small-molecule cyclocreatine selectively decreased the viability, promoted cell cycle arrest and apoptosis of EVI1-positive AML cells. Conclusions: Targeting CKMT1 is a promising therapeutic strategy for the EVI1-driven AML subtype that is highly resistant to current treatment regimens. Overall design: mRNA profiles for the EVI1-driven AML cell lines TF-1, UT-7 and UCSD-AML1 treated with either 3mM cyclocreatine for 24 hours or with vehicle  were generated in quadruplicate  by RNA sequencing (HiSeq, Illumina) at the BioMicroCenter from Massachusetts Institute of Technology (Cambridge, MA, USA).	Co-expression
SRP083140	Identification of extensive cellular diversity and maturation of active neuronal networks in long-term cultures of human brain organoids	We analyzed  gene expression in  over  80,000  individual  cells  isolated  from  31  human  whole-brain  organoids  that  has developed  for  3-6  months.  We  find  that  organoids  can  generate a  broad  diversity  of  cells, which  we  show  are  related  to  known  endogenous  classes, including  subpopulations  of neurons and progenitors of the cerebral cortex Overall design: Single cell Droplet sequencing of human cerebral organoid	Co-expression
SRP083189	GRO-seq from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin	To identify loci with transcriptionally engaged RNA polymerase, we performed GRO-seq analysis of colorectal carcinoma cell line HCT116, breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin. Overall design: HCT116, MCF7, and SJSA cells were subjected to a run-on experiment after 1 hour of treatment with either DMSO or 10 microM Nutlin.	Co-expression
SRP083281	Effect daunorubicin treatment on the transcriptome of HCT116 cells [RNA-seq]	We used RNA-seq to measure the transcriptome of HCT116 in response to the DNA damaging agent daunorubicin Overall design: HCT116 cells were treated for 8h with 250 nM daunorubicin or  with vehicle	Co-expression
SRP083311	Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma	Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1789 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma. We hope to inspire researchers to study the role of non-coding RNAs in glioblastoma. Overall design: RNA sequcence for 3 glioma and paired normal brain tissue	Co-expression
SRP083321	Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development	Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistochemistry, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. Overall design: Single-cell transcriptomes from human and chimpanzee cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Human data were generated from dissociated whole organoids derived from induced pluripotent stem cell line SC102-A1 (iPSC SC102-A1) at 60 days after the start of embryoid body culture. Chimpanzee data were generated from dissociated whole organoids from iPS cell line SandraA at 45 days and PR818-5 at 50 days, 55 days, 61 days and 80 days and microdissected cortical-like regions from chimpanzee iPS cell line PR818-5 at 51 days and 62 days.	Co-expression
SRP083725	RNAseq from polysomal RNA harvested from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin	To determine effects of p53 activation on levels of RNA associated with polysomes, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116, breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin. Overall design: Polysomal RNA was extracted from HCT116, MCF7 and SJSA cells treated with Nutlin, polyA enriched and subjected to RNA-seq protocol.	Co-expression
SRP083743	Total RNA-seq from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin	To determine effects of p53 activation on steady-state mRNA levels, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116 (p53+/+ and p53 -/-), breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin. Overall design: Total RNA was sequenced from HCT116 (p53+/+ and p53 -/-), MCF7 and SJSA cells treated with DMSO or 10 microM Nutlin for 12 hours.	Co-expression
SRP083758	Stranded-Cytoplasmic and whole-cell RNAs	This is Illumina Strand-Specific paired-end reads from HeLa cells, an XPD-deficient fibroblast cell line, and Akata lymphocytes	Co-expression
SRP083762	Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2	Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate the activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes. This genomic data, and an ETS1 deletion line are used to show that the opposite function of ETS2 is due to binding site competition and a weaker activation function of ETS2 compared to ETS1. This weaker activation was mapped to the ETS2 N-terminus and a specific interaction with the co-repressor BS69 (ZMYND11). Gene expression data from tumor cohorts was then used to show that BS69 expression level in tumors correlates with oncogenic and tumor suppressive roles of ETS2. Therefore, these data indicate a novel and specific mechanism allowing ETS2 to switch between oncogenic and tumor suppressive functions in a cell-type specific manner. Overall design: mRNA profiles of ETS2 knockdown DU145 cells were generated using deep sequencing, in triplicate, using Illumina NextSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin. This series includes re-analysis of three luciferase shRNA samples from GSE59020.	Co-expression
SRP083768	Targeting Glioma Stem Cells through Combined BMI1 and EZH2 Inhibition [RNA-seq]	Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis.  Here, we demonstrate that these features are associated with distinct transcriptional programs, with vascular regions showing a Proneural profile and hypoxic regions a Mesenchymal pattern.  As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches.  Proneural, perivascular GSCs activated EZH2, whereas Mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress.  Using both genetic and pharmacologic inhibition, we found that Proneural GSCs are selectively sensitive to EZH2 disruption, whereas Mesenchymal GSCs are sensitive to BMI1 inhibition.  Given that glioblastomas contain both Proneural and Mesenchymal GSCs, combined EZH2 and BMI1 targeting proved more effective than either agent alone both in culture and in vivo, suggesting that strategies that simultaneously target multiple epigenetic regulators within glioblastomas may be necessary to overcome resistance to therapies caused by intratumoral heterogeneity. Overall design: RNA-seq of CD133 positive cells from intracranial xenografts of patient-derived glioblastoma stem cells	Co-expression
SRP083770	Early Chronological Aging in Human Adipose-Derived Stem Cells Marked by Distinct Transcriptional Regulation Compared to Differentiated Cells	Aging is a complex process characterized by a progressive decline in physiological integrity that leads to impaired cellular and tissue function.  Adult stem cells play a critical role in organismal health and aging. Their age-related deterioration contributes to a reduced homeostatic and regenerative capacity. Notably, most studies of stem cell aging focus on the mechanisms of replicative aging in stem cells with high cellular turnover. Yet, the therapeutic potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASC), is increasingly recognized as potentially superior. The mechanism of aging in low turnover stem cells is thought to differ from those with high turnover and to more closely reflect chronological aging. The latter, however, is exceedingly difficult to study in slowly replicating primary human stem cells and thus remains poorly understood.  Here, we employ our unique model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks in early chronological aging using RNA-seq analyses.  Our findings demonstrate that the transcriptome of aging ASCs is more stable than that of age-matched fibroblasts. Limited transcriptional modifications in aging ASCs reveal more active transcriptional profiles of cell cycle genes and translation initiation genes when compared with aging differentiated cells.  Accordingly, nascent protein synthesis, measured by incorporation of op-puromycin, is increased in ASCs from older individuals, concurrent with a decreased phosphorylation at ser-51 of eIF2, a mechanism of inhibiting translation initiation.  A shortened G1 phase observed in the old ASCs could be linked to the increased protein synthesis activity, potentially resulting in more active cell proliferation.  This effect, however, is not detected in aging fibroblasts.  The altered regulation of cell cycle in aging ASCs could allow a more active cell proliferation to meet an increase demand to preserve tissue and organ functions.  These observations are consistent with data supporting the maintenance of ASC integrity in aging human adipose tissue and reveal early chronological aging mechanisms in ASCs that are inherently different from other cell types. Overall design: Examination of the transcriptome with RNA-seq in stem cells and fibroblasts	Co-expression
SRP083771	Regeneration of functional human respiratory epithelium by transplantation of expandable Sox9+ Basal Cell	We sequenced mRNA from 4 lung epithelium samples (2 brush samples and 2 clone samples) taken from chinese male person. Overall design: Examination of mRNA levels in brushed lung sample and its corresponding clone sample	Co-expression
SRP083916	Messenger RNA expression after silencing or inhibition of MEN1in MCF-7 breast cancer cells	We performed RNA-seq in MCF-7 cells after silencing of MEN1 using small hairpin RNA''s directed at the MEN1 mRNA or chemical inhibition of the MEN1 gene product, menin. We demonstrate that a selected group of transcripts is affected by reduced menin function. Overall design: Comparison of mRNA levels using RNA-seq in mCF-7 cells after silencing of MEN1 using small hairpin RNA''s directed at the MEN1 mRNA or chemical inhibition of menin.	Co-expression
SRP083918	Transcription profiling of PfSPZ Malaria Vaccine trial subjects in a malaria endemic region	The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season. Overall design: 44 samples from 2 time points, pre-vaccination (Day -7) and post-vaccination (Day 143), for 22 Malian adult participants ( 5 placebo controls and 17 vaccine recipients).  11 of the vaccinated participants remained infection free over the subsequent malaria transmission season.	Co-expression
SRP083950	SETBP1-WT and SETBP1-G870S transcriptional profiles [RNA-Seq]	RNA-Seq experiments on SETBP1-G870S and Empty cells was performed in order to assess if the presence of mutated SETBP1 may induce differential RNA expression. Overall design: n=6: 2 conditions, namely SETBP1-WT and SETBP1-G870S, in triplicate	Co-expression
SRP083954	Transcriptome profiling of 5 human adenocarcinoma cell lines	Purpose: The aim of this study is to compare the transcriptome profiles of a limited number of lung cancer cell lines with the intention of selecting the two most similar cell lines for a mixture experiment (GSE64098). Methods - Cell Culture: Five lung adenocarcinoma cell lines (H2228, NCI-H1975, HCC827, H838 and A549) from a range of passages (2-4) were grown on 2 separate occasions in RPMI media (Gibco) supplemented with Glutamax and 10\% fetal calf serum to a 70\% confluence. To replicate common experimental conditions cell lines were treated with 0.01\% Dimethyl sulfoxide (Sigma), which is commonly used as a vehicle in drug treatment experiments. After 6 hours of treatment, cells were collected, snap-frozen on dry ice and stored at -80 degree C until required. Methods - RNA preparation: Total RNA was extracted from between half a million and million cells using Total RNA Purification Kit (Norgen Biotek) according to the kit instructions. RNA quality and concentration were assessed using Nanodrop and Tapestation RNA ScreenTape (Agilent) respectively. Methods - RNA-seq: 1 ug of total RNA from each sample were used for RNA-seq library preparation using TruSeq Total Stranded RNA with Ribozero (Illumina) according to manufacturer''s instructions. Completed libraries were sequenced on HiSeq 2000 with TruSeq SBS Kit v3- HS reagents (Illumina) as 100 bp single end reads at the Australian Genome Research Facility (AGRF), Melbourne. We obtained on average 28 million for each sample (range from 25 to 29 million). Reads were aligned to the human reference genome hg19 using the Rsubread package (version 1.16.1) (Liao et al. 2013). Single reads were then summarized into gene-level counts using FeatureCounts in the reverse-stranded mode (Liao et al. 2014). Overall design: Total RNA was extracted from lung adenocarcinoma cell lines H2228, NCI-H1975, HCC827, H838 and A549 (2 independent samples for each cell line). Total RNA transcriptome from these samples was profiled by RNA-seq.	Co-expression
SRP083960	The effect on p53-induced gene transactivation by LIMA1 knockdown.	To explore the effect of LIMA1 on gene transactivation induced by p53, we evaluated the changes in gene expression by RNA-seq in LIMA1 knockdown or control A549 cells. Overall design: Lung cacncer A549 cells were stably infected with lentivirus expressing shRNA-LIMA1 or negative control shRNA. These cells were treated with nutlin-3a which activates endogenous p53. The change of p53-induced gene transactivation was analyzed.	Co-expression
SRP083974	TP53 RNA-Seq	No description.	Co-expression
SRP084270	Inhibition of ERG Activity in Patient Derived Prostate Cancer Xenografts using the Small Molecule Inhibitor YK-4-279	ERG activity was blocked using YK-4-279 in three subcutaneously implanted ERG+ (LuCaP 23.1, 86.2, and 35) and one ERG- (LuCaP 96) PDX.  Tumor volume (TV), body weight (BW), serum prostate specific antigen (PSA), and overall survival (OS) were compared to vehicle treated controls.  Changes in gene expression were assessed by RNASeq and tissue microarrays were constructed to assess necrosis, proliferation, apoptosis, microvessel density, and ERG expression. Overall design: RNA sequencing of tumors from from 16 animals (2 control, 2 treated from each of four patient derived xenograft lines) using Illumina HiSeq 2500.	Co-expression
SRP084316	Amplification of mutant BRCA2 gene confers resistance to PARP inhibitor	Breast cancer gene 2 (BRCA2) deleterious mutations confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition due to its critical role in DNA repair.   PARP inhibitor Olaparib is now approved and several other PARP inhibitors are now in different stages of clinical trials.  Development of resistance to PARP inhibitors limits their clinical utility.  The mechanism of resistance remains not fully understood.  Here we show that amplification of mutant BRCA2 confers PARP inhibitor resistance.  The amplification of mutant BRCA2 gene copies correlates with an increase in mutant BRCA2 expression and an increase in the levels of its interacting proteins PALB2 and RAD51. In addition, homologous recombination mediated DNA repair is rescued in these cells as evidenced by the formation of RAD51 focus formation.   The overexpressed mutant BRCA2 is essential for the observed PARP inhibitor resistance because knockdown of its expression is sufficient to re-sensitize these cells to PARP inhibition.  Collectively, our results indicate a new mechanism of resistance to PARP inhibitor in BRCA2 mutant cancer cells Overall design: RNA-seq profiling of parental CAPAN1 cell line and PARP resistant cell line.	Co-expression
SRP086078	Airway epithelial cells from smokers treated with myo-inositol or placebo	Samples were obtained as part of a randomized, double blind, placebo-controlled, phase IIb study to determine the effects of myo-inositol in smokers with bronchial dysplasia.  Smokers with greater than 1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once/day for two weeks and then twice/day for 6 months.  Cytologically normal airway epithelial cells were obtained via bronchoscopy from the right or left mainstem bronchus at baseline and 6 months post-treatment with myo-inositol or placebo from 69 study participants (n=138 samples).  The RNA from these samples was isolated and used to prepare libraries for mRNA sequencing.  Subjects were classified by response according to their change in dysplasia rate after 6-months.  Among subjects with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation. Overall design: Cytologically normal bronchial airway cells were profiled by mRNA-Seq from 69 phase IIb study participants with bronchial dysplasia before and after 6 months of treatment with oral placebo or myo-inositol.	Co-expression
SRP086245	Directional RNA-Seq on CD4+ T cells collected from children with asthma with/without obesity	We compare the CD4+ T cell transcriptome between obese and normal-weight children with asthma to identify molecules/pathways differentially expressed in obese asthmatic CD4+  T cells Overall design: CD4+ T cell transcriptome generated using Directional RNA-Seq library preparatio; A=Normal-weight, B=obese	Co-expression
SRP086612	Dual role of Act1 in keratinocyte differentiation and host defense: TRAF3IP2 silencing alters keratinocyte differentiation while inhibiting IL-17 responses	TRAF3IP2 is a candidate psoriasis susceptibility gene encoding Act1, a ubiquitin ligase that couples the IL-17 receptor to downstream signaling pathways. We investigated the role of Act1 in keratinocyte responses to IL-17 using a tetracycline inducible shRNA targeting TRAF3IP2. Tet exposure for seven days effectively silenced TRAF3IP2 mRNA and Act1 protein, resulting in 761 genes with significant changes in expression (495 down, 266 up, >1.5-fold, p<0.05). Gene Ontology analysis revealed that genes affected by TRAF3IP2 silencing are involved in epidermal differentiation, with early differentiation genes (KRT1, KRT10, DSC1, DSG1) being downregulated and late differentiation genes (SPRR2, SPRR3, LCE3) being upregulated.  AP1 binding sites were enriched upstream of genes up-regulated by TRAF3IP2 silencing. Correspondingly, nuclear expression of FosB and Fra1 was increased in TRAF3IP2-silenced cells.  Many genes involved in host defense were induced by IL-17 in a TRAF3IP2-dependent fashion. Inflammatory differentiation conditions (serum addition for 4 days postconfluence) markedly amplified these IL-17 responses, while increasing basal levels and TRAF3IP2 silencing-dependent upregulation of late differentiation genes. These findings suggest that TRAF3IP2 may alter both epidermal homeostasis and keratinocyte defense responses to influence psoriasis risk. Overall design: Immortalized N/TERT-2G keratinocytes were either untreated or treated with tetracycline (TET) for TRAF3IP2 knockdown. Additionally, cells were either untreated or treated with IL17, TNF, or IL17+TNF. The experiment was replicated 4 times (batch IDs 2, 3, 4 and 5). A total of 32 samples were generated for RNA-seq analysis (8 treatments x 4 replicated experiments = 32 RNA-seq samples).	Co-expression
SRP086626	Genes and pathways regulated by androgens as possible contributors to the male excess observed in autism [RNA-Seq]	We analyzed androgens effects on human neural stem cells (hNSCs) by RNA-sequencing after either DMSO (solvent), DHT 100nM, 10nM, Testosterone 100nM, 10nM, R1881 1nM or retinoic acid 1µM 24 hours treatment in order to find the role of androgen receptor (AR) during brain development. Overall design: Examination of DHT 100nM, 10nM, Testosterone 100nM, 10nM and R1881 1 nM (and retinoic acid 1µM) regulated genes in hNSCs by generating mRNA profiles of DMSO (3 or 4 technical replicates within the 3 biological replicates batches 1, 2 and 3: 10 samples in total) and DHT 100nM (natural metabolite of testosterone, AR agonist, 3 technical replicates within the 3 biological replicate batches 1, 2 and 3: 9 samples in total), DHT 10nM (3 technical replicate of 1 biological serie batch 1), Testosterone 100nM (3 technical replicate of 1 biological serie batch 1), Testosterone 10nM (3 technical replicate of 1 biological serie batch 1), R1881 1nM (3 technical replicate of 1 biological serie batch 1), retinoic acid (3 technical replicate of 1 biological serie batch 1) 24 hours treated hNSCs by deep sequencing using Illumina HiSeq 2500	Co-expression
SRP086706	RNA-seq of human HeLa cell	To study the effects of overexpression CD38 in Hela cell Overall design: 2 simples	Co-expression
SRP086866	Molecular signature for anastasis, recovery from the brink of apoptotic cell death	Cells can survive effector caspase (caspase 3/7) activation in response to transient apoptotic stimuli, a process named anastasis. To characterize the molecular events that occur during anastasis, we performed whole transcriptome RNA sequencing of untreated, apoptotic, and recovering cells. We found that anastasis is an active, two-stage program with unique transcriptional profiles in each stage. We also identified 10 genes that specific to the early stage of anastasis. Overall design: 3hr ethanol treatment was used to induce apoptosis in Hela cells. Ethanol was washed away after 3hr treatment to allow cells to recover. Total RNA was prepared from mock-treated cells, ethanol-treated cells and cells after 1hr, 2hr, 3hr, 4hr, 8hr, 12hr recovery, followed by ribosomal RNA depletion. 3 biological replicates were included for each group. Sequencing was done using Ion Proton.	Co-expression
SRP087123	miR-93 Targets in Human Endothelial Cells	miR-93-5p controls endothelial glycolysis and proliferation Overall design: For identification of miR-93 targets and affected biological functions, HUVECs were transfected with miR-93-5p mimic and inhibitor and respective controls. In addition, mock transfection and non-treated cells were prepared as control samples. RNA-seq was performed in duplicate or triplicate.	Co-expression
SRP087387	Menin Enhances c-Myc-mediated Transcriptional Activity To Promote Cancer Progression	MYC is a master regulator of transcription in growing cells. Menin is an enigmatic protein that displays unique ability to either suppress or promote tumorigenesis in a context dependent manner. It''s interesting to ask is there any relationship between MYC and menin.Here, we used RNA-seq to study global transcriptomic expression of MYC or MEN1 knockdown HT1080 cells to investigate whether there are any correlations between MYC- and menin- regulated gene expression. Besides, we performed ChIP-seq assays for MYC and Menin binding sequences to address whether Menin and MYC share some common binding sites on chromatin. Overall design: Human fibrosarcoma HT1080 cells were transfected with MYC shRNAs, MEN1 shRNAs or non-targeting control shRNA followed by RNA extraction and sequenced on Illumina HiSeq 4000 (Homo sapiens). And also we performed MYC ChIP-seq and Menin ChIP-seq to address whether Menin and MYC share some common binding sites on chromatin.RNA Pol II ChIP-seq for NTC and shMEN1 HT1080 cell samples were used to study the effect of Menin on RNA Pol II-mediated elongation.	Co-expression
SRP087410	RNA-sequencing of human AML cells expressing high and low levels of CD99	We FACS purified human AML cells based on CD99 expression and performed RNA-sequencing, demonstrating in CD99 high expression AML cells significant enrichment for hematopoietic stem cell and leukemic stem cell gene expression signatures. Overall design: FACS purification of two populations (CD99 high and CD99 low) from eight primary AML specimens.	Co-expression
SRP087439	Genome-wide mRNA expression in human glioblastoma cells and glioblastoma stem cells expressing or not Omomyc	MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programs but its activity is not clearly understood. We address MYC function in cancer stem  cells through the inducible expression of Omomyc – a MYC derived polypeptide interfering with MYC activity – taking as model the most lethal brain tumour, glioblastoma. Omomyc bridles the key cancer stem-like cell features and affects tumour microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper Myc localisation and binds to DNA, with a preference for sites previously occupied by MYC. This is accompanied by (leads to) selective repression of master transcription factors for glioblastoma stem-like cell identity like POU3F2, SOX2, and OLIG2, upregulation of effectors of tumour suppression and differentiation such as PTEN, ID4, MIAT, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion like EGFR and ZEB1. Data support a novel view of MYC as a network stabiliser that strengthens the regulatory nodes of the gene expression programs controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells. Overall design: We employed patient-derived glioblastoma stem cells BT168 harboring a Doxycycline-inducible FLAG-Omomyc construct (FO), to study mRNA expression in the presence or absence of Omomyc. RNAs prepared from cells treated or not with DOX for up to 48 hours were sequenced by Illumina HiSeq 2000 and 2500 platforms. The study includes 29 samples.	Co-expression
SRP087491	N-Myc induces an EZH2-mediated transcriptional program driving Neuroendocrine Prostate Cancer	The transition from castration resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) is emerging as an important mechanism of treatment resistance. NEPC are associated with over-expression and gene amplification of MYCN (encoding N-Myc). N-Myc is a bona fide driver oncogene in several rare tumor types, but its role in prostate cancer progression is not well established.  Integrating a novel genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc over-expression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC tumors which includes an abrogation of AR signaling and induction of Polycomb Repressive Complex 2 signaling and that N-Myc interacts with AR and this interaction depends on Enhancer of Zeste Homolog 2. Altogether, our data shows that N-Myc drives the neuroendocrine phenotype in prostate cancer. Overall design: RNA sequencing of mice prostates or human cell lines expressing N-Myc; ChIp-Seq of H3K27me3 +/- N-Myc in human cell line; RNA sequencing of human cell line expressing N-Myc after EZH2 knockdown or treatment with GSK343.	Co-expression
SRP087494	Two functionally distinct human Pan3 isoforms regulate mRNA turnover across the transcriptome	Human Pan3 protein has two functionally distinct isoforms required for proper decay of mRNA across the transcriptome. Overall design: Time-course experiments were performed using actinomycin D to block transcription to study global mRNA decay upon depletion of different Pan3 isoforms.	Co-expression
SRP087536	Deletions in the ATAD3 gene cluster cause cerebellar developmental defects with mitochondrial DNA abnormalities owing to local cholesterol insufficiency	The DNA in mitochondria is associated with the inner of two membranes and it co-fractionates with the limited amount of cholesterol in the organelles. However, the effects of mitochondrial cholesterol deficiency are largely unknown, and mitochondrial disorders relating to this area of cell metabolism have not been reported hitherto. Using detailed SNP array analysis we have identified patients with impaired cerebellar development and neurological dysfunction who have large deletions in the locus encoding the ATAD3A, ATAD3B and ATAD3C genes. Patient cells with inherited ATAD3 defects display aberrant mitochondrial DNA organization and synthesis associated with disrupted cholesterol metabolism. Moreover drug-induced perturbations of cholesterol metabolism cause mitochondrial DNA disorganization in control cells. The interdependence of mitochondria and cholesterol homeostasis is further corroborated by the presence of mitochondrial DNA aggregation in the genetic cholesterol trafficking disorder Niemann Pick type C disease. Thus, we conclude, mitochondria are fully integrated in the circuitry of cellular cholesterol homeostasis, in which ATAD3 plays a critical role, and the dual problem of perturbed cholesterol homeostasis and mitochndrila dysfunction may be widespread in neurological and neurodegenerative diseases. Overall design: We designed the experiment to compare the expression profiles of cells carrying deletions in the ATAD3 gene cluster (ATAD3CAS & ATAD3F) with that of a normal control cell line. Because we suspected that cholesterol metabolism would be altered by ATAD3 deficiency we also prepared RNA from the same three cell lines treated with a drug, pravastatin, that inhibits the rate limiting step of cholesterol synthesis, to determine if the drug produced similar effects on gene expression to ATAD3 deficiency. In practice, pravastatin had almost no signficant effects (FDR 0.05) on any of the cells and none related to cholesterol homeostasis, indicating the drug does not act at the level of gene expression. This proved convenient as two RNA samples from ATAD3CAS failed QC, but the ATAD3CAS + pravastatin versus control (with or without pravastatin) provided additional replicates and displayed almost identical differences to ATAD3CAS (no drug) vs Control.	Co-expression
SRP087576	Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer (FFPE RNA-Seq I)	Background: The KRAS gene is mutated in about 40% of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistatnce to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60% of patients with a wild type KRAS fail to respond to EGFRi treatment, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. Methods: In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter(NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq(t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Results: Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE(r=0.233, p=0.090); (2) NanoS_FFPE(r=0.608, p<0.0001); (3) RNA-Acc_FFPE(r=0.175, p=0.21); (4) t-RNA_FFPE (r=-0.237, p=0.085); and (5) t-RNA (r=-0.012, p=0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n=15) and gene (n=2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r=0.672, p<0.0001); NanoS_FFPE (r=0.738, p<0.0001); and RNA-Acc_FFPE (r=0.483, p=0.002). Conclusions: Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples. Overall design: Fifty-four (54) FFPE evaluable tumor specimens were selected from a larger multi-center cohort of 468 well-characterized colorectal adenocarcinoma patients whose tissues were obtained between October 2006 and September 2010 at the University of South Florida. The sample cohort was composed of tumor samples that were available as matched fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) pairs.	Co-expression
SRP087579	Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer (FFPE RNA-Seq III)	Background: The KRAS gene is mutated in about 40% of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistatnce to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60% of patients with a wild type KRAS fail to respond to EGFRi treatment, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. Methods: In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter(NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq(t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Results: Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE(r=0.233, p=0.090); (2) NanoS_FFPE(r=0.608, p<0.0001); (3) RNA-Acc_FFPE(r=0.175, p=0.21); (4) t-RNA_FFPE (r=-0.237, p=0.085); and (5) t-RNA (r=-0.012, p=0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n=15) and gene (n=2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r=0.672, p<0.0001); NanoS_FFPE (r=0.738, p<0.0001); and RNA-Acc_FFPE (r=0.483, p=0.002). Conclusions: Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples. Overall design: Fifty-four (54) FFPE evaluable tumor specimens were selected from a larger multi-center cohort of 468 well-characterized colorectal adenocarcinoma patients whose tissues were obtained between October 2006 and September 2010 at the University of South Florida. The sample cohort was composed of tumor samples that were available as matched fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) pairs.	Co-expression
SRP087627	ERK5 kinase activity is dispensable for cellular immune response and proliferation	Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain.  Genetic deletion of ERK5 is embryonic lethal and tissue-restricted deletions have profound effects on erythroid development, cardiac function and neurogenesis.  In addition, depletion of ERK5 is anti-inflammatory and anti-tumorigenic.  Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology.  Here we report the synthesis and biological characterization of potent, selective ERK5 inhibitors.  In contrast to both genetic depletion/deletion of ERK5 and inhibition with previously reported compounds, inhibition of the kinase with the most selective of the new inhibitors had no anti-inflammatory or anti-proliferative activity.  The source of efficacy in previously reported ERK5 inhibitors is shown to be off-target activity on bromodomains (BRDs), conserved protein modules involved in recognition of acetyl-lysine residues during transcriptional processes.  It is likely that phenotypes reported from genetic deletion or depletion of ERK5 arise from removal of a non-catalytic function of ERK5.  The newly reported inhibitors should be useful in determining which of the many reported phenotypes are due to kinase activity, and delineate which can be pharmacologically targeted. Overall design: Two cellular models with reported ERK5-regulated signaling were used: Pam3CSK4-stimulated HUVECs as a model of inflammation, and EGF-stimulated HeLa cells as an established cell model of ERK5 regulation.  Cells were pre-incubated with DMSO vehicle, AX15836 (ERK5 inhibitor), AX15839 (dual ERK5/BRD inhibitor), or I-BET762 (BRD inhibitor), then stimulated with agonist.  Cellular responses were verified by immunoassays and western blots using replicate wells in the same experiment.	Co-expression
SRP087720	Genome-wide RNA-sequencing of human islets 48 hour after transduction with adenoviruses expressing either GFP (control), or histone chaperone ASF1B.	Comparison of gene expression in pancreatic islets of BTBR-ob/ob mouse model of obesity-induced type 2 diabetes, and in non-diabetic control mice, B6-ob/ob identified Asf1b as an important gene candidate predictive of diabetic outcome. Asf1B expression was suppressed in response to age in both B6 and BTBR islets, induced by obesity only in B6 islets. This is consistent with other studies reporting a decline in ?-cell proliferation with age. Asf1b also strongly correlated (R ~ 0.98) with cellular proliferation marker Mki67. Overexpression of Asf1B induced ß-cell proliferation in human islets. We show that many genes involved in regulation of cell cycle or programmed cell death are differentially regulated by Asf1B overexpression. Overall design: Ten different human islet preparations were obtained from 9 individual donors (from IIDP program). Each preparation contained approximately 20,000 islet equivalent units. Each islet preparation was separated into two portions for adenoviral transduction to overexpress GFP (control) or ASF1B genes.	Co-expression
SRP087726	Single Cell RNA-Sequencing Identifies Diverse Roles of Epithelial Cells in Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease causing alveolar remodeling, inflammation, and fibrosis.  We utilized single cell RNA-sequencing (scRNA-Seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF.  Transcriptomic analysis of epithelial cells from normal human lung defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis.  In contrast, scRNA-seq of IPF cells identified three distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and, an additional atypical "transitional" cell that contribute to pathological processes in IPF.  Individual IPF cells frequently co-expressed alveolar AT1, AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development.  Pathway analysis predicted aberrant activation of canonical signaling via TGF-ß, HIPPO/YAP, P53, and AKT-PI3 Kinase.  Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells.  Single cell transcriptomic analyses of respiratory epithelial cells identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF.  Present scRNA-seq transcriptomic analysis of normal and IPF respiratory epithelial cells provides a rich data source to further explore lung health and disease. Overall design: Examination of expression profiling at single-cell level between IPF and Control.	Co-expression
SRP087753	IVT-SAPAS Library for VSV infection in macrophages	3’ UTR variation in response to vesicular stomatitis virus (VSV) infection in macrophages of human and mouse	Co-expression
SRP087936	RNA binding protein CPEB1 remodels host and viral RNA landscapes [RNA-Seq]	In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3'-untranslated regions (3'UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes. Overall design: We performed RNA-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated human foreskin fibroblasts (HFFs). We also performed RNA-seq for lentivirus mediated GFP overexpression (OE) and CPEB1 overexpression human foreskin fibroblasts. Lastly, we performed TAIL-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated HFFs.	Co-expression
SRP089680	Assessing the impact of loss of ATF7IP and SETDB1 on the transcriptome	By comparing HeLa cells lacking ATF7IP or SETDB1 generated through CRISPR/Cas9-mediated gene disruption to wild-type HeLa cells, the goal of the experiment was to determine the effect of loss of the SETDB1•ATF7IP complex on the transcriptome. Overall design: Total RNA-seq of three independent knockout HeLa clones lacking either ATF7IP or SETDB1	Co-expression
SRP089716	PPP1R1A in Ewing sarcoma pathogenesis	Control or PPP1R1A knockdown and RNA-seq analyses to identify genes and cellular processes regulated by PPP1R1A	Co-expression
SRP089788	Transcriptional profiling of Myotonic dystrophy muscle and heart	Autopsy and biopsy muscle and heart tissue was collected from consented human subjects with and without confirmed myotonic dystrophy type 1, myotonic dystrophy type 2, or Duchenne muscular dystrophy. RNA was isolated for preparation of RNAseq libraries and sequenced on the Illumina platform. Overall design: 126 samples, comprising 103 distinct individuals, were sequenced. In some cases, several tissues from the same individual were obtained (the anonymized patient identifier can be used to link these). Samples were obtained from 4 different centers around the world (anonymized center identifiers can be used to track these).	Co-expression
SRP089805	Comparison of RNA-sequencing  from Fresh Frozen or Formalin-fixed paraffin-embedded tissue in glioblastoma	We compared RNA-Seq data obtained from matched pairs of FF and FFPE GBM specimens. By performing several quality control measurements, we found that FFPE’s RNA was highly degraded but kept transcriptomic similarities with RNA from FF samples. Certain caveats regarding mutation analysis and subtype prediction were detected. Nevertheless, our results suggest that RNA-Seq of FFPE GBM specimens provides reliable gene expression data to be used in molecular studies of GBM.	Co-expression
SRP089808	KDM1A confers invasive and metastatic attributes in lung adenocarcinoma by modulating a non-canonical Integrin ß3-KRAS signaling pathway	KRAS mutations occur in approximately 25% of non-small cell lung cancer (NSCLC). They account for the therapy resistance to EGFR inhibitors and are suggested to be difficult to target by specific drugs. Therefore, new therapies for KRAS mutant NSCLC are urgently needed. The histone H3K4 and H3K9 di/mono-demethylase KDM1A is a key epigenetic writer, aberrantly upregulated in many cancer types, including NSCLC. In order to understand the functional role of KDM1A in the progression of lung adenocarcinoma, KDM1A expression profiles were analysed in tissue microarrays (TMAs) including 182 lung adenocarcinoma. KDM1A expression correlated with high grade and metastasized tumor. To investigate the impact of KDM1A in lung adenocarcinoma development, we used the KRAS mutated A549 cell line to establish a shRNA-mediated stable KDM1A knockdown cell clone. Unexpectedly, KDM1A knockdown had only a slight effect on retardation of cell growth. However, cell invasion and self-renewal capability was significantly decreased by KDM1A inhibition. KDM1A knockdown in A549 cell resulted in a dramatic change in the transcriptome profile as determined by RNA-Seq. Interestingly, genes involved in the KRAS signature and lung epithelial marker genes were significantly affected upon KDM1A knockdown. Ingenuity pathway analysis also suggested that the alternative integrin ß3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin ß3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-?B activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin ß3 level was validated in TMAs. Overall design: Determining the role of KDM1A in A549 cells, mRNA profiles of control and knockdown samples of A549 cells, generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.	Co-expression
SRP089814	Differentially Expressed Gene Transcripts Using RNA Sequencing from the Blood of Immunosuppressed Kidney Allograft Recipients	We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because it’s not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in adult kidney recipients, without clinical acute rejection (AR), treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs) were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2(Striking Image) compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s) responsible for differential gene expression may be important in selecting and personalizing immune suppressant drugs and may lead to targeted therapies. Overall design: RNAseq data are from blood specimens from kidney transplant patients as a time course  before and after kidney transplant from living donors. There are 96 samples analyzed in total from 34 patients; however, only 32 patients with baseline data and pre-transplant RNA. None of the patients in the study developed acute rejection within the 6 month study period. Time points include: pre-transplant, 1 week following transplant, 3 and 6 months following transplant.	Co-expression
SRP089821	Transcriptomic analyses for the CSC-like properties under monolayer and sphere culture conditions in 293T and MCF-7 cells	In order to verify the CSC-like properties in 3D spheres of 293T cells as compared to monolayer, MCF-7 breast cancer cells under monolayer and sphere culture conditions were used as a control. Corresponding author: Chul Geun Kim, Department of Life Science, Hanyang University, Seoul 133-791, Korea (e-mail, cgkim@hanyang.ac.kr). Overall design: mRNA profiles of the 293T and MCF-7 cells [monolayer (mMCF-7 and m293T) and sphere (sMCF-7 and s293T) culture conditions] were generated by deep sequencing using Illumina GAIIx.	Co-expression
SRP089857	Human iPSC glial mouse chimeras reveal glial contributions to schizophrenia	Genetic studies have suggested a role for glial pathology in the genesis of schizophrenia (SCZ).  To assess the nature of SCZ-associated human glial dysfunction in vivo, we established human glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotential cells (hiPSCs), derived from patients with juvenile-onset schizophrenia or healthy controls. To this end, hiPSC GPCs were implanted neonatally into either immunodeficient myelin wild-type mice, in which donor GPCs remained as progenitors or became astrocytes, or into myelin-deficient shiverer mice, in which the GPCs also gave rise to oligodendrocytes. When implanted into shiverers, the SCZ-derived GPCs exhibited less expansion in the white matter than did control GPCs, instead migrating prematurely into the cortex. The SCZ GPC-transplanted shiverers were consequently hypomyelinated relative to control GPC-engrafted mice. When established instead in myelin wild-type hosts, the SCZ hiPSC glial chimeras manifested markedly delayed and diminished astrocytic differentiation, which was associated with diminished prepulse inhibition and an aberrant behavioral phenotype across multiple modalities. Accordingly, RNA-seq revealed significant differences in both glial differentiation-associated and synaptic gene expression by SCZ GPCs. These data suggest a potent contribution of cell-autonomous glial dysfunction to the development of schizophrenia, and provide a model for the in vivo assessment of human glial pathology in this disorder. Overall design: mRNA was isolated by polyA-selection protocol from FACS-sorted PDGFRa-positive GPC cell lines produced from iPS cells derived from 4 schizophrenic patients (designated to SCZ lines 8 [N = 4 independent cell preparations], 29 [N = 3], 51 [N = 7], and 164 [N = 8]) and 3 healthy controls (designated to CTR lines 22 [N = 3], 37 [N = 4], and 205 [N = 7]). FASTQ files in the submission were edited by Trimmomatic. The software was used to trim adapter sequences and low-quality bases (see processing steps). The overall file structure and format remained unchanged. The count matrix in the submission is as obtained directly from featureCounts tool, that is, no manipulation was performed to the count data. The data normalization was performed internally in the analysis and the raw count data was used in differential expression analysis. Please refer to the Materials and Methods section in supplementary files. The complete reproducible workflow, including R scripts, sample information sheet, and count matrix, was deposited to https://github.com/cbtncph/GoldmanetalSCZ2016	Co-expression
SRP089880	Dermal fibroblasts play a central role in skin model protection against C. albicans invasion	This study shows that, in the presence of CD4+ T cells, dermal fibroblasts shift towards an antimicrobial phenotype leading to reduced dermal invasion by C. albicans. This is dependent on TLR2 activation and pro-IL-1ß cleavage and results in expression of genes involved in defense against various classes of pathogens. Overall design: Dual RNA-Seq of keratinocytes and fibroblasts with or without Candida albicans from infected humen reconstituted skin models with or without CD4+ T cells. Sequenced were fibroblasts, Keratinocytes and C. albicans isolated from these models. For each sample biological triplicates were analyzed.	Co-expression
SRP089882	Exercise-induced transcriptome changes in skeletal muscle adapted to aerobic training	We sequenced mRNA in vastus lateralis muscle samples from two amateur endurance-trained males (V'O2max 57 ml/min/kg) before and after acute endurance exercise Overall design: Examination of mRNA prior to, 4 h, and 8 h after acute intensive cycling session (70 min, 70% V'O2max )	Co-expression
SRP089922	Genes regulated by SPDEF or FOXA3 in A549 lung carcinoma cells [RNA-seq]	To identify genes regulated by SPDEF or FOXA3 in A549 lung carcinoma cells, we analyzed the whole-transcriptomic mRNA profiles of A549 cells expressing SPDEF or FOXA3 based on RNA-seq. Overall design: A549 cells expressing NKX2-1 (Maeda et al., J Clin Invest. (2012) doi: 10.1172/JCI64048) were infected with Control (pGK), SPDEF or FOXA3-expressing lentivirus. For each lentivirus infection, RNA-seq experiments were performed on three biological replicates. Differential expression analyses were performed using DESeq2.	Co-expression
SRP089975	Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation	Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement.	Co-expression
SRP090061	REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS [Smart-seq]	During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.      During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.     During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. Overall design: The transcriptomes of 1846 single cells were profiled by SmartSeq2 at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types.  Some cells were positively labeled by a expression of a barcoded viral transgene to help establish clonality (marked by an "SK").	Co-expression
SRP090070	REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS [population]	During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.      During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.     During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. Overall design: Bulk RNA-seq at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types.  Each sample was composed of 10^5 or 10^6 cells.	Co-expression
SRP090072	REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS [Cel-seq]	During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. Overall design: The transcriptomes of 2684 single cells were profiled by CelSeq at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types.	Co-expression
SRP090090	Dynamic gene regulatory networks of human myeloid differentiation [RNA-seq_siRNA]	We utilize gene expression and open chromatin footprinting data to build a gene regulatory network of key transcription factors that capture the cell and time-specific regulatory programs specified during human myeloid differentiation. Overall design: RNA-seq profiling of undifferentiated HL-60, differentiating macrophage, neutrophil, monocyte, following siRNA control and siPU.1 treatment for 24 hours.	Co-expression
SRP090091	Comprehensive RNA sequencing of healthy human endometrium at two time points of the menstrual cycle	mRNA, sncRNA and lncRNA show a clear difference in expression between proliferative phase and 7–9 days after ovulation, thorough described together with lncRNA, snoRNA and snRNA not previously reported in healthy human endometrium Overall design: 7 small RNA and 7 total RNA samples sequenced from endmometrial tissue from two time points of the menstrual cycle. Gene expression from the two time points compared. Additionally 12 small RNA from stromal cells was sequenced.	Co-expression
SRP090132	KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression	We used CD34-positive cells isolated from cord blood to differentiate to granulocytic and monocytic lineages, respectively. Poly A-enriched RNA-seq was performed on the day 5, 10 and 15 samples of both granulocytic and monocytic lineages. Overall design: We forcused on the RNA binding proteins involved in granulocytic and monocytic lineage differentiation.	Co-expression
SRP090170	Transcritptome profiling of HASMCs under delta-133p53-overexpression and Ang II treatment	To delineate the mechanism underlying SRSF1/delta133p53-mediated alterations in vascular smooth muscle cell (VSMC) proliferation, we analyzed the genome-wide gene expression profiles in cultured human aortic smooth muscle cells (HASMCs) with delta133p53-overexpression and Ang II treatment versus GFP controls using RNA-Seq approach.	Co-expression
SRP090188	INO80 governs super-enhancer-mediated oncogenic transcription and tumor growth in melanoma [RNA-seq]	Super-enhancers (SEs) are large genomic regions with high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared to normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, as well as tumorigenesis and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies more than 90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9.  Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are specifically expressed in melanomas compared to melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function, and suggest a novel strategy for disrupting SEs in cancer treatment. Overall design: Human melanoma cell line A375 cells were infected with shNT or shIno80, and total RNA was extracted 2, 3, 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, either wild type A375 and SK-MEL-147, or A375 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.	Co-expression
SRP090226	Long noncoding RNA related-competing endogenous RNAs in retinal pigment epithelial cells induced by clusterin	long noncoding RNAs (lncRNAs) play crucial roles in regulating gene expression by acting as competing endogenous RNAs (ceRNAs). Overall design: Based on high throughput sequencing data of RPE cells treated by clusterin or not, we first identified differentially expressed mRNAs, lncRNAs and miRNAs. Then, we constructed an lncRNA-mRNA-miRNA network (ceRNA network) based on bioinformatic database miRanda and microRNA (miRNA) targets database miRTarBase.	Co-expression
SRP090241	RNA-Seq from human neutrophils from patients with cystic fibrosis reveals distinct transcriptional differences before and after therapy for pulmonary exacerbations	RNA sequencing on neutrophils of 32 samples consist of 16 CF patients befroe and after therapy	Co-expression
SRP090251	The anti-leukemic effect of R-2HG depends on its acting as an m6A mRNA modifier-RNA Seq-Resistant, sensitive and healthy control	To identify the potential genes/signaling pathways related to R-2HG sensitivity in leukemia cells. Overall design: Via MTT assays, we determined the various sensitivities to R-2HG treatment in leukemia cells. We selected five resistant leukemia cells (NB4, TF-1, HEL, MA9.3RAS and K562), for sensitive leukemia cells (ML-2, NOMO-1, U937 and MA9.3ITD) and four healthy control samples (two CD34+ hematopoietic stem/progenitor cells (CD34+ HSPC) and two mononuclear cells (MNC)) for RNA-sequencing. NOTE: The original processed data files were replaced with updated processed data files (containing 'cell line name' column headers, instead of 'sample id') on May 2019 to avoid confusion.	Co-expression
SRP090252	The anti-leukemic effect of R-2HG depends on its acting as an m6A mRNA modifier-RNA Seq-PBS / R-2HG treatment	RNA-seq from R-2HG sensitive leukemia cells treated with R-2HG or PBS. Overall design: With MTT assays, we identified R-2HG exhibits an anti-leukemia function. We conducted RNA-Seq in the two sensitive cells (NOMO-1 and MA9.3ITD) with R-2HG or without R-2HG treatment for 48 hours to investigate which genes/a-ketoglutarate-dependent dioxygenases/signaling pathways are responsible for the anti-leukemia function of R-2HG. For each group, there are three duplicates.	Co-expression
SRP090260	RNA sequencing quantitative analysis of RNA editing levels in ADAR1, ADAR2, AIMP2 overexpression and wild type HEK293 cells	We overexpressed ADAR1, ADAR2 and AIMP2 in HEK293 cells and examined editing using RNA-seq. Overall design: mRNA profiles of wild type (WT) and ADAR1, ADAR2 and AIMP2 overexpression HEK293 cells were generated by deep sequencing using Illumina HiSeq 2000.	Co-expression
SRP090282	Safety and Immunogenicity of the Recombinant BCG Vaccine AERAS-422 in Healthy BCG-naïve Adults: A Randomized, Active-controlled, First-in-human Phase 1 Trial	We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin. Interpretation: The unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation. Overall design: This was a randomized, double-blind, dose-escalation trial in HIV-negative, healthy adult, BCG-naïve volunteers, negative for prior exposure to Mtb, at one US clinical site. Volunteers were randomized 2:1 at each dose level to receive a single intradermal dose of AERAS-422 (>105–< 10e6 CFU = low dose, =106– < 10e7 CFU = high dose) or non-recombinant Tice BCG (1–8 × 10e5 CFU). Randomization used an independently prepared randomly generated sequence of treatment assignments. The primary and secondary outcomes were safety and immunogenicity, respectively, assessed in all participants through 182 days post-vaccination. ClinicalTrials.gov registration number: NCT01340820	Co-expression
SRP090298	Epigenome maps of time-resolved monocyte to macrophage differentiation and innate immune memory (RNA-Seq)	Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as LPS.  We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time dependent manner. ChIP-seq, RNA-seq, WGBS and ATAC-seq data were generated. This analysis identified epigenetic programs in tolerance and trained macrophages, and the potential transcription factors involved. Overall design: Time-course in vitro culture of human monocytes. Two innate immune memory states can be induced in culture through an initial exposure of primary human monocytes to either LPS or BG for 24 hours, followed by removal of stimulus and differentiation to macrophages for an additional 5 days. Cells were collected at baseline (day 0), 1 hour, 4 hour, 24 hour and 6 days.	Co-expression
SRP090306	Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (RNA-Seq)	Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement. Overall design: Fourteen total independent samples were analyzed. Ten are from UCLA1 hESC line and four are from UCLA4 hESC line. Independently processed samples from same culture condition are called replicates and labedled as rep1/rep2, where available. All UCLA1 clones are from 5iLAF culture condition, and all UCLA4 samples are from 5iLAF culture condition.	Co-expression
SRP090309	Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (single cell RNA-Seq)	Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement. Overall design: Differentiated naïve human embryonic stem cells and naïve human embryonic stem cells at different passages (Exp1 for late passage, Exp2 for early passage) were subjected to single cell RNA sequencing by the Fluidigm C1 Single-Cell Auto Prep System.	Co-expression
SRP090317	Systematic mapping of functional enhancer-promoter connections with CRISPR interference	Gene expression in mammals is regulated by noncoding elements that can impact physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses CRISPR interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase (Mb) of sequence in the vicinity of 2 essential transcription factors, MYC and GATA1, and identify 9 distal enhancers that control gene expression and cellular proliferation. Quantitative features of chromatin state and chromosome conformation distinguish the 7 enhancers that regulate MYC from other elements that do not, suggesting a strategy for predicting enhancer-promoter connectivity. This CRISPRi-based approach can be applied to dissect transcriptional networks and interpret the contributions of noncoding genetic variation to human disease. Overall design: We examined the effects of using CRISPRi to inhibit a putative enhancer of GATA1, eHDAC6. We performed RNA sequencing on K562 cells expressing individual sgRNAs targeting the transcription start site of GATA1 (2 sgRNAs), eHDAC6 (2 sgRNAs) and non-targeting, negative controls (4 sgRNAs). We generated paired-end RNA sequencing libraries from 3 biological replicates for each sgRNA.	Co-expression
SRP090328	SMN deficiency in spinal muscular atrophy causes widespread intron retention and DNA damage	Spinal muscular atrophy is the leading genetic cause of infant mortality and is caused by homozygous loss of the SMN1 gene.  We investigated global transcriptome changes in the spinal cord of inducible SMA mice. SMN depletion caused widespread retention of introns with weak splice sites or belonging to the minor (U12) class.  We further demonstrated accumulation of DNA double strand breaks in the spinal cord of SMA mice and in human SMA cell culture models.  DNA damage was partially rescued by suppressing the formation of R-loops, which accumulated over retained introns.  We propose that instead of single gene effects, pervasive splicing defects caused by SMN deficiency trigger a global DNA damage and stress response, thus compromising motor neuron survival. Overall design: mRNA-seq: Total spinal cord from SMA and Control mice (rescue experiment) at d20 and d30; human SH-SY5Y cells expressing SMN or Control shRNA for 7d; human iPSC-derived motor neurons expressing SMN or Control shRNA for 5d; total spinal cord from SMA and Control mice (induction experiment) at d10, d20, and d30. DRIP-seq:  SH-SY5Y cells expressing SMN or Control shRNA for 7d and immunoprecipitated with S9.6 antibody targeting RNA:DNA hybrids.	Co-expression
SRP090333	RUNX1-ETO and RUNX1-EVI-1 differentially program the chromatin landscape in t(3;21) and t(8;21) AML but share global C/EBP-alpha dysfunction (RNA-Seq)	RUNX1 is a frequent target of translocations in acute myeloid leukemia whereby its DNA binding domain fuses to different epigenetic regulators. To assess how different RUNX1 fusion proteins interact with the epigenome we compared the global binding patterns and the chromatin landscape of t(8;21) and t(3;21) AML which express RUNX1-ETO and RUNX1-EVI-1, respectively. We found that differential prognosis for these types of AML is reflected in fundamental differences in gene expression, chromatin landscape, binding patterns of the fusion proteins and other transcription factors as identified by genome-wide digital footprinting in patients. As previously shown for RUNX1-ETO, knockdown of RUNX1-EVI-1 expression initiates differentiation of t(3;21) cells which is associated with up-regulation of genes vital for myeloid differentiation, including C/EBPa. Furthermore, by expressing either dominant-negative C/EBP or an inducible C/EBPa construct in t(3;21) cells we show that C/EBPa is necessary and sufficient for the differentiation response of these cells to RUNX1-EVI-1 knockdown. Overall design: RNA-seq expreiments have been used to study the chromatin landscape of t(8;21) and t(3;21) AML	Co-expression
SRP090337	RNA-seq of human peripheral blood mononuclear cells	Inflammatory cytokine responses to activation of innate immunity differ between individuals, yet the genomic and transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that mRNA and lincRNA expression is modulated in disease-relevant tissues in humans in vivo during inflammation, and differs between individuals with divergent evoked inflammatory responses. In the Genetics of Evoked Response to Niacin and Endotoxemia (GENE) Study, we performed an inpatient endotoxin challenge (1ng/kg LPS) in healthy humans. We selected individuals in the top (high-responders) and bottom (low-responders) extremes for inflammatory responses, and applied RNASeq to peripheral blood mononuclear cells (PBMC, n=15) before and after LPS administration. At baseline, there were limited differences in gene expression by sex or race. Further, only a small number of genes differed between high and low responders at baseline. Post-LPS, there were clear differences in the magnitude of the transcriptional response between high and low responders, with a far greater number of genes differentially expressed post-LPS in high responders, consistent with the clinical response. We also found a number of differentially expressed long intergenic non-coding RNAs (lincRNAs) post-LPS. We show that differences in gene expression may drive differences in clinical inflammatory response, and that differentially expressed genes and lincRNAs represent novel candidates for modulation of immune and metabolic responses in acute and chronic diseases. Overall design: Peripheral blood mononuclear cells (PBMCs) from 15 healthy subjects were sequenced by Illumina HiSeq 2000 with poly-A selection	Co-expression
SRP090369	Gene and microRNA expression changes induced by overexpression of SphK1 in papillary thyroid cancer cells [RNA-seq]	The oncogenic roles of Sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, miRNAs associated with the oncogenic roles of SphK1 remains largely unknown. The goal of this study is to detect the global gene and microRNA (miRNA) expression in response to Sphk1 over-expression and identify potential therapeutic targets. To achieve this, SphK1 was stably overexpressed in papillary thyroid cancer cell line TPC1. Then the mRNA and miRNA expression were quantified using digital gene expression (DGE) analysis and small RNA-seq in TPC1-Vector and TPC1-SphK1 cells, respectively. miRNA-mRNA interactions were explored by microT-CDS and the predicted networks were visualized using CytoScape. In this study, we found that over-expression of SphK1 differentially regulates 46 miRNAs and 506 mRNAs expression in TPC1 cells. Combining bioinformatics prediction of mRNA targets and DGE data on mRNA expressions allowed to identify mRNA targets of deregulated miRNAs. The direct interaction between miR-144-3p and FN1 mRNA, which mediates the pro-invasive role of SphK1 in thyroid cancer cells, was experimentally validated. In general, our results provided a miRNA-mRNA regulatory network in response to SphK1 overexpression in thyroid cancer cells. We also demonstrated a role of miR-144-3p and FN1 in mediating oncogenic function of SphK1, which enhance the understanding of etiology of thyroid cancer. Overall design: The mRNA profiles of TPC1-Vector and TPC1-SphK1 cells were generated by sequencing, in duplicate, using a Illumina HiSeq 2500.	Co-expression
SRP090389	RNA binding protein KSRP mediated miRNAs processing reciprocally regulates granulocytic and monocytic differentiation	KSRP is involved in RNA processing at multiple levels including alternative splicing, mRNA stability, mRNA localization and translation efficiency. Dysregulation KSRP can cause to hematological malignancies. However, the direct contribution of KSRP to myeloid lineage differentiation is poorly understood. KSRP, as a KH-type splicing regulatory protein, which interacts with single-stand AU-rich element containing mRNA and mediated mRNA decay, also serves as a component of Drosha and Dicer complexes and regulates the biogenesis of miRNAs. Whether KSRP mediated miRNAs maturation participated in myeloid lineage differentiation is unknown. Here, we analysis the miRNAs processing during over-expression KSRP in THP-1 cells by poly-A(riched) RNA-seq and miRNA-Seq. Our results suggest that KSRP regulate a class of miRNAs maturation and have a critical function in myeloid lineage differentiation. Overall design: The design was meant to identify differential miRNAs processing which regulated by KSRP in THP-1 cells.	Co-expression
SRP090390	Cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer-Independent (RNA-seq)	Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets. Overall design: Expression profiles of NEK6 SE1 wild-type and deletion subclones of GM12878 were generated by deep sequencing, using Illumina Hi-Seq 2500.	Co-expression
SRP090396	Exploiting drug addiction mechanisms to select against MAPKi resistant melanoma	Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal–induced pERK rebound upregulated p38–FRA1–JUNB–CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death–predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction. Overall design: BRAF/MEK inhibitors resistant cell lines M249DDR5 and SKMEL28DDR1 were assayed for their responses after 6 hr of BRAF/MEK inhibitor treatment and after inhibitors withdrawal (by washin) for 6 and 24 hours	Co-expression
SRP090454	LBO D170	No description.	Co-expression
SRP090460	Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers	Background. Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers. Methods. Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes. Results. Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. These overlap mutants were preferentially expressed in mRNA with consistently higher allele frequency in mRNA than in DNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival. Conclusions. The recurrent mutations present in both DNA and RNA are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development. Overall design: 27 pairs of tumor and normal tissues from lung adenocarcinoma patients were sequenced by both exome-seq and RNA-seq. This series contains the RNA-seq data only.	Co-expression
SRP090472	Morphological and molecular characterization of human dermal lymphatic collectors	Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE-1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRa, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors a2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy. Overall design: The transcriptome of 6 different normal human lymphatic collectors (Lyko1, Lyko 4-12, Lyko 5, Lyko12, Lyko13, Lyko26) from the dermis of the thigh of women between 44 and 61 years of age was compared to cultures of human dermal lymphatic endothelial cells (LEC1, LEC2, HD-LEC9A) and a mixture of 3 different human dermal blood endothelial cells (HD-BEC-CA) to identify potential drug targets in the media of the collectors.	Co-expression
SRP090496	Homo sapiens Transcriptome or Gene expression	High density and low density extracellular RNA from mast cells. Both whole transcriptome and small RNA sequencing samples are included here.	Co-expression
SRP090509	Comparison of Eomes-negative and Eomes-positive human liver NK cells by RNASeq	We sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed. Overall design: Examination of mRNA levels in paired Eomes-negative/Eomes-positive NK cells from the same donor.	Co-expression
SRP090547	Enhancer Remodeling During Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacological Targeting of the P-TEFb Complex (RNA-seq)	Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms.   Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment.  In preclinical models MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation and p300 that drives transcriptional adaptation.  Inhibition of P-TEFb associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts and syngeneic mouse TNBC models.  Pharmacological targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance. Overall design: 64 experimental samples; replicates are indicated in sample title	Co-expression
SRP090552	RNA-seq of human adipose tissue following n-3 PUFA supplementation and evoked endotoxemia	Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge. Overall design: Adipose tissue RNA from 14 healthy subjects (before and after supplementation with n-3 PUFA or placebo) was sequenced by Illumina HiSeq 2000 with poly-A selection	Co-expression
SRP090689	Immune escape in breast cancer during in situ to invasive carcinoma transition	To dissect mechanisms of immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinomas in situ (DCIS), and HER2+ and triple negative invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Analysis of gene expression profiles of T cells demonstrated enrichment for activated GZMB+MKI67+CD8+ effector T cell signatures in DCIS. TCR clonotypes also showed highest diversity in DCIS. Naïve T cell signatures predominated IDCs, especially triple negative subtypes. TIGIT and PDL1 immune checkpoint proteins showed differential expression between DCIS and IDCs with amplification of CD274 (encoding PDL1) only detected in triple negative IDCs. Our results imply that DCIS progression is limited by an anti-tumor immune response that becomes muted in invasive tumors due to selection for cancer cells and microenvironment that suppress activated T cells or no longer trigger their activation. Overall design: RNA-Seq: Gene expression analyses in leukocytes sorted from normal breast tissues, ductal carcinomas in situ (DCIS), and HER2+ and triple negative invasive ductal carcinomas (IDC).	Co-expression
SRP090704	Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function	Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors. Overall design: PC-3 cells were infected with a pRetroX-Tet-On-Advanced retrovirus and selected for by G418 resistance. Then the G418-resistant cells were secondarily infected with either a pRetroX-Tight-pPGK-tdTomato or a pRetroX-Tight-TTP-pPGK-tdTomato retrovirus and selected for by the expression of tdTomato. G418-resistant, tdTomato-positive cells were used for experiments, in triplicate for each cell type. Cells were treated with 300 ng/ml doxycycline (Dox) for 4h prior to collection. Cells infected with pRetroX-Tight-pPGK-tdTomato were used as controls.	Co-expression
SRP090709	Systematic identification of molecular pathways driving GBM invasion	Glioblastoma multiforme (GBM) is the most prevalent and deadliest adult brain tumor. To systematically characterize the pathways governing brain invasion, we developed a three-dimensional (3D) ex vivo organotypic invasion model with clinical relevance to GBM. We used this model to enrich for highly invasive GBM cell population. Using next-generation sequencing to transcriptomically profile highly invasive and poorly invasive GBM cell populations, we have identified a network of extracellular matrix (ECM) components, including multiple collagens and collagen-interacting proteins, which are upregulated by invading GBM cells and strongly correlate in expression with clinical glioma progression outcomes. We identify the interferon regulatory factor 3 (IRF3) as a direct transcriptional repressor of ECM factors in GBM and show that IRF3 acts as an endogenous suppressor of GBM invasion. Therapeutic activation of IRF3 by inhibiting casein kinase 2 (CK2) -- a negative regulator of IRF3 phosphorylation -- downregulated the expression of ECM factors and suppressed GBM invasion in ex vivo and in vivo models across a panel of patient-derived GBM cell lines representative of the main molecular GBM subtypes in the clinic. Our findings illustrate an integrated and systematic approach for the discovery of novel pathways regulating brain tumor invasion and provide a strong mechanistic insight into the notorious, yet poorly understood, invasion capacity of GBM tumors. Overall design: Next-gen sequencing and mRNA transcriptome analysis on 2 independently derived highly invasive GBM cell populations (invasive clones 1 and 2) and 2 poorly invasive control populations (controls 1 and 2). U87 control 1 was analyzed together with and serves as a control for U87 invasive clone 1, and U87 control 2 was analyzed together with and serves as a control for U87 invasive clone 2.	Co-expression
SRP090767	Transcriptional study of ARN8 cells treated with novel DHODH inhibitors	We have previously observed protein level changes after treating human cells with two novel inhibitors of the enzyme DHODH. This study was designed to study up to what degree these protein differences can be also observed at level of mRNA. As part of the de novo pyrimidine synthesis pathway, DHODH inhibition is expected to decrease the levels of total RNA in cells. However, some effector proteins associated with the p53 pathway are increased after treatment with these inhibitors. This study aims to answer if the observed protein differences are based on an increased transcription or due to protein stabilization. Overall design: The data represent three independent experiments. In each experiment ARN8 cells were treated with two DHODH inhibitors (DrugA and DrugM) and a vehicle control.	Co-expression
SRP090779	RNA-seq in endometrial stromal tumors	We describe the first analysis of gene expression in endometrial stromal tumors by RNA-seq. We demonstrate that undifferentiated uterine sarcomas have a unique gene expression profile that is distinct from other uterine mesenchymal tumors. Overall design: Paired-end whole-transcriptome sequencing was performed on 19 endometrial stromal tumors (8 low-, 3 high-grade ESS and 8 UUS).	Co-expression
SRP090787	Subcutaneous Adipose and Skin Expression as a Function of Genotype in Polycystic Ovary Syndrome	RNA expression in adipose and skin from women with polycystic ovary syndrome (PCOS) was examined using RNA sequencing (Illumina HiSeq 50 cycle single-read sequencing) as a function of the genotype at 16 PCOS genetic risk variants. We hypothesized that the tissue expression pattern in adipose and skin would help identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci.	Co-expression
SRP090799	Expression profiling by high throughput sequencing and transcriptome-wide association study study the metabolic mechanism of the formation of atorvastatin lactone and the risk to statin-induced myotoxicity	Statin-induced myotoxicity (SIM) is one of the principal reasons for atorvastatin (AT) non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. To date, the genetic mechanism of SIM is far from well-illustrated. Published data in vitro and in vivo indicated that atorvastatin lactone (ATL) is the key metabolite to induce myotoxicity. We therefore hypothesis that genetic variants increasing the formation of ATL can increase the risk to statin-induced myotoxicity. And a transcriptome-wide association study (TWAS) integrating genome wide variants and gene expression data will applied to identify expression quantitative trait loci (eQTL) associated with the formation of ATL and different bioinformatic tools will then be applied to reveal the potential causal impact of eQTLs on the formation of ATL. Overall design: Liver mRNA profiles of 26 non-liver-cancer and 27 liver-cancer patients were generated by deep sequencing, in triplicate, using Illumina HiSeqTM 2000	Co-expression
SRP090819	Homo sapiens Raw sequence reads	RNAseq of Homo sapience: patient derived glioblastoma neurospheres	Co-expression
SRP090830	ASCL1 mediates neuronal differentiation of primary GBM stem cell cultures upon Notch signalling blockade [RNA-seq]	ASCL1 mediates neuronal differentiation of GBM stem cell (GSC) cultures upon Notch signalling inhibition. We sought to identify gene expression changes that were specific to ASCL1 function. In this dataset, we include RNA-seq data obtained from GSC cultures harbouring wildtype or CRISPR-deletion of ASCL1. We assessed differential gene expression between wildtype and ASCL1-knockout after treatment with gamma-secretase inhibitor for 7 days. Overall design: Glioblastoma cells with a genetic knockout of ASCL1 is compared to wildtype ASCL1 glioblastoma cells treated with vehicle (DMSO) or gamma-secretase inhibitor (n = 3 biological replicates; total = 12 samples)	Co-expression
SRP090831	Identifying ASCL1 target genes in primary GBM stem cell cultures [RNA-seq]	ASCL1 mediates neuronal differentiation of GBM stem cell (GSC) cultures. We sought to identify targets of ASCL1 in primary human GSC cultures. In this dataset, we include RNA-seq data obtained from GSC cultures harbouring a CRISPR-deletion of ASCL1. We assessed differential gene expression between control and GSC cultures induced to overexpress ASCL1 after 7 days of doxycycline treatment. Overall design: Glioblastoma cells with a genetic knockout of ASCL1 is compared to genetic knockout of ASCL1 overexpressing ASCL1 (n = 3 biological replicates; total = 6 samples)	Co-expression
SRP090849	Next-gen RNA sequencing of human osteosarcoma tumors	Trascriptome analysis of osteosarcoma samples were performed Overall design: Tumor samples were obtained from UMN BioNet or HTCC, cell lines were purchased from ATCC and sequenced using Illumina HiSeq 2000	Co-expression
SRP090853	Interaction between mitoNEET and NAF-1 in cancer cells	The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. MitoNEET and NAF-1 are also implicated in a number of other human pathologies including diabetes, neurodegeneration and heart disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in cancer cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria. Nevertheless, it is unknown whether these two proteins interact in cells, and how they mediate their function. Here we demonstrate, using yeast two-hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling analysis (DCA), RNA- sequencing, ROS and iron imaging, and single and double shRNA lines with suppressed  mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1 interact in cancer cells and function in the same cellular pathway. We further show using an in vitro cluster transfer assay that mNT can transfer its clusters to NAF-1. Our study suggests that mNT and NAF-1 could function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the levels of iron and Fe-S clusters under control in the mitochondria of cancer cells, thereby preventing the activation of apoptosis and/or autophagy and thus promoting rapid cellular proliferation. Overall design: Examination of the effect of suppression of mNT in the breast cancer cell line MCF-7. Two sample types were analyzed, MCF-7 suppressed for mNT and MCF-7 Empty vector control, three replicates for each.	Co-expression
SRP090891	Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly-dividing de-differentiated state	Treatment of BRAF-mutant melanomas with MAP-kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest and a remaining fraction adapts to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g. NGFR), a melanocyte precursor, and grow slowly. To identify genes associated with acquisition of the slowly-cycling, vemurafenib-adapted state, we performed RNA sequencing (RNA-seq) on COLO858 cells (that show the slowly-cycling phenotype) exposed to drug for 24 and 48 h; drug-treated MMACSF cells served as a control. Transcriptional profiling implicates a c-Jun/ECM/FAK/Src cascade in adaptive resistance to RAF inhibition. Overall design: Gene expression analysis of the response of two melanoma cell lines to 24 and 48 h treatment with RAF inhibitor vemurafenib	Co-expression
SRP090893	Low-cost, low-bias and low-input RNA-seq with High Experimental Verifiability based on Semiconductor Sequencing	We developed a new method on sequencing low-input RNA. This method shows much low-bias with the advantage of semiconductor while competing with smart-seq2. In order to analyze the low-input RNA datasets sensitively, we also develop FANSe2splice with high experimental verification rate as the analysis tool in our method. Overall design: The RNA of HBE and A549 were sequenced in our method. And smart-seq2 was also examined in HBE RNA.	Co-expression
SRP090905	p53 activity results in DNA replication fork processivity	p53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. We report that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This was observed in tumor-derived U2OS cells, but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion, and in freshly isolated thymocytes from mice with differential p53 status. Mdm2, a p53-inducible gene product, similarly supported DNA replication even in p53-deficient cells, suggesting that sustained Mdm2-expression is at least one of the mechanisms allowing p53 to prevent replicative stress. Thus, p53 helps to protect the genome during S phase, by preventing the occurrence of stalled or collapsed replication forks. These results expand p53’s tumor-suppressive functions, adding to the ex-post model (elimination of damaged cells) an ex-ante activity, i.e. the prevention of DNA damage during replication. Overall design: Expression profiling by high throughput sequencing	Co-expression
SRP090916	UPF1 knockdown in differentiating human myoblasts	Human myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA. Overall design: Human myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA.	Co-expression
SRP090929	Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface	Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In?this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome? by assessing the gene expression of receptor-ligand pairs across cell types. Moreover, we find that the expression of G-protein coupled receptors is highly cell-type?specific, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a relatively large?number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability ?to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, suggesting a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene ?expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast. Overall design: We sequenced mRNA from primary human endometrial stromal fibroblasts and in vitro human decidualized stromal fibroblasts.	Co-expression
SRP090937	Effects of plasticizers (bisphenol A, bisphenol AF) and an herbicide in MCF7 human breast cancer cells	We studied alterations in gene expression profiles of the MCF7 human breast cancer cells caused by bisphenol A, bisphenol AF and glyphosate using Illumina RNA sequencing platform. Overall design: Examination of endocrine disrupting effects of xenobiotics using the MCF7 cell line	Co-expression
SRP090942	Term placenta tissue-level transcriptome	We provide the tissue-level human placental transcriptomes from two term uncomplicated pregnancies. Tissue was collected at term C-section (no labor), from villous part of the placenta. Overall design: mRNA-seq of placenta from two term healthy pregnancies.	Co-expression
SRP090944	Term placenta single cell transcriptome	We provide single cell transcriptomes from the placental-uterine interface. Tissue was collected at term C-section (no labor) from two healthy pregnancies, from villous part of the placenta. Cells were disassociated and processed using Fluidigm technology. RNA-seq was performed on RNA from 33+54 single cells, at approx. 3.5 mio paired reads per cell. Clustering resulted in 4 trophoblast and a single immune cell clusters. As the placenta is an epitome of cell signaling, we combined the present cell-level transcriptomes with uterine cell transcriptomes to study the potential inter-cell communication. To this end, we inferred the cell-cell-interactome by assessing the gene expression of receptor-ligand pairs across cell types. We find among the signals transmitted a predominance of growth and immune signals, and suggest a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene expression profiles of term intravillous and extravillous trophoblasts. Overall design: Single cell mRNA-seq of placenta from two term healthy pregnancies.	Co-expression
SRP091017	Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits [mRNA-Seq]	Genome-wide association studies (GWAS) have successfully identified thousands of associations between common genetic variants and human disease phenotypes, but the majority of these variants are non-coding, often requiring genetic fine-mapping, epigenomic profiling, and individual reporter assays to delineate potential causal variants. We employ a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. We show that this assay identifies elements with endogenous erythroid regulatory activity. Across 23 sentinel variants, we conservatively identified 32 MPRA functional variants (MFVs). We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MFVs that predominantly affect the transcription of SMIM1, RBM38, and CD164. Functional follow-up of RBM38 delineates a key role for this gene in the alternative splicing program occurring during terminal erythropoiesis. Finally, we provide evidence for how common GWAS-nominated variants can disrupt cell-type-specific transcriptional regulatory pathways. Overall design: RNA-seq for control (shLuc) and RBM38 knockdown (shRBM38-1 and shRBM38-2) was performed for primary human erythroid cells in Day 16 of in vitro culture.	Co-expression
SRP091061	An electrical pulse stimulation protocol to study acute epigenetic response to muscle cell contraction uncovers acute hydroxymethylation of the exercise-responsive gene Nr4a3 [RNA-Seq]	Physical exercise triggers numerous positive adaptations through the regulation of genes controlling muscle structure and function. Epigenetic factors like DNA methylation participate in transcriptional activation by allowing the recruitment of the transcription machinery to gene promoters. Exercise induces dynamic DNA demethylation at gene promoters, but the contribution of the demethylation precursor hydroxymethylcytosine is unknown. Given the evanescent nature of  hydroxymethylcytosine, a model of muscle contraction amenable to collection of repeated and acute time series is requested to determine if contraction-induced demethylation is preceded by increased hydroxymethylcytosine levels. Here, we aimed to establish an acute skeletal muscle contraction model that could, at least partly, mimic the effect of acute exercise on gene expression, in order to investigate the effect of muscle contraction in DNA demethylation and hydroxymethylation. We refined an Electrical Pulse Stimulation (EPS) protocol in C2C12 myotubes that we benchmarked to the nuclear receptor subfamily 4 group A member 3 (Nr4a3) gene, a gene selected for having the highest increase in expression in response to acute exercise in humans. Using targeted bisulfite sequencing, we found that a region of the Nr4a3 promoter is rapidly demethylated 60 minutes after EPS and subsequently re-methylated after 120 minutes. Of interest, hydroxymethylation of the differentially methylated region of Nr4a3 promoter after EPS was elevated at 0 minutes and reached lowest levels at 60 minutes after EPS. We established a cell culture-based protocol to mimic acute transcriptional responses to exercise and provide insight into the mechanism by which exercise-responsive genes are demethylated after muscle contraction Overall design: Ten human subjects sampled pre and post exercise	Co-expression
SRP091303	Comprehensive RNA-seq transcriptomic profiling in the malignant progression of gliomas	To delineate comprehensive transcriptomic profiling in the malignant progression of human gliomas	Co-expression
SRP091307	Homo sapiens Transcriptome or Gene expression	RNA-seq data for human hand, foot and mouth disease virus infected SH-SY5Y cells	Co-expression
SRP091345	primary human brain microvascular endothelial cells long non-coding RNAs transcriptome	Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli	Co-expression
SRP091375	Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis: Expression data (RNA-seq)	Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains. Genes found to have DM included examples encoding transporters (SLC22A23), signaling components (BDNF, DAPK1, ROR1, and WNT5A) and transcription factors (GATA family, HAND2, HOXA cluster, NR5A1, OSR2, TBX3). Intriguingly, among the TF genes with DM we also found JAZF1, a proto-oncogene affected by chromosomal translocations in endometrial stromal tumors. Using RNA-Seq we identified a subset of the DM genes showing differential expression (DE), with the likelihood of DE increasing with the extent of the DM and its location in enhancer elements. Supporting functional relevance, treatment of stromal cells with the hypomethylating drug 5aza-dC led to activation of DAPK1 and SLC22A23 and repression of HAND2, JAZF1, OSR2, and ROR1 mRNA expression. We found that global 5hmC is decreased in endometriotic versus normal stroma, and for JAZF1 and BDNF examined by oxidative bis-seq, found that when 5hmC is detected, patterns of 5hmC paralleled those of 5mC. Together with prior studies, these results define a consistent epigenetic signature in endometriosis stromal cells and nominate specific transcriptional and signaling pathways as therapeutic targets. Overall design: Total RNA from 9 primary cell cultures of endometriosis stromal cells from ovarian ectopic sites (OESC) and control endometrial stromal cells (CESC)  were examined using RNA-Seq.	Co-expression
SRP091419	Homo sapiens Transcriptome or Gene expression	SOX2 deregulation in organotypic culture	Co-expression
SRP091435	Adaptive chromatin remodeling in glioblastoma stem cell plasticity and drug tolerance	Many cancers are postulated to harbor developmental hierarchies in which cells display variability in stem-like character, tumor propagating ability, and proliferation. In glioblastoma (GBM), glioma stem cells (GSCs) reside atop such a tumor cellular hierarchy, and are thought to resist current therapies and thus underlie inevitable relapse. Here we show that GSCs can evade RTK inhibition by reversibly regressing to a slow-cycling state reminiscent of quiescent neural stem cells. This process involves up-regulation of numerous histone demethylases, including KDM6A/B, which remodel the chromatin landscape and are selectively essential for drug persister survival. Chromatin remodeling is accompanied by activation of various neurodevelopmental master regulators and Notch signaling, changes which closely parallel critical aspects of neural stem cell biology. Thus our findings illustrate how cancer cells may hijack native developmental programs for deranged proliferation, adaptation, and tolerance in the face of stress. Our studies highlight key roles for chromatin remodeling and developmental plasticity in GBM biology, and suggest strategies for overcoming therapeutic resistance by targeting epigenetic and developmental pathways. Overall design: ChIP-seq for histone modifications and Notch factors in glioblastoma stem cell lines with various drug treatments RNA-seq in glioblastoma stem cell lines with various drug treatments	Co-expression
SRP091453	Lymphocyte activation gene3 and coronary artery disease.	Purpose: Utilized Next-generation sequencing (NGS) to profile transcriptional differences between two populations, carriers (CC) of rs10846744 SNP associated with cardiovascular disease (CVD) and non-carriers (GG) who are disease free. Methods: Total RNA was isolated from three subjects homozygous for the rs10846744 reference (GG) allele and three subjects homozygous for the rs10846744 risk (CC) allele and then subjected to full transcriptome sequencing using the Perkin Elmer next gen sequencing  platform (Perkin  Elmer,  Branford, CT). Bioinformatics was performed using Perkin Elmer GeneSifter software program. The data was adjusted by selecting total map reads, quality reads >20, log transformation, and using Benjamini Hochberg to correct for multiple testing. RNA targets of interest were validated by qRT–PCR using TaqMan assays and western blotting using standard methodologies. Results: Using Perkin Elmer''s Genesifter Analysis Edition Software, we mapped about 100 million sequence reads per sample to the human genome (build 37.2), normalized the raw read count by total mapped million reads and identified 937 upregulated and 587 downregulated transcripts in the EBV (Epstein Barr Virus)-transformed B lymphocyte cells isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele with BWA workflow. RNA-seq data confirmed differential expression of LAG3 and this was validated with qRT–PCR. Conclusions: Our study represents the first detailed analysis of differential LAG3 expression, contributing to CVD, with biologic replicates, generated by RNA-seq technology. Overall design: mRNA transcriptional profiles from EBV (Epstein Barr Virus)-transformed B lymphocyte cells, isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele, were generated by deep sequencing, in triplicate, using Illumina platform technology.	Co-expression
SRP091510	Diarrhoeal mechanisms of the Campylobacter jejuni enteritis	Campylobacter jejuni is the most prevalent cause of foodborne bacterial enteritis worldwide. This study aims at the characterisation of pathomechanisms and signalling in Campylobacter-induced diarrhoea in the human mucosa. During routine colonoscopy, biopsies were taken from patients suffering from campylobacteriosis. RNA-seq of colon biopsies was performed to describe Campylobacter jejuni-mediated effects. Mucosal mRNA profiles of acutely infected patients and healthy controls were generated by deep sequencing using Illumina HiSeq 2500. This data provide the basis for subsequent upstream regulator analysis. Overall design: Colon mucosa mRNA profiles from 4 acutely infected patients and 6 healthy controls were generated by paired end sequencing using Illumina HiSeq 2500	Co-expression
SRP091521	Hematoporphyrin derivative and x-ray treatment of human lung adenocarcinoma cells	High-throughput sequencing method to screen the important differential expression genes and signal pathways involved in this regulatory pathway, and provide the theoretical basis for subsequent treatment and research.	Co-expression
SRP091544	Cooptation of tandem DNA repeats for the control of epithelial-to-mesenchymal transition [RNA-Seq]	During normal or pathological epithelial-to-mesenchymal transition, epithelium-specific gene expression is shut down, with the DNA-binding factor ZEB1 acting as a master suppressor of epithelial identity. Here, we show that ZEB1 occupies primate-specific tandem repeats (TRs) harboring dozens of copies of its DNA-binding motif and located within genomic loci relevant for epithelial identity. Deletion of one such repeat in a quasi-mesenchymal human cancer cell line induced the reacquisition of epithelial features and phenocopied the effects of ZEB1 gene deletion. Since ZEB1 binds clustered motifs in a non-cooperative manner, changes in its nuclear concentration enable graded adjustments of TR occupancy, thus fine-tuning repression level. In addition, high motif density in TRs allows ZEB1 binding (and shutdown of epithelial programs) despite differences in chromatin organization and accessibility among epithelial cell types. Overall design: Total RNA from human pancreatic ductal adenocarcinoma cell lines was processed for multiparallel sequencing. Experiments were carried out in genome edited clonal MiaPaCa2 cells (3 ZEB1-deleted CRISPR-Cas9 clones and 3 wt clones).	Co-expression
SRP091546	Gene expression changes in human melanoma cell lines compared to primary melanocytes	Gene expression changes in 3 human melanoma cell lines were compared to freshly isolated normal primary melanocytes Overall design: Three biological replicates for each melanoma cell line and primary melanocytes were labeled and run Illumina HiSeq2500. The transcriptome of melanocytes was compared to cell line SK-Mel-28, SK-Mel-147 or UACC-62.	Co-expression
SRP091556	Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [RNA-seq]	The success of targeted therapies hinges on our ability to understand the molecular and cellular mechanism of action of these agents. Here we modify various BET bromodomain inhibitors, an exemplar novel targeted therapy, to create functionally conserved compounds that are amenable to click-chemistry and can be used as molecular probes in vitro and in vivo. Using click-proteomics and click-sequencing we provide new mechanistic insights to explain the gene regulatory function of BRD4 and the transcriptional changes invoked by BET inhibitors. In mouse models of acute leukaemia, we use high resolution microscopy and flow cytometry to highlight the underappreciated heterogeneity of drug activity within tumour cells located in different tissue compartments. We also demonstrate the differential distribution and effects of the drug in normal and malignant cells in vivo. These data provide critical insights that reveal the cellular and molecular details for the efficacy and limitations of these agents. This study provides a framework for the pre-clinical assessment of other conventional and targeted therapies. Overall design: RNASeq of MV4;11 cell treated with DMSO, JQ1 or JQ1–PA	Co-expression
SRP091558	Linking prostate cancer cell AR heterogeneity to distinct castration and Enzalutamide responses	Molecular mechanisms underlying resistance to androgen deprivation therapy (ADT) and, in particular, to antiandrogen Enzalutamide, in treating castration-resistant prostate cancer (CRPC), remain incompletely understood. Through screening >120 CRPC patient samples, we observed 3 expression patterns of androgen receptor (AR) protein: primarily nuclear (nuc-AR), mixed nuclear/cytoplasmic expression (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft CRPC modeling in 4 models (i.e., LNCaP, VCaP, LAPC4, and LAPC9) recapitulated the 3 AR expression patterns in castration-resistant tumors developed from parental androgen-dependent tumors. Strikingly, although the 3 CRPC models that retained AR expression (LNCaP, VCaP, and LAPC4)  responded, to different levels and in different kinetics, to Enzalutamide, the AR-/lo LAPC9 CRPC was completely refractory to Enzalutamide. By combining whole-genome RNA-Seq and biochemical analyses together with experimental combinatorial therapy in the LNCaP and LAPC9 models, we identified BCL-2 as a critical therapeutic target in both AR+/hi and AR-/lo, Enzalutamide-resistant CRPC models. Overall design: 1) In LNCaP model, total RNA profiles of 4 pairs of LNCaP AD, LNCaP Primary CRPC and LNCaP Secondary CRPC tumors were generated by deep sequencing. 2) In LAPC9 model, total RNA profiles of 5 paris of LAPC9 AD and LAPC9 CRPC tumors were generated by deep sequencing.	Co-expression
SRP091573	Networks of cultured iPSC-derived neurons reveal the human synaptic activity-regulated adaptive gene program	We studied the synaptic activity-regulated gene expression response in the human genetic background using cultured human iPSC-derived (hiPSCd) neuronal networks and networks of hiPSCd neurons mixed with mouse primary neurons. Our results confirm that genetic changes affect the synaptic activity-regulated gene program, proposing a functional mechanism how they have driven evolution of human cognitive abilities. Overall design: We compared RNA profiles of untreated hiPSCd neurons and hiPSCd neurons treated with bicuculline and 4-aminopyridine for 1 or 4 hours. Samples were collected from hiPSCd neuron-only cultures and from co-cultures of hiPSCd neurons and mouse primary hippocampal neurons.	Co-expression
SRP091675	Appropriately Differentiated ARPE-19 Cells Regain a Native Phenotype and Similar Gene Expression Profile	The retinal pigment epithelial (RPE) cell line ARPE-19 provides a widely-used alternative to native RPE. However, retention of the native RPE phenotype becomes problematic after multiple passages. We wished to determine if suitable culture conditions and differentiation could restore RPE-appropriate gene expression to ARPE-19. ARPE-19 cells at passages p9 to p12, grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum, were differentiated for up to 4 months. Using RNA-Seq, we compared the transcriptome of ARPE-19 cells kept in long-term culture with those cultured for 4 days. The 4 month cells developed the classic native RPE phenotype with heavy pigmentation. RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of genes in the 4 month cells. Of the 16,757 genes with detectable signals, nearly 2435 genes were upregulated, and 931 genes were down-regulated with a fold change differences of 2 or more. Genes characteristic of RPE, including RPE65, RDH5 and RDH10, were greatly increased in ARPE-19 cells maintained at confluence for 4 months. Comparison with microarray data sets from human primary cell lines revealed important overall similarities in expression of "signature" genes. The results of this study demonstrate that ARPE-19 cells can express genes specific to native human RPE cells when appropriately cultured, and thus, can provide a relevant system to study differentiated cellular functions of RPE in vitro. Overall design: RNA-Seq profiles of ARPE-19 cells grown for 4 days or 4 months; triplicate replicates were sequenced.	Co-expression
SRP091680	Assessing characteristics of RNA amplification methods for single cell RNA sequencing	We conducted a large-scale control experiment to assess the transfer function of three scRNA-seq methods and factors modulating the function. Our approach was to dilute bulk total RNA (from a single source) to levels bracketing single-cell levels of total RNA (10 pg and 100 pg) in replicates and amplifying the RNA to levels sufficient for RNA sequencing. Overall design: We performed replicate transcriptome amplifications of Universal Human Reference RNA (UHR) and Human Brain Reference RNA (HBR) that were diluted to single-cell and ten-cell abundances (10 and 100 picograms (pg.) total RNA or ~200,000 and 2 million mRNA molecules, respectively) and were amplified using three single-cell RNA amplification methods. Methods included the antisense RNA IVT protocol (aRNA), a custom C1 SMARTer protocol (SmartSeq Plus) performed on a Fluidigm C1 96-well chip, and a modified NuGen Ovation RNA sequencing protocol (NuGen). Bulk ribo-depleted UHR and HBR RNA were sequenced and served as a reference. The general experimental scheme was consistent for all dilution replicates; however, there were differences across experimental groups in the specifics of experimental protocols, necessitated by particular methodologies. Because of these experimental differences, head-to-head comparison of methods is not appropriate and our goal is to provide quantitative analyses of factors affecting individual methods. Current results should be used in experimental planning, data analysis, and method optimization rather than as a performance test of any particular method. Detailed experimental design: Each collaborating center obtained reference RNA with the same lot number for Universal Human Reference (UHR) RNA (Agilent 740000, Lot 0006141415) and Human Brain Reference (HBR) (Ambion AM6050, Lot-105P055201A) and performed replicate amplification using a single amplification method, detailed below. SmartSeq Plus: Reference RNA was diluted to an intermediate stock solution by serial dilution. A final 1000-fold dilution occurred on the C1 chip, such that individual wells in a given batch contained 9.99 pg. sampled from a common intermediate dilution. ERCC spike-in RNA mix 1 (Ambion 4456740) was also added for a final mass of approximately 7 femtograms (fg.) per sample, a 4,000,000x dilution from stock. Samples for each source RNA were prepared in single batches. After amplification, cDNA from the entire C1 96-well plate was quantified using picogreen. C1 chips with an average yield of less than 3 nanograms were discarded. The top 15 reactor wells by cDNA concentration were selected as representative 10 pg. samples for sequencing library preparation. Another 50 wells were selected by the same criteria. These were pooled in sets of 10, generating 5 100 pg. samples for each HBR and UHR. All samples for a given source were prepared in a single sequencing library preparation batch using Nextera XT C1 protocol. NuGen: HBR samples were prepared in a single batch using amplification protocol 1, generating 4 10 pg. and 4 100 pg. amplified replicates. UHR samples were prepared in two batches, using either amplification protocol 1 or 2, generating 15 10 pg. and 11 100 pg. samples. A single sequencing library preparation was performed for each batch of samples using either Lucigen NxSeq or NuGen Ovation Rapid protocol. aRNA: Amplification was performed as previously described (Morris J, Singh JM, Eberwine JH. Transcriptome analysis of single cells. J. Vis. Exp. [Internet]. 2011; Available from: http://www.jove.com/video/2634/transcriptome-analysis-of-single-cells). HBR samples were prepared in 4 batches from separate dilutions of reference RNA, generating 19 10 pg. and 3 100 pg. amplified replicates. ERCC spike-ins were added to 5 of the 10 pg. replicates before amplification at a dilution of 4,000,000x from stock. UHR samples were diluted and amplified in 2 batches from separate dilutions of reference RNA, generating 12 10 pg. and 7 100 pg. amplified replicates. A single sequencing library preparation was performed using Illumina TruSeq Stranded mRNA protocol modified to begin with amplified aRNA. A small numbers of reads were assigned to ERCC transcripts in replicates from the batch where ERCCs had been added that did not have spike-ins added (average of 0.5% of the number of reads assigned in spiked samples). 18 additional HBR 10 pg. replicates were amplified using aRNA for protocol optimization experiments. These samples were treated separately and were excluded from primary analysis. Bulk UHR and HBR: For each reference RNA, three sequencing libraries were generated from bulk material at the same laboratory as the SmartSeq Plus replicates. Cytoplasmic and mitochondrial ribosomal RNA (rRNA) were depleted using Ribo-Zero Gold as part of Illumina TruSeq Stranded Total RNA protocol. Samples were sequenced on Illumina HiSeq 2000. Because of differences in experimental design, direct comparison across methods of precision and the effect of input RNA abundance is difficult. For example, input RNA amount as a factor have different meanings for the different amplification methods: for SmartSeq Plus, because 100pg samples were constructed by pooling 10 pg. samples after cDNA amplification, any resulting effects involve library construction, while for aRNA and NuGen resulting effects reflect both cDNA amplification steps and library steps.	Co-expression
SRP091685	The Nature and Nurture of Cell Heterogeneity: Accounting for Macrophage Gene-environment Interactions with Single-cell RNA-Seq	Background: Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome’s limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic ‘snapshots’ of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic (‘nature’) and environmental (‘nurture’) modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages. Results: We introduce the programmable PolarisTM microfluidic lab-on-chip for single-cell sequencing, which performs live-cell imaging while controlling for the culture microenvironment of each cell. Using gene-edited macrophages we demonstrate how previously unappreciated knockout effects of SAMHD1, such as an altered oxidative stress response, have a large paracrine signaling component. Furthermore, we demonstrate single-cell pathway enrichments for cell cycle arrest and APOBEC3G degradation, both associated with the oxidative stress response and altered proteostasis. Interestingly, SAMHD1 and APOBEC3 are both HIV-1 inhibitors (‘restriction factors’), with no previously known co-regulation. Conclusion: As single-cell methods continue to mature, so will the ability to move beyond simple ‘snapshots’ of cell populations towards studying the determinants of population dynamics. By combining single-cell culture, live-cell imaging, and single-cell sequencing, we have demonstrated the ability to study cell phenotypes and microenvironmental influences. It’s these microenvironmental components - ignored by standard single-cell workflows - that likely determine how macrophages, for example, react to inflammation and form treatment resistant HIV reservoirs. Overall design: Stem cell derived macrophages (wildtype and SAMHD1 knockout) were single-cell cultured for 1h or 8h under for different media conditions (with/without lipopolysaccharide, with/without conditioned media to account for inter-macrophage signalling)	Co-expression
SRP091714	A monocyte gene expression signature in the early clinical course of Parkinson's disease	Recent studies suggest that the activation of the innate immune system is an integral part of Parkinson's disease (PD) pathology. Monocytes have a critical role as effectors and regulators of the innate immune system, and a recent expression quantitative trait locus (eQTL) study links monocytes to PD. Patients diagnosed with PD according to the National Institute of Neurological Disorders and Stroke  diagnostic criteria for PD were included. We applied a standardized procedure with blood drawing from fasting participants. PD patients with Hoehn and Yahr > 2 and/or cognitive impairment were not recruited. Participants with a history of cancer, infectious diseases within the past three months, or taking anti-inflammatory drugs were excluded. Altogether, we analyzed the monocytic transcriptome profiles of 10 PD patients and 9 age- and sex-matched controls using mRNA sequencing. Overall design: Monocyte mRNA profiles of 10 early stage Parkinson's disease patients and 9 age-and-sex-matched controls	Co-expression
SRP091767	Human embryonic stem cells do not change their X-inactivation status during differentiation [RNA-Seq]	Female human ESC-lines can carry active X-chromosomes (Xa) or an XIST-RNA-coated inactive X-chromosome (XiXIST+). Additionally, many ESC lines have abnormal X-chromosomeinactivation (XCI)-states where the Xi no longer expresses XIST-RNA and has transcriptionally active regions (eroded Xi=Xe). The fate of each XCI-state upon differentiation is unclear because individual lines often contain a mixture of XCI-states. Here, we established homogeneous XiXa, XeXa, and XaXa ESC-lines. Employing RNA-FISH, RNA-sequencing and DNA methylation analyses, we found that these lines were unable to initiate XIST-expression and X-chromosome-wide silencing upon differentiation indicating that the ESC XCI-state is maintained in differentiated cells. Consequently, differentiated XeXa and XaXa cells displayed higher levels of X-linked gene-expression than XiXa cells. Although global transcriptional compensation between X-chromosomes and autosomes is not required for female ESC-differentiation, the degree of X-chromosome-silencing influences differentiation efficiencies. Our data suggest that the XiXIST+Xa state is inherent to human ESCs and that all other XCI-states, including XaXa, are abnormal and arise during ESC-derivation or maintenance. Overall design: RNA-seq was used to measure the expression state of X-linked and autosomal genes in undifferentiated human embryonic stem cells with different X-chromosome states and their differentiated cells.	Co-expression
SRP091771	Gene expression profiling associated with knockdown of RNF20 in human normal and malignant lung epithelial cell lines	The experiment was designed to display differential gene expression profiling in one lung epithelial cell BEAS2-B, and three lung cancer cell lines A549, H1299, H460 cells upon knockdown of RNF20, by using RNAseq technology. Overall design: RNF20 was first attenuated in duplicated normal lung epithelial cell BEAS2-B, and three lung cancer cell lines A549, H1299, H460 by siRNA-mediated knockdown. Total RNA was extracted from duplicated cancers cells transfected with two independent control siRNA (Ctrl1/2) and RNF20 specific siRNAs (RNF1/2) at 72h post-transfection for RNAseq analysis. Differentially expressed genes in RNF20-attenuated lung epithelial cells were identified in comparison to that in cells transfected with control siRNA.	Co-expression
SRP091772	High-Throughput Screening of Human Induced Pluripotent Stem Cell Cardiomyocytes Predicts Tyrosine Kinase Inhibitor Cardiotoxicity	High-Throughput Screening of Human Induced Pluripotent Stem Cell Cardiomyocytes Predicts Tyrosine Kinase Inhibitor Cardiotoxicity Overall design: day 30 hiPSC-CMs from TKI project control lines treated with/without 1uM Sorafenib (TKI) for 72 hours	Co-expression
SRP091774	Colonic Organoids Derived from Human Pluripotent Stem Cells for Modeling Colorectal Cancer and Drug Discovery	mRNA expression from tubular adenomas of patients with Familial Adenomatous Polyposis Overall design: 3 tubular adenoma samples analyzed	Co-expression
SRP091775	Improved post thaw function and genetic changes for mesenchymal stromal cells cryopreserved using multicomponent osmolyte solutions	We report genome-wide expression changes that occur in H9-iMSCs frozen with different freezing methods that include DMSO and non-DMSO experimental solutions such as SGC (sucrose-glycerol-creatinine, SMC (sucrose-mannitol-creatinine), and SGI (sucrose-mannitol-isoleucine). mRNA-Seq analysis shows that DMSO samples cluster with fresh samples in the same clade, while all samples using the experimental solutions cluster together. In addition, we also see that cells frozen using experimental solutions have upregulation of a number of key molecular function pathways including extracellular matrix structural genes, receptor binding, and growth factor expression. Overall design: H9 MSCs were cultured in alpha-MEM base (Life Technologies), 10% FBS (qualified), and 1% non-essential amino acids (Life Technologies). Culture flasks were coated with 0.01% porcine gelatin (Fisher) for a minimum of 2 hours before H9 MSC seeding.  H9 MSCs were seeded in gelatin-coated flasks at a density of approximately 2500 cells/cm2.  Cells were split when they reached 70% confluence and were used for experiments only from passages 8 to 12.  Control cells in media were similarly combined stepwise with DMSO at a 1:1 final volume ratio.  Each of these vials was incubated at room temperature for 0, 1, or 2 hours.  Experimental solutions were frozen using a 3°C/min cooling rate while DMSO solutions were frozen using a 1°C/min cooling rate. Samples were submerged in a 37ºC bath to just under cap level, and agitated until only a small ice crystal was present. The cells were combined with acridine orange/propidium iodide (AO/PI) and enumerated using a hemocytometer. Samples were diluted, centrifuged and supernatant was aspirated, followed by preparation for RNA isolation. Purified RNA was then submitted for RNA-sequencing.	Co-expression
SRP091785	CD74 role in transcription regulation [RNA-seq]	CD74 activation was previously shown to affect gene transcription. The goal of this study was to reasarch its role as a transcriptor regulator. CD74 was activated in primary CLL cells obtained from patients for 2 and 8 h. mRNA was then extracted, and mRNA-seq was conducted. Overall design: mRNA seq was done for CD74 ot IgG activated cells 2 and 8 h following activation in triplicated	Co-expression
SRP091838	Identification of target genes regulated by NANOG-HDAC1 axis	To gain insight into the role of HDAC1 in NANOG-mediated transcriptional regulation, we performed genome-wide RNA-sequencing analysis (RNA-seq) in CaSki-no insert-siGFP, CaSki-NANOG-siGFP and CaSki-NANOG-siHDAC1 cells. Overall design: Total RNAs from CaSki-no insert and CaSki-NANOG cells transfected with the indicated siRNA were subjected to genome-wide total RNA-sequencing analysis	Co-expression
SRP091839	Gene expression of human gastric carcinoma cell line NCI-N87 under quercetin treatment	gene expression of human gastric carcinoma cell line NCI-N87 under quercetin treatment	Co-expression
SRP091854	A total RNA-Seq screen reveals that the splicing inhibitor Isoginkgetin blocks transcription elongation	Pharmacological perturbation is a powerful tool for understanding gene expression, but identification of the specific steps of this multi-step process targeted by small molecules remains challenging. Here we apply total RNA-Seq to distinguish specific pharmacological effects on transcription and pre-mRNA processing, revealing unexpectedly that the splicing inhibitor isoginkgetin blocks transcription elongation.An RNA-Seq screen reveals that the compounds TBBz and CYT387 mimic the transcriptional effects of isoginkgetin and are inhibitors of CSNK2A2, suggesting that isoginkgetin blocks transcription elongation via inhibition of CSNK2A2. Our results reveal RNA-Seq screening as a tool for disentangling complex pharmacological effects on gene expression. Overall design: Total RNA sequencing of drug treated Hela cells for 6 or 18 hours.	Co-expression
SRP091886	Human tracheobronchial epithelial (HTBE) cell transcriptome response to infection with H1N1, H3N2, and H5N1 influenza virus.	Human tracheobronchial epithelial (HTBE) cells are considered to serve as a good correlate of influenza virus infection in the human respiratory tract. mRNA-Seq analysis was used to profile the cellular transcriptome of HTBE cells at multiple time points in response to infection with influenza A/California/04/09 (H1N1), A/Wyoming/03/03 (H3N2), and A/Vietnam/1203/04 (H5N1) HALo virus. The Influenza A/Vietnam/1203/04 (H5N1) HALo mutant virus is an attenuated H5N1 virus generated from wild-type Influenza A/Vietnam/1203/04 (H5N1) virus as described in Steel, J., et al. J Virol. 2009 Feb; 83(4):1742-53. Overall design: Human tracheobronchial epithelial (HTBE) cells that have been isolated from normal donor airway epithelial tissue were infected with influenza A/California/04/09 (H1N1), A/Wyoming/03/03 (H3N2), and A/Vietnam/1203/04 (H5N1) HALo virus at an MOI of 5. H3N2- and H5N1-infected samples and time-matched mock-infected samples were collected in duplicates at 3, 6, 12, and 18 hrs post infection for mRNA-Seq analysis. Sample from H1N1-infected cells and mock controls were collected at 3, 6, 12, 18, and 24 hrs.	Co-expression
SRP091890	lncRNA-seq analysis samples	4 sequencing samples,Two femoral neck fracture samples (C1, C2) were used as controls,Two femoral head necrotic tissue samples (D1, D2)	Co-expression
SRP091936	RNA-seq of SOX5 overexpressing primary human neuronal progenitors	Purpose: The goal of this study was to assess gene expression changes in neurons overexpressing SOX5 using human primary neuronal culture system. Methods: 6 samples each from control GFP and SOX5 overexpressing neurons were used to isolate total RNA using miRNeasy kit, Qiagen.  We performed rRNA-depleted 69bp paired end stranded RNA-seq on neurons overexpressing either GFP or SOX5 tagged with GFP. Overexpression of SOX5 in neurons validated that a significant proportion of Attenuated cortical patterning (ACP) genes are regulated by SOX5, and that predicted SOX5 targets exhibit a net downregulation, consist with its repressive function. This supports the prediction that attenuated patterning of SOX5 between cortical regions contributes to direct alterations in SOX5 targets and likely to indirect alterations in SOX5 non-targets in the ACP set. delpleted 69 bp stranded RNA-seq in Overall design: SOX5 was overexpressed in primary human neuronal cultures using a lentiviral system. Briefly full-length human SOX5 gene was cloned in pLVU/GFP vector (gift from Lars Ittner [Addgene plasmid #24177]) using the gateway recombination technique. Lentivirus was produced in HEK293T cells using a second generation packaging vector system (psPAX2, a gift from Didier Trono [Addgene plasmid #12260] and pCMV-VSV-G, a gift from Bob Weinberg [Addgene plasmid #8454]) as described by Stewart et al., 200331. Primary human neurons were infected at plating at a multiplicity of infection (MOI) of 10 with either the SOX5 overexpressing construct or a control pLVU-GFP backbone vector. 14 days after infection, RNA from the samples were isolated using miRNeasy micro kit (Qiagen, Carlsbad) and 50bp paired-end libraries were prepared using SMARter Stranded Total RNA sample prep kit (Clontech) with rRNA depletion. Libraries were then multiplexed and sequenced with HiSeq 2500 instrument (Illumina).	Co-expression
SRP091944	Cis-regulatory evolution in primates - RNA-seq	Cis-regulatory evolution has played a critical role in shaping animal and plant phenotypic diversity. We include data of five primate species (excluding human samples) used to study the evolution of promoters and enhancers in the livers of six species selected from all major clades of the primate lineage. We produced ChIP-seq data for two different histone modifications to profile active and poised regulatory elements, and performed RNA-seq on the same samples to produce corresponding transcriptional profiles.	Co-expression
SRP091947	Development of an In Vitro Human Liver System for Interrogating Non-Alcoholic Steatohepatitis	A barrier to drug development for non-alcoholic steatohepatitis (NASH) is the absence of translational pre-clinical human-relevant systems. An in vitro liver model was engineered to incorporate hepatic sinusoidal flow, transport, and lipotoxic stress risk factors (glucose, insulin, free fatty acids) with co-cultured primary human hepatocytes, hepatic stellate cells (HSC), and macrophages. Transcriptomic, lipidomic, and functional endpoints were evaluated and compared to clinical data from NASH patient biopsies. The lipotoxic milieu promoted hepatocyte lipid accumulation (4-fold increase, p<0.01) and a lipidomics signature similar to NASH biopsies. Hepatocyte glucose output increased with decreased insulin sensitivity. These changes were accompanied by increased inflammatory analyte secretion (e.g. IL6, IL8, ALT). Fibrogenic activation markers increased with lipotoxic conditions, including secreted TGFß (>5-fold increase, p<0.05), extracellular matrix gene expression, and HSC activation. Significant pathway correlation existed between this in vitro model and human biopsies. Consistent with clinical trial data, 0.5µM obeticholic acid in this model promoted a healthy lipidomic signature, reduced inflammatory and fibrotic secreted factors, but also increased ApoB secretion, suggesting a potential adverse effect on lipoprotein metabolism. Lipotoxic stress activates similar biological signatures observed in NASH patients in this system, which may be relevant for interrogating novel therapeutic approaches to treat NASH. Overall design: 17 Samples. 8 NASH, 9 Control (Low Glucose, Low Insulin)	Co-expression
SRP091948	human decidual macrophage clustering	We have cluster decidual macrophages into three subpopulations	Co-expression
SRP091956	Integrated Transcriptomic and Proteomic Dynamics of Rituximab Treatment in B Lymphoblastoid Cells	The investigation aims to profile the molecular dynamics of Rituximab treatment in cells.  Specifically, a B-lymphoblast cells line was treated with Rituximab, and sampled every hour over a 24hour period. Treated and untreated cells were processed to extract RNA and protein that were subsequently used in high-throughput analysis of the transcriptome (RNA-Sequencing) and proteome (mass spectrometry). We expect our approach not only to provide a unique reference dataset to the scientific community but to also act as a paradigm as an approach to identify novel transcriptome-proteome molecular markers utilized in mapping drug action pathways. We have identified specific expression at both the gene and protein levels and are inferring associations between the omics through the use of temporal pattern identification, thus defining time-varying networks. This study will provide the next steps in the development of reference dynamic omics data that may be used in creating integration models, with further applications in dynamic monitoring of samples in precision medicine implementation. Overall design: Examination of dynamics in a treated cell line and a parallel untreated control line, both sampled over 24hrs every hour. Validation using a new repeated experiment, with treated and untreated tracks, sampled over 6 selected time points.	Co-expression
SRP091957	Integrative analysis of reprogramming human fibroblast cells to naïve pluripotency [RNA-seq]	Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental studies and therapeutic manipulations. However, the molecular mechanisms involved in establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with 5iLAF naïve induction strategy, we performed integrative analysis across the timeline from human fibroblasts to naïve iPSCs, which reveals ordered expression waves of gene networks sharing signatures with embryonic development process from post-implantation to pre-implantation stages. We also observed a significant transient re-activation of transcripts with 8-cell-stage-like characteristics in late naïve reprogramming stages. Moreover, combined quantitative proteomics analysis with transcriptional dynamics during naïve pluripotency induction, we identified ALPPL2 as the specific surface marker for human naïve pluripotency. Altogether, our study deepens the understanding of molecular mechanisms of human naïve pluripotency. Overall design: mRNA  profiles of transitioning cells at different time points in the naïve reprogramming process were performed by deep sequencing.	Co-expression
SRP091981	Transcriptome dynamics of CLK dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor	Here we describe a highly selective novel CLK small molecule inhibitor with high specificityto CLK1/CLK2/CLK3 protein isoforms and favourable stability and in vivo activity, called T3. We show that CLK dependent reactions occur in distinct genomic sequencecontexts with sequence-encoded features that are relatively conserved between different epithelial cell types. We also reveal an unexpected role for CLK proteins in suppression of conjoined gene (CG) transcription, implicating CLK in 3' end processing of transcripts.	Co-expression
SRP091988	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells	The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 down-regulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53 deficient cancer cells increased levels of the allosteric regulator fructose 2,6-bisphophate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53 deficient cancer cells. Moreover, depletion of PFKFB4 attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4 induced apoptosis in p53 deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment. Overall design: Gene expression changes in HCT116 p53+/+ and p53-/- xenograft tumours after PFKFB4 silencing	Co-expression
SRP091992	Sodium butyrate ameliorates aSyn-induced transcription deregulation and DNA damage	Alpha-synuclein (aSyn) is widely portrayed as the main culprit on Parkinson’s Disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed to evaluate the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms behind aSyn-induced transcriptional deregulation. We performed RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased WT or A30P aSyn levels. Compared to control, LUHMES cells expressing aSyn exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. Expressing WT aSyn, unlike A30P aSyn, led to increased DNA damage and phosphorylated p53 levels. In our dopaminergic neuronal cell model, aSyn expression promoted lower histone 3 acetylation levels. Excitingly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), was able to rescue WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide compelling, pioneer evidence for a novel mechanism associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with a HDACi. Prospective studies will be crucial to further validate these findings and its relevance to our knowledge of PD. Overall design: RNA from Lund Human Mesencephalic (LUHMES) cells was used to assess the impact of alpa-synuclein (aSyn) on cellular transcription. For this purpose, three different cell lines were generated. Briefly, proliferating LUHMES cells were infected with equimolar amounts of lentiviral particles encoding for: IRES-GFP (samples set C); full-length human wild-type (WT) aSyn (SNCA, NM_000345), WT aSyn-IRES-GFP (samples set E) or familial mutant A30P aSyn, A30P aSyn-IRES-GFP (samples set A). Positive green fluorescent cells were selected by fluorescence activated cell sorting. Three independent replicates were generated for each cell line. Total RNA from differentiated LUHMES cells, at differentiation day 8, was extracted and purified using the RNeasy mini kit (Qiagen), according to the instructions of the manufacturer.	Co-expression
SRP091998	Gene expression of collecting duct carcinoma of the kidney	The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 -7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies. Overall design: Paired tumor and normal samples from 7 patients ------------------------------------ The author states that the CDC5 normal sample is unavailable: CDC samples are rare and for CDC5, we don''t have a matched normal	Co-expression
SRP091999	hMTR4 plays a central role in creating balanced nuclear RNA pools for degradation and export IV	To define the in vivo targets of the human nuclear exosome, we performed stranded RNA-seq using rRNA-depleted RNAs isolated from HeLa cells. Overall design: rRNA-depleted RNAs isolated from control, hRRP40 or hMTR4 siRNA treated HeLa cells were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP092000	Effects of Wnt3A on the transcriptome of CCD-18Co human colon fibroblasts	Purpouse: To compare the transriptome of CCD-18Co human colon fibroblasts treated with vehicle or Wnt3A. Methods: We treated triplicate plates of CCD-18Co cells with vehicle or Wnt3A during 24 h. Afterwards, we obtained total RNA and used it in RNA-seq experiments. Results: Our analysis rendered a total of 1136 differentially expressed genes (FDR<0.05), of which 662 were up-regulated and 474 were downregulated in response to Wnt3A. Conclusions: Wnt3A regulates a wide set of genes in CCD-18Co human colon fibroblasts Overall design: Study of gene expression profile of CCD-18Co human colon fibroblasts in response to Wnt3A	Co-expression
SRP092004	Suppression of adaptive responses to targeted cancer therapy by transcriptional repression [RNA-seq]	Large-scale genomic profiling efforts have facilitated the characterization of molecular alterations in cancers and aided the development of targeted kinase inhibitors for a wide array of cancer types. However, resistance to these targeted therapies invariably develops and limits their clinical efficacy. Targeting tumours with kinase inhibitors induces complex adaptive survival programs that promote the persistence of a fraction of the original cancer cell population, facilitating the eventual outgrowth of inhibitor-resistant tumour clones following clonal evolution. Here we show that the addition of a newly identified transcriptional repressor, THZ1, to targeted cancer therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in cellular and in vivo cancer models with diverse genetic dependencies. We propose that targeted therapy induces a state of transcriptional dependency in a subpopulation of cells poised to become drug tolerant. THZ1 can exploit this dependency by blocking dynamic transcriptional responses, remodelling of enhancers and key signalling outputs required for tumour cell survival in the setting of targeted cancer therapies. These findings suggest that the addition of THZ1 to targeted cancer therapies is a promising broad-based strategy to hinder the emergence of drug-resistant cancer cell populations. Overall design: RNA-seq in tumor cell lines treated with targeted therapies and/or transcriptional inhibitors	Co-expression
SRP092010	Hit-and-run'' programing of CAR-T cells using mRNA nanocarriers	RNAseq of ex vivo CD8 T cell lineages and in vitro differentiated CD8 T cells treated with nanocarriers encapsulating control or Foxo1-3A transcription factor mRNA Overall design: Gene expression in central memory CD8 and in vitro Foxo1-3A nanoparticle treated CD8 were compared to control cells cultured in vitro with eGFP mRNA encapsulating nanoparticles.	Co-expression
SRP092031	RBM25 is a global splicing factor promoting inclusion of alternatively spliced exons	The goal of this study was to determine the role of RBM25 in pre-mRNA splicing and examine whether lysine 77 contributes to this function. Overall design: We examined mRNA transcript level and splicing events in 293T cells in two experiments. First is CRISPR/Cas9 depletion of RBM25 vs control sgRNA. Second is over-expression of GFP, RBM25 or RBM25 K77R mutant.	Co-expression
SRP092049	Transcriptome of EMT induced MCF10A cells by TGFb treatment or SNAIL S6A expression.	EMT, Epithelial to mesenchymal transition is a developmental biology process associated with migration, known to be involved in cancer metastasis. To study this process, we used the breast epithelial cell line MCF10A that enter in EMT after treatment with the cytokine TGFB or by expression of EMT transcriptor factor SNAIL. Overall design: mRNA profiles of MCF10A cells treated for 1 or 6 days with TGFb (done in duplicate), and mRNA profiles of Snail inducible line, MCF10A-SNAIl, induced for 1 or 6 days.	Co-expression
SRP092065	MRTF activates TEAD-YAP target gene expression	Yes Associated Protein (YAP) and Myocardin Related Transcription Factor (MRTF) play similar roles and crosstalk in directing the transcriptional responses to chemical and physical extracellular cues. However the mechanism by which the two proteins crosstalk has been unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity. We show this interaction of MRTF and YAP is critical for LPA-induced cancer cell invasion in vitro and breast cancer metastasis to the lung in vivo. We also demonstrate the significance of MRTF-YAP binding in mechanotransduction by showing that the nucleo-cytoplasmic shuttling of MRTF induced by changes in the actin cytoskeleton constitutes the LATS-independent regulation of YAP activity. Our results provide clear evidence of crosstalk between MRTF and YAP independent of the LATS kinases that normally act upstream of YAP signaling and suggest a mechanism by which extracellular stimuli can coordinate physiological events downstream of YAP. Overall design: To examine the impact of MRTFB overexpression on TEAD-YAP target genes, we overexpressed G-actin binding deficient MRTFB mutants (MRTFB dN) that are otherwise wildtype, YAP binding deficient (dPY), SRF binding deficient (YA), both-binding deficient (YA/dPY) in MCF-10A cells by retroviral infection and performed RNA sequencing experiment. We were able to identify genes whose expressions are activated by MRTFB overexpression, and genes whose expressions are depedent on MRTF-YAP or MRTF-SRF binding.	Co-expression
SRP092075	Generation of human microglia-like cells to study neurological disease	Microglia play important roles in developmental and homeostatic brain function, and influence the establishment and progression of many neurological disorders. Here, we demonstrate that renewable human iPSCs can be efficiently differentiated to microglial-like cells (iMGL) to study neurological diseases, such as Alzheimer''s disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to adult and fetal human microglia. Functional assessment of iMGLs reveal that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. We also show novel use of iMGLs to examine the effects of fibrillar Aß and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Taken together, these findings demonstrate that iMGLs can be used in high-throughput studies of microglial function, providing important new insight into human neurological disease. Overall design: Human cells were collected and analyzed for gene expression using RNA-seq.	Co-expression
SRP092107	RNA-sequencing in TGF-beta treated MDA-231-D cells transfected with ZEB1/ZEB2 siRNAs [RNA-seq]	We searched for roles of ZEB1 during EMT by RNA-seq in breast cancer cells. Overall design: Expression of mRNA in a basal type breast cancer cell line MDA-231-D transfected with ZEB1/ZEB2 siRNAs and stimulated with TGF-beta for 24 h.	Co-expression
SRP092131	Novel RNA biomarkers of prostate cancer revealed by RNA-seq analysis of formalin-fixed samples obtained from Russian patients	Due to heterogeneous multifocal nature of prostate cancer (PCa), there is currently a lack of biomarkers that stably distinguish it from benign prostatic hyperplasia (BPH), predict clinical outcome and guide the choice of optimal treatment. In this study, RNA-seq analysis was applied to formalin-fixed paraffin-embedded (FFPE) tumor and matched normal tissue samples collected from Russian patients with PCa and BPH. We identified 3384 genes differentially expressed (DE) (FDR < 0.05) between tumor tissue of PCa patients and adjacent normal tissue as well as both tissue types from BPH patients. Overexpression of four of the genes previously not associated with PCa (ANKRD34B, NEK5, KCNG3, and PTPRT) was validated by RT-qPCR. Furthermore, the enrichment analysis of overrepresented microRNA and transcription factor (TF) recognition sites within DE genes revealed common regulatory elements of which 13 microRNAs and 53 TFs were thus linked to PCa for the first time. Moreover, 8 of these TFs (FOXJ2, GATA6, NFE2L1, NFIL3, PRRX2, TEF, EBF2 and ZBTB18) were found to be differentially expressed in this study, making them not only candidate biomarkers of prostate cancer but also potential therapeutic targets. Overall design: Whole transcriptome profiling of tumor tissue and matched adjacent normal tissue from 15 patients with PCa and 2 with BPH.	Co-expression
SRP092132	Metformin RNA-seq	Transcriptomic response to metfromin treatment.	Co-expression
SRP092158	Regulatory T cells exhibit distinct features in human breast cancer	The goal of this study is to compare transcriptional profiles of regulatory T cells and conventional CD4 T cells in human breast cancer to regulatory T cells and conventional CD4 T cells in normal breast parenchyma and in peripheral blood. Overall design: RNA sequencing of 2 different cell types in 3 different tissues	Co-expression
SRP092159	Analysis of gene expression (RNAseq) from shTP53:RB1 LNCaP/AR cell lines	Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. Here we show, using in vitro and in vivo prostate cancer models, that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR) dependent luminal epithelial cells to AR independent basal-like cells. This lineage plasticity is enabled by loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2 and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching. Overall design: LNCaP/AR prostate cell line was transduced with shNT or shTP53:RB1 hairpins and then RNA was harvested from these cell lines for gene epxression analysis.	Co-expression
SRP092177	Transcriptome profiling of single HEK293 cells with UMIs on Ion Torrent Proton (Run 20150702)	5' selective RNA-seq of 38 Single HEK293 cells RNAseq profiling with N4H4 unique molecular identifiers processed on a Fluidigm C1. Overall design: Single cell HEK293 cell 5' selective RNAseq profiling, 38 cells, unique molecular identifiers, custom library preparation.	Co-expression
SRP092180	UMI-based, single cell RNA sequencing of human nasal epithelial cells grown for 52 days at air liquid interface	5' selective RNA-seq of 96 single cells from human nasal epithelial cells. Cells grown for 52 days at an air liquid interface. RNAseq profiling  was performed with N4H4 unique molecular identifiers processed on a Fluidigm C1. Sequencing was performed on a Ion Proton (Life Technologies). Overall design: Single cell from human nasal epithelium. 5' selective RNAseq profiling, 96 cells, unique molecular identifiers, custom library preparation.	Co-expression
SRP092181	UMI-based, single cell RNA sequencing of human nasal epithelial cells grown for 33 days at air liquid interface	5' selective RNA-seq of 96 single cells from human nasal epithelial cells. Cells grown for 33 days at an air liquid interface. RNAseq profiling  was performed with N4H4 unique molecular identifiers processed on a Fluidigm C1. Sequencing was performed on a Ion Proton (Life Technologies). Overall design: Single cell from human nasal epithelium. 5' selective RNAseq profiling, 96 cells, unique molecular identifiers, custom library preparation.	Co-expression
SRP092222	Homo sapiens Raw sequence reads	we compared the gene expression of CD106+MSCs and CD106-MSCs	Co-expression
SRP092266	Functional significance of the HIV-1 Tat signature amino acid residues	We sequenced the mRNA from a stably transduced Human T-cell line expressing the HIV-1 Tat protein. The inducible Tat expression has been used to understand and compare the cellular molecules and pathways being modulated by the wild type subtype-C Tat versus its single signature amino acid residue variant.  Additionaly, the HIV-1 subtype B and C Tat comparitive analysis has also been included in the study to evaluate the  gene expression profile as a reponse to subtype specific Tat proteins. Overall design: Evaluation of the genes and pathways differentially modulated by the epression of the variant HIV-1 Tat proteins or suntype specific Tat proteins in a Human T-cell line using RNASeq analysis.	Co-expression
SRP092359	DDX54 regulates transcriptome dynamics during DNA damage response [4SU-seq]	The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing irradiation (IR). Interestingly, more than 260 proteins including many nucleolar proteins showed increased binding to poly(A) RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well defined class of pre-mRNAs which harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Since DDX54 promotes survival after exposure to IR its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR. Overall design: Primary and mature transcript profiling of MCF-7 cells exposed to ionizing radiation using 4SU-seq	Co-expression
SRP092361	DDX54 regulates transcriptome dynamics during DNA damage response [RNA-seq1]	The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing irradiation (IR). Interestingly, more than 260 proteins including many nucleolar proteins showed increased binding to poly(A) RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well defined class of pre-mRNAs which harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Since DDX54 promotes survival after exposure to IR its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR. Overall design: Gene expression profiling of MCF-7 cells exposed to 4SU, UV and ionizing radiation	Co-expression
SRP092362	DDX54 regulates transcriptome dynamics during DNA damage response [RNA-seq2]	The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing irradiation (IR). Interestingly, more than 260 proteins including many nucleolar proteins showed increased binding to poly(A) RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well defined class of pre-mRNAs which harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Since DDX54 promotes survival after exposure to IR its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR. Overall design: Gene expression profiling of MCF-7 cells upon DDX54 knockdown exposed to ionizing radiation	Co-expression
SRP092397	Genome-wide Gene Expression Profiling in DLBCL Cell Lines Treated with CUDC-907	CUDC-907 is a small-molecule dual-acting inhibitor of HDACs and PI3Ks, which effectively suppresses the growth and survival of MYC-altered DLBCL. To evaluate the effect of CUDC-907 on MYC-associated genes, two DLBCL cell lines were treated with CUDC-907, a total of 948 differentially regulated genes were identified. 24 genes from the CUDC-907–regulated 948-gene set present either in the "HALLMARK_MYC_TARGETS_V1” 200-gene set or in the “HALLMARK_MYC_TARGETS_V2” 58-gene set in the Molecular Signatures Database (MSigDB). We then computed the correlation coefficients (r) between gene expression levels and MYC protein levels across all samples in the TCGA DLBCL dataset. We found that mRNA expression changes induced by CUDC-907 in the two DLBCL cell lines are negatively correlated with correlation coefficients between expression levels and MYC protein level in the TCGA DLBCL dataset Overall design: Examination of differentially regulated genes in 2 cell lines treated with CUDC-907	Co-expression
SRP092400	Differences in RNA expression between primary and metastatic colon tumor	Here, we report the genomic-scale characterization of metastatic colon cancer transcriptome. Fresh-frozen samples was used to asses differences between normal colon, primary colon tumor an liver metastasis. Overall design: Total RNA was isolated from three location from each recruited patient: normal colon, colon tumor and metastatic lesion in liver.	Co-expression
SRP092402	A blood RNA signature for predicting the treatment outcome in the Tuberculosis Treatment Response Cohort	Identification of blood biomarkers that prospectively predict Mycobacterium tuberculosis treatment response. Overall design: There are a total of 914 samples used in this design. This involves samples from 100 cases and 38 controls. Most of the samples have 2 technical replicates where as 2 samples have 4. Samples from the TB cases have been collected on the start day of TB treatment and on 1,4 and 24 weeks after treatment as well. For some subjects we also have samples after the subject has been cured. The case or TB Subjects have been categorized by the nature of their response as definite,probable or possible cure. The day of cure is presented in the time to negativity column. Also provided in the metadata are the MGIT -Mycobacteria Growth Indicator Tube and XPERT (cartridge based nucleic acid amplification test, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB)) values at the various times of sample collection for all TB Subjects.	Co-expression
SRP092408	RNAseq study of synovial biopsies	Total RNA sequencing was performed on samples isolated from joint synovial biopsies from subjects with and without rheumatoid arthritis Overall design: One biopsy sample per subject was analysed without replicates	Co-expression
SRP092413	Transcriptomic Profiling of 39 Neuroblastoma Cell Lines	Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. This data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (eg: MYCN amplification status, ALK mutation status, 11q status, sensitivity to pharmacological pertubation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma. Overall design: We sequenced neuroblastoma cell lines (N=39) with varying genomic characteristics, disease stages, and phases of therapy. We also sequenced the hTERT-immortalized retinal pigmented epithelial cell line, RPE-1 (N=1), which is commonly used as a non-neuroblastoma control, as well as RNA from the fetal brain (N=1), which can serve as a non-neuroblastoma neural-cell derived control.	Co-expression
SRP092429	RNA-seq analysis of EZH1 knockdown in 5F cells, or EZH1 heterozygous and homozygous knockout YS and AGM cells	Blood develops in distinct stages. Haematopoietic progenitors in the embryo manifest restricted differentiation potential relative to definitive haematopoietic stem cells in adult bone marrow, which support lifelong multilineage haematopoiesis. To identify regulators of embryonic haematopoiesis, we screened chromatin modifiers and identified the Polycomb group protein EZH1 as a barrier to multilineage potential from pluripotent stem cells (PSCs). EZH1 was directly bound to bivalently poised, yet restricted, HSC and lymphoid genes in primitive progenitors; knockdown enabled robust generation of multilineage progenitors. Moreover, EZH1 haploinsufficiency promoted the generation of HSCs with long-term, multilineage and self-renewal potential from sites of embryonic haematopoiesis in vivo. Together, this work identifies EZH1 as a key epigenetic barrier to definitive haematopoiesis during embryonic development, and highlights the utility of chromatin modifiers as cell engineering targets to enhance blood differentiation from PSCs. Overall design: RNA-seq was performed to determine gene expression changes in EZH1 deficient 5F cells or in mouse yolk sac (YS) and AGM cells.	Co-expression
SRP092432	Transcriptomic data of triple negative breast cancer revealed GBP1 as potential new therapeutic target	Background: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression (ESR and PGR, respectively) and an absence of human epithelial growth factor receptor (ERBB2) amplification. Approximately 15–20% of breast malignancies are TNBC. Patients with TNBC often have an unfavorable prognosis. In addition, TNBC represents an important clinical challenge since it does not respond to hormone therapy.  Methods: In this work, we integrated high-throughput mRNA sequencing (RNA-Seq) data from normal and tumor tissues (obtained from The Cancer Genome Atlas, TCGA) and cell lines obtained through in-house sequencing or available from the Gene Expression Omnibus (GEO) to generate a unified list of differentially expressed (DE) genes. Methylome and proteomic data were integrated to our analysis to give further support to our findings. Genes that were overexpressed in TNBC were then curated to retain new potentially druggable targets based on in silico analysis. Knocking-down was used to assess gene importance for TNBC cell proliferation. Results: Our pipeline analysis generated a list of 243 potential new targets for treating TNBC. We finally demonstrated that knock-down of Guanylate-Binding Protein 1 (GBP1), one of the candidate genes, selectively affected the growth of TNBC cell lines. Moreover, we showed that GBP1 expression was controlled by epidermal growth factor receptor (EGFR) in breast cancer cell lines.  Conclusions: We propose that GBP1 is a new potential druggable therapeutic target for treating TNBC with enhanced EGFR expression.	Co-expression
SRP092452	Rapid Recall Ability of Memory T cells is Encoded in their Epigenome	Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both na誰ve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the na誰ve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting na誰ve, central and effector memory T cells using ChIP-Seq and found that unlike the na誰ve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory. Overall design: Chromatin state of resting Human Naive, Central memory (TCM) and Effector Memory (TEM) T cells was analyzed by ChIP-Seq; Gene expression in resting and activated for 40 min, 150 min and 15hrs Naive, TCM and TEM cells was analyzed by RNA-Seq	Co-expression
SRP092457	Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy	Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli activating immune cells are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA (pRNA) complexes and CpG-P. We found that GM-CSF and pRNA have similar effects on their target cells, whereas pRNA and CpG-P induce stronger tType I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, all novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects detrimental for vaccine efficacy. Overall design: mRNA profiles of CD1c+ mDCs and pDCs, MACS isolated from 3 healthy volunteers and stimulated with 4 clinical grade stimuli, were generated by deep RNA sequencing using HiSeq 2000 System (TruSeq SBS KIT-HS V3,Illumina)	Co-expression
SRP092465	Global reduction in H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas	A subgroup of  Posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin. Overall design: RNA-sequencing was performed  in 5 posterior fossa (PF) and three supratentorial (ST) ependymoma samples. All 5 PF samples show low H3K27me3 and designated PF_H3K27me3-ve; all 3 ST ependymoma samples show high H3K27me3 and desginated ST_H3K27me3+ve	Co-expression
SRP092468	RNA Seq analysis of NKX2-5 Null and Het human embryonic stem cells in cardiomyogenesis	Differentiation of human pluripotent stem cells (hPSCs) can be used to model human heart development and, in turn, to analyze the developmental consequences of genetic abnormalities. Here, we deleted NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs) and identified a novel genetic interaction between NKX2-5 and HEY2 that is required for heart development Overall design: Comparision of Null and Het NKX2-5 hESCs	Co-expression
SRP092491	Endothelial cells derived from iPSC in response to diabetic medium	Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids. Overall design: Vascular organoids were differentiated from human iPS cells and treated for 3 weeks with a diabetic media containing 75mM Glucose, 1ng/mL TNF-a, 1ng/mL IL6 (DI) or left untreated in 17mM Glucose (NG). Endothelial cells were FACS sorted for CD31 directly into Trizol and stored at -80°C before RNA preparation. The 2 NG and 2 DI are pools of sorted endothelial cells from multiple vascular organoids (>100) from 2 independent differentiations/treatments.	Co-expression
SRP092501	Low H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas	A subgroup of  Posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin. Overall design: RNA-sequencingwas performed  in 15 posterior fossa (PF) ependymoma samples. 11 samples show low H3K27me3 and designated PF_H3K27me3-ve; 4 samples show high H3K27me3 and designated PF_H3K27me3+ve	Co-expression
SRP092509	Different TCM syndromes in gastric cancer using nest-generation sequencing	lncRNA-seq	Co-expression
SRP092519	Regionally distinct astrocyte interferon signaling promotes blood-brain barrier integrity and limits immunopathology during neurotropic viral infection	The role of astrocytes in innate immunity during viral infections of the central nervous system (CNS) remains to be fully elucidated. Here, we demonstrate that type I interferon (IFN) receptor (IFNAR) signaling in astrocytes regulates blood-brain barrier permeability and protects the cerebellum from infection and immunopathology. Mice with astrocytes lacking IFNAR signaling showed decreased survival after West Nile virus infection that was not due to expanded viral tropism or increased replication. Pattern recognition receptors and IFN-stimulated genes (ISGs) had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes compared to cerebral cortical astrocytes. Our data identify cerebellar astrocytes as key responders to viral infection and highlight distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS. Overall design: Primary human astrocytes were maintained on collagen-coated tissue culture plates in a complete astrocyte medium (ScienCell Laboratories) in 2% FBS. Prior to isolation of RNA, cells were treated for 4 hours with 10U/ml recombinant human IFN-ß or a PBS vehicle. Cells were then lysed in buffer RLT (Qiagen).	Co-expression
SRP092524	Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche	In this work, we generated early human amnion-like tissues by culturing human pluripotent stem cells (hPSCs) in a bioengineered implantation-like niche in vitro. To explore the gene expression profile of hPSC-derived amnion-like cells (hPSC-amnion), we performed mRNA-sequencing for both undifferentiated hPSCs and hPSC-amnion. Here we show that hPSC-amnion differs from hPSCs by actively regulating a comprehensive set of transcriptional regulation network and developmental signaling pathways such as BMP-SMAD signaling. Overall design: hPSCs cultured in conventional maintenance condition (mTeSR1-based feeder-free culture system; three biological replicates) as well as in the engineered implantation-like niche (the Gel-3D system composed of mTeSR1 and Geltrex; three biological replicates) were harvested and subjected to RNA-seq.	Co-expression
SRP092533	Selective modulation of inflammatory Natural Killer (NK) cell phenotypes following histone H3K27 demethylase inhibition [RNA-Seq]	Natural Killer cells are innate lymphocytes, participate in immune surveillance and elimination of stressed or transformed cells and critically shape the inflammatory cytokine environment to interact with cells of the innate and adaptive immune system, including macrophages, dendritic and Tcells. By performing a focused compound library screening, further validated by knockdown approaches, we here identify Jumonji-type histone 3 lysine 27 (H3K27) demethylases as key regulators of cytokine production in various human NK cell subsets. The prototypic H3K27 demethylase inhibitor GSK-J4 increases global levels of the repressive H3K27me3 mark around transcription start sites including NK cell effector cytokines, and thereby reduces IFN-?, TNFa, GM-CSF and IL-10 levels in IL-15 stimulated NK cells whilst sparing the cytotoxic killing capacity against cancer cells. The anti-inflammatory effect of GSK-J4 in highly inflammatory NK cell subsets, isolated from peripheral blood or tissue from rheumatoid arthritis patients, coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggests a wider role and utility of histone demethylase inhibition in immunity and inflammation. Overall design: We constructed 6 RNA-seq libraries; two conditions in triplicate. NK cells were cultured in media in the presence of IL-15 stimulation then cultured in the presence of DMSO and GSK-J4 treated NK cells. RNA was collected at 24 hours.	Co-expression
SRP092544	Delineating survival from a fatal outcome in Ebola virus disease in humans	In 2014 Western Africa experienced an unanticipated explosion of infections with Ebola virus (EBOV). What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. Here transcriptome data for peripheral blood taken from infected and convalescent, recovering patients, was used to identify early stage host factors that were associated with acutely ill patients that ultimately either survived or succumbed to the disease.	Co-expression
SRP092548	Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta	In this study, we isolated human villous stromal cells (STRs), CTBs, the STB, and EVTs at the first and second trimester of pregnancy and monitored the transcriptome dynamics of 1567 cells at single-cell resolution. We identified 14 subtypes of placental cells and characterized their functions, especially the unexpected secretion of 102 polypeptide hormone using bioinformatics analyses and immnunostaining verifications. Our study builds a strong foundation for understanding how the human placenta develops and functions to maintain a healthy pregnancy. Overall design: single cell transcriptome profiles of stomal cells and trophoblast cells from 8 week and 24 week gestation of placenta were generated by next generation sequencing using Illumina Hiseq4000.	Co-expression
SRP092559	CD86 regulates a pro-survival signal in myeloma cells	While multiple myeloma patient prognosis has improved over the past decade, research towards discovery of new therapeutic avenues is important, and could lead to a cure for this chronic plasma cell malignancy. Data analysis from a myeloma patient database shows that the CD28-CD86 signaling module may provide a survival advantage in myeloma cells that negatively impacts patient outcome. Here we show that blocking the CD28-CD86 pathway, by silencing or with CTLA-4-Ig, leads to myeloma cell death. Blockade of this pathway leads to downregulation of nutrient transporters, integrins, and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical "ligand" in this pathway, is mediating a pro-survival signal via the cytosolic domain that has not been previously described. These findings indicate that blockade of this pathway is a promising therapeutic avenue for myeloma, as it leads to modulation of different processes important in cell viability. Overall design: The myeloma cell lines MM.1s, RPMI8226, KMS18, and RPMI8226 that overexpresses the anti-apoptotic protein Mcl1 were transfected with short hairpin RNAs targeting CD28, CD86, Gapdh (control), or empty vector (pLK0.1) control and gene expression analysis was performed by RNA-seq.	Co-expression
SRP092584	PC1/3 deficiency impacts POMC processing in human embryonic stem cell-derived hypothalamic neurons	We developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. Overall design: We tried to idenitify transcripitional profiles and specific transcription factors that involved in of different stages during hypothalamic neuron differentiation from single cell sequencing for hESC-derived Day27 hypothalamic neurons, Day 12 neuron progenitors and undifferentiated stem cells	Co-expression
SRP092751	Convergent exaptation of Alu and B/ID SINEs for Staufen-mediated mRNA decay	Identifying orthologous mRNAs subject to SMD in both mouse and human myoblasts using siRNA depletion of Staufen or Upf1 Overall design: mRNAs subject to Staufen-mediated decay should increase in level upon depletion of either Staufen or Upf1. Cultured myoblasts (mouse or human) treated with control, Staufen, or Upf1 siRNAs were extracted and RNA was purifed, polyA selected and sequenced. Changes in level were detected by DESEQ analysis.	Co-expression
SRP092795	Ion Channel Expression Patterns in Glioblastoma Stem Cells with Functional and Therapeutic Implications for Malignancy	Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that stratify by molecular subtype and are associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown or pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance. Overall design: Ion channel expression in glioblastoma stem cells	Co-expression
SRP092975	Inhibition of H3K4 demethylation induces autophagy in cancer cell lines	Epigenetic factors and related small molecules have emerged to be strongly involved in autophagy process. Here we report that two inhibitors of histone H3K4 demethylase KDM1A/LSD1, 2-PCPA and GSK-LSD1, are able to induce autophagy in multiple cell lines. The two small molecules induced accumulation of LC3II, formation of autophagosome, fusion of autophagosome with lysosome and SQSTM1/p62 degradation. 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA. The autophagy induced by 2-PCPA requires LC3-II processing machinery. But depletion of BECN1 and ULK1 with siRNA did not affect the LC3-II accumulation triggered by 2-PCPA. 2-PCPA treatment induces the change of global gene expression program, including a series of autophagy-related genes, such as SQSTM1/p62. Taken together, our data indicate that KDM1A/LSD1 inhibitors induce autophagy through affecting the expression of autophagy-related genes and in a BECN1-independent manner. Overall design: Examination of RNA from U2OS cell with 10 kinds of small molecules treatment	Co-expression
SRP093125	Whole transcriptome sequencing of FACS isolated KDR+CD235a- and KDR+CD235a+ Day 3 mesoderm	Day 3 mesoderm generated from H1 PSCs by differentiation protocol found in:"Sturgeon CM, Ditadi A, Awong G, Kennedy M, Keller G. Wnt Signaling Controls the Specification of Definitive and Primitive Hematopoiesis From Human Pluripotent Stem Cells. Nature biotechnology. 2014;32(6):554-561."Definitive hematopoiesis was specified using CHIR99021 treatment to agonize Wnt signaling and KDR+CD235a- mesoderm at Day 3 was FACS isolated. Primitive mesoderm was specified using IWP2 treatment to antagonize Wnt signaling and KDR+CD235a+ primitive mesoderm and KDR+CD235a- mesoderm was FACS isolated. There are 5 replicates of each sample type:CHIR CD235a-IWP CD235a-IWP CD235a+	Co-expression
SRP093173	Homo sapiens Transcriptome or Gene expression	Genome-wide profiling of the placenta trophoblast transcriptome	Co-expression
SRP093176	RNAseq analysis of NAP1L1 depleted hepatocytes	Whole-genome transcriptome analysis of NAP1L1 depleted cells was performed to gain insights into NAP1L1 differentially modulated genes whose expression might be relevant during HCV infection.	Co-expression
SRP093217	Reconstructing pathway modification induced by nicotinamide using multi-omics network analyses in triple negative breast cancer	Triple negative breast cancer (TNBC) is characterized by an aggressive biologic behavior without specific targeted agent. Nicotinamide has recently been proved as a novel therapeutic agent for skin tumors in ONTRAC trial. Here we performed combinatory transcriptomic and in-depth proteomic analyses to characterize network of molecular interactions in TNBC cells treated by nicotinamide. Multi-omics with The Illumina sequencing (HiSeqâ„¢ 2500) for transcriptomics and iTRAQ LC-MS/MS techniques for proteomics profiles identified that nicotinamide causes significant functional alterations to major cellular pathways, including cell cycle, DNA replication, apoptosis and DNA damage repair. Pathway enrichment analyses were conducted using multiple web-based analytic tools to categorize functions of genes and peptides. This approach reveals that nicotinamide treatment rewires interaction networks towards dysfunction of DNA damage repair and away from pro-growth state in TNBC. We are expecting that our multi-omics findings will provide knowledge of integrational signaling networks alteration with NA treatment in TNBC and act as an evidence for application of NA as a novel chemotherapeutic agent in the future.	Co-expression
SRP093226	Transcriptome/RNA sequencing of human leukocytes in atrial fibrillation compared to healthy population	To investigate the differentially-expressed genes and long non-coding RNAs in human leukocytes from atrial fibrillation compared to healthy controls.	Co-expression
SRP093240	Differential gene expressions in the heart of hypertrophic cardiomyopathy patients	Differential gene expressions were constructed through expression profiling of a total of 20,127 genes in the heart tissue of hypertrophic cardiomyopathy patients, then 1799 significant differential genes were filtered based on the criteria (p<0.05 and fold change > 1.5), respectively. Overall design: In the study presented here, human hypertrophic heart tissue samples were obtained from patients previously diagnosed with hypertrophic cardiomyopathy, undergoing septal myectomy surgery (n=5). Control samples were obtained from normal heart donor left ventricles (n=4). The heart tissues were collected and performed transcriptome analysis by RNA-sequencing. Compared to normal heart, 1799 significant differentially expressed genes (filtering criteria p<0.05, fold change>1.5) were identified 7-days or 28 days post-Ang II infusion.	Co-expression
SRP093249	Modulation of nonsense-mediated decay by rapamycin	Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells revealed genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms. We demonstrate that despite well-documented attenuation of cap-dependent mRNA translation, rapamycin can augment NMD of certain transcripts. Rapamycin-treatment significantly reduces the levels of both endogenous and exogenous PTC-containing mRNA isoforms and its effects are dose-, UPF1- and 4EBP-dependent manner. The PTC-containing SRSF6 transcript exhibits a shorter half-life upon rapamycin-treatment as compared to the non-PTC isoform. Rapamycin-treatment also caused depletion of PTC-containing mRNA isoforms from polyribosomes, underscoring the functional relationship between translation and NMD. Enhanced NMD activity also correlates with an enrichment of the nuclear Cap Binding Complex (CBC) in rapamycin-treated cells. Our data demonstrate that rapamycin modulates global RNA homeostasis by NMD. Overall design: We performed cytoplasmic RNA-seq of HEK 293 T cells stimulated with rapamycin, emetine or control, in triplicates.	Co-expression
SRP093253	RNA Sequencing of HUES8 WT and HUES8 TET1/2/3 TKO hESCs	The TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish due to challenges of distinguishing global versus locus-specific effects. Here we show that TET1/2/3 triple knockout (TKO) human embryonic stem cells (hESCs) exhibit preferential hypermethylation at bivalent promoters without corresponding gene expression changes in undifferentiated hESCs. In the absence of the TET proteins, abnormal accumulation of DNMT3B at bivalent promoters results in hypermethylation and impaired gene activation upon differentiation. Broadly, the competitive balance between the TET proteins and de novo methyltransferases at bivalent promoters could facilitate rapid changes of their methylation state to either activate or silence transcription in a cell-lineage and gene dependent manner. Overall design: For RNA-Sequencing total RNA was isolated with the RNeasy Mini Kit (Qiagen, 74136) from HUES8 WT and TKO hESCs	Co-expression
SRP093255	The mRNA expression analysis of psoriasis skin lesion mesenchymal stem cell	RNA sequencing for 6 samples from psoriasis skin lesion mesenchymal stem cell, to examine the differentilly expressed mRNAs between two differernt conditions. Overall design: Examining 2 conditions, each with 3 replicates	Co-expression
SRP093256	Quantitative Analysis of PPARD Transcriptomes  in Colon Cancer Cells by Next Generation Sequencing (NGS)	Purpose: NGS has revolutionized systems-based analysis of cell signaling pathways. The goal of this study is to determine the effects of PPARD in colon cancer cell transcriptomes in relation to the metastatic potential. Methods: NGS-derived colon cancer cell mRNA transcriptome profiles of HCT116 WT (HCT116) and HCT116 with genetic PPARD-knockout (KO1) cells were generated by deep sequencing, in quadruplicate, using Illumina  HiSeq2000 .The transcriptomes of HCT116 and KO1 cells will be compared to determine the differentially expressed genes between HCT116  and KO1 cells. Differentially expressed genes will be examined in relation to the metastatic potential  and  validated by qRT-PCR. Results: Using an optimized data analysis workflow Tophat2, we mapped about 25 million sequence reads per sample to the human genome. Out of 22229 genes, we identified 12118 transcripts  with >50 reads in at least one sample of HCT116 and KO1 cells with edgeR package and identified 6668 differentailly expressed genes with FDR 0.001 and P value cutoff  0.0022 using GLM tests fitted with BUM model. We further fltered the genes with both p-value and fold change and identified 416 genes  with FDR 0.001 and fold change larger than 2.  Among the differentially expressed genes, 311 were downregulated and 105 were upregulated in the KO1 cells compared with the WT cells. Twenty-three of the differentially expressed genes had significant association (i.e., a tendency towards co-occurrence) with PPARD expression (P < 0.05; log odds ratio > 1.5) in the TCGA colorectal adenocarcinoma database. Of these 23 genes, 7 were linked to metastasis by PubMed literature searches: GJA1, VIM, SPARC, NRG1, CXCL8 (IL-8), STC1, and  SNCG, which were validated by q-RT-PCR. Conclusions: Our study represents the detailed analysis of PPARD transcriptomes in colon cancer cells, generated by mRNA-seq technology. Our results  show that NGS offers a comprehensive and  accurate quantitative and qualitative evaluations of mRNA contents in cells. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: The transcriptome profiles of HCT116 WT and KO1 colon cancer cells were generated by deep sequencing, in quadruplicate, using Illumina HiSeq2000.	Co-expression
SRP093266	Identifying deer antler proliferation and mineralization genes using comparative RNA-seq	Purpose: The goal of this study is to compare (RNA-seq) transcriptomes of in vitro cultured human bone marrow-derived mesenchymal stem cells (hMSCs) and fallow deer antler-derived skeletal progenitors (FD RM Cells) under multiple conditions to identify candidate proliferation and mineralization genes responsible for fast antler regeneration Methods: hMSCs and FD RM Cells were cultured in vitro under 1) serum-free (0% serum) or serum (10% serum) conditions for 2.5 days or 2) Control (0 ng/mL BMP-2 and 0 nM dexamethasone) and osteogenic (100 ng/mL BMP-2 and 100 nM dexamethasone) media for 24 days. mRNA profiles were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000. The sequence reads were analyzed at the transcript isoform level STARS followed by Cufflinks. Validation for genes of interest was performed using immunofluorescence staining. Results: Comparison of human and fallow deer skeletal progenitor datasets yielded proliferation and mineralization gene candidates Conclusions: Our study represents the first detailed analysis of human and fallow deer transcriptomes of skeletal progenitor cells under proliferation and mineralization conditions, with biologic replicates, generated by RNA-seq technology. Our in vitro comparative approach circumvent some of the logistical and technical challenges in identifying candidate proliferation and mineralization genes responsible for rapid deer antler regeneration. We conclude that in vitro comparison of RNA-seq based transcriptomes identified candidate proliferaiton and mineralization genes to advance bone biology and holds promise to rapidly regenerate large bone volumes for regenerative medicine. The comparative approach utilized here can be adapted for almost any tissue to study a specific phenomenon of interest. Overall design: Design: hMSCs and FD RM Cells were cultured in vitro under 1) serum-free (0% serum) or serum (10% serum) conditions for 2.5 days or 2) Control (0 ng/mL BMP-2 and 0 nM dexamethasone) and osteogenic (100 ng/mL BMP-2 and 100 nM dexamethasone) media for 24 days. mRNA profiles were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000.	Co-expression
SRP093268	The cohesin complex prevents Myc-induced replication stress	The cohesin complex is mutated in cancer and in a number of rare familiar syndromes collectively known as Cohesinopathies. In the latter case, cohesin deficiencies have been linked to transcriptional alterations affecting Myc and its target genes. Here, we set out to understand to what extent the role of cohesins in controlling cell cycle is dependent on Myc expression and activity. Inactivation of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest due to both transcriptional impairment of Myc target genes and alterations of replication forks, which were fewer and preferentially unidirectional. Ectopic activation of Myc in RAD21 depleted cells, fully rescued transcription and promoted S-phase entry but failed to sustain S-phase progression thus leading to a strong replicative stress response, which was associated to a robust DNA damage response, DNA damage checkpoint activation and synthetic lethality. Thus, the cohesin complex is dispensable for Myc dependent transcription but essential to prevent Myc induced replicative stress. This suggests the presence of a topological checkpoint orchestrated by cohesins that by regulating Myc level prevents S-phase entry and replicative stress in cohesion compromised cells. Overall design: RNAseq samples of U2OS -MycER cells (in the presence or absence of OHT) and transfected with non-targeting siRNA or siRNA against RAD21 after 24 and 48 hours of transfection/treatment	Co-expression
SRP093275	Anti-Warburg effect elicited by mitochondrial biogenesis drives differentiation of glioblastoma cells into astroglial cells	Glioblastoma (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed to be potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established the induced differentiation model of GBM by using cAMP activators, which specifically directed GBM into astroglia. Next, transcriptomic and proteomic analyses uncovered oxidative phosphorylation and mitochondrial biogenesis were involved in induced differentiation of GBM. Further investigation showed dbcAMP reversed Warburg effect evidenced by increase of oxygen consumption and reduction of lactate production. Stimulated mitochondrial biogenesis downstream of CREB/PGC1a pathway triggered metabolic shift and differentiation. Blocking mitochondrial biogenesis by mdivi1 or silencing PGC1a abrogated differentiation, reversely over-expression of PGC1a elicited differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induced tumor growth inhibition and differentiation. This study shows mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation process of tumor cells. Overall design: mRNA profiles of cell line DBTRG-05MG after 0h, 6h, 12h, 24h and 48h of dbcAMP treatment	Co-expression
SRP093293	Glucose metabolism induced chromatin remodeling in pulmonary artery endothelial cell [RNA-Seq]	Maintaining endothelial cells (EC) as a monolayer in the vessel wall depends on a gene expression profile and the metabolic state, features influenced by contact with neighboring cells eg, pericytes and smooth muscle cells (SMC). Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) signaling disrupts EC metabolism and monolayer formation and is associated with vascular diseases such as pulmonary arterial hypertension. We show that BMPR2 in either EC or SMC is required for contact-dependent activation of Notch1 in EC. Notch1, through the glycolysis inducer PFKFB3, mediates an increase in the citrate pool and histone acetylation required for Notch1 and MYC target gene expression. This maintains Notch1-dependent EC proliferative capacity, coordinating with Notch1 activation of mitochondria. We report how Notch1 and p300 binding to chromatin and H3K27ac status are influenced by glucose metabolism and regulate gene expression in endothelial cells. Overall design: Examination of RNA-sequencing in pulmonary artery endothelial cells with or without PFKFB3 silencing in contact co-culture with pulmonary artery smooth muscle cells.	Co-expression
SRP093311	Whole-transcriptome maps of HepG2 cells after exposure to cationic liposomes and controls	Cationic liposomes (CLs) are non-viral vectors that play a major role in DNA transfer and gene therapy. The cellular toxicity of CLs has been validated in HepG2 cells. To address the basis of the CLs toxicity, we performed RNA-seq analysis on untreated HepG2 cells and HepG2 cells following exposure to IC50 concentration (120µM) CLs for 24h. Overall design: Examination of gene expression level in CLs treated HepG2 cells and untreated cells	Co-expression
SRP093315	Metabolic Labeling of Newly Transcribed RNA for High Resolution Gene Expression Profiling of RNA Synthesis and Decay in response to hypoxia in HUVEC cells	Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output. Overall design: Exponentially growing non-synchronized HUVEC were exposed to normoxia or hypoxia (21% or 1%  oxygen respectively) for 8 hours and pulse-labelled with 4-thiouridine during the last two hours of treatment. RNA was extracted from samples in each condition (total RNA) and an aliquot was subjected to affinity chromatography to purify the 4-thiouridine-labelled (newly transcribed RNA, Newly Tr) and non-labelled (Pre-existent) RNA fractions. All  three RNA fractions (total, newly transcribed and pre-existent) from each sample were analyzed by high-throughput sequencing. Submission includes 12 samples corresponding to 3 independent biological replicates.	Co-expression
SRP093323	Pluripotent Reprogramming of Human AML Resets Leukemic Behavior and Models Therapeutic Targeting of Subclones [RNA-seq]	Understanding the contribution of abnormal genetic and epigenetic programs to acute myeloid leukemia (AML) is necessary for the integrated design of targeted therapies. To investigate this, we determined the effect of epigenetic reprogramming on leukemic behavior by generating induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements. AML-derived iPSCs (AML-iPSCs) retained leukemic mutations, but reset leukemic DNA methylation/gene expression patterns and lacked leukemic potential. However, when differentiated into hematopoietic cells, AML-iPSCs reacquired the ability to give rise to leukemia in vivo and reestablished leukemic methylation/gene expression patterns, including an aberrant MLL signature, indicating that epigenetic reprogramming was insufficient to eliminate leukemic behavior. In one case, we identified distinct AML-iPSC KRAS mutant and wildtype subclones that demonstrated differential growth properties and therapeutic susceptibilities, predicting KRAS wildtype clonal relapse due to increased cytarabine resistance. Increased cytarabine resistance was further observed in a cohort of KRAS wildtype MLL-rearranged AML samples, demonstrating the utility of AML-iPSCs in predicting subclonal relapse and facilitating clonal targeting in AML. Overall design: RNA seq profiling of normal and leukemic differentiated and iPSC populations	Co-expression
SRP093327	Hypoxic regulation of transcription in HUVEC is mediated by EPAS1	Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output. Overall design: Exponentially growing non-synchronized HUVEC were transduced with lentiviral particles encoding for shRNA targeting EPAS1 or control shRNA. 72h after infection, cells were exposed to normoxia or hypoxia (21% or 1%  oxygen respectively) for 8 hours and pulse-labelled with 4-thiouridine during the last two hours of treatment. RNA was extracted from samples in each condition (total RNA) and an aliquot subjected to affinity chromatography to purify the 4-thiouridine-labelled RNA fraction (newly transcribed RNA, Newly Tr). Both RNA fractions from each condition were analyzed by high-throughput sequencing. Data includes 8 samples from a single biological replicate.	Co-expression
SRP093328	Hypoxic regulation of gene expression in HUVEC is dominated by EPAS1	Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output. Overall design: Exponentially growing non-synchronized HUVEC were transduced with lentiviral particles encoding for shRNA targeting HIF1A or EPAS1 or a control shRNA. 72h after infection cells were exposed to normoxia or hypoxia (21% or 1%  oxygen respectively) for 16 hours. RNA was extracted from samples and analyzed by high-throughput sequencing. Data includes 6 samples from a single biological replicate.	Co-expression
SRP093349	Swarm intelligence-enhanced detection of non-small cell lung cancer using tumor-educated platelets	We report RNA-sequencing data of 779 blood platelet samples, including 402 tumor-educated platelet (TEP) samples collected from patients with non-small cell lung cancer (NSCLC). In addition, we report RNA-sequencing data of blood platelets isolated from 377 individuals without reported cancer, but not excluding individuals with inflammatory conditions. This dataset highlights the ability of TEP RNA-based 'liquid biopsy' diagnostics in patients with NSCLC. Overall design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the humane reference genome using STAR, and intron-spanning reads were summarized using HTseq.	Co-expression
SRP093357	Reduced mitochondrial activity in colonocytes facilitates AMPKa2-dependent inflammation	Intestinal inflammation is associated with mitochondrial dysregulation, however its role in the pathophysiology is unclear. We performed RNA-seq on colonic cancer cells with decreased mitochondrial function (?0 cells) to investigate links between dysregulated mitochondrial function and inflammation.	Co-expression
SRP093372	Differential gene expression of cigarettes and next generation products	Raw Next Generation sequencing data from 3R4F cigarettes and e-cigarettes	Co-expression
SRP093378	A cost-effective RNA sequencing protocol for large-scale gene expression studies	We present a simple RNA sequencing protocol with substantially reduced costs. Overall design: This protocol uses as little as 10 ng of total RNA, allows multiplex sequencing of up to 96 samples per lane, and is strand specific. H1p16 (3 replicates) and H1p43 (3 replicates) are sequenced by Illumina TruSeq. Lane1 - Lane 4 are sequenced by LM-Seq (Hou, Zhonggang, et al. 2015). Lane 1 - Lane 4 samples are multiplexed by 95, 48, 24 and 6 samples per lane, respectively.	Co-expression
SRP093382	Transcriptome profiling (RNA-seq) of CREBBP+/+ and CREBBP+/- clones of U2932 DLBCL cell line	Purpose: Diffuse large B cell lymphomas (DLBCL) frequently harbor mutations in the histone acetyltransferase CREBBP, however their functional contribution to lymphomagenesis remains largely unknown. This study aims at elucidating and characterizing the molecular pathways affected by mutations in CREBBP. Methods: U2932, a DLBCL cell line that has wild type expression of CREBBP was manipulated by CRISPR-Cas9 strategy to mutate one allele of CREBBP and examine the pathways affected. RNA was isolated using the NucleoSping RNA Kit (Macherey-Nagel) from five wild type (CREBBP+/+) and five heterozygous clones (CREBBP+/-). RNA quality was assessed by Bioanalyzer 2100 followed by library preparation using the TruSeq RNA Sample Prep Kit v4 (Illumina). Sequencing was subsequently performed on the Illumina HiSeq 2500 instrument. RNA-seq reads were quality-checked with fastqc, which computes various quality metrics for the raw reads. RNA-seq reads were mapped to the GRCh38 reference human genome using STAR and reads were counted according to Ensembl gene annotation using the featureCounts function in the Rsubread Bioconductor package. Statistical analysis of differential expression was conducted with the DESeq2 package. Overall design: Trascriptomic profiles of CREBBP+/+ and CREBBP+/- clones were generated by deep sequencing.	Co-expression
SRP093386	RNA-seq analysis of ESR1 mutations in T47D and MCF7 cell lines	Purpose: Transcriptome analysis of ESR1 mutant cells was performed via sequencing total RNA in T47D and MCF7 cell lines containing Y537S and D538G mutations. Overall design: Methods: Individual ESR1 WT and mutant T47D and MCF7 clones were hormone deprived in CSS for three days, pooled, and plated in quadruplicates in 6-well plates. The cells were treated with veh or 1nM E2 for 24 hrs, RNA was isolated and subjected to sequencing. Differential expression analysis was performed by DEseq2 and R was used to conduct statistical analysis tests	Co-expression
SRP093640	The RNA-seq (miRNA and mRNA) analysis of three human osteosarcoma cells	RNA-seq analysis was performed by BGI-Tech of China, and RNA-seq library preparation and sequencing were performed by BGI (Shenzhen, China). Overall design: Following purification, the RNA was fragmented using divalent cations at an elevated temperature, and first-strand cDNA was synthesized using random hexamer primers and Superscript TMIII (Invitrogenâ„¢, Carlsbad, CA, USA). Second-strand cDNA was synthesized using buffer, dNTPs, RNaseH, and DNA polymerase I. Short fragments were purified with a QiaQuick PCR extraction kit (Qiagen) and resolved with EB buffer for end repair and poly (A) addition. The short fragments were subsequently connected using sequencing adapters. After agarose gel electrophoresis, suitable fragments were used as templates for PCR amplification. During the QC steps, an Agilent 2100 Bioanalyzer and an ABI StepOnePlus Real-Time PCR System were used for the quantification and qualification of the sample library. Finally, the library (200 bp insert) was sequenced using an Illumina HiSeq 2000 (Illumina Inc., San Diego, CA, USA). The single-end library was prepared following the protocol of the Illumina TruSeq RNA Sample Preparation Kit (Illumina)	Co-expression
SRP093642	Species-Specific Developmental Timing is Maintained by Pluripotent Stem Cells Ex Utero	We performed whole transcriptome RNA sequencing experiments on two sets of differentiation time course starting from human ES cells (EGFP-H1) and mouse EGFP-EpiS cells: (1) in vitro neural differentiation, and (2) teratoma formation Overall design: In vitro differentiation time courses were sampled every day for the first 8 days, then every other day over 3 weeks for mouse cells and 6 weeks for human cells (day 28 was missed).  Mouse teratomas were sampled on days 1, 2, 4, 8, 9, 10, 11, 14, 16 ,18, and 21; human teratomas on days 2, 8, 10, 11, 14, 16, 18, 21, 23, 28, 36, and 42	Co-expression
SRP093646	RNA-Seq in PWS iPSC-derived neurons	Transcriptional analysis of PWS iPSC-derived neurons compared to unaffected controls Overall design: 9 unaffected control lines, 2 PWS microdeletion lines, 2 PWS large deletion lines	Co-expression
SRP093655	Exosomal short RNA sequencing experiments	The characterization of extracellular vesicular RNA (EV RNA) derived from nine cell types demonstrated the diversity of cell type specific RNA biotypes. A large proportion of these cell type specific RNAs are denoted by their processing into shorter versions of their full length structures as they function with the cells of origin.   specific portions of annotated pre-miRNA, tRNA, YRNA and other RNAs within EVs.  Our results also establish the cell state specific dynamicity in EV RNA distributions, qualifying one of the important aspects of communication. In addition, the study highlights both the temporal dynamics and spatial localization of intact EV RNA after transfer into a recipient cell, and their ability to elicit a wide range of transcriptional changes within them. We also demonstrated the cell type specificity in response from two different cell types, when exposed to the same EV RNA stimuli, underscoring the context dependent interpretation of the complex EV RNA message. In doing so, we shed light on a novel and under-appreciated medium of non-cell autonomous regulation of gene expression, through which cells in a complex multicellular organism may shape the transcriptional landscape of other cells and achieve synchronized functioning of involved cells in response to a certain micro-environment at the system level. Overall design: Exosomal short RNA sequencing experiments	Co-expression
SRP093667	Digital Gene Expression (DGE) Analysis of Human Umbilical Vein Endothelial Cells (HUVECs) At 24 Hours Post Hantaavirus Infection	Hantavirus infection causing zoonotic diseases with a high mortality rate in humans has long been a global public health concern. Over the past decades, accumulating evidences suggest that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. To explore the potential role of long non-coding RNAs in host innate immune responses, DGE analysis of HUVECs for whole genome profiling was performed at 24 hours post HTNV infection. Overall design: RNA isolated from HUVECs, which were either mock infected or treated with live or Co60-inactivated HTNV at MOI 1 for 24 hours, was sequenced on an Illumina Platform. More than 3.4 million reads per sample were obtained. One sample in the Mock, HTNV infection or Co60-inactivated HTNV infection group were collected for DGE. No replicates were applied in each group.	Co-expression
SRP093672	HBEC-shp53-PCHD7	We studied the effects of ectopic expression of Protocadherin 7 (PCDH7) on Human Bronchial Epithelial Cells (HBECs). Overall design: Immortalised HBECs were established with overexpression of CDK4 and telomerase, and knocking down p53 in these cells was achieved using stable expression of shRNA specific for TP53 gene. PCDH7 or GFP were ectopically expressed in the resulted HBEC-shp53 cells using Lenti-virus. Stable infected cells were selected and harvested for RNA isolation in triplicates. RNA-seq was performed to study the effects of PCDH7 on the expressional profile of the HBEC-shp53 cells.	Co-expression
SRP093677	Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular	Circular RNAs (circRNAs) are numerically abundant in human, predominantly derived from protein coding genes, and some can act as microRNA sponges or cis-acting transcriptional regulators. Changes in circRNA abundance have been identified during human development which may be functionally important, but lineage-specific analyses are currently lacking. To address this, we performed RNAseq analysis of human embryonic stem (ES) cells differentiated for 90 days towards 3D laminated retina. A transcriptome-wide increase in circRNA abundance, size, and exon count was observed which reached a plateau by day 45. Parallel analyses, controlling for sample and locus specific effects, identified 239 circRNAs with expression patterns distinct from the transcriptome-wide pattern, but these also increased in abundance over time. Surprisingly, circRNAs derived from long non-coding RNAs (lncRNAs) were found to account for a significantly larger proportion of transcripts from their loci of origin than circRNAs from coding genes. The most abundant, circRMST:E12-E6, showed a >100X increase during differentiation which was associated with altered promoter usage, and accounts for >99% of RMST transcripts in many adult tissues. The second most abundant, circFIRRE:E10-E5, accounts for >98% of FIRRE transcripts in differentiating human ES cells, and is one of 39 FIRRE circRNAs many of which include multiple unannotated exons. Our results suggest that during human ES cell differentiation, changes in circRNA abundance are primarily globally controlled. They also suggest that RMST and FIRRE, genes with established roles in neurogenesis and topological organisation of chromosomal domains respectively, encode circular lncRNAs with only minor linear species. Overall design: Human H9 embyonic stem cells (ESC) were differentiated towards retinal pigment epithelium cells (with and without Igf1), and rRNA depleted total RNA samples from 3 biological replicates at days 0, 45 and 90 were sequenced. All samples were analysed using PTESFinder v 1 (http://sourceforge.net/projects/ptesfinder-v1/ [Izuogu et al., 2016]) to identify back-splice junctions. Differential expression analyses of circRNAs identified from H9 ESC were performed separately for circRNAs originating from protein-coding and non-coding loci, after controlling for locus-specific expression changes and global changes in expression upon differentiation. Cluster anlyses of total canonical junctions and circRNA expression were performed to identify relative expression changes upon differentiation. This series includes amplicon sequencing to verify FIRRE splice junctions.	Co-expression
SRP093679	LMO1 Synergizes with MYCN to Promotes Neuroblastoma Initiation and Metastasis	High levels of LMO1 expression synergizes with MYCN to accelerate neuroblastomagenesis, enhance disease penetrance and promote widespread metastasis in zebrafish. Transcriptomic analysis of human neuroblasotma cells with programed expression of LMO1 vs vector control or neuroblastoma cells with differential endogenous LMO1 expression revealed that gene signitures affecting tumor cell-extracellular matrix interaction are significantly associated with high levels of LMO1 expression. Our findings provide compelling evidence for a major pathogenic role of LMO1 in MYCN-driven neuroblastoma. Overall design: Examination of transcriptiome profiles in LMO1 overexpression neuroblastoma cells	Co-expression
SRP093689	Transcriptional profiling of human fibroblasts	Compare transcriptional profiles of naïve and primed pluripotent stem cells using high throughput RNA sequencing.	Co-expression
SRP093699	Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis	Purpose: The goal of the study was to integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signalling networks, relevant for rheumatoid arthritis (RA). Method:RNA-seq based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated RA patients, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of “connector” genes derived from pathway analysis was then tested for differential expression in the initial discovery cohort. Results: 11 qualifying genes were selected for pathway analysis and grouped into 2 evidence-based functional networks, containing 29 and 27 additional “connector” molecules.  The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. 3 genes showed similar expression difference in both treated and non-treated RA patients and additional nine genes were differentially expressed in at least one patients' group compared to healthy controls. Conclusion: Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes in the pathogenesis of RA. Overall design: Illumina RNA-seq was performed on RNA from pereferial blood mononuclear cells taken from 12 healthy individuals, 5 untreated RA patients, and 7 treated RA patients	Co-expression
SRP093707	Novel RNA biomarkers in urine and plasma of patients with prostate cancer.	Current prostate cancer diagnostic tests suffer from insufficient sensitivity and specificity. Novel biomarkers that can be detected by minimally invasive methods are of a particular value. This study was aimed at screening for candidate RNA biomarkers of prostate cancer. To that end, we performed whole transcriptome profiling of urine and plasma of patients with prostate cancer by RNA-Seq. Samples obtained from patients with benign prostatic hyperplasia were used as a control group to ensure high specificity of identified biomarkers.	Co-expression
SRP093710	Epithelial-mesenchymal transition markers screenedina cell-based model and validated in lung adenocarcinoma	The epithelial-to-mesenchymal transition (EMT) process in cancer enables the migratory and invasive capabilities associated with metastatic competence. The cancer microenvironment plays an important role in inducing the occurrence of EMT. A number of extracellular stimuli and associated signaling pathways have been identified to promote EMT, however, molecular features during the early stages of EMT are poorly understood. Here we have established a novel in vitro EMT-inducing system that mimi cs tumor microenvironment and allows for close monitoring of the EMT progress. Using RNA-seq and miRNA-seq, we analyzed the transcriptomic transitions accompanying the progression of EMT, and pinpointed several molecular features during early EMT of the lung carcinoma cells. Overall design: CAF conditioned medium treated and control A549 cells were collected at six different time points (3h, 6h, 12h, 24h, 48h, 72h) for RNA-seq and miRNA-seq, two biological replicates for each sample.	Co-expression
SRP093737	Proliferation pause as an early blockade of human cellular reprogramming toward pluripotency [RNA-seq analysis]	Human induced Pluripotent Stem cells (iPSCs) can be generated by enforced-expression of OCT3/4, SOX2, KLF4 and c-MYC (OSKM) via intermediate state that is labeled with a surface antigen TRA-1-60.  However the event during conversion of somatic cells to TRA-1-60 positive (+) fate by OSKM is still unclear. Here we show that TRA-1-60 (+) cells emerged from ESRG (+) cells with proliferation independent manner.   Overcoming the proliferation pausing phase is crucial for further progression of reprogramming. Inactivation of RB pathway is associated with the expansion of early TRA-1-60 (+) cells. Indeed, extended RB activation   drastically decreased the proportion of TRA-1-60 (+) cells with marked premature senescence. An RNA-binding protein LIN41 promotes the RB inactivation and facilitates reprogramming efficiency in early stage via   post-transcriptional suppression of cycline dependent kinase inhibitor p21. This LIN41/p21/RB axis was invalidated in immortalized cells which showed a resistance to oncogene-induced senescence. Thus, LIN41-  mediated RB inactivation promotes to bail out of transient quiescence as a major blockade in initial phase of reprogramming. Overall design: RNA-seq profiles of Human dermal fibroblasts (N=3), Teratoma-derived fibroblasts (N=3).	Co-expression
SRP093771	Functional genomics of HDAC class-I specific inhbitor 4SC-202 in pancreatic cell lines  [RNA-seq]	We examined transcriptome-wide effects of 4SC-202 in L3.6, BXPC3 and PANC1 cells as well as its effect on TGFß signaling Overall design: We performed  mRNA sequencing from L3.6, BXPC3 and PANC1 cells following following DMSO, 4SC-202 and/or TGFß treatment. The mRNA-Seq includes following conditions: 4SC-202 vs DMSO (for L3.6, BXPC3 and PANC1 cells), TGFß vs DMSO and 4SC-202+TGFß vs TGFß (for PANC1  cells). The libraries were performed in triplicates.	Co-expression
SRP093774	Bromodomain protein BRD4 is a transcriptional repressor of autophagy and lysosomal function	Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation. Overall design: RNA-Seq of KP-4 pancreatic adenocarcinoma cells transfected with control, BRD4 #1 or BRD4 #2 siRNA for 72hrs (n=3 independent sample preparations)	Co-expression
SRP093786	Genetic determinants and epigenetic effects of pioneer factor binding [RNA-seq]	Transcription factors (TFs) are the core drivers of gene regulatory networks that control developmental transitions and a complete understanding of how they access, alter and maintain specific gene expression patterns remains an important goal. To begin a systematic dissection of the molecular components that either enable or constrain TF activity, we investigated the genomic occupancy of two distinct TFs, the pioneer factor FOXA2 and the pluripotency-associated factor OCT4 (POU5F1), in both endogenous and ectopic settings. We find that, while stable binding of FOXA2 is highly cell type specific and similar to what is observed for most TFs including OCT4, pioneer activity can be distinguished by notable sampling of additional loci that are occupied in alternative lineages. In our ectopic system, FOXA2 binding can be selectively stabilized at previously sampled sites by co-expressing the lineage specific regulator GATA4. Alternatively, we observe minimal influence of chromatin state on discrete, stabilized binding choices for FOXA2 but a strong bias towards open chromatin for ectopic OCT4 targets. Finally, we demonstrate that FOXA2 binding and nucleosome remodeling at silent loci can occur when the cell cycle is halted in G1, but surprisingly subsequent changes in DNA methylation require DNA replication. Taken together, our results provide several new molecular insights that contribute to our basic understanding of gene regulation and pave the way for a more rational use of ectopic TFs for cellular reprogramming. Overall design: To understand the effect of FOXA2 induction on expressed we profiled genowide-wide abundance of RNA using RNA-seq. RNA was isolated with RNeasy columns (Qiagen) and non-stranded libraries were performed using Illumina's standard Tru-Seq kit.  Libraries were sequenced on a HiSeq 2500 at 11pmol.	Co-expression
SRP093793	Proliferation pause as an early blockade of human cellular reprogramming toward pluripotency [single cell RNA-seq analysis]	Human induced Pluripotent Stem cells (iPSCs) can be generated by enforced-expression of OCT3/4, SOX2, KLF4 and c-MYC (OSKM) via intermediate state that is labeled with a surface antigen TRA-1-60.  However the event during conversion of somatic cells to TRA-1-60 positive (+) fate by OSKM is still unclear. Here we show that TRA-1-60 (+) cells emerged from ESRG (+) cells with proliferation independent manner.   Overcoming the proliferation pausing phase is crucial for further progression of reprogramming. Inactivation of RB pathway is associated with the expansion of early TRA-1-60 (+) cells. Indeed, extended RB activation   drastically decreased the proportion of TRA-1-60 (+) cells with marked premature senescence. An RNA-binding protein LIN41 promotes the RB inactivation and facilitates reprogramming efficiency in early stage via   post-transcriptional suppression of cycline dependent kinase inhibitor p21. This LIN41/p21/RB axis was invalidated in immortalized cells which showed a resistance to oncogene-induced senescence. Thus, LIN41-  mediated RB inactivation promotes to bail out of transient quiescence as a major blockade in initial phase of reprogramming. Overall design: Single cell RNA-seq profiles of Human dermal fibroblasts, Human induced Pluripotent Stem cell, intermediate reprogrammed cells.	Co-expression
SRP093823	Age-Related Gene Expression Changes in Prostate Cancer Patients [RNA-Seq]	Formalin-fixed, paraffin-embedded (FFPE) from prostate cancer patients Overall design: Gleason-score matched tumor and adjacent normal samples were collected to compare gene expression differences in early-onset versus late-onset prostate cancer patients	Co-expression
SRP093834	Retinoic Acid Induced Transcriptional Repressor HIC1 is Required for Suppressive Function of Human Induced Regulatory T cells [RNA-Seq 1]	Comparing the gene expression in control siRNA samples and HIC1 siRNA samples Overall design: Two time points; 48h and 72h. For each time point 3 replicates from HIC1 siRNA and 3 replicates from NT siRNA.	Co-expression
SRP093883	List of TIAM1 differentially expressed genes in SW620 cells [RNA-seq]	The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. To determine the nuclear role of TIAM1, we performed RNA-seq on SW620 cells transfected either with a specific pre-validated siRNA for TIAM1 (siTIAM1) or a negative control siRNA (siNT) and generated a list of TIAM1 differentially expressed genes. GSEA revealed significant enrichment among TIAM1-regulated genes for YAP-associated molecular signature. To investigate the interplay of TIAM1 with YAP/TAZ we used RNA-seq, generated a list of YAP/TAZ differentially expressed genes from SW620 cells transfected either with specific siRNAs for YAP/TAZ or a negative control siRNA and compared it with the siTIAM1 RNA-seq dataset. Interestingly, we found that 50% of the TAZ/YAP regulated genes were also TIAM1 dependent. Overall design: mRNA profiles of control, TIAM1 or YAP/TAZ knockdown SW620 cells were generated from three independent experiments using RNA-seq	Co-expression
SRP093918	Transcriptomic alterations in fibroblasts from Parkinson''s disease patients carrying Parkin mutations	In this study, we evaluate the hypothesis that transcriptome pattern of a cell model of Parkinson's disease (PD) could be altered compared to healthy individuals. We cultured fibroblasts from Parkin-associated PD (PRKN-PD; n=4) and healthy controls (HC; n=4) and analysed the transcriptome profile by using whole RNA sequencing.   We found 343 differentially expressed transcripts (DET) between patients and controls being 206 up-regulated and 137 down-regulated. These genes are related with the gene ontology terms cell adhesion, cell growth, aminoacid biosynthesis and folate metabolism amongst others. Our findings indicate that PRKN mutations are associated with global gene expression changes as observed in fibroblasts, and support an emerging view of PD as a systemic disease affecting also peripheral non-neural tissues such as the skin. Overall design: Evaluation of transcript expression by RNA sequencing of fibroblasts from Parkin-associated Parkinson''s Disease patients versus fibroblasts from healthy controls	Co-expression
SRP093921	Basal-A Triple Negative Breast Cancer Cells Selectively Rely on RNA Splicing for Survival	Development of targeted therapies for triple-negative breast cancer (TNBC) has failed at least in part because of the heterogeneity of these poor prognosis cancers. To identify common dependencies of basal-like TNBCs, we performed a targeted siRNA lethality screen in 7 human breast cancer cell lines focusing on 154 previously identified dependency genes of one basal-A TNBC line. Thirty genes were shared basal-A TNBC dependencies. Genes for proteins involved in RNA splicing, in particular those associated with the U4/U6.U5 tri-snRNP complex (e.g. PRPF8, PRPF38A), were prominent shared dependencies. Spliceosome genes were commonly up-regulated in primary basal-like TNBCs. Knockdown of PRPF8 or PRPF38A led to widespread intronic retention, expression of immune system genes and aberrant splicing of transcripts involved in protein translation, proteasome function, mitosis and apoptosis, including the TNBC dependency gene MCL1. These transcripts were susceptible to inhibition of RNA splicing more generally, since they were similarly affected by the RNA splicing inhibitor drug E7107. In particular, E7107 caused splicing of MCL1 to its pro-apoptotic splicing variant in multiple cell lines, killed MCL1-dependent basal-A cells in vitro, and suppressed the growth of 2 basal-A cell-lines and 1 of 2 patient-derived basal-like TNBC xenografts in vivo. Thus, TNBCs critically rely on RNA splicing  and could be susceptible to RNA splicing inhibitors. Overall design: Two datasets: 1) 5 control samples, 5 PRPF8 knockdown and 5 PRPF38 knockdown samples 2) 4 control samples, 4 E7107 treated samples	Co-expression
SRP093978	In Vivo Chemical Screen Nominates Valproic Acid as Pharmacologic Modulator of Hematopoietic Stem and Progenitor Cell Activity	The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties. Overall design: Gene expression analysis of in vitro expanded human HSPCs (CD34+ cells) by valproic acid	Co-expression
SRP093988	Krüppel-like Transcription Factor-10 (KLF10) Provides a Negative Feedback Mechanism to Suppress TGFß-Induced Epithelial-to-Mesenchymal Transition [RNA-Seq]	We examined transcriptome-wide effects of pertrurbation in KLF10 function (siKLF10) on TGFß-regulated genes and EMT in two different cells lines: A549 and Panc1. Overall design: We performed  mRNA sequencing from A549 and Panc1 cells following following  TGFß treatment and KLF10 knockdown. The mRNA-Seq includes following conditions: siControl, siKLF10, TGFß, siKLF10+TGFß (A549 and Panc1 cells). mRNA-sequencing was performed in duplicates for A549 and triplicates for Panc1 cells.	Co-expression
SRP093990	Retinoic Acid Induced Transcriptional Repressor HIC1 is Required for Suppressive Function of Human Induced Regulatory T cells [RNA-Seq 2]	Human CD4 positive T cells were isolated from cord blood using CD4 positive isolation kit from Dynal.  Cells were activated with plate bound anti-CD3 and soluble anti-CD28 in presence (iTreg) or absence (Th0) of IL2, TGF beta and ATRA. The cells were harvested at 0, 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours. Overall design: Comparing the gene expression in activated CD4+ cells and iTreg differentiated cells in human. 9 time points, 3 replicates for each time point.	Co-expression
SRP093991	Homo sapiens Transcriptome or Gene expression	Genome-wide analysis of miR-106b targets in cholangiocarcinoma cells identifies tumor suppressors Kruppel-like factor-2 and-6, characterization of an antiapoptotic microRNA	Co-expression
SRP094007	Quantitative Proteomics Reveals a Unique Wiring of Signaling Pathways that Protects Human Regulatory T Cell Identity	Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we have compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Among these CD4+ T cell subsets, we detected differential expression of 421 proteins and 640 mRNAs, with only 48 molecules shared. Fifty proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFkB-, PI3 kinase/mTOR-, NFAT- and STAT pathways and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFkB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, while transitional FOXP3+ cells can. Our collective data reveal that Tregs protect their identity by a unique “wiring” of signalling pathways Overall design: mRNA profiles of 5 CD4+ T cell populations were generated by deep sequencing, in triplicate	Co-expression
SRP094059	Bioengineered brain organoids for probing impaired neurogenesis in prenatal alcohol exposure	We propose a microfluidic strategy to generate abundant brain organoids and further explore neurogenesis in fetal brain exposed to ethanol.	Co-expression
SRP094100	IGF2BP proteins Enhance mRNA stability	To evaluate the effect of IGF2BPs on mRNA stability and gene expression output, we conducted RNA-seq in individual IGF2BP knockdown and control HepG2 cells with or without actinomycin D treatment. Our RNA-seq and RNA stability profiling revealed that IGF2BPs were involved in RNA stability regulation and contributed to the stabilization of the transcriptome. Overall design: HepG2 cells were infected with individual lentiviral IGF2BP shRNA and non-specific control (shNS), and selected by puromycin to generate stable knockdown lines. We treated HepG2 cells with actinomycin D to inhibit transcription and collected cells at indicated time points (i.e., 0h, 1h, 3h, 6h). The total RNA was extracted by miRNeasy Kit (Qiagen) and sequenced by Illumina.  For IGF2BP-dependent gene expression, untreated cells (i.e., 0h samples) were sequenced in triplicate and analyzed. For RNA stability profiling, RNA half-life was calculated by comparing the gene expression at 1, 3, 6 hours with actinomycin treatment to that in un-treated samples, with two biological replicates for each group.	Co-expression
SRP094107	Homo sapiens Genome sequencing and assembly	SF3B1 is a component of U2, so we suspect that the SF3B1 K700E mutation may reduce the fidelity of branch site utilization. We use a variety of library preps to attempt to enrich for lariat reads in both SF3B1 K700K and SF3B1 K700E knocked-in NALM6 cell lines.	Co-expression
SRP094118	Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype	The remarkable feature of Schwann cells (SCs) to transform into a repair phenotype turned the spotlight on this powerful cell type. SCs provide the regenerative environment for axonal re-growth after peripheral nerve injury (PNI) and play a vital role in differentiation of neuroblastic tumors into a benign subtype of neuroblastoma, a tumor originating from neural crest-derived neuroblasts. Hence, understanding their mode-of-action is of utmost interest for new approaches in regenerative medicine, but also for neuroblastoma therapy. However, literature on human SCs is scarce and it is unknown to which extent human SC cultures reflect the SC repair phenotype developing after PNI in patients. We performed high-resolution proteome profiling and RNA-sequencing on highly enriched human SC and fibroblast cultures, control and ex vivo degenerated nerve explants to identify novel molecules and functional processes active in repair SCs. In fact, we found cultured SCs and degenerated nerves to share a similar repair SC-associated expression signature, including the upregulation of JUN, as well as two prominent functions, i.e., myelin debris clearance and antigen presentation via MHCII. In addition to myelin degradation, cultured SCs were capable of actively taking up cell-extrinsic components in functional phagocytosis and co-cultivation assays. Moreover, in cultured SCs and degenerated nerve tissue MHCII was upregulated at the cellular level along with high expression of chemoattractants and co-inhibitory rather than -stimulatory molecules. These results demonstrate human SC cultures to execute an inherent program of nerve repair and support two novel repair SC functions, debris clearance via phagocytosis-related mechanisms and type II immune-regulation. Overall design: mRNA of 27 samples were sequenced (50bp, single end) and analyzed. Biological replicates were performed.	Co-expression
SRP094125	Integration of kinase and calcium signaling at the level of chromatin underlines inducible gene activation in T cells	Aim: to perform a genome-wide investigation of chromatin landscape and gene expression patterns downstream of calcium and kinase signaling in Jurkat T cells. Methods: PMA and ionomycin were used to activate the calcium and kinase signalling networks involved in T cell activation. Global gene expression was measured using RNA-seq, whilst ATAC-seq was used to probe chromatin landscape following 3 hours of stimulation with PMA, ionomycin or both. All experiments were performed in triplicate. For RNA-seq all sequencing was performed using paired-end sequencing on an Illumina HiSeq2500 instrument. For ATAC-seq sequencing was performed using a HiSeq 1500. Results: we mapped approximately 60 million reads per sample for ATAC-seq, and 22 million reads per library for RNA-seq. Overall we identified 57,825 transcripts and 19,763 ATAC-seq peaks. We identifiead 1648 genes whose expression was increased by 2-fold or more by at least one treatment in comparison to untreated cells. Similarly, we identified 3972 ATAC peaks that were induced by at least 2-fold by treatment in comparison to untreated cells. Conclusions: we found that chromatin landscape was associated with gene expression downstream of calcium and kinase signaling in Jurkat cells. Further to this we found that activation of the full complement of TCR-responsive genes is dependent upon both PMA and ionomycin, and amounts to more than just the sum of both. Overall design: RNA-sequencing and ATAC-sequencing were performed after 3 hours of treatment with either PMA, ionomycin or co-treatment with PMA and ionomycin.	Co-expression
SRP094413	RNA sequencing of ESC/iPSC-derived purified PAX6-GFP neural progenitors form control and Phelan-Mcdermid patients	The goal of this study was to generated and transcriptionally analyze purified populations of Phelan-McDermid and control pluripotent stem cells-derived neural progenitors. This type of analysis allowed us to identify prevoisly unknown transcriptional phenotypic changes in patient neural progenitors which appear to be independent of functional synapses. Overall design: Patient and control pluripotent stem cells were targeted by CRISPR/Cas9 and a PAX6-GFP reporter plasmid. Correctly modified clones were selected and subsequently differentiated into PAX6 expressing neural progenitors.	Co-expression
SRP094417	Primate-specific gene TMEM14B promotes cortical expansion and folding	A massively expanded outer subventricular zone (OSVZ) in the primate and human has been proposed for generating majority of neocortical neurons, which consists of basally located radial glia cells. Previous studies with various strategies have tried to recognize genes specifically expressed in those cells; however, the molecular and cellular features of these cells still remain uncertain.  By profiling gene expression across single cells isolated from cellular anatomy location and subtype sorting, we identified a primate-specific gene TMEM14B as a novel marker for basally located radial glia. Expression of TMEM14B induced dramatic increase in the number of radial glial and OSVZ region. Finally, we found that OSVZ progenitor's extensive proliferative potential was up regulated through IQGAP1 phosphorylation and nuclear translocation, and remarkably, led to the gyrification in postnatal mouse.  These results highlight that evolutionary expansion promoted by primate-specific genes enabling the evolutionary expansion and folding of the human neocortex. Overall design: Find specific markers from dataset of 4 different types of cells	Co-expression
SRP094424	Induced Pluripotent Stem Cell Differentiation Provides an Approach for Functional Validation of GWAS Variants in Metabolic Disease	Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis and validation remains a challenge.  Here we describe an approach to functionally validate these variants through the differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology.  We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs.  We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression changes in differentiated hepatocytes, in particular expression of SORT1, CELSR2 and PSRC1, consistent with previous analysis of this variant using other approaches.  Initial investigation of additional SNPs also highlighted correlations with gene expression.  Thus, iPSC-based population studies seem promising for further development as a tool for the functional validation of GWAS variants. Overall design: 68 Induced Pluripotent Stem Cell Lines derived from 34 Participants Differentiated into white adipocytes and hepatocyte like cells	Co-expression
SRP094450	Reconstitution of the human pancreatic niche stimulates differentiation of hESCs into beta cells and reveals new signals for pancreatic endocrine cell maturation	RNA-seq was performed for hESC-derived endocrine progenitors (EPs) treated with WNT5A for short-term (12h) and long-term (5 days) to investigate the downstream targets of WNT5A in EPs. Sequencing of untreated cells and those treated with WNT5A for 12h, which are at EP stage, and for 5 days, which are at beta cell stage, allowed for observation of developmental changes during in vitro differentiation. Overall design: Two controls as 12h or 5 days untreated (maintained in B27) and two 12h or 5 days WNT5A-treated EPs.	Co-expression
SRP094482	Transciptiome of human primary resting CD4 T lymphocytes infected with HIV-1	Assessing the impact of HIV-1 infection on trancriptional program of quiescent CD4 T lymphocytes. Such cells were made susceptible to HIV-1 by dowmodulating SAMHD1 restriction factor using VLP-Vpx without any activation signal.	Co-expression
SRP094486	Single cell analysis of SFTPC+ cells and CPM-high progenitor cells derived from human induced pluripotent stem cells (hiPSCs)	We stepwisely induced SFTPC+ cells from hiPSCs via CPM-high progenitor cells with or without coculturing human fetal lung fibroblasts. Single-cell RNA-seq of CPM-high progenitor and hiPSC-derived SFTPC+ cells demonstrated their differentiation process and cellular heterogeneity. Overall design: scRNA-seq: 6 sample. FF-SFTPC_scRNA-seq : 1 sample.	Co-expression
SRP094494	Integrative proteogenomic characterization of colorectal cancer cell lines and primary tumors	Integrative analysis of global RNASeq and proteomic data comparing human colorectal cancer (CRC) cell lines to primary tumors and normal tissues. Overall design: Examination of mRNA expression levels across 44 colorectal cell lines.	Co-expression
SRP094498	Systemic human ILC precursors provide a substrate for tissue ILC differentiation	Innate lymphoid cells (ILC) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We observed that a population of CD117+ ILC from peripheral blood (PB) of healthy donors does not represent any conical ILC subset, but expressed marker (CD117) commonly expressed by hemato-lymphoid progenitors. We therefore hypothesized PB CD117+ ILC might include uncommitted lymphoid precursors. In order to further understand the identity of PB CD117+ ILC, we profiled the transcriptome of highly purified circulating CD117+ ILC compared to CD34+ HSC, the latter representing immature hematopoietic progenitors with multi-lineage potential. Clear differences in gene expression profiles emerged, with a large cluster of 1540 genes expressed at substantially higher levels in CD117+ ILC. In contrast, CD34+ HSC cells highly expressed genes involved in the broad development of diverse hematopoietic lineages. Compared to HSC, CD117+ ILC express high levels of TF that have been shown to be essential for murine ILC development and we did not detect transcripts characteristic of T and B cells development. Transcriptomic analysis suggested that CD117+ ILC represent lymphoid-biased progenitors carrying a TF expression profile resembling a multi-potent ILC precursor (ILCP). Overall design: CD117+ ILC and CD34+ HSC were freshly isolated by FACS of peripheral blood of two healthy adult individuals. In total, 4 samples were analyzed and comparing between two cell populations.	Co-expression
SRP094528	Predominant TRUB1-dependent pseudouridylation of mammalian mRNA via a predictable and conserved code	In this accession we provide pseudouridylation measurements upon knockdown and/or overexpression three pseudouridine synthases, two of which (TRUB1 and PUS7) we find to be with predominant activity on mammalian mRNA. Overall design: Examination of pseudouridylation upon genetic perturbation of three pseudouridine synthases	Co-expression
SRP094565	An erythroid-specific enhancer of ATP2B4 mediates red blood cell hydration and malaria susceptibility [RNA-seq]	Few genotype-phenotype associations identified by genome-wide association studies (GWAS) have been defined mechanistically, precluding thorough assessment of their impact on human health. We conducted an expression quantitative trait loci (eQTL) mapping analysis in human erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (RBC). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine-mapped the genetic signal to an erythroid-specific enhancer bound by GATA1 and TAL1. These results illustrate the importance to combine transcriptome, epigenome, and genome editing approaches in phenotype-relevant cells to characterize non-coding regulatory elements associated with human complex diseases and traits. Our studies suggest ATP2B4 as a potential target to modulate RBC hydration in erythroid disorders and malaria infection. Overall design: mRNA profiles of fetal (N=12) and adult (N=12) erythroblasts were generated by RNA-sequencing with an Illumina HiSeq2000 sequencer using stranded cDNA library and a paired-ends 100 bp protocol.	Co-expression
SRP094572	Expression data for hiPSC-derived RPE treated with 10mM Nicotinamide or vehicle	We did the RNA-seq analysis to examine the global impact of Nicotinamide (NAM) on hiPSC-derived RPE transcriptome in order to better understand the mechanism of action of NAM. NAM inhibited the expression of Age related Macular degeneration (AMD) associated protein transcripts in hiPSC-derived RPE. Overall design: Seven hiPSC-RPE lines (4 AMD donors and 3 Control donors) that had been cultured with 10mM NAM or vehicle for three weeks were used for RNA extraction and RNA-seq analysis. We treated 4 AMD hiPSC-RPE and 3 Control hiPSC-RPE lines with 10mM NAM or vehicle.	Co-expression
SRP094573	Presence of NAD+-capped RNA in human cells: function and removal by the DXO deNADing Protein	Eukaryotic mRNAs generally possess an N7 methyl guanosine cap at their 5? end to promote their translation and stability. Here we demonstrate mammalian mRNAs can carry a 5''-end nicotinamide adenine dinucleotide (NAD+) cap. We further demonstrate fungal and mammalian noncanonical DXO family of decapping enzymes can efficiently remove NAD+ caps from mRNAs in vitro and cocrystal structures of DXO with 3´ phosphate NAD+ illuminates the molecular mechanism for the “deNADing” reaction.  An NAD+ cap promotes mRNA decay in wild type mammalian cells and confers mRNA stability in the absence of DXO.  Importantly, mammalian cells possess a capping mechanism that NAD+ caps a subset of intronic small nucleolar RNAs that are selectively enriched in DXO deficient cells.  Our data establish NAD+ as a bona fide mammalian RNA cap and identifies the DXO proteins as potent deNADing enzymes that modulate the levels of NAD+-capped RNAs in cells. Overall design: Two replicates of HEK293T cell RNA were prepared and sequenced using standard methods.  Three replicates each of HEK293T (Wt) and HEK293T-DXO-KO (DXO-KO) cell RNA were prepared and enriched by NAD-Capture for sequencing library preparation and seqeuencing.	Co-expression
SRP094575	Circulating CXCR5+CXCR3+PD-1Lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth	HIV-1-specific broadly-neutralizing antibodies (bnAb) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5+ CXCR3+ PD-1Lo CD4 T cells. These CXCR3+ PD-1Lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3+ PD-1Lo Tfh-like cells contain higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1Hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5+ CXCR3+ PD-1Lo cells represent a dendritic cell-primed precursor cell population for PD-1Hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high–level viremia. Overall design: We analyzed transcriptional profiles of mDC from 4 neutralizer controllers compared to cells from 4 non-neutralizer controllers.	Co-expression
SRP094652	Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1a stabilization	Solid tumors are less oxygenated than normal tissues, and for this reason the cancer cells have developed several molecular mechanisms of adaptation to hypoxic environment. Moreover, his poor oxygenation is a major indicator of an adverse prognosis and leads resistance to standard anticancer treatment. Previous reports from this laboratory showed an involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions, and on the basis of these observations, we hypothesized that Che-1 might have a role in the response of cancer cells to hypoxia. Methods: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA, was subjected to normoxic and hypoxic conditions to perform studies about the role of this protein in metabolic adaptation and cell proliferation. The expression of Che-1 under normoxia or hypoxia was detected using western blot assays; cell metabolism was assessed by NMR spectroscopy and functional assays. Further molecular studies were performed by RNA seq, qRT-PCR and ChIP analysis. Results: In this paper we report that Che-1 expression is required for the adaptation of the cells to hypoxia, playing and important role in metabolic modulation. Indeed, Che-1 depletion impacted on glycolysis by altering the expression of several genes involved in the response to hypoxia by modulating the levels of HIF-1alpha. Conclusions: These data demonstrate a novel player in the regulation of a HIF1alpha in response to hypoxia. We found that the transcriptional down-regulation of a members of E3 ubiquitin ligase family SIAH2 by Che-1, produces a failure in the degradation by the hydroxylase PHD3 with a decrease in HIF-1alpha levels during hypoxia. Overall design: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA was profiled for mRNA high-troughput sequencing (RNA-seq)	Co-expression
SRP094654	A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response	Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured.  We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. A genome-scale CRISPR interference (CRISPRi) screen identified genes whose depletion perturbs ER homeostasis. Subjecting ~100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses revealed epistasis among the three UPR branches, bifurcated UPR branch activation between cells subject to the same perturbation, and differential activation of the branches across hits, including a feedback loop between the translocon and the IRE1a branch. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses. Overall design: 3 different pooled CRISPR screening experiments were conducted via Perturb-seq	Co-expression
SRP094710	Cystathionine-ß-Synthase Promotes Colon Carcinogenesis	Purpose: The goal of this study is to investigate the role of CBS enzyme in colorectal carcinogenesis Methods: RNA-Seq transcriptome analysis of CBS-overexpression in NCM356 cels compared to control vector cells Overall design: RNA-seq transcriptome profiling of NCM356-CBS overexpressing cells vs. vector cells	Co-expression
SRP094716	Homo sapiens strain:HepaRG Raw sequence reads	The goal of the study is to elucidate the roles of miRNAs in APAP-induced liver injury, by systematically analyzing the expression profiles of genes and miRNAs in APAP-exposed HepaRG cells.	Co-expression
SRP094725	Global transcriptional profiling changes upon knockdown of LKB1 in human glioblastoma cell lines	The experiment was designed to display differential gene expression profiling changes in two human glioblastoma cells upon knockdow of LKB1 tumor suppressor, by using RNAseq technology. Overall design: LKB1 was first silenced in two glioblastoma cells: U87 and T98 by siRNA-mediated knockdown. Total RNA was extracted from duplicated cancers cells transfected with control siRNA and LKB1 specific siRNA at 72h posttransfection for RNAseq analysis. Differentially expressed genes in LKB1-attenuated glioblastoma cells were identified in comparison to that in glioblastoma cells transfected with control siRNA.	Co-expression
SRP094747	Gene expression response to 5 microbial stimuli in Detroit562 cells [RNA-seq]	NFKB is a family of transcription factors (TF), which are master regulators of the innate immune system. It is activated downstream of pathogen recognition receptors after ligand binding and regulates the expression of antimicrobials, cytokines and chemokines, thus helping to fight infections as well as recruiting the adaptive immune system. Although NFKB responds to a wide variety of signals, the processes in which stimulus-specificity is attained are still unclear. We characterized the response of one of the NFKB members, RELA, to five stimuli mimicking infection in nasopharyngeal epithelial cells. We wanted to investigate gene expression in response to these stimuli as well, in order to relate RELA binding to differences to expression regulation. Although most RELA binding sites where common among stimulation, we distinguished a minority of stimulus-specific RELA binding sites. Interestingly, some of these seemed to have a biological effect as they correlated with corresponding gene expression. Especially, the response to Poly I:C mimicking viral dsRNA gave a distinct RELA profile binding the vicinity of antiviral genes. Some of which were overexpressed under Poly I:C stimulation specifically. Overall design: Treatment of Detroit 562 cells with 5 stimuli: LPS, TNFa, Pam2CSK4, Poly I:C or M tri-DAP followed by gene expression analysis by RNA-seq. Two biological duplicates were analyzed for each condition.	Co-expression
SRP094753	IL10 and CpG stimulations of P493-6 cells	Micro-environmental factors have been recognized to play important roles in tumor growth and proliferation. Here, we studied how treatment of P493-6 cells for 24 hours with CpG, IL10 or both affects gene expression levels. P493-6 cells were first MYC-deprived (''MYC-low'') with doxycycline before applying the stimuli. Unstimulated MYC-low and MYC-high (no doxycycline) cells served as controls.	Co-expression
SRP094756	Gene expression changes after microenvironmental stimuli of a B-cell model	Different stimulations of P493-6 cells	Co-expression
SRP094781	Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy	Immune checkpoint blockade (ICB) has demonstrated significant promise for the treatment of advanced malignancies. Anti-CTLA4 and ant-PD1 therapy can activate the immune system and result in durable control in diseases such as melanoma and non-small cell lung cancer. Overall design: 109 RNASeq samples (58 On-treatment and 51 Pre-treatment) from 65 patients	Co-expression
SRP094802	DRB/GRO-Seq -/+ UV	The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage. Overall design: Cells were treated with DRB (100 µM, 3.5 hrs), followed by UVC irradiation (15 J/m2) or left untreated. Cells were washed with PBS to remove DRB immediately after UV irradiation and incubated for 10, 25 or 40 minutes, followed by cell lysis and nuclei isolation. Nuclei were processed for GRO-Seq.	Co-expression
SRP094834	Homo sapiens Transcriptome or Gene expression	RNA-sequencing analysis of RBP2 overexpressing MCF7 cell lines. RBP2 (also known as JARID1A), a member of the JARID1 family of histone H3 lysine K4 demethylases, has been considered to have an oncogenic potential in several cancer including breast cancer. Results provide insight into the transcriptional regulation of RBP2 in estrogen receptor positve breast cancer.	Co-expression
SRP094844	RNA-Seq comparative analysis of human neuroblastoma cells before and after their confrontation to the embryonic microenvironment	We set up an innovative model for neuroblastoma that consists in using the chick embryo to place human neuroblastoma cells back to their original environment: the trunk neural crest. In this context, human neuroblastoma cells migrate towards sympathetic derivatives and form proliferative tumor masses. To assess the impact of the embryonic microenvironment on neuroblastoma cells gene program, we performed an RNASeq comparative analysis of neuroblastoma naïve cells and tumor masses settled in sympathetic derivatives. Overall design: We performed independent graft experiments and for each, we collected neuroblastoma naïve cells (before the graft) and tumor masses formed in sympathetic ganglia (50 hours after the graft). 12-13 tumor masses formed in independent chick embryos were microdissected and pooled for each experiment to achieve enough RNA material.	Co-expression
SRP094851	The antineoplastic drug, trastuzumab, dysregulates metabolism in iPSC derived cardiomyocytes.	Background: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 hours and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2. Methods: Transcriptome sequencing was performed on four replicates from each group (48 hours untreated, 48 hours trastuzumab and 48 hours lapatinib) and differential gene expression analyses were performed on each treatment group relative to untreated cardiomyocytes. Results: 517 and 1,358 genes were differentially expressed, p<0.05, respectively in cardiomyocytes treated with trastuzumab and lapatinib. Gene ontology analyses revealed in cardiomyocytes treated with trastuzumab, significant down-regulation of genes involved in small molecule metabolism (p=3.22x10-9) and cholesterol (p=0.01) and sterol (p=0.03) processing. Conclusions: Our study suggests dysregulation of cardiac gene expression and metabolism as key elements of ERBB2 signaling that could potentially be early biomarkers of cardiotoxicity. Overall design: Differential expression of iPSC-dervied cardiomyocytes treated with trastuzumab or lapatinib	Co-expression
SRP094862	A Trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling	The use of gene expression signatures to classify compounds, identify efficacy or toxicity, and differentiate close analogs relies on the sensitivity of the method to identify modulated genes. We used a novel ligation-based targeted whole transcriptome expression profiling assay, TempO-Seq®, to determine whether previously unreported compound-responsive genes could be identified and incorporated into a broad but specific compound signature. TempO-Seq exhibits 99.6% specificity, single cell sensitivity, and excellent correlation with fold differences measured by RNA-Seq (R2 = 0.9) for 20,629 targets. Unlike many expression assays, TempO-Seq does not require RNA purification, cDNA synthesis, or capture of targeted RNA, and lacks a 3' end bias. To investigate the sensitivity of the TempO-Seq assay to identify significantly modulated compound-responsive genes, we derived whole transcriptome profiles from MCF-7 cells treated with the histone deacetylase inhibitor Trichostatin A (TSA) and identified more than 9,000 differentially expressed genes. The TSA profile for MCF-7 cells overlapped those for HL-60 and PC-3 cells in the Connectivity Map (cMAP) database, suggesting a common TSA-specific expression profile independent of baseline gene expression. A 43-gene cell-independent TSA signature was extracted from cMAP and confirmed in TempO-Seq MCF-7 data. Additional genes that were not previously reported to be TSA responsive in the cMAP database were also identified. TSA treatment of 5 cell types revealed 1,136 differentially expressed genes in common, including 785 genes not previously reported to be TSA responsive. We conclude that TSA induces a specific expression signature that is consistent across widely different cell types, that this signature contains genes not previously associated with TSA responses, and that TempO-Seq provides the sensitive differential expression detection needed to define such compound-specific, cell-independent, changes in expression. Overall design: Commercially available human reference and tissue RNAs, unpurified cell lysates from MCF-7 and MDA MB 231 cells, and synthetic ERCC RNAs were used to assess performance of a targeted whole transcriptome expression profiling method. In addition, MCF-7 cells, PC3 cells and HL60 cells were exposed to Trichostatin A, then lysed and profiled, to define a novel TSA-specific expression signature. Samples GSM2429258 - GSM2429287 were purified reference RNAs and brain RNAs and mixtures between them that were run in the TempO-Seq assay in replicates of 6 each. Samples GSM2429258 - GSM2429287 have no associated raw data due to data loss. The GSM2460368-GSM2460377 samples represent human reference RNA replicates that were processed in parallel, pooled in a single library and sequenced twice on the same instrument.	Co-expression
SRP094893	mammalian cells response to hypoxia stress	To study mammalian cells translational and transcriptional regulation under hypoxia stress	Co-expression
SRP094899	RNASeq -/+ UV 8 and 24 hr	The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage Overall design: MRC5VA cells were either left untreated or treated with 15J/m2 of UVC irradiation, followed by recovery for 8 or 24 hours. Two biological replicates were performed for each sample.	Co-expression
SRP094900	Transcriptional response of human astrocytes to Zika virus infection	In order to assess the transcriptional response of human fetal astrocytes to Zika virus infection, we conducted RNAseq and Bioinformatics analysis	Co-expression
SRP094909	Homo sapiens Transcriptome or Gene expression	we performed immune repertoire sequencing on five biopsy sites of each tumor and on matched adjacent normal tissues and peripheral blood from five patients diagnosed with PLC, to investigated the spatial heterogeneity of TIL	Co-expression
SRP094926	RNA Sequencing Facilitates Quantitative Analysis of Wild Type and MEIS1 deleted H1 drived cells at day6 of megakaryocytic differentiation	Purpose: The goals of this study are to investigate the molecular mechanism by which MEIS1 controls megakaryocytic maturation and thrombopoiesis through compareing the mRNA profiling of Wild Type and MEIS1 deleted H1 drived cells at  day6 of megakaryocytic differentiation. Overall design: Methods: mRNA profiles of Wild Type and MEIS1 deleted H1 drived cells at day6 of megakaryocytic differentiation. were generated by deep sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays	Co-expression
SRP094931	A cell cycle-based functional screen to identify lncRNA-based cancer biomarkers	We report S-phase cancer associated lncRNAs which were identified using nascent RNA capture assay in HeLa cells. Coupling high throughput RNA sequencing with clinical investigation across TCGA datasets we identified a number of lncRNAs that act as prognostic biomarkers for survival in different cancer types Overall design: The differential expression levels of S-phase specific lncRNAs across TCGA datasets were assessed. The clinical values of the differentially expressed lncRNAs were predicted using Kaplan-Meir, univariate and multivariate Cox regression analysis. Functional characterization for different lncRNAs was done using knockdown strategies followed by RNA-seq	Co-expression
SRP094955	Comparative Transcriptomic Analysis of Hematopoietic System Across Species by Microwell-Seq	Traditional single-cell RNA-seq technologies have shown limitations for large scale experiments. Here, we constructed a single-cell resolution transcriptomic atlas of (HSPCs) in human and mouse,including a total number of 71,729 single cells clustered into 39 subpopulations by computational analysis. In human, we found 20 progenitors primed with unique lineages like megakaryocyte, neutrophil and B cell progenitor can project directly from HSPCs. Within the c-Kit positive cells from mouse bone marrow, we described 19 progenitor subgroups at single cell resolution. Overall design: We sampled 7 batches (CD34+_b1-7) of Human CD34+ mobilized peripheral blood stem cells (PBSCs); 2 batches (CD34+_thawed_l6-7) of thawed Human CD34+ mobilized peripheral blood stem cells (PBSCs) and 2 batches (CD34-_b1-2) of thawed Human CD34- mobilized peripheral blood stem cells (PBSCs), around 5000 single cells per sample. 1 batch of mouse-transferred CD34+ cells; 3 batches of Mouse c-kit+ cells and 5 batches of mouse bone marrow cells.1 batch of zebrafish kidney marrow-derived hematopoietic cell. Human CD34+ cells were selected by human CD34 selection kit (StemCell Technologies Cat #18056), following the protocol provided by the manufacturer. After spin at 300 x g for 5min, the supernatant was removed and CD34+ cells were suspended in 1x DPBS + 2mM EDTA and diluted to ~ 100,000/mL for Microwell-seq. After thawing in IMDM medium, human CD34+ cells were suspended in 100µL of PBS+5% FBS for exposure of antibodies. mPB CD34+ cells were transplanted into sublethally irradiated NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju, Nanjing Biomedical Research Institute of Nanjing University) mice via an injection into the femur cavity (approximately, 1X105 cells per mouse). Two months after transplantation, hCD45+CD34+ cells (mouse-transferred CD34+ cells) were sorted from mice bone marrow cells collected from the femur and tibia. Mouse c-kit + cells were were sorted by flow cytometry, following the protocol provided by the manufacturer. The following antibodies were used for MPP(CD34+CD38-Thy1-CD45RA-CD49f-) cell sorting: CD34 PE (Biolegend, clone 581, cat #343506), CD34 FITC (BD bioscience, clone 581, cat #555821), CD38 PE-Cy7 (BD bioscience, clone HIT2, cat #560677), CD90 APC (BD bioscience, clone 5E10, cat #559869), CD45RA APC/Fire 750 (Biolegend, clone HI100, cat #304151), CD49f BV421 (Biolegend, clone GoH3, cat #313623).	Co-expression
SRP094958	Genomic profiling of human spermatogonial stem cells [scRNA-Seq]	To better understand human spermatogonial stem cells (SSCs), we profiled their transciptome and epigenome, which revealed the mechanism how human SSCs regulates their self-renewal versus differentiation dermination, as well as how latent pluripotency is established in human SSCs. Remarkly, we discovered signaling pathways (e.g. LIF, BMP, WNT) that differentially regulated self-renewal vesus differentiation in SSCs. We also discovered that SSCs repress core pluripotent factors (Sox2, Pou5f1 and Nanog) yet activate ancillary factors (e.g. Klf4, Mbd3, Tcf3, Sall4) transcriptionally and epigenetically. Overall design: Using SSEA4 as self-renewal marker and Kit as differentiating marker, we isolated self-renewal and differentiation SSCs by magnetic antibody cell sorting (MACS). SSEA4+ or Kit+ cells were loaded into 5-10 µm integrated fluidic circuits (IFCs) using Fluidigm C1 instrument. Single cells in IFCs were lysed and total RNA was harvested for polyadenylation selection, reverse transcription and PCR amplification. Library constructions were performed according to Fluidigm Library preparation with Nextera XT protocol and sequenced on a 50-cycle single end run.	Co-expression
SRP094959	Genomic profiling of human spermatogonial stem cells [BulkRNA-Seq]	To better understand human spermatogonial stem cells (SSCs), we profiled their transciptome and epigenome, which revealed the mechanism how human SSCs regulates their self-renewal versus differentiation dermination, as well as how latent pluripotency is established in human SSCs. Remarkly, we discovered signaling pathways (e.g. LIF, BMP, WNT) that differentially regulated self-renewal vesus differentiation in SSCs. We also discovered that SSCs repress core pluripotent factors (Sox2, Pou5f1 and Nanog) yet activate ancillary factors (e.g. Klf4, Mbd3, Tcf3, Sall4) transcriptionally and epigenetically. Overall design: Using SSEA4 as self-renewal marker and Kit as differentiating marker, we isolated self-renewal and differentiation SSCs by magnetic antibody cell sorting (MACS). Total RNA were extracted from those populations, and standard RNA sequencing libraries were prepared for sequnecing on a 50-cycle single end run.	Co-expression
SRP094977	RNA-seq in neutrophils from Juvenile Idiopathic Arthritis	In this study, we explored transcriptional complexity in human neutrophils from juvenile idiopathis arthritis and healthy control. We obtained differentially expressed genes among 3 ADU (active disease, untreated), 3 ADT (active disease, treated) and 2 HC (healthy control) samples using Cuffdiff2 software. Overall design: 3 ADU (active disease, untreated), 3 ADT (active disease, treated) and 2 HC (healthy control) samples were carried out RNA-Seq by next-generation sequencing strategy	Co-expression
SRP095007	mRNA expression levels in splenic human mononuclear cells of mock- and HIV-1-infected humanized mice	Through RNA sequencing and gene ontology analyses, we report that immune activation is elicited in the spleen of 4 HIV-1-infected humanized mice when compared to 4 mock-infected humanized mice. Overall design: mRNA expression profiles in the splenic human mononuclear cells of HIV-1-infected humanized mice at 6 weeks post-infection (n=4) and mock-infected humanized mice (n=4) were generated by RNA sequencing. RNA was extracted using QIAamp RNA Blood Mini kit (Qiagen). RNA sequencing was conducted in Medical & Biological Laboratories, co (Nagoya, Japan).	Co-expression
SRP095017	circRNA-sequencing	circRNA sequencing for 10 samples. Overall design: Examing 2 conditions, each with 5 replicates	Co-expression
SRP095032	Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B	In order to obtain an overview of gene expression changes in CHMP2B-dependent frontotemporal dementia (FTD3), RNA sequencing analyses were performed in FTD3 patient neurons compared to their gene-corrected isogenic controls. Overall design: Examination of 7 samples in totoal, including 3 samples of FTD3 paitent iPSC-derived neurons, 3 samples of corresponded isogenic controls and 1 sample of age-matched independent healthy control.	Co-expression
SRP095037	Expression charcaterization of an internal protocol developed to differentiate RPE cells	We performed RNA-seq and miRNA-seq  in fetal RPE cells differentated during 5 weeks in a transwell set up Overall design: Samples from days 7, 14, 21, 28 and 35 were characterized. Cells were grown in a proliferation medium during the first week (EpiCM) and then in a maturation medium (MAM medium) that enahnces differentiation towards the desired phenotype.	Co-expression
SRP095109	Gene expresison studies of lupus and healthy B cell subsets through RNA sequencing	Dramatic expansions of class switched B cells lacking IgD and CD27 (double negative; DN), are characteristic of Systemic Lupus Erythematous (SLE).  However, their origin, clinical and immunological significance and their relationship to CD27+ memory B cells remain unclear. We demonstrate that SLE DN expansions are dominated by a CXCR5- CD21- subset with a pre-plasma cell phenotype and distinctive transcriptional, and functional properties.  SLE patients with an expansion of CXCR5- DN are predominantly African-American with higher disease activity and anti-Smith/RNP autoantibodies.  CXCR5- DN cells display a distinct transcriptome characterized by differential expression of cytokine receptors, transcription factors, and signaling molecules. DN express high levels of the key INFg effector factor, T-bet  and associated transcription factor Zeb2 and uniquely among B cell subsets, do not express TRAF5, a negative regulator of TLR signaling.   Consistent with this pattern gene expression SLE DN have enhanced responsiveness to TLR7 and can differentiate into autoantibody secreting plasma cells Overall design: Based on the expression of IgD, CD27, and CXCR5, 4 different B cell subsets were isolated from 3 healthy control donors and 3 SLE patients,  gene expression was compared both between SLE and HCD B cells within each subset and between B cell subsets.	Co-expression
SRP095139	Impact of MRP RNA removal on human pre-rRNA steady-state levels	To investigate the role of MRP RNA in pre-rRNA processing, RNAseq was performed on total RNA from HeLa cell populations treated with control or RMRP-targeting CRISPR guides.	Co-expression
SRP095190	In vitro modelling of Hypoplastic Left Heart Syndrome (HLHS)	We reprogrammed fibroblasts from 5 HLHS patients and 2 controls into iPSCs and differentiated into cardiomyocytes. By comparison of HLHS and control groups we uncovered the developmental, structural and functional defects of HLHS cells. Through high through-put screening, the underlying molecular mechnisms of HLHS ontology was explored. Overall design: Cardiomyocyte mRNA profiles of normal control and HLHS samples were generated by deep sequencing, in duplicate, using Illumina HiSeq4000.	Co-expression
SRP095194	Transcriptome analysis of dominant-negative Brd4 mutants identifies Brd4-specific target genes of BET inhibitor JQ1	We analyzed anti-proliferative dominant-negative Brd4 mutants that compete with the function of distinct Brd4 domains. We used these Brd4 mutants to compare the Brd4-specific transcriptome with the transcriptome of JQ1 treated cells. Overall design: We performed polyA RNA-seq of Raji cells expressing Brd4 constructs f3 and f9 (dnBrd4_f3/f9) and Raji cell expressing the luciferase control vector treated with JQ1 (luc_JQ1) or DMSO as control (luc_DMSO).	Co-expression
SRP095209	Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants	Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk.  Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear.  The majority of the human genome is transcribed yet its biologic significance is incompletely understood.  We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk.  We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets. Overall design: We extracted RNA from peripheral whole blood across healthy control and disease subjects.	Co-expression
SRP095212	Influence of PepFect14 transfection on cellular response	Cell-penetrating peptides (CPP) uptake mechanism is still to be clarified to have a better understanding of their action in the mediation of oligonucleotide transfection. In this study, the effect on early events (1 h treatment) in transfection by Pepfect 14, with or without oligonucleotide cargo on gene expression, on HeLa cells, have been investigated. The RNA expression was characterized by RNA sequencing. Overall design: The quality of purified total RNA was estimated by Agilent 2200 TapeStation analysis (Agilent Technologies, Santa Clara, USA). One µg of total RNA was used as an input to prepare next-generation sequencing libraries according to the Illumina TruSeq Stranded mRNA sample preparation protocol (Illumina, San Diego, USA). Final library mixtures were quantified by Qubit 2.0 Fluorometer (Life Technologies, Grand Island, USA) and validated with Agilent 2200 TapeStation analysis. Libraries were quantified by qPCR with Kapa Library Quantification Kit (Kapa Biosystems, Woburn, USA) to optimize cluster generation and sequenced on HiSeq2500 platform (Illumina, San Diego, USA) with 2 x 50 bp paired-end reads. Over 93.9% of the bases sequenced were above the quality of Q30. Demultiplexing was done with CASAVA 1.8.2. (Illumina, San Diego, USA) Allowing one mismatch in 6 bp index read. Initial data analysis was conducted by the RNA-Seq pipeline of Estonian Genome Centre, University of Tartu. Shortly, fastQ files were trimmed (removal of adapter sequences and bases below the quality Q20) with FASTX-Toolkit version 0.013 (http://hannonlab.cshl.edu/fastx_toolkit) and then aligned to the human reference genome (hg19/GRCh37) with Bowtie version 2.1.019 in combination with TopHat version 2.0.1320. Transcript quantification (measured as FPKM) was conducted with Cuffdiff program from Cufflinks version 2.2.121 with reference annotation Homo_sapiens.GRCh37.72.gtf (http://ftp.ensembl.org/pub/release-72/gtf/homo_sapiens) Cuffdiff analysis, which summarizes expression changes for all annotated gene variations, was filtered by lowest q-values (corrected p-values for multiple testing) from output file gene_exp.diff and the top list of differentially expressed genes were analyzed through the use of QIAGEN’s Ingenuity® Pathway Analysis (IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity).	Co-expression
SRP095254	Modulation of microRNA-mRNA Target Pairs by Human Papillomavirus 16 Oncoproteins	The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs). While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects expression of cellular noncoding RNAs.  The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR) levels and to determine the potential consequences on cellular gene expression.  We performed deep sequencing of small and large cellular RNAs in primary, undifferentiated cultures of human foreskin keratinocytes (HFKs) with stable expression of HPV16 E6/E7 or a control vector.  After integration of the two data sets we identified 51 differentially expressed cellular miRs associated with modulation of 1,456 potential target mRNAs in HPV16 E6/E7 expressing HFKs.  We discovered that the degree of differential miR expression in HFKs expressing HPV16 E6/E7 was not necessarily predictive of the number of corresponding mRNA targets or the potential impact on gene expression.  Additional analyses of the identified miR-mRNA pairs suggest modulation of specific biological activities and biochemical pathways.  Overall, our study supports the model that perturbation of cellular miR expression by HPV16 E6/E7 importantly contributes to the rewiring of cellular regulatory circuits by the high-risk HPV E6 and E7 proteins that contribute to oncogenic transformation. Overall design: A total of 8 samples were analyzed, including two replicates of donor and passage matched human foreskin keratinocyte populations transduced with a control LXSN vector, a vector expressing HPV16 E6 alone, HPV16 E7 alone or both HPV16E6 and E7. Large and smal RNA was harvested from each of these samples.  RNAseq was performed using large RNA from two populations expressing a control vector and two populations expressing HPV16 E6 and E7 together only (a total of 4 samples).  All 8 samples were subjected to small RNAseq (miRNAseq).	Co-expression
SRP095259	Time series RNA profiling of endotheilal cells in response to atheroprone and atheroprotective flows	To profile shear stress-regulated endothelial transcriptomes, we performed RNA-seq with HUVECs subjected to different shear flow conditions, including atheroprotective pulsatile shear (PS, 12±4 dyn/cm2) and atheroprone oscillatory shear (OS, 0.5±4 dyn/cm2), or kept as static control (ST) for four time periods (1, 4, 12 and 24 hours) Overall design: HUVECs cultured on collagen I-coated slides were exposed to PS, OS  or ST.  RNA were extracted with TRIzol and sequenced on Illumina HiSeq platform.	Co-expression
SRP095272	Analysis of parent-of-origin bias in gene expression levels	In order to study parent-of-origin effects on gene expression, we performed RNAseq analysis (100bp single end reads) of 165 children who formed part of mother/father/child trios where genotype data was available from the HapMap and/or 1000 Genomes Projects. Based on phased genotypes at heterozygous SNP positions, we generated allelic counts for expression of the maternal and paternal alleles in each individual. This analysis reveals significant bias in the expression of the parental alleles for dozens of genes, including both previously known and novel imprinted transcripts. Overall design: This submission contains RNAseq data from 165 children from mother/father/child trios studied as part of the 1000 genomes and/or HapMap projects. We provide raw fastq format reads, and processed read counts per gene. Allelic count information can be provided by directly contacting the authors.	Co-expression
SRP095287	Altered regulation and expression of genes by BET family of proteins in alveolar macrophages from COPD patients	BET proteins (BRD2, BRD3, BRDT and BRD4) belong to the family of bromodomain containing proteins, which form a class of transcriptional co-regulators.  BET proteins bind to acetylated lysines in the histones of nucleosomal chromatin and function either as co-activators or co-repressors of gene expression. An imbalance between HAT and HDAC activities resulting in hyperacetylation of histones has been identified in COPD.  We hypothesized that BET inhibitor (JQ1) treatment of BET protein interactions with hyperacetylated sites in the chromatin will regulate excessive activation of pro-inflammatory genes and survival of key inflammatory drivers, alveolar macrophages (AM) in COPD. Transcriptome analysis of AM from COPD patients indicated up-regulation of macrophage type 1 genes upon LPS stimulation. BET inhibitor JQ1 treatment attenuated expression of multiple genes, including pro-inflammatory cytokines and regulators innate and adaptive immune cells. We demonstrated for the first time that JQ1 regulates differentially LPS-induced cytokine release from AM or peripheral blood mononuclear cells (PBMC) of COPD patients than PBMC of healthy controls. Using BET regulated gene signature, we identified a subset of COPD patients, which we propose to benefit from BET inhibition.  This work demonstrates that the effects of BET inhibition through JQ1 treatment of inflammatory cells has the potential to restore gene expression dysregulated in COPD patients vs healthy controls, and the expression of BET regulated genes is altered in COPD. The findings provide evidence of histone hyperacetylation as a mechanism driving chronic inflammatory changes in COPD. Overall design: Alveolar macrophages were incubated with JQ1 (10uM) for 1h at 37°C and subsequently challenged with 100ng/ml of LPS from E. coli (serotype 026:B6, Sigma) for 6h or 24 h at 37°C in CO2 incubator. DMSO-treated cells were used as a vehicle control.	Co-expression
SRP095307	IFN-? Stimulated MSCs RNA-Seq Profiling	Mesenchymal stromal cells (MSCs), which have immunosuppressive and trophic abilities that are induced by inflammatory cytokines, have emerged as a promising option for cell-based therapy. The cytokine profiles vary substantially across different diseases and stages of disease progression, which has been shown to influence the curative properties of MSCs. Our knowledge about how MSCs respond systemically to cytokines is still limited. Here, we individually stimulated MSCs in vitro with IFN-?and used RNA-Seq to analyze their expression profiles.	Co-expression
SRP095329	Evolving Spindlin1 Small Molecule Inhibitors Using Protein Microarrays	Using a library of tagged UNC1215 analogs, we screened a protein domain microarray of methyl-lysine effector molecules to rapidly detect compounds with novel binding profiles. Using this approach, we identified a compound (EML405) that acquired a novel interaction with the Tudor domain-containing protein Spindlin1 (SPIN1). Structural studies revealed that the symmetric nature of EML405 allows it to simultaneously engage two of SPIN1's Tudor domains, and also facilitated the rational synthesis of more selective SPIN1 inhibitor (EML631). The EML631 compound engages SPIN1 in cells, blocks its ability to “read” H3K4me3 marks, and inhibits its transcriptional coactivator activity. Overall design: RNA-seq of control, SPIN1 siRNA knockdown (24 hour post-transfection) and EML631 treated (10 mM, 3 days) T778 cells	Co-expression
SRP095351	Mapping of DHT-responsive or -independent AR-binding sites induced by activated Src in prostate cancer cell lines [RNA-seq]	Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent.  Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival. Overall design: RNA-seq of NGS libraries and sequencing of prostate cancer cell lines. 16 samples are seqeunced.  For VCaP, LnCap, LnCap-SRC, 22RV1, and LNCap-C4-2, we have both DHT treated and control cell lines.  For LuCaP 35.1 cell line, xenografted scid mice tumors are seqeucned, 3 androgen-dependent and 3 castration-recurrent samples ar sequenced.	Co-expression
SRP095354	Characterization of sperm lncRNA and its differently expression in the sperm of asthenozoospermic patients	Growing evidences have shown that many transcripts have been discovered in sperm and small noncoding RNAs, such as miRNA and tsRNA, of sperm paly an important role in the transgenerational transmission of paternal lifetime experiences. However, the expression profile of long noncoding RNAs (lncRNAs) in mammalian sperm has not been systematically investigated. Furthermore, Abnormal expression of lncRNA whether or not related with the asthenozoospermic is completely unknown. In the present study, highly purified RNA was served to investigate lncRNA expression profiles in human mature sperm by stranded-specific RNA-seq. We identified 38,307 known and 27,472 novel lncRNA genes, and the existence of intact LncRNA transcripts was confirmed by RT-PCR and fluorescence in situ hybridization (FISH) on two representative LncRNAs. Many lncRNAs exclusive were expressed in testis and sperm. 880 lncRNA sequences were conserved between human and mouse with > 80% overlap. Compared with normal population, the lncRNA profiles in asthenozoospermic patients' sperm showed significant difference with 2437 up-regulation and 306 down-regulation of lncRNA. This study will provide a preliminary database valuable for identifying lncRNAs critical on sperm function regulation or important for screening the lncRNA markers of asthenozoospermia. Overall design: LncRNA profiles of sperm and testis were generated by stranded-specific RNA-seq, using Illumina HiSeqTM 4000 with PE100.	Co-expression
SRP095357	Pluripotent stem cell disease modeling of GATA6 haploinsufficiency in human pancreatic development	To better understand molecular mechanisms of human pancreatic development associated with GATA6 haploinsufficiency, we performed RNA-seq analysis to characterize the biological processes affected by GATA6 heterozygous mutation. We found majority of top downregulated transcription factors are known to play key roles in pancreatic development and top downregulated genes were enriched with factors involved in developmental processes, with the pancreas being the top affected lineage. Overall design: Examination of two wild-type lines and two GATA6-/+ lines at the PP2 stage.	Co-expression
SRP095361	mRNA Sequencing of Ideopathic Pulmonary Fibrosis (IPF) and Control Samples from the Lung Tissue Research Consortium (LTRC)	IPF (n=20) and control (n=19) samples were obtained through the LTRC and were sequenced on an Illumina HiSeq 2000 following TruSeq RNA Sample Prep Kit v2 library preparation. Overall design: Cross-sectional samples were analyzed. IPF diagnosis was based on American Thoracic Society and European Respiratory Society criteria, and all IPF samples displayed typical patterns of usual interstitial pneumonia. RNA libraries were prepared from 200 ng of high quality total RNA according to the manufacturer’s instructions for the TruSeq RNA Sample Prep Kit v2 (Illumina, San Diego, CA). The concentration and size distribution of TruSeq libraries was determined on an Agilent Bioanalyzer DNA 1000 chip (Santa Clara, CA), and a final quantification, using Qubit fluorometry (Invitrogen, Carlsbad, CA), was conducted to confirm sample concentration. Libraries were loaded onto paired end flow cells at concentrations of 8-10 pM to generate cluster densities of 700,000/mm2 following Illumina’s standard protocol using the Illumina cBot and cBot Paired end cluster kit version 3. The flow cells were sequenced as 51 X 2 paired end reads on an Illumina HiSeq 2000 using TruSeq SBS sequencing kit version 3 and SCS version 1.4.8 data collection software. Base-calling was performed using Illumina’s RTA version 1.12.4.2.	Co-expression
SRP095402	IFN-? induced modes regulated by histone deacetylases and protein tyrosine phosphatases in human choriocarcinoma cells.	In the current study, we investigated the collective roles of protein tyrosine phosphatases (PTPs) and histone deacetylases (HDACs) on regulation of IRG expression in human choriocarcinoma cells by genome-wide transcriptional profiling. Logic-rules were optimized to derive rules governing gene expression patterns observed upon different combinations of treatment with PTP and HDAC inhibitors. The data reveal that IRGs can be divided into distinct subsets that are differentially modulated by co-treatment of Jar cells with IFN-? and PTP versus HDAC inhibitors, respectively. Furthermore, promoter analysis of the genes governed by the rules identifies transcription factor binding sites associated with the different gene subsets. Thus, the regulatory modes identified in this study provide insights into the complex regulation of inflammatory pathways at the fetal-maternal interface, as well as mechanisms that choriocarcinoma cells may utilize to promote their survival.	Co-expression
SRP095403	PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs	Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions. Overall design: We compared the transcriptome of deletion of core components of PRC2 in human embryonic stem cells and their wildtype counterparts by RNA-Seq.	Co-expression
SRP095405	Identification of genes induced by NOTCH1 in a chronic lymphocytic leukaemia (CLL) cell line and tracking of these genes in primary CLL patients	NOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease. Overall design: RNA-Seq analysis	Co-expression
SRP095407	Human embryonic stem cells in E8 and AKIT culture medium	Analysis of undifferentiated KhES-1 human embryonic stem cells in growth factors-dependent (E8) and -independent (AKIT) culture medium. Results provide insight into genes differentially expressed in pluripotent states maintained by AKIT and E8 culture medium. Overall design: Gene expression analysis of KhES-1 human ES cells mainteined in AKIT culture medum (3 replicates) compare to that in control E8 medium (3 replicates).	Co-expression
SRP095422	Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398	Activation of fibroblast growth factor receptor (FGFR) signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, or 4 are seen in multiple tumors including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid tumors. As we move forward with FGFR inhibitors clinically, we anticipate emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated cancer cell lines. We identified cancer cell lines that have activating mutations in FGFR1, 2, or 3, and treated them chronically with the selective FGFR inhibitor, BGJ398. We observed resistance to chronic BGJ398 exposure in DMS114 (small cell lung cancer, FGFR1 amplification), and RT112 (urothelial carcinoma, FGFR3 fusion/amplification) cell lines based on viability assays. Reverse phase protein array (RPPA) analysis showed increased phosphorylation of Akt (T308 and S473) and its downstream target GSK3 (S9 and S21) in both the resistant cell lines when compared to matching controls. Results of RPPA were confirmed using immunoblots. Consequently, the addition of an Akt inhibitor (GSK2141795) or siRNA was able to restore sensitivity to BGJ398 in resistant cell lines. These data suggest a role for Akt pathway in mediating acquired resistance to FGFR inhibition. Overall design: Observing mechanisms of resistance to BGJ398 in DMS114 and RT112 cell lines	Co-expression
SRP095426	OTX2 activity at distal regulatory elements shapes the chromatin landscape of Group 3 medulloblastoma [RNA-seq]	Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as Wnt, SHH, Group 3 and Group 4. Here we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2 bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1. These sites are responsive to OTX2 and NEUROD1 knockdown and could also be generated de novo upon ectopic OTX2 expression in primary cells, showing that OTX2 cooperates with NEUROD1 and plays a major role in maintaining and possibly establishing regulatory elements as a pioneer factor. Among OTX2 target genes we identified the kinase NEK2, whose knockdown and pharmacological inhibition decreased cell viability. Our studies thus show that OTX2 controls the regulatory landscape of Group 3 medulloblastoma through cooperative activity at enhancer elements and contributes to the expression of critical target genes. Overall design: Primary Group 3 Medulloblastomas tumor samples were analyzed by RNA-seq. Group 3 medulloblastoma cell line (D341) was analyzed by RNA-seq. OTX2 was depleted by infection with lentiviral shRNAs (sh OTX2 and sh GFP control). Raw data not provided for primary Medulloblastoma  samples due to patient privacy concerns. Submitter states that the raw data for these samples will be submitted to dbGaP.	Co-expression
SRP095428	Case Report - TNBC TP53 positive patient	Whole exome and RNA sequencing of a triple negative breast cancer patient. Whole exome sequencing was performed on peripheral blood, primary tumor and two metastatic sites. RNA sequencing was performed on the final metastasis.	Co-expression
SRP095447	Elucidating the cancer-specific genetic alteration spectrum of  glioblastoma  derived  cell  lines  from  whole  exome  and  RNA  sequencing	Cell lines derived from tumor tissues have been used as a valuable system tostudy gene regulation and cancer development. Comprehensive characterization ofthe genetic background of cell lines could provide clues on novel genes responsiblefor carcinogenesis and help in choosing cell lines for particular studies. Here, we havecarried out whole exome and RNA sequencing of commonly used glioblastoma (GBM)cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotidevariations (SNVs), indels, differential gene expression, gene fusions and RNA editingevents. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) werepotentially cancer-specific. The cell lines showed frequent SNVs and indels in someof the genes that are known to be altered in GBM- EGFR, TP53, PTEN, SPTA1 andNF1. Chromatin modifying genes- ATRX, MLL3, MLL4, SETD2 and SRCAP also showedalterations. While no cell line carried IDH1 mutations, five cell lines showed hTERTpromoter activating mutations with a concomitant increase in hTERT transcript levels.Five significant gene fusions were found of which NUP93-CYB5B was validated. Anaverage of 18,949 RNA editing events was also obtained. Thus we have generated acomprehensive catalogue of genetic alterations for six GBM cell lines.	Co-expression
SRP095483	Gene expression profiling of KSHV-infected periodontal ligament cells	We reported the potential and mechnism of oral mesenchymal stem cell to become Kaposi Sarcoma progenitor cell. Human periodontal ligament cells were infected for 48 hours and 96 hours, then subjected to RNA extraction and sequencing. We found that KSHV-infected PDLSC shared a better similarity with KS biosies in cytokine production, including chemotaxis, angiogenesis, inflammation and differentiation. Furthermore, infection of PDLSC upregulated a spectum of genes involving mesenchymal-to-endothelial differentiation, a process which has been revealed in KS spindle cells. This study reveals the potential and mechnism in which oral mesenchymal stem cell is transformed by KSHV to KS progenitor cell. Overall design: Gene expression profiling of uninfected PDLSC and KSHV-infected PDLSC after 48h and 96h.	Co-expression
SRP095491	Transcriptome analysis for KDM6A mutated urothelial bladder carcinoma and EZH2 inhibitor treated KDM6A mutated urothelial bladder carcinoma	Purpose:  The goals of this study are to compare 1. The transcription profile in KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma. 2. The transcriptional changes in KDM6A mutated urothelial bladder carcinoma upon EZH2 inhibitor treatment. Overall design: Transcriptome profiling of KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma were generated by deep sequencing, 10 cases in each group, using Hiseq2000. Transcriptome profiling of EZH2 inhibitor-treated KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma were generated by deep sequencing, in triplicate, using Hiseq2000.	Co-expression
SRP095512	Dermal endothelial cells of type 2 diabetic patients	The prevalence of type 2 diabetes mellitus (T2D) is increasing constantly and various risk factors such as obesity, aging, nutritional states and physical inactivity, in addition to genetic pre-dispositions in different populations has been identified. The consequences of high blood glucose include damaged blood vessels, leading to arteriosclerosis and chronic diabetic microangiopathies. These changes lead to occlusive angiopathy, altered vascular permeability, or tissue hypoxia, resulting in complications such as heart disease, strokes, kidney disease, blindness, impaired wound healing, chronic skin ulcers, or amputations. We isolated dermal endothelial cells from diabetic patients (Pat) and control individuals (Ctrl) and performed RNASeq to compare differentially expressed genes. Overall design: Surgical samples of human skin were taken from Type 2 diabetic patients and non-diabetic patients. The study was approved by the local ethics committee and all included patients gave their informed consent (no. 449/2001; 81/2008). Endothelial cells (CD31+, CD45-, Podoplanin-) from 4 diabetic patients (Pat) and 6 controls (Ctrl) were FACS sorted and processed for RNA Seq.	Co-expression
SRP095513	AMPK signaling for na誰ve pluripotency [Hs]	We show activation of AMP kinase (AMPK) with single chemical compounds can endow na誰ve pluripotency. AMPK activators reverted early-stage differentiating cells or epi-stem cells to na誰ve state. Moreover, AMPK activators reverted human ESCs to na誰ve state with pluripotent gene expression profiles and X-chromosome reactivation. Overall design: We analyzed gene expression profiles of human ESCs with AICAR during differentiation and reversion	Co-expression
SRP095556	Maturation of human iNSCs	The expression profiles of human iNSCs were compared to skin fibroblasts and brain-derived neural progenitor cells Overall design: Each cell line was expanded in culture, replicates were collected and analyzed	Co-expression
SRP095566	Generation and functional characterization of MDSC-like cells	Myeloid derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with IL-10 during their differentiation to dendritic cells (moDC) results in the generation of an APC population with a CD14+HLA-DRlow phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Here, we show that co-incubation of IL-10-APC and moDC caused a reduction of DC-induced T cell proliferation, of the expression of maturation markers and of secreted cytokines and chemokines. Furthermore, addition of IL-10-APC increased the immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4 on moDC. Using transcriptome analysis, we could identify a set of molecules and pathways  mediating the immunosuppressive effects of IL-10-APCs. In addition, we found that IL-10-APC as well as human isolated MDSC, expressed higher levels of programmed death (PD)-1, PD-ligand-1, glucocorticoid-induced-tumor-necrosis-factor-receptor-related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4, PD-1 or PD-L1 on MDSC using blocking antibodies restored the stimulatory capacity of DC in co-incubation experiments. Our results demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are profoundly involved in the inhibitory effects of MDSC on DC function and might be promising tools for an application in the clinics. Overall design: Isolated human monocytes from peripheral blood were differentiated to monocyte-derived dendritic cells (moDC) in presence or absence of interleukin-10 (IL-10). Additional cell maturation by application of LPS leads to a total number of 4 conditions with 3 samples each.	Co-expression
SRP095590	RNA-sequencing celecoxib-treated lung squamous cell carcinoma cell line	Celecoxib is an inhibitor of cyclooxygenase-2-incuced lung squamous cell carcinoma (LSQCC). The study aims to provide novel insight into celecoxib’s chemoprevention	Co-expression
SRP095604	Genome-wide transcriptome profiles in Control and Schizophrenia hiPSC-dervied NPC [RNA-seq]	We Report the genome-wide RNA expression levels in control and schizophrenia hiPSC dervied NPC treated with neuronal media for 2 days.  In total about 15,000 gene expression were detected in all samples, of which 1349 were dysregualted. Overall design: Examination, identification and comparision of mRNA expression profliles in control and schizophrenia npc	Co-expression
SRP095613	EWS-FLI1 represses Rho-actin signaling via MRTFB/YAP-1/TEAD perturbation in Ewing Sarcoma [RNA-Seq]	Ewing Sarcoma (EwS) is a EWS-FLI1- fusion driven pediatric bone cancer with high metastatic potential. Cellular plasticity, typically regulated via the Rho-pathway, is a prerequisite for metastasis initiation. Here we interrogated the role of the Rho transcriptional effectors MRTFA/B in EwS. We find MRTFB transcriptional function strongly repressed by EWS-FLI1. Under EWS-FLI1-low (knock-down) conditions, MRTFB is activated and antagonizes global EWS-FLI1-dependent transcription. Furthermore, ChIP-Seq revealed strong overlaps in MRTFB and EWS-FLI1 chromatin occupation, especially for EWS-FLI1 suppressed-(anticorrelated) genes. Enrichment of TEAD binding motifs in these shared genomic binding regions, and overlapping transcriptional footprints of MRTFB and TEAD1-4 perturbation led us to propose synergy between MRTFB and TEAD in the regulation of EWS-FLI1 suppressed-anticorrelated genes. Finally, we find F-actin assembly to be already perturbed in our EwS model, F-actin polymerization is perturbed by EWS-FLI1 in our model cell line, however,but pharmacological inhibition of actin polymerization still reduced expression serum-induced expression of MRTFB/YAP-1/TEAD target genes. In summary our data support a model of indirect and direct EWS-FLI1-driven perturbation of MRTFB/YAP-1/TEAD target gene regulation . Overall design: 1. Transient si-RNA mediated knockdown of MRTFA (MKL-1), MRTFB (MKL-2) and doxycyline-induced EWS-FLI1 knockdown in A673/TR/shEF EwS cells (8 samples/replicate: 2 replicates total); 2. Combined transient knockdown of MRTFA, MRTFB and EWS-FLI1 in SK-N-MC EwS cells (4 samples/replicate: 2 replicates total); 3. Combined knockdown of TEAD1-4 by pooling si-RNA against TEAD1, TEAD2, TEAD3 and TEAD 4 combined with doxycycline-inducible EWS-FLI1 knockdown (4 samples/replicate: 8 samples total)	Co-expression
SRP095640	Impact of HypERrlnc Knockdown on the human pericyte transcriptome	Pericytes are essential for vessel maturation and endothelial barrier function. Long non-coding RNAs (lncRNAs) regulate endothelial cell function, but their role in pericyte biology remains unexplored. Here we characterize the human pericyte transcriptome following knockdown of lncRNA HypERrlnc (RP11-65J21.3). Overall design: To investigate the impact of the knockdown of long noncoding RNA HypERrlnc on the pericyte transcriptome. HypERrlnc was silenced by LNA GapmeRs, controls were treated with scramble LNA GapmeR control. HypERrlnc was silenced in 3 independent experiments and total, ribosomal depleted RNA was subsequently analyzed via RNA deep sequencing. Mouse pericytes were kept in pre-equilibrated culture medium in a hypoxic incubator (Labotect) with humidified atmosphere at 5% CO2, 1% O2, 37°C. Mouse Pericytes were subjected to hypoxia for 24 h. Hypoxia was verified with measurement of culture medium pO2 levels with a hypoxia sensing probe (Oxford Optronix) as described elsewhere (Zehendner et al Plos One 2013).	Co-expression
SRP095644	Gene expression profiling of histone deacetylase inhibition in triple-negative breast cancer	Analysis of changes in gene expression levels after after prolonged exposure of triple-negative breast cancer cell lines to low doses of Panobinostat (LBH589), a pan-histone deacetylase inhibitor. Overall design: RNA-sequencing was performed after 96 hours and 4 weeks of incubation 10 nmol/L of LBH589 of two triple-negative breast cancer cell lines (HCC1806 and MDA-MB-231). All the expreiments were performed in biological triplicates	Co-expression
SRP095672	RNA-Seq analysis of human colorectal cancer with liver metastasis	Nine specimens from three colorectal cancer (CRC) patients including adjacent normal tissue, primary tumor, and lever metastasis tissue, and three specimens from 3 CRC patients without liver metastasis were collected for RNA sequencing analysis. Overall design: Nine specimens from three colorectal cancer (CRC) patients including adjacent normal tissue, primary tumor, and lever metastasis tissue, and three specimens from 3 CRC patients without liver metastasis were collected for RNA sequencing analysis. The mRNA libraries were separately generated from total RNA and constructed according to the standard Illumina mRNA library preparation (Illumina Inc, USA). Sequencing was done on the Illumina Nextseq 500 platform according to the manufacturer's instructions. Images generated by Nextseq 500 were converted into nucleotide sequences by a base calling pipeline and stored in FASTQ format and the dirty raw reads were filtered out prior to analyzing the data. Clean reads were mapped to reference Homo sapiens transcriptome sequences from the UCSC website (hg19) using Bowtie2 and Tophat 2.0.1 software. To annotate gene expression, reads per kilo bases per million reads (RPKM) values of each gene were calculated, and differentially expressed genes (DEGs) were extracted using this value.	Co-expression
SRP095674	Transcriptional profile in human S. haematobium infection	Genome-wide transcriptional survey in peripheral blood mononuclear cells (PBMCs) by RNA-Seq in schoolchildren living in an endemic area in Gabon, with and without Schistosoma haematobium infection before and after treatment with the anthelminthic drug praziquantel. Overall design: 14 samples; paired pre- and post-treatment for 4 S. haematobium-infected individuals, plus 3 controls	Co-expression
SRP095703	Genomewide analysis of EGF-induced alternative splicing	We performed EGF treatment and hnRNP A1 knockdown in HeLa cells and analyzed alternative splicing patterns by high-throughput RNA sequencing. Overall design: The mRNA profiles of control/EGF-treated/hnRNP A1-knockdown HeLa cells were generated by deep sequencing using Illumina HiSeq2000.	Co-expression
SRP095737	FGF2 regulation of gene expression in stable inducible Neurons	Stable inducible neurons were generated using Tol2 recombinase to generate human embryonic stem cells that expressed human NEUROG2 in a doxycycline regulated maner.  Treatment with doxycycline caused neuronal differentiation of the stem cells (samples 55649-55653). The post-mitotic excitatory neurons derived from the stem cells were used to examine FGF2 regulation of gene expression (samples 57089-57096). Overall design: Forced overexpression of human NEURGO2 was used to differentiate human embryonic stem cells (H9) into a homogeneous population of post-mitotic excitator neurons	Co-expression
SRP095746	The flightless I protein is involved in the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells	We report the function of Flightless I involved in the overall nuclear export, and genome-wide translation of mRNAs in H1299 cells. By using high-throughput transcriptome and translatome sequencing combined with cell fractionation, we generated genome-wide transcriptome and translatome maps of lung carcinoma cells and normal cells. We find that flightless I protein could modulate the genome-wide translation and mRNA traffiking, suggesting that the post-transcriptional regulation of mRNA might be a major mechanism of action for Flightless I. Overall design: Examination of mRNA expression, ribosome-nascent chain complex (RNC) expression and mRNA traffiking in overexpressed-FLII H1299cells and knockdown-FLII HBE cells.	Co-expression
SRP095921	Effect of method of deduplication on estimation of differential gene expression using RNA-seq	RNA-seq is a useful tool for analysis of gene expression. However its robustness is greatly affected by different artifacts. One of such artifacts is the presence of duplicated reads.To infer the influence of different methods of removal of duplicated reads on estimation of gene expression for cancer genomics we analyzed samples of normal liver tissue and hepatocellular carcinoma. For each sample, four protocols of data analysis were applied: processing without deduplication, deduplication with method implemented in samtools, and deduplication based on one or two unique molecular indexes (UMI). We also analyzed the influence of sequencing layout (single read or paired end) and read length. We found that deduplication without UMI greatly alters estimated expression values; this effect is the most pronounced for highly expressed genes.The use of unique molecular identifiers greatly improves accuracy of RNA-seq analysis, especially for highly expressed genes. We developed a set of scripts that enable handling of UMI and their incorporation into RNA-seq analysis pipelines. Deduplication without UMI alters results of differential gene expression analysis, creating high fraction of false negative results. The absence of duplicate read removal is biased towards false positives. In cases where the use UMI is not possible, we recommend to use paired-end sequencing layout.	Co-expression
SRP095943	Virus Mimicry in the Tumor Microenvironment Activates RIG-I Through Unshielding of Endogenous RNA in Exosomes [exoRNA-Seq]	The goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA isolated from stroma cell (MRC5) or stroma/breast cancer cell co-culture (MRC5 and 1833).	Co-expression
SRP095944	Virus Mimicry in the Tumor Microenvironment Activates RIG-I Through Unshielding of Endogenous RNA in Exosomes [RNA-Seq]	The goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA and cellular RNA with and without micrococcal nuclease treatment	Co-expression
SRP095948	Virus Mimicry in the Tumor Microenvironment Activates RIG-I Through Unshielding of Endogenous RNA in Exosomes [patients RNA-Seq]	The goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling of exosomal RNA isolated from breast cancer patients before, during and after radiation therapy.	Co-expression
SRP095950	Transcriptome sequencing (RNA-Seq) of non-tumor kidney tissues from 36 patients undergoing nephrectomy for exploring the metabolic mechanism of sorafenib and identifying the major transcriptional regulation factors in sorafenib metabolism in kidney	The multi-kinase inhibitor drug sorafenib is used as first line treatment for hepatocellular carcinoma and advanced renal cell carcinoma. Sorafenib mainly undergos cytochrome P450 (CYP) 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT) 1A9-mediated glucuronidation in liver, but the biotransformation of sorafenib in kidney remains unclear. Therefore, we integrated the mRNA expression data of 36 kidney samples and the corresponding metabolic activities for sorafenib to study the metabolic mechanism of sorafenib in kidney. Overall design: Kidney mRNA profiles of 36 patients undergoing nephrectomy were generated by deep sequencing, using Illumina HiSeqTM 4000	Co-expression
SRP095955	Role of remodeling and spacing factor 1 in histone H2A ubiquitination mediated gene silencing	Posttranslational modification of histones plays important roles in regulating chromatin-based nuclear processes. Histone H2A ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing; however, the mechanism by which H2Aub represses gene expression remains largely unclear. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF (remodeling and spacing factor) complex, as a novel H2Aub binding protein which mediates the repressive function of H2Aub on gene expression. RSF1 preferentially associates with H2Aub nucleosomes through a previously uncharacterized region designated as the ubiquitinated H2A binding (UAB) motif. RSF1 interacts with H2Aub nucleosomes specifically and the UAB motif is required for RSF1 to interact with H2Aub nucleosomes in vitro and in vivo. Genes regulated by RSF1 overlap significantly with genes regulated by RNF2 or Ring1B, the catalytic subunit of Polycomb repressive complex 1, in both human and mouse cells. RSF1 binds to gene promoter regions, and over 92% of H2Aub enriched genes, including the classic PRC1 target Hox genes, are co-bound by RSF1. Reduction of H2Aub levels by Ring1B knockout results in a significant reduction of RSF1 binding. RSF1 knockout does not affect RNF2/Ring1B or H2Aub levels but results in re-expression of H2Aub target genes, accompanied by a reduction in the spacing and stability of H2Aub nucleosomes. The direct role of RSF1 in repressing H2Aub target gene expression is further demonstrated by chromatin based in vitro transcription assay. Finally, RSF1 regulates Xenopus early embryonic development and gene expression in a fashion similar to that of PRC1 subunit Ring1A. Therefore, this study identifies RSF1 as a novel H2Aub binding protein and reveals that RSF1 contributes to H2Aub mediated gene silencing by maintaining a regular spaced, stable nucleosome array at promoter regions. Overall design: Examination of binding pattern of RSF1, gene expression profiles and nucleosome position in wildtype and RSF1 knock out mouse embryonic stem cells. And binding pattern of RSF1 and gene expression profiles in wildtype and RSF1 knock down HeLa cells.	Co-expression
SRP096016	Germline competency of human embryonic stem cells depends on eomesodermin	In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFß and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES. Overall design: There are 91 RNAseq samples  in total.	Co-expression
SRP096035	Full-coverage landscape of extracellular RNAs, coding and non-coding, secreted by human glioma stem cells	Communication between glioblastoma brain tumor (GBM) and its microenvironment alters the parameters of tumor growth and host responses, and may be mediated in part by tumor-secreted RNA. The global repertoire of extracellular RNAs (exRNAs) released by GBM, however, has not been investigated. We have developed a protocol enabling quantitative, minimally biased analysis of vesicular and non-vesicular exRNA complexes, including microvesicles (MVs) and exosomes (collectively called extracelluar vesicles; EVs), as well as ribonucleoproteins (RNPs) and applied it to study exRNA in patient-derived glioma stem-like cultures (GSC). Despite the intertumoral heterogeneity, further exacerbated at the exRNA level, the extracellular complexes exhibit distinct RNA composition, with microvesicles most closely reflecting the cellular transcriptome, and exRNPs exhibiting the most discrete repertoire. Up to 90% of exRNA reads represent fragmented rRNA; the remaining content is enriched in small ncRNA species, such as miRNAs in exosomes, and precisely processed tRNA and Y RNA fragments in both EVs and exRNPs. EV-enclosed mRNAs are mostly fragmented, and UTRs are more abundant than ORF regions; nevertheless, some full-length transcripts are present. Overall, there is less than one copy of non-rRNA per EV. Our results suggest that massive EV/exRNA uptake would be required to ensure functional impact of transferred information to the normal recipient cells of the brain and predict the most impactful miRNAs in such conditions. This study also provides a catalog of diverse vesicular and non-vesicular exRNA species useful for biomarker discovery. Overall design: Four low-passage patient-derived glioblastoma stem cell cultures were grown as neurospheres in serum-free media. Microvesicles (MVs), exosomes, and ribonucleoproteins (RNPs) were separated from conditioned media using sequential filtration, and RNA was isolated from each fraction. Cellular RNA was isolated from cultures in parallel. RNA was also isolated from MVs, exosomes, and RNPs from fresh media. Both long RNA library and small RNA libraries were prepared for each RNA sample, and sequenced on HiSeq2000. Cellular RNA of human or mouse primary normal brain cells (neurons, astrocytes, microglia, and endothelial cells) were also sequenced for small RNA libraries.	Co-expression
SRP096049	Targeting the androgen receptor N-terminus via the cochaperone Bag-1L [RNA-Seq KO]	Targeting the activation function-1 (AF-1) at the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the BAG domain of the cochaperone Bag-1L. Mutations in this domain or loss of Bag-1L abrogates AR signaling and reduces PCa growth. Correspondingly, Bag-1L protein levels increase with progression of primary prostate tumors to castration-resistant PCa, correlating inversely with patient response to abiraterone therapy. Intriguingly, BAG domain residues important for its interaction with the AR AF-1 overlap a potentially druggable pocket of this protein. Bag-1L is therefore a putative therapeutic target for the inhibition of AR AF-1 activity. Overall design: We performed transcriptome analysis (RNA-Seq) of 2 cell lines (LNCaP-Talen Control and LNCaP-Talen Bag1L KO) cultured in full medium (FM), or under hormone-starvation conditions for 72 h and then treated with vehicle (ethanol, EtOH) or 10 nM Dihydrotestosterone (DHT) for 16 h. Biological duplicate samples were analyzed for each cell line and each treatment condition.	Co-expression
SRP096070	The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and is Counteracted by the HBV X Protein Shortly after Infection	RNA-Seq analysis of HBV-infected primary human hepatocyte Overall design: RNA-Seq was conducted in two independent primary human hepatocyte (PHH) donors. Duplicate samples for each donor were analyzed on day 13 post-infection, with single samples per donor at other time-points (4 hr, 8 hr, 12 hr, 24 hr, day 2, day 3, day 6, day 8, day 10). Cell culture media was changed on days 1, 3, 6, 8 and 10	Co-expression
SRP096072	Diffuse Large B Cell Lymphoma cell line with Acquired Resistance to PI3Kd Inhibitor Idelalisib	RNAseq profile of TMD8 cell lines resistant to Idelalisib treatment.  Idelalisib resistant TMD8 cells were generated by continuous passage in the presence of 1 µM idelalisib for 8 weeks until stable resistance to idelalisib was established. Parallel cultures were grown in the presence of 0.1% DMSO as passage-matched, drug-sensitive control lines. Sensitive and resistant TMD8 cells were clonally isolated through two rounds of single cell limiting dilution Overall design: 8 Idela-resistant TMD8 clones were evaluated and compared to 3 passage-matched idela-sensitive TMD8 clones	Co-expression
SRP096073	Gene expression profiling of human MSC-educated macrophages vs. classical macrophages from bone marrow and blood	In comparison to MØs, MEMs have increased expression of the inhibitory molecules PD-L1, PD-L2, in addition to markers of alternatively activated macrophages: CD206 and CD163. RNA-Seq analysis of MEMs, as compared to MØs, show a distinct gene expression profile that positively correlates with multiple pathways important in tissue repair. MEMs also show increased expression of IL-6, TGF-ß, Arginase-1, CD73, and decreased expression of IL-12 and TNF-a. We show that IL-6 secretion is controlled in part by the COX-2, arginase and JAK1/STAT1 pathway. When tested in vivo, we show that human MEMs significantly enhance survival from lethal GVHD, and improve survival of mice from radiation injury. Overall design: Human macrophages were isolated from PBMCs and then exposed to MSCs. RNA was isolated then subjected to RNA-Seq.	Co-expression
SRP096110	RNA sequencing  quantitative analysis of exosome miRNAs in plasma in Metastatic renal cell carcinoma (mRCC)	Purpose: Since clinical characteristics are often inaccurate and subjective, we evaluated the prognostic value of plasma exosomal miRNAs to predict survival in metastatic renal cell cancer (mRCC). Methods: RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 41 mRCC patients.Candidate miRNAs were further evaluated for prognosis by TaqMan quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in a follow-up cohort of 65 mRCC patients. Results: RNA sequencing in screening cohort generated 3.75 million mappable reads per patient, of those with normalized read counts>8 RPM (reads per million), 93.8% were mapped to miRNAs for a total of 322 unique miRNAs. Cox regression analysis identified 20 miRNAs that were associated with overall survival (OS, FDR< 0.05). Among these 20 significant miRNAs, three were validated in a separate independent cohort of 65 patients with mRCC.Patients with lower expression of miR-26a1-3p, miR-let-7i-5p and miR-615-3p had a significantly poorer OS than those with higher expression. Multivariate model by combining miR-let-7i-5p and the Memorial Sloan-Kettering Cancer Center (MSKCC) score significantly improved survival prediction. Conclusions: Our study identifies multiple plasma exosomal miRNAs showing association with survival in mRCC stage patients. Multivariate model by combining miR-let-7i-5p and the Memorial Sloan-Kettering Cancer Center (MSKCC) score significantly improved survival prediction. Overall design: exosomal miRNAs profiles of 41 mRCC patients were generated by 50 bp single read sequencing using Illumina HiSeq2000 DNA sequence analyzer.	Co-expression
SRP096137	Interactome (iCLIP) and Translatome ( Polysome profiling) of Musashi 2 (MSI2) targets in K562	iCLIP was performed for FLAG-tagged MSI2 in K562 cells. Polysome profiling was performed for MSI2-knockdown and control shRNA K562 cells Overall design: iCLIP and Polysome profiling	Co-expression
SRP096169	Transcriptomic profiles of human foreskin fibroblast cells in response to orf virus	Using RNA sequencing technology, we compared speci?c changes in the transcriptomic pro?les in human foreskin fibroblast cells (HFF-1) following ORFV infection. ORFV speci?cally upregulated and downregulated a variety of genes, including genes involved in antiviral immune response, apoptosis, cell cycle and a series of signaling pathways, such as the IFN and p53-signaling pathways. A range of genes were downregulated at early stage. In contrast, the virus up-regulates a number of cellular genes at late stage. Overall design: HFF-1 mRNA profiles of 0, 3, and 8 hours post infection with orf virus were generated by deep sequencing, in triplicate, using Illumina Hiseq2500.	Co-expression
SRP096177	Deep sequencing reveals novel Set7 networks	Methyl-dependent regulation of transcription has expanded from a traditional focus on histones to encompass transcription factor modulation. While the Set7 lysine methyltransferase is associated with pro-inflammatory gene expression in vascular endothelial cells, genome-wide regulatory roles remain to be investigated. From initial characterization of Set7 as specific for methyl-lysine 4 of H3 histones (H3K4m1), biochemical activity toward non-histone substrates has revealed additional mechanisms of gene regulation.  mRNA-Seq revealed transcriptional deregulation of over 8,000 genes in an endothelial model of Set7 knockdown. Gene ontology identified up-regulated pathways involved in developmental processes and extracellular matrix remodeling, whereas pathways regulating the inflammatory response as well as nitric oxide signaling were down-regulated. Chromatin maps derived from ChIP-Seq profiling of H3K4m1 identified several hundred loci with loss of H3K4m1 at gene regulatory elements associated with an unexpectedly subtle effect on gene expression. Transcription factor network analysis implicated six previously described Set7 substrates in mRNA-Seq changes, and we predict that Set7 post-translationally regulates other transcription factors associated with vascular endothelial gene expression through the presence of Set7 amino acid methylation motifs.  We describe a role for Set7 in regulating developmental pathways and response to stimuli (inflammation/immune response) in human endothelial cells of vascular origin. Set7-dependent gene expression changes that occurred independent of H3K4m1 may involve transcription factor lysine methylation events. The method of mapping measured transcriptional changes to transcription factors to identify putative substrates with strong associations to functional changes is applicable to substrate prediction for other broad-substrate histone modifiers. Overall design: We used lentiviral delivered shRNA to knock down the expression of Set7 protein in HMEC-1 cells. As a control, we used a non-targeting shRNA. RNA-seq was performed in biological triplicate. Set7 knock down datasets are labeled “Set7KD” and non-targeting control datasets are labeled “NTC”	Co-expression
SRP096178	Endothelial transcriptome in response to pharmacological methyltransferase inhibition	The enzymatic activities of protein methyltransferases serve to write covalent modifications on histone and non-histone proteins in the control of gene transcription. Here, we describe gene expression changes in human endothelial cells caused by treatment with methyltransferase inhibitors 7,7'-carbonylbis (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) and disodium-2-(2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). Deep sequencing of mRNA indicated robust change on transcription following AMI-5 treatment compared with AMI-1. Functional annotation analysis revealed that both compounds suppress the expression of genes associated with translational regulation, suggesting arginine methylation by protein arginine methyltransferases (PRMTs) could be associated with regulation of this pathway. Interestingly, AMI-5 but not AMI-1 was found to decrease methylation of H3 histones at lysine 4 and down-regulate gene expression associated with interleukin-6 (IL-6) and activator protein-1 (AP-1) signaling pathways. These results imply that inhibition of protein methylation by AMI-1 and AMI-5 can differentially regulate specific pathways with potential to interrupt pathological signaling in the vascular endothelium. Overall design: HMEC-1 cells were treated with either 7,7'-carbonylbis (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) or disodium-2-(2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). These compounds were dissolved in DMSO and added to cells to make a final concentration of 100 µM. As a control, cells were exposed to DMSO only. Exposure time was 16 h.	Co-expression
SRP096196	LIN28A Over-expression RNAseq	To explore the effects of LIN28Ain human erythroid cell development, lentiviral transduction was used for LIN28A over-expression in erythroblasts cultured from mobilized CD34+ cells from six healthy adult human donors. LIN28A over-expression in cultured adult erythroblasts reduced the expression of let-7 and significantly increased HbF expression. Cellular maturation was maintained including enucleation. LIN28Aexpression in adult erythroblasts increased the expression of gamma-globin, and the HbF content of the cells rose to levels >30% of their hemoglobin. mRNA was isolated on culture day 14 (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). [Acknowledgement] We would like to thank Gerard Bouffard and the National Human Genome Research Institute for their expertise and assistance with RNA-seq. Overall design: Human CD34+ cells from healthy donor transduced with lentivirus expressing human LIN28A in serum free culture.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction.	Co-expression
SRP096204	Incomplete MyoD-induced transdifferentiation is mediated by chromatin remodeling deficiencies [RNA-Seq]	MyoD is known to transdifferentiate fibroblasts into muscle-like cells. Despite phenotypic resemblance and expression of myogenic marker genes in transdifferentiated cells, our global gene expression data suggests that ~100 genes, many involved in muscle development and function, remain non-reprogrammed. To understand this incomplete reprogramming, we characterized genome-wide chromatin accessibility and MyoD binding in human primary myoblasts and in MyoD-induced skin fibroblast cells. Our analyses revealed thousands of sites with incomplete chromatin reprogramming.Combined analyses of gene expression and epigenetic profiles revealed that many myogenic genes not upregulated during the transdifferentiation process have undergone MyoD-dependent chromatin remodeling, but to a significantly lower extent than reprogrammed genes. Our findings suggest that incomplete MyoD-induced transdifferentiation is due to chromatin-remodeling deficiencies, and that additional factors are required to transdifferentiate cells into a state more similar to myoblasts. Overall design: Fibroblast cells were transduced with a vector carrying human MyoD gene and induced by tetracycline for expression. Dnase-seq, ChIP-seq and RNA-seq were used to identify transcription factors binding, differential chromtin structural change, and differential expression at on-target and off-target sites.	Co-expression
SRP096209	Long noncoding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function [RNA-Seq]	LTR retrotransposons are repetitive DNA elements comprising ~10% of the human genome. However, Whether or how the LTR lncRNAs serve biological functions is largely unknown. Here we show that in primary human erythroblasts, lncRNAs transcribed from the LTR retrotransposons of ERV-9 human endogenous retrovirus regulated transcription of key erythroid genes. Global knock-down of ERV-LTR lncRNAs was performed in the in vitro erythropoiesis system of human CD34 cells, and genome wide RNA-seq was carried out to detect the effect on transcription. Overall design: Examination of transcriptome changes of 2 shRNA knock-down cells and a scrambled control knock-down cells	Co-expression
SRP096253	Gene expression changes after LOC550643 silencing	Differential analysis of gene expression in HEK293T cells treated with a pool of siRNA targeting LOC550643, or non-silencing siRNA. Overall design: LOC550643 encodes a polypeptide that binds to EDC4, and therefore may regulate RNA decay. This experiment tests whether steady-state gene expression levels are different in HEK293T cells treated with non-silencing siRNA, or with siRNA targeting LOC550643, by performing differential expression analysis of total RNA from both of these samples (triplicates of each).	Co-expression
SRP096285	Homo sapiens Raw sequence reads	Raw next generation sequencing data from acute exposure of MucilAir to 3R4F cigarettes and electronic cigarettes aerosols compared to air controls. 1hr exposure at the air liquid interface. RNA collected at 24h and 48h post-exposure. Aerosol dilution set to match for nicotine delivery between products.	Co-expression
SRP096329	Improved prediction of endogenous HLA-associated   epitopes based on mono-allelic mass spectrometry   profiling	LC-MS/MS-based identification of HLA-peptides is poised to provide a deep understanding of the rules underlying antigen presentation. However, a key obstacle limiting the utility of MS data is the ambiguity arising from the co-expression of multiple HLA alleles. Here, we introduce a  strategy for profiling the HLA ligandome one allele at a time. By using cell lines expressing a single HLA allele, optimizing immunopurifications, and developing a novel spectral search algorithm, we identified thousands of peptides bound to 16 different HLA class I alleles. These data enabled the discovery of novel binding motifs, and an integrative analysis quantifying the contribution of factors critical to epitope presentation, such as protein cleavage and gene expression. We trained neural network prediction algorithms with our large dataset (>24,000 peptides) and outperformed algorithms trained on datasets of peptides with measured affinities. We thus demonstrate a scalable strategy for systematically learning the rules of endogenous antigen presentation. Overall design: RNA transcript expression was quantified to in order to assess its contribution to Class I peptide prediction	Co-expression
SRP096338	Gene expression from laser capture microdissected pancreatic cancer epithelium and stroma	This study used laser capture microdissection to obtain paired tumor epithelium and stroma RNA samples from human pancreatic ductal adenocarcinoma (PDA) frozen sections. Libraries were prepared using the Nugen Ovation RNA-Seq System V2 and sequenced to a depth of 30 million 100bp single-end reads. These data were used to model compartment-specific gene expression density on a genome-wide scale and build an algorithm for transcriptional devonvolution (ADVOCATE). RNA sequencing of macrodissected bulk PDA sections was performed on 15 samples in order to systematically compare TruSeq and NuGEN RNA-Seq libraries and (ii) correlate histopathological and molecular assessment of tumor composition. Overall design: Gene expression data are presented for 65 pairs of tumor epithelium and stroma LCM samples and 15 bulk tumors using NuGEN and TruSeq library preparation, respectively. Gene expression data are presented for 57 additional tumor stromas.	Co-expression
SRP096339	Novel Non-catalytic Substrate-selective p38a-specific MAPK Inhibitors with Endothelial-Stabilizing and Anti-inflammatory Activity	We developed a novel substrate-selective inhibitor of p38 MAPK, UM101, and compared its effects on TNF-induced gene expression by human lung microvascular endothelial cells (HMVECLs) with the prototypical p38 catalytic inhibitor, SB203580 Overall design: HMVECLs were pretreated with DMSO (vehicle), UM101, or SB203580, then stimulated with TNF for 3h. Total RNA from treated cells and untreated control HMVECLs was isolated, poly(A) mRNA enriched and sequenced using the Illumina HiSeq platform.	Co-expression
SRP096357	Expression level is a key determinant of E2F1-mediated cell fate	Purpose: dose response analysis of E2F1 target genes expression in flow-sorted fractions with increasing amounts of fluorescently labled E2F1 Methods:U2OS pTRIPZ-YFP-ER-E2F1 cells were grown in full serum-containing growth medium and treated with 500 ng/ml doxycycline for 48 hours followed by addition of 90 nM OHT for an additional 20 hours. Cells from different YFP fractions were sorted by flow cytometry. mRNA profiles were generated by deep sequencing  using Illumina HiSeq 4000. Results: different target genes have different E2F1 activation thresholds. Numerous proliferation-related target genes are induced already by the lowest E2F1-levels. Intermediate E2F1 levels induce cdk inhibitors, which might be responsible for cell cycle arrest. Finally, although some apoptotic E2F1 targets are induced already by low E2F1 levels, many key apoptotic genes require higher E2F1 levels for induction. Conclusions: induction of different cell fates by increasing E2F1 levels might pertain to differential affinities of the targets. Overall design: Methods:U2OS pTRIPZ-YFP-ER-E2F1 cells were grown in full serum-containing growth medium and treated with 500 ng/ml doxycycline for 48 hours followed by addition of 90 nM OHT for an additional 20 hours. Cells from different YFP fractions were sorted by flow cytometry. mRNA profiles were generated by deep sequencing  using Illumina HiSeq 4000.	Co-expression
SRP096367	Differential responses of human fetal brain neural stem cells to Zika virus infection	Purpose: The goal of this study is to investigate the effect of Zika virus infection on neural stem cells Methods: RNA-Seq transcriptome analysis of neural stem cells infected with Zika virus compared to mock infected Overall design: RNA-seq transcriptome profiling of Zika infected human fetal neural stem cells	Co-expression
SRP096368	Total RNA was extracted from three samples of CD33 CAR or control T cells from three different donors	In vivo persistence of chimeric antigen receptor (CAR) T cells correlates with therapeutic efficacy, yet CAR-specific factors that support persistence are not well resolved. Using a CAR containing a single chain variable fragment (scFv) specific for CD33 linked to a 4-1BB and CD3 zeta signaling domain that is currently in advanced clinical trials, we show that CAR-expression, in a ligand-independent manner, alters T cell differentiation during ex vivo expansion. CAR-transduced T cells displayed decreased naïve and stem memory populations and increased effector subsets relative to vector-transduced control cells, and this was associated with reduced in vivo persistence. Altered persistence was not due to antigen specificity or tumor presence, but was linked to tonic signaling through the CAR, most notably CD3 zeta ITAMs, prior to transfer. We identified the PI3K/AKT pathway in CD33 CAR T cells as responsible. Treatment with a PI3K inhibitor modulated the differentiation program of CAR T cells, preserved a less differentiated state without affecting T cell expansion, and improved in vivo persistence relative to control cells. These results help resolve mechanisms by which tonic signaling modulates CAR T cell fate, and identifies a novel pharmacologic approach to enhance the durability of CAR T cells for cell-based immunotherapy. Overall design: RNA-Seq differential expression analysis comparing CD33 CAR T-cells vs control T-cells from three healthy indivduals	Co-expression
SRP096372	Pathologically expanded peripheral B cell-helper T cells in rheumatoid arthritis	"PROSET-HD aims to identify and study immune cell populations altered in patients with autoimmune and inflammatory diseases. We have identified a population of PD-1hi CXCR5- ''peripheral helper'' T (Tph) cells that are expanded in the joints and circulation of patients with seropositive rheumatoid arthritis. This T cell population uniquely combines potent B cell-helper function with a migratory program that directs homing to inflamed tissues. RNA sequencing was performed on sorted memory CD4+ T cell subpopulations to compare the global gene expression profiles of PD-1hi CXCR5- CD4+ T cells, PD-1hi CXCR5+ follicular helper T cells, and other T cell populations obtained from blood of rheumatoid arthritis patients."	Co-expression
SRP096375	Gene expression profile of human multiple myeloma cell line MM.1S after knockdown of KDM6B	Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFa or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKß inhibitor MLN120B, suggesting KDM6B is regulated by NF-?B signaling in MM cells. RNA-sequencing and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates these genes expression without affecting H3K27 methylation level. Overexpression of catalytically-inactive KDM6B activates expression of MAPK pathway-related genes, confirming its function independent of demethylase activity. We further demonstrate that downstream targets of KDM6B, ELK1 and FOS, confer MM cell growth. Our study therefore delineates KDM6B function that links NF-?B and MAPK signaling pathway mediating MM cell growth and survival, and validates KDM6B as a novel therapeutic target in MM. Overall design: Human multiple myeloma cell line MM.1S was transduced with either shRNA against KDM6B or luciferase (control) in triplicate. A total of 6 RNA samples (3 KDM6B knockdown and 3 control) were used for RNA-sequencing analysis.	Co-expression
SRP096557	Widespread Influence of 3'-end Structures on Mammalian mRNA Processing and Stability [CENPB-3''-end-library]	Understanding the physiological relevance of structures in mammalian mRNAs remains elusive, especially considering the global unfolding of mRNA structures in eukaryotic organisms recently examined, as well as the decade-long observation that mRNAs generally seem no more likely than random sequences to be stably folded. Here we show that RNA secondary structures, mostly weak and close-to-random, facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. Folding of these 3'-end structures also enhances mRNA stability. Global structure probing shows that 3'-end regions are indeed folded in cells despite substantial unfolding of PAS-upstream regions. Analyses of thousands of ectopically expressed variants prove that folding both enhances processing and increases stability. Mutagenesis of a genomic locus further implicates structure-controlled processing in regulating neighboring gene expression. These results reveal widespread roles for RNA structure in mammalian mRNA biogenesis and metabolism. Overall design: This series includes 8 samples designed to measure the efficiency of 3'' end processing from a reporter library expressed in HEK293T cells and HeLa cells, in steady state or in nascent RNAs (by 4sU labeling and capture).	Co-expression
SRP096576	A genome-wide analysis of human pluripotent stem cell-derived endothelial cells cultured in synthetic hydrogels compared to standard 2D or 3D cell culture platforms	The influence of 2D and 3D cell culture platforms on vascular function was investigated by comparing gene expression for human pluripotent stem cell-derived endothelial cells (H1-ECs), primary human brain vascular pericytes (pericytes), and human umbilical vein endothelial cells (HUVECs) cultured on tissue culture polystyrene (TCP, “2D”), on or in poly(ethylene glycol) (PEG) hydrogels formed via “thiol-ene” photopolymerization, and on or in gelled Matrigel.  ECs cocultured with pericytes in PEG formed vascular networks with global gene expression that was highly correlated to a standard 3D Matrigel assay (Spearman's coefficients = 0.98).  H1-ECs, HUVECs, and pericytes  were characterized gene expression signatures associated with the cell cycle and mitosis when cultured on TCP surfaces compared to cells cultured on top of or encapsulated in PEG hydrogels or Matrigel. The proliferative signature was not necessarily a function of the 2D format, since endothelial cells cultured on PEG hydrogels were not characterized by increased proliferation or a proliferative gene signature compared to cells encapsulated in PEG hydrogels. The proliferative phenotype for H1-ECs on TCP was regulated by FAK-ERK activity, and inhibition or knockdown of ERK pathway signaling decreased proliferation and cell cycle genes while increasing expression of “3D-like” vasculature development genes.  Our results suggest that cells in 2D culture adopt a highly proliferative state that interferes with normal vascular function and provides unique insight into the importance of cellular and extracellular context for in vitro tissue modeling. Overall design: 30 samples for RNA-Seq Experiment #1 ("RNAseq1": H1 human embryonic stem cells, “H1-ESC-1”; H1 ES cells-derived endothelial cells, "H1-EC1"; HUVECs, "HUV1"; pericytes, "PC"; and H1-EC1 cocultured with PC, H1-EC1-PC cocultures). Poly(ethylene glycol) (PEG) hydrogels : 4 million endothelial cells/mL (H1-EC1 or HUVECs) and/or 2 million pericytes/mL were encapsulated in 30 µL PEG hydrogels in the bottom of 24-well transwell inserts . Matrigel (MG): 2 million endothelial cells/mL and 1 million pericytes/mL were encapsulated in 30 µL gelled Matrigel (4.5 mg/mL). Endothelial cells, pericytes, and cocultures encapsulated in PEG or Matrigel were maintained under hypoxic conditions (1.5% O2) in E7V medium supplemented with 1% bovine serum albumin.  H1-ECs were also seeded on gelled Matrigel (4.5 mg/mL, “2D on Matrigel”) at a density of 60,000 cells/cm2 and incubated for one day in E7V medium with 1% BSA under normoxic conditions.  Tissue culture polystyrene (TCP): TCP surfaces were coated with Matrigel at a dilute concentration that does not form a gel (H1-ES cells), recombinant vitronectin (H1-ECs or HUVECs), or poly-l-lysine (pericytes, as per manufacturer's instructions) and cultured under normoxic conditions. 18 samples for RNA-Seq Experiment #2 ("RNAseq2": H1-ECs, “H1-EC2”; or HUVECs “HUV2”; cultured using PEG hydrogels, gelled Matrigel (6.4 mg/mL), or on Matrigel-coated TCP surfaces.  For 3D culture, 4 million endothelial cells/mL were encapsulated in 30 µL PEG hydrogels (50% crosslinking, 2 mM CRGDS) or gelled Matrigel formed in single wells of 24-well TCP plates. For 2D culture, 200,000 endothelial cells per well of a 12-well TCP plates were seeded on Matrigel-coated surfaces (“MG-TCP”) or on 300 µL PEG hydrogels (50% crosslinking, 2 mM CRGDS) or gelled Matrigel formed in the bottom of the well. H1-ES cells were included as a control for both experiments. Duplicate samples are provided for each condition.	Co-expression
SRP096589	Gene signature profiles in respiratory epithelium infected with nontuberculous mycobacteria	The incidence of pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but host susceptibility factors are not fully understood. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium complex (MAC) or Mycobacterium abscessus (MAB) and performed transcriptome sequencing (RNA-Seq) to identify relevant gene expression differences. We used cells from 4 different donors in order to try to obtain generalizable data. The differentiated respiratory epithelial cells in ALI were infected with MAC or MAB at MOI of 100:1 or 1000:1, and RNA-seq was performed at 1 and 3 days after infection. We found downregulation of ciliary genes, including several identified with polymorphisms in previous PNTM cohorts. The cytokine IL-32, the superpathway of cholesterol biosynthesis and downstream targets within the IL-17 signaling pathway were all elevated. The integrin signaling pathway was more upregulated by MAB than MAC infection. Working with primary respiratory epithelial cells infected with nontuberculous mycobacteria at ALI, we identified ciliary function, cholesterol biosynthesis, chemokine production and the IL-17 pathway as major targets of host responses to infection. Some of these pathways may be amenable to therapeutic manipulation. Overall design: 44 strand-specific RNA libraries for high-throughput sequencing were prepared (samples from 4 different donors, 57F, 75M, 69F, and 42F, for each condition) using the TruSeq Stranded mRNA Sample Preparation Kit with 750ng of total RNA according to manufacturer's instructions.	Co-expression
SRP096593	Transcriptome analysis of human immortilized astrocytes reprogrammed into dopaminergic neurons	We directly reprogram human astrocytes (hIA) in vitro into induced dopaminergic neurons (iDAs). This process requires three transcription factors, NEUROD1, ASCL1 and LMX1A as well as one microRNA, mir218. This combined protocol gives rise to human astrocyte-derived iDAs with appropriate midbrain markers as defined by analyzing markers derived from human embryonic ventral midbrain samples at 7 and 9 weeks of age. Overall design: Four replicates of the uninduced astrocyte cell line, four replicates of astrocytes induced into dopaminergic cells, and two samples each of human embryonic midbrain tissue at 7 and 9 weeks of age	Co-expression
SRP096609	Effect of Paclitaxel on Gastric Cell Line	No description.	Co-expression
SRP096629	RNAseq of quiescent (Q) and stress induced premature senescent (SIPS) fibroblasts treated with plant extract (1201) from Solidago vigaurea subspecies alpestris	Quiescent (Q) and stress induced premature senescent (SIPS) fibroblasts were treated for the duration of 4 days with growth medium supplemented with a plant extract (1201) from Solidago vigaurea subspecies alpestris. Rna was isolated with Trizol and sent to GATC for next generation sequencing with Ilumina technology. The plant extract proofed to block the negative effects of senescence in human skin fibroblasts in various experiments by delaying the acquisition of a senescent phenotype/favouring a papillary-like phenotype and attenuating the senescence associated secretory phenotype. The RNAseq was performed to understand the underlying molecular mechanism of the observed effects. SIPS was induced by chronic oxidative stress treatment (9 days with 1 h 100 µM H2O2 per day). Overall design: 12 samples in total. Quiescent cells (Q), quiescent cells treated with 1201 for 4 days (Q1201), stress induced premature senescent cells (SIPS) and stress induced premature senescent cells treated with 1201 for 4 days (SIPS1201), all conditions in triplicates. Quiescent cells are considered the appropiate control for senescent cells.	Co-expression
SRP096633	Evaluating and comparing the Transcriptome of (human) Hek 293 based cells, expressing either CHD3 or CHD4	Purpose: Identifying target genes of the two human chromatin remodeling enzymes CHD3 and CHD4 Methods: see below in protocols Results: Libraries were sequenced on Illumina HiSeq2000 platform resulting in 37-71 Mio 50 bp paired-end reads per sample. We identified 16 (i) and 115 (ii) distinctly regulated genes when CHD3-GFP (i) or CHD4-GFP (ii) were overexpressed. Nine  genes seem to be commonly regulated by CHD3 and CHD4. We successfully validated four genes from our RNA-seq via qPCR with two new (independent from those, used for RNA-seq) biological replicates. Conclusion: CHD3 and CHD4 regulate distinct genes. Overall design: Total RNA was prepared from 24 hours induced (1 ng/µl Dox) and non-induced Flp-In™ T-REx™ 293 cells, expressing GFP, hCHD3-GFP (UniProt: Q12873) or hCHD4-GFP(UniProt Q14839). Library preparation and Illumina Sequencing was perfprmed by EMBL GeneCore facility in Heidelberg (Germany: Dr. Vladimir Benes)	Co-expression
SRP096656	Crizotinib v. DMSO in SW480 cells	SW480 cells were treated with 2uM crizotinib for 72h (versus DMSO) Overall design: Examination of differential up- or down-regulated genes after crizotinib treatment	Co-expression
SRP096666	Sulfonamide anti-cancer toxins target the RBM39 splicing factor for degradation by recruiting the DCAF15 ubiquitin ligase receptor	Indisulam is a small molecule with selective anti-cancer activity. The mechanism of action for indisulam and the basis for its selectivity is unknown. Here, we used a forward genetics strategy to discover that mutations in the gene encoding the RBM39 RNA binding protein cause indisulam resistance. Indisulam promotes interaction between RBM39 and the CUL4-DCAF15 E3 ubiquitin ligase, leading to polyubiquitination and proteasomal degradation of RBM39. Mutations in RBM39 reduce its interaction with CUL4-DCAF15, increase its stability and confer resistance to indisulam toxicity. RBM39 is essential for pre-mRNA splicing and inactivation of RBM39 by indisulam results in aberrant pre-mRNA splicing. Cancer cell lines originating from the hematopoietic and lymphoid tissue lineages frequently exhibit sensitivity to indisulam, and their response to indisulam can be predicted by the expression levels of DCAF15. Our studies reveal RBM39-DCAF15 as the target of indisulam, and identify DCAF15 expression as a potential biomarker to guide clinical trials of indisulam.	Co-expression
SRP096678	Novel BET protein Proteolysis Targeting Chimera (BET-PROTAC) exerts superior lethal activity than Bromodomain Inhibitor (BETi) against post-myeloproliferative Neoplasm (MPN) Secondary (s) AML Cells	The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Whereas the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reversed Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in mRNA and protein expressions than OTX015 in sAML cells. Specifically, compared to OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, pSTAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared to OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against the established and PD-CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML. Overall design: SET2 cells (biologic triplicates for control and ARV-825; biologic duplicates for OTX015-treated cells) and patient-derived, post-MPN secondary AML cells (biologic replicates).	Co-expression
SRP096716	Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration	Inhibition of FOXO1 activity in kidney microvascular endothelial cells improves angiogenesis Overall design: Kidney microvascular endothelial cells were serum starved and treated with DMSO control or FOXO1 inhibitor for one hour, then stimulated with VEGF for 30 minutes	Co-expression
SRP096722	Transcriptome-wide identification of CELF2 functional targets in T cells	CELF2 is a critical regulator of alternative splicing during T cell development and during stimulation-induced T cell activation. Here we utilize RNA-seq to globally profile the functional targets of CELF2 in a monoclonal Jurkat T cell line (JSL1 cells), including transcriptome-wide splicing targets and genes regulated at other levels of mRNA processing Overall design: We performed strand-specific RNA-seq on JSL1 cells that were unstimulated or stimulated with the phorbol ester PMA, as well as cells in both of these conditions that were depleted for CELF2 through stable lentiviral transfection of shRNAs in duplicate	Co-expression
SRP096727	Single cell RNAseq characterization of cell types produced over time in an in vitro model of human inhibitory interneuron differentiation.	Diverse cell types are produced from dorsal and ventral regions of the developing neural tube. In this study we describe a system for generating human inhibitory interneurons by ventralizing human embryonic stem cells in vitro and characterizing the gene expression of the cell types produced over time. We engineered a DCX-Citrine/Y hESC line to sort and characterize progenitor and neuron transcriptomics separately at both the subpopulation and single cell level. The cells generated in vitro were compared to similar populations present in human fetal brain samples by mapping gene expression data from human fetal cells onto the principal component analysis (PCA) space of in vitro-derived populations. Weighted gene co-expression network analysis (WGCNA) was used to determine the discreet cell types present at D24, D54, D100 and D125 of culture, and describe the gene expression changes that occur in progenitor and neuron populations over time. Immature lateral ganglionic eminence and medial ganglionic eminence cells are present at early timepoints, along with MGE-like and dorsal pallium-like neuronal progenitors. At later timepoints we observe the emergence of SST-expressing interneurons, as well as oligodendrocyte and astrocyte progenitors. We also identified genes that were upregulated in somatostatin-expressing interneurons as they mature. Overall design: The transcriptomes of 1732 ventralized single cells were profiled by SmartSeq2 at different timepoints throughout a 125-day differentiation protocol that converted H1 human embryonic stem cells to a variety of ventrally-derived cell types.	Co-expression
SRP096736	Flura-Seq Identifies In Situ Transcriptomes of Micrometastases	Understanding the biology of rare cell populations in the context of their microenvironment requires an accurate analysis of the transcriptomes of these cells as expressed in situ. We developed fluorouracil-tagged RNA sequencing (Flura-seq) to characterize the transcriptomes of small cell subpopulations from a whole organ in model systems. The method utilizes cytosine deaminase (CD), which converts the non-natural pyrimidine base fluorocytosine to fluorouracil. Expression of S. cerevisiae CD in cells of interest and exposure to fluorocytosine generates fluorouracil, which is metabolically incorporated into newly synthesized RNAs. The fluorouracil-tagged RNAs can then be immunopurified and sequenced. We applied Flura-seq to define the transcriptome of human breast cancer xenografts, representing as few as 0.003% of host organ cell population during the early stages of metastatic colonization of mouse lungs. The robustness, simplicity and lack of toxicity of Flura-seq make this tool broadly applicable to many studies in developmental, regenerative, and cancer biology. Overall design: RNAs were tagged withfluorouracil, and the tagged RNAs were immunopurified before sequencing. MDA_Con-Dox = MDA231 control cells that does not express CD/UPRT MDA_FC50uM4hr = MDA231 cells treated with Doxycycline for 24 hours to express CD/UPRT and further treated with 50 uM 5-fluorocytosine for 4 hours. MDA_FC50uM12hr = MDA231 cells treated with Doxycycline for 24 hours to express CD/UPRT and further treated with 50 uM 5-fluorocytosine for 12 hours. MDA_FC250uM4hr = MDA231 cells treated with Doxycycline for 24 hours to express CD/UPRT and further treated with 250 uM 5-fluorocytosine for 4 hours. MDA_FC250uM4hr = MDA231 cells treated with Doxycycline for 24 hours to express CD/UPRT and further treated with 250 uM 5-fluorocytosine for 12 hours. MDA_SBCon = MDA231 cells treated with 2.5 uM SB-505124 for 150minutes. MDA_TGFBCon = MDA231 cells treated with 200 pM TGFB for 150minutes. MDA_SB_IP = MDA231 cells treated with Doxycyline for 24 hours to express CD/UPRT, then with 250 uM of 5-fluorocytosine for 30 minutes before adding 2.5 uM of SB-505124 for additional 150 minutes, and the mRNAs from the cells were immunoprecipitated with anti-BrdU antibody. MDA_TGFB_IP = MDA231 cells treated with Doxycyline for 24 hours to express CD/UPRT, then with 250 uM of 5-fluorocytosine for 30 minutes before adding 200 pM of TGFB for additional 150 minutes, and the mRNAs from the cells were immunoprecipitated with anti-BrdU antibody. MDA_msLung_4h Input = MDA231 cells injected in mouse lung through tail vien, and 4 weeks after the injection CD/UPRT was induced by feeding Doxycycline diet for 2-3 days, and 250 mg/kg 5-fluorocytosine was injected intraperitoneally and 125 mg/kg thymine subcutaneously, and 4 hours later mouse lungs were harvested, homogenized, mRNAs were isolated and sequenced. MDA_msLung_4h IP = MDA231 cells injected in mouse lung through tail vien, and 4 weeks after the injection CD/UPRT was induced by feeding Doxycycline diet for 2-3 days, and 250 mg/kg 5-fluorocytosine was injected intraperitoneally and 125 mg/kg thymine subcutaneously, and 4 hours later mouse lungs were harvested, homogenized, mRNAs were isolated, immunopurified with anti-BrdU antibody and sequenced. MDA_msLung_12h Input = MDA231 cells injected in mouse lung through tail vien, and 4 weeks after the injection CD/UPRT was induced by feeding Doxycycline diet for 2-3 days, and 250 mg/kg 5-fluorocytosine was injected intraperitoneally and 125 mg/kg thymine subcutaneously, and 12 hours later mouse lungs were harvested, homogenized, mRNAs were isolated and sequenced. MDA_msLung_12h IP = MDA231 cells injected in mouse lung through tail vien, and 4 weeks after the injection CD/UPRT was induced by feeding Doxycycline diet for 2-3 days, and 250 mg/kg 5-fluorocytosine was injected intraperitoneally and 125 mg/kg thymine subcutaneously, and 12 hours later mouse lungs were harvested, homogenized, mRNAs were isolated, immunopurified with anti-BrdU antibody and sequenced.	Co-expression
SRP096749	Time-course expression data from HEK293?RAF1:ER cells stimulated with 4OHT and labelled with 4SU	We integrate experimental data and mathematical modelling to unveil how ERK signal duration is translated to mRNA dynamics. Overall design: HEK293 cells were transfected with an inducible form of RAF (?RAF1:ER), labelled with 4-thiouridine (4SU) one hour before harvesting and induced with tamoxifen (4OHT) for different periods of time (0h-8h).	Co-expression
SRP096753	Gene expression in HT-29-MTX intestinal epithelial cells treated with Ancylostoma ceylanicum hookworm larvae	HT-29-MTX cells were treated with Ancylostoma ceylanicum hookworm larvae or left untreated.  The differences in gene expression between treated and untreated samples was observed. Overall design: HT-29-MTX cells were grown for 7 days post-confluency (total 21 days) and were either treated with iL3 A. ceylanicum larvae for 24 hours or left untreated.  RNA from treated and untreated samples was collected and differences in gene expression were observed using RNA-Seq.	Co-expression
SRP096757	Profiling of Ileal Transcriptome in Pediatric Crohn Disease	We report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn''s disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents (<17 years) who presented with symptoms of IBD. Non-IBD control label corresponds to those with suspected IBD, but without inflammation and normal endoscopic findings. Biopsies were stored at -80 degrees.	Co-expression
SRP096765	Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute lymphoblastic leukemia [RNA-seq]	This Series contain trascriptional profiling via RNA-seq for two ALL-B cell lines, one commercial (NALM-6), one patient-derived (LAL-B), in presence or absence of AATF transcript. In NALM-6, also MYC was depleted and sequenced in triplicate. Furthermore, the Burkitt''s Lymphoma P493 cell line has been sequenced in presence or absence of Tetracycline (MYC On-Off) and in CN vs siAATF. Overall design: RNA-seq of B-cell cell lines after knockdown of Che-1/AATF or MYC. The submitter declares that the raw data for the LAL-B cell line Samples (GSM2459108-GSM2459113) will be made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap) due to patient privacy concerns.	Co-expression
SRP096767	Synectin Promotes Fibrogenesis by Regulating PDGFR Isoforms Through Distinct Mechanisms	The scaffold protein synectin plays a critical role in the trafficking and regulation of membrane receptor pathways.   As the platelet derived growth factor receptor (PDGFR)  pathway is essential for hepatic stellate cell (HSC) activation and liver fibrosis, we sought to determine the role of synectin on the PDGFR pathway in HSC.  To study the role of synectin in the development of liver fibrosis,  mice with selective deletion of synectin from HSC were generated and found to be protected from fibrosis.  RNAseq revealed that knockdown of synectin in HSC demonstrated reductions in the fibrosis pathway of genes including PDGFR-ß, but not PDGFR-a.  Chromatin Immunoprecipitation assay of the PDGFR-ß promoter upon synectin knockdown revealed a pattern of histone marks associated with decreased transcription, dependent on p300.  In contradistinction, synectin was found to regulate PDGFR-a through an alternative mechanism: protection from autophagic degradation.  Site directed mutagenesis revealed that ubiquitination of specific PDGFR-a lysine residues is responsible for its autophagic degradation.  Furthermore, functional studies showed decreased PDGF dependent proliferation and migration after synectin knockdown.  Finally, human cirrhotic livers demonstrated increased synectin expression.  This work provides insight into differential transcriptional and post-translational mechanisms of synectin regulation of PDGFRs, which are critical to fibrogenesis. Overall design: To gain insight into molecular mechanisms by which the genetic inactivation of synectin impacts on liver fibrosis, we performed next generation sequencing of mRNA isolated from HSC in which the levels of this protein were significantly reduced using shRNA-mediated knock down.	Co-expression
SRP096784	WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel	The Wilms'' Tumour gene 1 (WT1), encodes for a complex protein with transcription factor activity which is essential in mammals throughout life. We provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis. Using in vitro cell lines, clinical samples and publicly available gene expression datasets, we demonstrate that WT1 plays a role in regulating the epithelial-mesenchymal balance of breast cancer cells and that WT1-expressing tumours are mainly associated with a mesenchymal phenotype. WT1 gene expression also correlates with CYP3A4 levels and is associated with poorer response to taxane treatment. Overall design: RNA profiles of breast cancer cells (MDA-MB-157) were generated by deep sequencing on the Illumina HiSeq 2000 platform. Untreated MDA-MB-157 cells, MDA-MB-157 cells transduced with a lacZ control vector, and MDA-MB-157 cells transduced with a lentiviral vector carrying a Wt1 shRNA were sequenced (titled untreated, lacZ and Wt1 respectively).	Co-expression
SRP096788	Gene expression analysis of human spinal motor neurons (MN) differentiated from ALS patient derived iPSC	iPSC derived from a patient heterozygous for the SOD1 E100G mutation were genome edited to homozygous wild type using the CRISPR-Cas9 system. Both disease and isogenic corrected iPSC were differentiated into spinal motor neurons that were ISL1+ and CHAT+. Gene expression changes in MN were analyzed by RNA-sequencing.	Co-expression
SRP096798	Next Generation Sequencing Facilitates lncRNA  Analysis of  undifferentiated  Periodontal ligament stem cells(uPDLSCs), differentiated Periodontal ligament stem cells without TNF-a stimulation(dPDLSCs)  and TNF-a-dPDLSCs	the goal of this study are to reveal potential functions of novel lncRNAs in PDLSCs ,systematicly characterize PDLSC related lncRNAs and protein coding genes in uPDLSCs,dPDLSCs and TNF-a-dPDLSCs with Next Generation Sequencing.	Co-expression
SRP096819	Genome-wide mapping of DROSHA cleavage sites on primary microRNAs and novel substrates [RNA-seq]	MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gate-keeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated on a genomic scale, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here we establish a protocol termed ‘formaldehyde crosslinking and immunoprecipitation followed by sequencing (fCLIP-seq)’ that allows identification of DROSHA cleavage sites at single nucleotide resolution. fCLIP identifies numerous cleavage sites that do not match the ends of annotated mature miRNAs, particularly at the 3' termini, suggesting widespread end modifications during miRNA maturation such as trimming and tailing. fCLIP also finds many pri-miRNAs undergoing alternative processing, yielding multiple miRNA isoforms. Moreover, we discover dozens of novel substrates that are bound and cleaved by DROSHA. These substrates are processed less efficiently than canonical pri-miRNAs, and produce only minute amounts of small RNAs. Depletion of DROSHA results in an increase of the hairpin-containing transcripts. Thus, the hairpins may serve mainly as cis-elements for DROSHA-mediated gene regulation rather than as miRNA genes. fCLIP-seq not only accurately maps the cleavage sites of DROSHA and suggests noncanonical functions of DROSHA, but also could be a general tool for investigating interactions between dsRNA binding proteins and structured RNAs. Overall design: RNA-seq of total RNA in siRNA-transfected HEK293T cells (3 replicates)	Co-expression
SRP096825	ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis	Propose: We used next-generation RNA sequencing (RNA-seq) to characterize the transcriptional changes  in primary human melanocytes during recessive Cole disease. Our patient carried missense mutation in the ENPP1 gene (c.358T>C; p.C120R). RNA-seq was performed using mRNA extracted from primary hypo- and hyper-pigmented melanocytes isolated from  affected patient  and melanocytes from his healthy heterozygous sibling  and an aged- and ethnicity-matched control. Results: A pairwise fold-change comparison was performed and genes were computationally filtered using a cutoff of more than 2 fold change and P<0.01. We first compared hyper-pigmented melanocytes to each control individually and  then overlapped the results to obtain a list of 1041 up-regulated and 692 down-regulated genes. The same analysis was done for hypo-pigmented melanocytes to found that 535 genes were up-regulated and 520 were down-regulated. Finally, to obtain a profile of the overall differential gene expression, down-regulated genes in hyper and hypo-pigmented cells were overlapped to identify 143 genes that were down-regulated in patient melanocytes compared to controls regardless of pigmentation status. Similar analysis was performed to obtain the list of 172 up-regulated genes. We selected 36 deregulated genes, most of which were associated with melanocyte development and pigmentation signaling pathways, and validated 32 of them by Q-PCR, indicating that our RNA-Seq data was accurate and reliable. Conclusion: Our study represents the first analysis of hypo- and hyper-pigmented primary melanocytes isolated from affected patient  versus healthy controls in recessive Cole disese pathology. Overall design: mRNA profiles of hyper- and hypo-pigmented mutant melanocytes, heterozygous and wild type melanocytes were sequenced in triplicate on the Hiseq 2500 High output 100PE	Co-expression
SRP096834	Low-Cell-Number, Single-Tube Amplification (STA) of RNAs Revealed miRNA Changes from Pluripotency to Endothelium	Non-coding RNAs (ncRNAs) are essential components in cellular machineries for translation and splicing. In addition to their housekeeping functions, ncRNAs are involved in cell type-specific regulation of translation, mRNA stability, genome structure and accessibility. To decipher their functions in different cell types, a method to comprehensively quantify them in a sensitive manner is highly desirable. Using miRNA as an example, we showed that cDNA from total RNA could be amplified and specifically detected from a few cells within a single tube. The sensitivity of the system was maximized by avoiding purification from cell lysis to amplified cDNA and by optimizing the buffer conditions. With 100 human embryonic stem cells (hESCs) and their differentiated endothelial cells as input for high-throughput sequencing, the single-tube amplification (STA) system revealed both well-known and other miRNAs selectively enriched in each cell type. The selective enrichment of the miRNAs was further verified by qPCR with 293FT cells and a human induced pluripotent stem cell (hiPSC) line. In addition, the STA system was capable of detecting miRNA expression down to single cells, albeit with some loss of sensitivity and power. Finally, the detection of other non-miRNA transcripts indicated that the STA target was not limited to miRNA, but extended to other ncRNAs and mRNAs as well. Overall, STA offered a simple and extremely sensitive way to collect the quantitative miRNA and other RNA information from individual cells. Grant ID: MOST-104-2314-B-006-038-MY3 Funding source: Ministry of Science and Technology, Taiwan Grantee First Name: Po-Min Grantee Last Name: Chiang Overall design: total RNA from 3 types of cells was amplified and sequenced using HiSeq2500 platform	Co-expression
SRP096884	Next Generation Sequencing Facilitates Quantitative Analysis of Human Pluripotent Stem Cell-Derived Endocardial-like And Primary Cardiac Endothelial Cell Transcriptomes	Next-generation sequencing (NGS) has significantly advanced the elucidation of developmental signaling mechanisms that are important for different cell lineage formation from human pluripotent stem cells (hPSCs). We report here the application of RNA-sequencing technology for transcriptome profile of human primary cardiac microvascular endothelial cells and hPSC-derived endocardial endothelial cells, and compare to those of other cell lineages including hPSCs, mesoderm, cardiomcyotyes as well as mouse cardiac microvascular and endocardial endothelial cells. Six cardiac endothelial cell samples from two different hPSC lines and one donor were performed in IIIumina HiSeq2500. The resulting sequence reads (about 20 million reads per sample) were mapped to human genome (hg19) using HISAT, and the RefSeq transcript levels (RPKMs) were quantified using the python script rpkmforgenes.py. Our RNA-seq data confirmed the stable expression of key endocardial endothelial cell markers including CDH5, vWF, PECAM1, NFATC1 and NPR3, and the gene set enrichment analysis (GSEA) showed enrichment in angiogenesis and vasculature development. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to endocardial function. This study represents the first detailed analysis of endocardial-like endothelial cell transcriptomes generated by RNA-seq technology, providing insight into the mechanisms underlying the differentiation of hPSCs into endocardium. Overall design: Endothelial transcriptome profiles of human primary cardiac microvascular endothelial cells and hPSC-derived endocardium were generated by RNA-seq technology using IIIumina HiSeq2500	Co-expression
SRP096887	Human prefrontal cortex Ribominus RNA sequencing	miRNA sponge, a special class of miRNA target,  has been emerging as a pivotal player in miRNA mediated regulatory network. Currently, the identified miRNA sponge genes mostly act on sequestering conserved miRNAs (e.g. miR-7, miR-145), however, the existence, potential function and evolutionary process of miRNA sponge genes for species-specific miRNA, especially for human specific miRNA, are largely unknown. In this study, we conducted a systematic analysis including sponge gene identification and subsequent function and evolutionary analyses for an authentic human-specific miRNA, miR-941. Overall design: Total RNA after depleting Ribosomal RNA of four human prefrontal cortex samples were generated by deep sequencing using Illumina HiSeq 2000	Co-expression
SRP096892	Transfection experiment with vector containing TP73-AS1 sponge region and miR-941	miRNA sponge, a special class of miRNA target,  has been emerging as a pivotal player in miRNA mediated regulatory network. Currently, the identified miRNA sponge genes mostly act on sequestering conserved miRNAs (e.g. miR-7, miR-145), however, the existence, potential function and evolutionary process of miRNA sponge genes for species-specific miRNA, especially for human specific miRNA, are largely unknown. In this study, we conducted a systematic analysis including sponge gene identification and subsequent function and evolutionary analyses for an authentic human-specific miRNA, miR-941. Overall design: Total RNA after transfecting with vector containing TP73-AS1 sponge region and miR-941 and empty vector were generated by deep sequencing using Illumina HiSeq 2000	Co-expression
SRP096893	miR941 overexpression experiment	miRNA sponge, a special class of miRNA target,  has been emerging as a pivotal player in miRNA mediated regulatory network. Currently, the identified miRNA sponge genes mostly act on sequestering conserved miRNAs (e.g. miR-7, miR-145), however, the existence, potential function and evolutionary process of miRNA sponge genes for species-specific miRNA, especially for human specific miRNA, are largely unknown. In this study, we conducted a systematic analysis including sponge gene identification and subsequent function and evolutionary analyses for an authentic human-specific miRNA, miR-941. Overall design: Total RNA after miR-941 duplex or mock control transfection in 293T cells  were generated by deep sequencing using Illumina HiSeq 2000	Co-expression
SRP096943	Identification of target genes of TAZ in the prostate cancer cells	We found that the transcriptinal co-activator TAZ is a basal cell marker for the prostate epithelium which is lost in the prostate cancer tissues and re-expression of TAZ in the prostate cancers may be a indicator of malignancy. TAZ promotes cell migraiton, EMT and metastasis in the prostate cancers. To elucidate the underlying mechanism, we performed the RNA-seq analysis of TAZ knockdown DU145 cells using two independent TAZ shRNA and pLKO control cells. Overall design: Two TAZ knockdown DU145 cells using two independent TAZ shRNA and two pLKO control DU145 cells were used for RNA-seq.	Co-expression
SRP096948	UBR7 is a novel E3 ubiquitin ligase for H2BK120 and acts as a tumor-suppressor in breast cancer [RNA-Seq]	Plant Homeo Domain (PHD) is a versatile chromatin reader/effector module which recognizes methylated, acetylated or unmodified histone substrates and regulates cellular gene expression programs. Although PHD domains shows selective epigenetic recognition of methylated, acetylated and unmodified histone substrates, there has been no previous report on its catalytic function regulating malignant transformation of cells. Here we report that PHD finger of UBR7 (Ubiquitin Protein Ligase E3 Component N-Recognin 7 (Putative)), in isolation or in context of full length protein, harbors E3 ubiquitin ligase activity towards monoubiquitination of histone H2B at lysine 120 . Knockdown of UBR7 in MCF10a and breast cancer cells decreased H2BK120ub both at the global levels and on specific genes. Conversely, overexpression of wild type, but not catalytic mutant, rescued H2BK120ub levels. Low UBR7 expression was associated with basal-like and triple negative breast cancers as well as showed poor expression in metastatic tumors. Consistently, UBR7 loss resulted in invasion properties, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 reduced cell growth, invasion and tumor growth in mouse fat pad. Mechanistically, UBR7 reduced H2BK120ub gene body of cell-adhesion related genes as well as gene expression including on CDH4 gene. Importantly, rebuilding CDH4  levels rescued invasion phenotypes seen in UBR7-low cells. Collectively, our results establish that UBR7 PHD has novel H2B ubiquitin ligase activity and it suppresses tumor growth in basal-like breast cancers. Overall design: Triplicate total RNA profiles in Wild Type and UBR7-shRNA MCF10A Cell Line	Co-expression
SRP096981	Distinct driver genes and the expression of Hedgehog defines morphoeic basal cell carcinoma	Morphoeic basal cell carcinoma (mBCC) has a high risk of local recurrence compared to the more indolent nodular subtype. Little is known about the genetic and molecular makeup of mBCC that determines its invasive behaviour; this study represents the first comprehensive analysis of mBCC within the periocular region. A specific set of driver genes were found in mBCC including FLNB and HECTD4 leading to a loss of function. NodBCC had a different set of driver genes including TP53, FADS1 and PPM1D. BCC located within the face confers a higher risk especially within the H zone, however, this did not confer a higher UV signature or mutational burden. Wnt signalling and natural killer cell cytotoxicity (NK) were two common pathways in nodular and mBCC. NK importance may be greater in mBCC and represents a novel therapeutic target. Aberrant Hedgehog (Hh) pathway signalling was shown to be more critical in mBCC than nodBCC on three molecular levels: mutational burden, transcriptome profile and protein expression. Surrounding mBCC stroma is abnormal, containing mutations in EPHA3, ATR, and GLI3. Hh pathway over-expression is seen in the tumour and stroma of morphoeic tissue, but not nodular, with the stroma potentially contributing to the morphoeic's aggressive nature and local recurrence risk. These findings have implications for clinical practice by highlighting novel therapeutic targets for mBCC and the potential need to remove surrounding stroma to prevent local recurrence. Overall design: RNA-seq experiments of tumour-stroma pairs for three patients in each mBCC and nodBCC subtype were performed.	Co-expression
SRP096986	Sub-population RNAseq characterization of cell types produced over time in an in vitro model of human inhibitory interneuron differentiation.	Diverse cell types are produced from dorsal and ventral regions of the developing neural tube. In this study we describe a system for generating human inhibitory interneurons by ventralizing human embryonic stem cells in vitro and characterizing the gene expression of the cell types produced over time. We engineered a DCX-Citrine/Y hESC line to sort and characterize progenitor and neuron transcriptomics separately at both the subpopulation and single cell level. The cells generated in vitro were compared to similar populations present in human fetal brain samples by mapping gene expression data from human fetal cells onto the principal component analysis (PCA) space of in vitro-derived populations. Weighted gene co-expression network analysis (WGCNA) was used to determine the discreet cell types present at D24, D54, D100 and D125 of culture, and describe the gene expression changes that occur in progenitor and neuron populations over time. Immature lateral ganglionic eminence and medial ganglionic eminence cells are present at early timepoints, along with MGE-like and dorsal pallium-like neuronal progenitors. At later timepoints we observe the emergence of SST-expressing interneurons, as well as oligodendrocyte and astrocyte progenitors. We also identified genes that were upregulated in somatostatin-expressing interneurons as they mature. Overall design: The transcriptomes of 1732 ventralized single cells were profiled by SmartSeq2 at different timepoints throughout a 125-day differentiation protocol that converted H1 human embryonic stem cells to a variety of ventrally-derived cell types.	Co-expression
SRP096997	Single cell profiling of hCS and hSS derived from human iPSC	Single gene expression proifiling of dissociated hiPSC-derived 3D cultures of the pallium and subpallium at day 105 of differentiation (n= 11,838 cells; BDTM Resolve system), revealing the various cell types and heterogenity within cell types in the cultured organoids Overall design: 2 samples: hCS and hSS	Co-expression
SRP097000	Exploiting Prmt5-orchestrated intron detention signatures to treat splicing-addicted malignant glioma tumors	The presence of introns within otherwise completely spliced mRNA molecules has been associated with splicing errors. Recent evidence however suggests that intron-based transcript inactivation is widespread and regulates the cytoplasmic availability of productive transcript isoforms. The regulatory and functional details of this process have remained unclear. We here present the arginine methyltransferase Prmt5 as the top hit from an in vivo RNAi screen for therapeutic vulnerabilities of malignant gliomas. Inhibition of Prmt5 inactivates hundreds of pro-proliferative genes by increasing the inclusion of so-called “detained” introns (DIs) within mRNAs. DI-based inactivation of these genes causes cessation of cell proliferation and exhibits potent anti-tumor effects in vitro and in vivo. Gliomas become increasingly sensitive to Prmt5 inhibition upon tumor progression. Furthermore, DI-based gene expression regulation is not restricted to cancer, but contributes to cell differentiation by governing the expression levels of gene sets related to both cell cycle and cell identity. Overall design: 2 experimental conditions (vehicle DMSO treatment, EPZ015666 treatment), in triplicate, for 72h, of human U-87 MG tumor cells.	Co-expression
SRP097005	Human Adult Sorted Live Cell Erythroblasts RNA-Seq.	Erythroblasts cultured from mobilized CD34+ cells from six healthy adult human donors were used to generate an erythroblast transcriptome. Cellular maturation was maintained including enucleation.  On culture day 14 total RNA was isolated (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). Overall design: Human CD34+ cells from health donor cultured in serum free medium.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction.	Co-expression
SRP097126	mRNA Profiling of miR-17 family inhibition using TuD lentiviral vector in HepG2 and SK-Hep1 hepatocellular carcinoma cell lines [RNA-Seq]	To functionally characterize the role of miR-17 family in HCC, lentiviral vector-based miR inhibitor TuD was used to inhibit miR-17 family of microRNAs in HepG2 and SK-Hep1 HCC cell lines Overall design: Methods: HepG2 and SK-Hep1 HCC cell lines were acquired from American Type Culture Collection (ATCC) and miR-17 TuD or NC TuD expressing lines were generated. mRNA profiling of miR-17 TuD or NC TuD expressing samples was performed using Illumina NGS. Total RNA was extracted as per manufacturer’s instructions (RNeasy kit, Qiagen). RNA quality was assessed using BioAnalyzer (Agilent). mRNA expression profiles were determined using next-generation sequencing (NGS) on the Illumina HiSeq 2000 platform producing 50bp paired-end reads. Bowtie/TopHat suites were used to align the reads to mouse genome or transcriptome and RSEM were used to quantify gene abundances. Gene level counts were then normalized with the R/Bioconductor package limma using the voom/variance stabilization method.	Co-expression
SRP097129	Transcriptomics of siCTRL, siNSUN2 and ALYREF-RIP HeLa cells, and multiple mouse tissues	RNA was isolated from siCTRL, siNSUN2 and ALYREF-RIP HeLa cells, and multiple mouse tissues using the TRIzol (Invitrogen) reagent by following the company manual. Approximately 2.5 µg of total RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer’s protocol.The libraries were sequenced using HiSeq3000 (Illumina) or HiSeq2500 in paired-read mode, creating reads with a length of 101 or 125 bp. Sequencing chemistry v2 or v4 (Illumina) was used. Overall design: Examination of gene expressive levels in siCTRL, siNSUN2 and ALYREF-RIP HeLa cells, and multiple mouse tissues	Co-expression
SRP097153	Functional Screening in Human Cardiac Organoids Reveals a Metabolic Mechanism for Cardiomyocyte Maturation	The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of the adult. However, the key drivers of this process remain poorly defined. We developed as 96-well screening platform, using human pluripotent stem cell derived cardiac organoids, to determine the molecular requirements for in vitro cardiomyocyte maturation. Here, we describe gene expression changes resulting from culturing human cardiac organoids in standard cell culture conditions and under optimized maturation conditions. We assessed our maturation conditions by comparing transcriptional changes of human cardiac organoids to RNA isolated from human heart. Interesting, analysis of these data revealed that a switch to fatty acid oxidative metabolism is a key governor of cardiomyocyte maturation and mature cardiac organoids were refractory to mitogenic stimuli. Overall design: 3D cardiac organoids were cultured in CTRL or MM for 11 days before collecting for RNA-seq.	Co-expression
SRP097226	RNA-Seq in SMARCD2 k/d NB4 cells with/without ATRA differentiation	We report differential gene expression in the human AML cell line NB4 that can be partially differentiated into neutrophil granulocytes by 1µM ATRA for 2d or the vehicle DMSO only ((mock)) Overall design: Chromatin accessibility in CTRL vs SMARCD2-specific shRNA1 and SMARCD2-specific shRNA2. All biological samples were sequenced twice, i.e. technical replicates.	Co-expression
SRP097448	Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated ß-catenin signaling	Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies.  The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism.  Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways.  RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and ß-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated ß-catenin activation in a Keap1 and HO-1 double knockdown experiment.  This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated ß-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival. Overall design: Total mRNAs were directly extracted from primary human melanocytes with or without silencing of Keap1 expression. Isolated RNA was labelled and used for RNA-sequencing.	Co-expression
SRP097469	Effect of BCL11B knockdown on transcriptome of human T-cell precursors	To investigate the role of BCL11B in the initial stages of human thymopoiesis, we  performed loss of function (knockdown) studies in an in vitro human thymopoiesis model (cord blood CD34+ cells co-cultured on OP9DLL1 stromal cell line).  Gene expression profiling by RNA-Seq demonstrated that BCL11B knockdown resulted in downregulation of T-lineage genes and upregulation of stem cell, myeloid and NK genes, indicating BCL11B is required for the establishment of a T-lineage commitment transcriptional program. Overall design: Cord blood CD34+ cells were transduced with a BCL11B knockdown or scrambled control shRNA lentivral vector containing a GFP reporter.  GFP+ cells were isolated by fluorescence activation cell sorting (FACS) at 48 hours post transduction and cultured on OP9DLL1 stroma in the presence of  FLT3 ligand (5 ng/ ml) and IL-7 (5 ng/ ml). On day 14 of co-culture, CD45+GFP+CD7+CD1a- and CD45+GFP+CD7+CD1a+ T-cell precursors were isolated from control and knockdown co-cultures by FACS and analyzed by RNA-Seq to determine the effect of BCL11B knockdown on the transcriptome of T-cell precursors. N=3 experiments, each done with a different pool of cord blood donors.	Co-expression
SRP097605	RNA-Seq data from ZR75-1 cells	We report the transcription factor Six1 directly increases the expression of many glycolytic genes by performing RNA sequencing using Six1 stable knockdown ZR75-1 breast cancer cell line and control cell line. Overall design: Examination of ZR75-1 cells stably infected with lentivirus carrying Six1 shRNA or control shRNA	Co-expression
SRP097611	A comprehensive assessment of RNA-seq protocols for degraded and low-quantity samples	RNA-sequencing (RNA-seq) has emerged as the most sensitive tool for gene expression analysis. Among the library preparation methods available, the standard poly(A)+ enrichment provides a comprehensive, detailed, and accurate view of polyadenylated RNAs. However, on samples of suboptimal quality ribosomal RNA depletion and exon capture methods have recently been reported as better alternatives. In this study, we compare for the first time three Illumina library preparation kits (TruSeq Stranded mRNA, TruSeq Ribo-Zero rRNA Removal, and TruSeq RNA Access) as representatives of these three different approaches using well-established human reference RNA samples from the MAQC/SEQC consortium on a wide range of input amounts (from 100 ng down to 1 ng) and degradation levels (intact, degraded, and highly degraded). We assessed the accuracy of the generated expression values by comparison to gold standard TaqMan qPCR measurements and gained unprecedented insight into the limits of applicability in terms of input quantity and sample quality of each protocol. In particular, we show that the exome-capture protocol RNA Access performs well on samples with low amount and highly degraded RNA.	Co-expression
SRP097613	Studying iPSCs from a hibernating mammal reveals molecular mechanisms of cold resistance in neural tissues	To explore the cold resistant feature of ground squirrel neuron cells, we compared transcriptomes of human and ground squirrel iPSC derived neurons in the response to cold treatment. We identified several key pathways that are critical for the maintenance of neuronal microtubule cytoskeleton integrity at low temperature. Overall design: Neuron cultures of human and ground squirrel iPSC derivate incubated at 4 °C or the normal 37 °C for 1 hour or 4 hours, respectively. Totally, we obtained 18 transcriptomes, including 3 replicates of squirrel_4c_1h, 3 of squirrel_37c_1h, 2 of human_37c_1h, 2 of human_4c_1h, 2 of squirrel_37c_4h, 2 of squirrel_4c_4h, 2 of human_37c_4h and 2 of human_4c_4h.	Co-expression
SRP097615	RNA-seq of laser captured oculomotor, cervical and lumbar spinal motor, and Onufs nucleus motor neurons in post mortem material of control human subjects	Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Towards this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of Phox2a in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry and RNA sequencing, that in vitro generated neurons are bona fide oculomotor neurons based on their similarity to their in vivo counterpart in rodent and man. We also show that in vitro generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro which display a resilience similar to that seen in vivo. Overall design: A total of 39 samples were analyzed. Each sample is consists of between 30-120 laser-captured motor neurons from post-mortem human tissue. Samples are divided over 3 groups: lumbar/cervical spinal cord motor neurons (n=12), oculomotor neurons (n=20) and motor neurons of Onuf's nucleus in the sacral spinal cord (n=7).	Co-expression
SRP097630	Human Cord Blood Sorted Live Cell Erythroblasts RNA-Seq	Erythroblasts cultured from six healthy commercial available cord blood CD34+ cells were used to generate an cord blood erythroblast transcriptome. Cellular maturation was maintained including enucleation.  On culture day 14 total RNA was isolated (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). Overall design: Human CD34+ cells from health donor cultured in serum free medium.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction. We would like to thank Gerard Bouffard and the National Human Genome Research Institute for their expertise and assistance with RNA-seq.	Co-expression
SRP097664	Gene expression in PANC-1 and AsPC-1 human pancreatic carcinoma cells under hypoxia, nutrient starvation and low pH culture condition.	The conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification. Overall design: Cells were treated for 24 h under each condition. RNA-seq reads were aligned to human transcriptome (UCSC gene) and genome (GRCh37/hg19) references respectively using Burrows-Wheeler Aligner. After transcript coordinate was converted to genomic positions, an optimal mapping result was selected either from transcript or genome mapping by comparing the minimal edit distance to the reference. Local realignment was performed within in-house short reads aligner with smaller k-mer size (k=11). Finally, fragments per kilobase of exon per million fragment mapped (FPKM) values were calculated for each UCSC gene while considering strand-specific information.	Co-expression
SRP097668	The transition from proliferation to quiescence in glioblastoma stem-like cells requires Ca2+ signaling and mitochondria remodeling	Quiescence is a reversible cell-cycle arrest used by Cancer Stem Cells (CSCs) to evade killing following conventional therapies. Quiescent CSCs are therefore one of the main cause of cancer recurrence. In glioblastoma, the most common and aggressive primary brain tumors, the quiescent glioblastoma stem-like cells (GSCs) are localized in hypoxic and acidic microenvironments and microenvironmental changes can control cell cycle re-entering of the GSCs. Here, we show that proliferating GSCs isolated from patients can be induced and maintained in a quiescent state by lowering the extracellular pH. Through RNA-seq analysis we characterized the RNA signatures of quiescent versus proliferating GSCs. We identified genes involved in the control of Ca2+ signaling and differentially expressed between the two states. Using the bioluminescent Ca2+ reporter EGFP-aequorin targeted to the mitochondria or the cytosol we explored the changes in Ca2+ homeostasis occurring during the switch from proliferation to quiescence. This remodeling is controlled through store-operated channels (SOCs). SOCs play a causal role since the inhibition of the Ca2+ influx through SOC drives proliferating GSCs to quiescence. We showed that the switch to quiescence is characterized by both an increased capacity of GSCs' mitochondria to capture Ca2+ and a dramatic and reversible change of mitochondrial morphology from a tubular to a donut shape. Our data suggest that the remodeling of the Ca2+ homeostasis and the reshaping of mitochondria during the transition from proliferation to quiescence constitute a protective mechanism that favors cancer stem-like cells' survival and their aggressiveness in glioblastoma. Overall design: To establish RNA signatures of proliferative and quiescent GSLCs we have adopted the following strategy. Several experiments were performed in order to take into account different type of variabilities (Table S1); (1) Variability due to laboratories environments; experiments have been done in two laboratories ( Strasbourg and Toulouse) following identical protocols. The cells were obtained from the same master cell bank and the composition of the growing media was identical. (2) Cellular variability: two cell lines TG1 and OB1 were used. (3) Variability in inducing quiescence; the switch to quiescent state was obtained by either the non replacement of the medium during 9 days, acidification of the medium to pH 6.5 or 6.2 for 5 days or treatment of the cell by 10 µM SKF-96365 in the growing medium (pH 7.4) at day 1 and 3 and analysis at day 5. In normal medium at pH 7.4, the cells are in a proliferative state. Total RNA was extracted as described above and RNA quality was controlled with AATI Fragment Analyser (Advanced Analytical Technologies, Inc). RNA-seq was obtained from the IGBMC platform and the short reads were aligned using the reference genome hg38 (http://genomeast.igbmc.fr). The Qlucore software (http://www.qlucore.org) was used for the analysis.	Co-expression
SRP097671	Differential Gene Expression between ATRA treated and control HL-60 Cells [RNA-seq]	These RNA-seq data were generated to correlate with genomic interaction data in a related Hi-C analysis. Analysis revealed differential expressed genes in ATRA treated and control HL-60 cells. Changes of gene expression with topological associated domains (TADs) were showd to be correlated with chromatin structure alteration Overall design: HL-60 cells with ATRA or ethanol treated for 4 days were used to generate RNA-seq library, in replicate.	Co-expression
SRP097673	Transcriptome Profiling of Influenza A Virus-infected Lung Epithelial (A549) Cells with Lariciresinol-4-ß-D-glucopyranoside Treatment	The influenza A virus is an acute contagious pathogen that affects the human respiratory system and can cause severe lung disease and even death. Lariciresinol-4-ß-D-glucopyranoside is a lignan that is extracted from Isatis indigotica, which is a medicinal herb plant that was commonly applied to treat infections, the common cold, fever and inflammatory diseases. Our previous study demonstrated that lariciresinol-4-ß-D-glucopyranoside possesses anti-viral and anti-inflammatory properties. However, the comprehensive and detailed mechanisms that underlie the effect of lariciresinol-4-ß-D-glucopyranoside interventions against influenza virus infection remain to be elucidated. In this study, we employed high-throughput RNA sequencing (RNA-seq) to investigate the transcriptomic responses of influenza A virus-infected lung epithelial (A549) cells with lariciresinol-4-ß-D-glucopyranoside treatment. The transcriptome data show that infection with influenza A virus prompted the activation of 368 genes involved in RIG-I signalling, the inflammatory response, interferon?????signalling and gene expression that was not affected by lariciresinol-4-ß-D-glucopyranoside treatment. Lariciresinol-4-ß-D-glucopyranoside exerted its pharmacological actions on the immune system, signal transduction, cell cycle and metabolism, which may be an underlying defence mechanism against influenza virus infection. In addition, 166 differentially expressed genes (DEGs) were uniquely expressed in lariciresinol-4-ß-D-glucopyranoside-treated cells, which were concentrated in the cell cycle, DNA repair, chromatin organization, gene expression and biosynthesis domains. Among them, six telomere-associated genes were up-regulated by lariciresinol-4-ß-D-glucopyranoside treatment, which have been implicated in telomere regulation and stability. Collectively, we employed RNA-seq analysis to provide comprehensive insight into the mechanism of lariciresinol-4-ß-D-glucopyranoside against influenza virus infection. Overall design: We used RNA-seq technology to systematically assess the transcriptome profile of influenza A virus-infected lung epithelial (A549) cells following lariciresinol-4-ß-D-glucopyranoside treatment	Co-expression
SRP097684	Canonical and non-canonical regulatory roles of androgen receptor variant 7 in prostate cancer	The androgen receptor splice variant 7 (AR-V7) lacks the ligand-binding domain; is detected with increased frequency in advanced prostate cancer and is postulated to be one crucial mechanism for disease progression and therapeutic resistance to androgen deprivation in castration–resistant prostate cancer (CRPC). Targeting AR-V7 or unique downstream targets could provide novel therapeutic approaches for CRPC. Here, we report that, independent of ligand, AR-V7 binds not only to the androgen-responsive element (ARE) sites inducing canonical AR signaling but also to non-canonical target sites where ligand-stimulated full-length AR (AR-FL) does not bind. These AR-V7 “solo” binding sites are mainly found at gene promoters and are co-occupied by a zinc-finger transcription factor ZFX and the co-activator BRD4, both of which physically interact with AR-V7. Consequently, AR-V7 not only recapitulates AR-FL action without androgen but uniquely regulates transcripts correlating with AR-V7 expression in the TCGA prostate cancer cohort. Mechanistically, ZFX appears to function as a pioneer factor for AR-V7 at solo-binding sites and BRD4 inhibitors but not anti-androgens suppress AR-V7 action at solo-binding sites as well as AR-V7-dependent growth. Additionally, knockdown of ZFX, or two downstream targets uniquely co-activated by AR-V7 (ZNF32 and FZD6), also suppressed growth of AR-V7-dependent CRPC cells. AR-V7 directly activated genes differentiate tumor from normal prostate tissues and predict poor prognosis in patients. Thus AR-V7 has both canonical and non-canonical regulatory functions in CRPC, which may provide new therapeutic avenues. Overall design: mRNA profiles of knocking down AR-FL, AR-V7 or control vector in 22Rv1 cells were generated by deep-sequencing, in duplicate. mRNA profiles of knocking down ZFX or control vector in 22Rv1 cells were generated by deep-sequencing, in duplicate. mRNA profiles of 22Rv1 cells which were charcoal stripped for 3 days and then treated with vehicle, DHT, DHT plus MDV3100 or DHT plus JQ1 were generated by deep-sequencing, in duplicate. Examination of the genome-wide binding of full-length androgen receptor (AR-FL), AR-V7, Brd4 and ZFX in an castration-resistant prostate cancer cell line in the presence of different drug treatments.	Co-expression
SRP097696	Transcriptomic Analysis of Endothelial Cells from Fibrovascular Membranes in Proliferative Diabetic Retinopathy	Purpose: Identification of RUNX1 via next-generation sequencing (NGS) of fibrovascular membranes in patients with proliferative diabetic retinopathy. Methods: Transcriptomic analysis with Illumina HiSeq2000 of fibrovascular membrane and control retina CD31+ samples. The sequence reads were analyzed with ANOVA (ANOVA) and targets with significance (fold change > +/-1.5 and p-value < 0.05) were selected for with Cufflinks, DeSeq2, Partek E/M, and EdgeR. qRT–PCR validation was performed using SYBR Green assays along with Western blots, siRNA, and MUSE proliferation assays. Results: Using an optimized data analysis workflow, we mapped sequence reads per sample to the human genome (hg19) and identified genes that were statistically significant in all four statistical packages. P-values ranged from 8.78E-10 to 0.05. Using this gene list for ontology, highly significant annotation clusters included inflammatory, vascular development, and cell adhesion pathways. Conclusions: Our study represents the first detailed transcriptomic analysis of CD31+ cells from fibrovascular membrane and CD31+ cells from control retinas with biologic replicates, generated by RNA-seq technology. The preferential selection of inflammatory and angiogenic pathways using this gene list is highly consistent with DR pathogenesis, which involves leaky and aberrant vessel growth. Overall design: CD31+ retinal mRNA profiles were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.	Co-expression
SRP097735	Neuroblastoma cells undergo transcriptomic alterations during dissemination into the bone marrow and subsequent tumor progression	Background: Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of stage M patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle in the treatment of neuroblastoma patients, their transcriptomic profile was not intensively analyzed so far. Results: RNA-Seq of stage M primary tumors, enriched BM-derived DTCs and the corresponding non-tumor mononuclear cells (MNCs) revealed that DTCs largely retained the gene expression signature of tumors. However, we identified 322 genes that were differentially expressed (q < 0.001, |log2FC|>2). Particularly genes encoded by mitochondrial DNA were highly up-regulated in DTCs, whereas e.g. genes involved in angiogenesis were down-regulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8x10-75 log2FC > 6). Interestingly, we found that the gene expression profiles of diagnostic DTCs largely resembled those of relapse DTCs with only 113 differentially expressed genes under relaxed cut-offs (q < 0.01, |log2FC| > 0.5). Notably, relapse DTCs showed a positional enrichment of 31 down-regulated genes encoded by chromosome 19, including five tumor suppressor genes (SIRT6, PUMA, STK11, CADM4 and GLTSCR2).  Conclusion: This first RNA-Seq analysis of DTCs from neuroblastoma patients revealed their unique expression profile in comparison to the corresponding MNCs and tumor samples, and, interestingly, also expression differences between diagnostic and relapse DTCs preferentially affecting chromosome 19. As these alterations might be associated with treatment failure and disease relapse, they should be considered for further functional studies. Overall design: Tumor (n=16), bone marrow-derived disseminated tumor cells (n=42) and corresponding bone marrow-derived non-tumor cells (n=28) of stage M neuroblastoma patients were used for RNA-Seq	Co-expression
SRP097736	Progesterone Receptor- and FOXO1-dependent transcriptomes decidualized human endometrial stromal cells	We report the gene expression profile of primary human endometrial stromal cells treated for 48 hours with control non-targeting, PGR-targeting, or FOXO1-targeting siRNA prior to decidualization stimulus for 72 hours. Overall design: RNA-seq in decidualizing human endometrial stromal cells	Co-expression
SRP097744	A sister of NANOG regulates genes expressed in pre-implantation human development	We examined the ability of human NANOGNB to regulate gene expression by ectopically expressing the gene in human dermal fibroblasts. Overall design: NANOGNB and an empty control vector were transfected individually to drive ectopic expression in human dermal fibroblasts, in triplicate.	Co-expression
SRP097792	Homo sapiens Raw sequence reads	These are 6-ethylthioinosine-resistant and non-resistant Primary Effusion Lymphoma (PEL) subclones of the BC-3 cell line.	Co-expression
SRP097870	RNA-seq analysis of the effects of BCL6-inhibiting and BCL6-degrading compounds in lymphoma cell lines	The goal of this experiment is to measure the changes in gene expression induced by small molecules that either inhibit the interaction of the transcription factor BCL6 with co-repressor proteins, or that induce degradation of BCL6, in lymphoma cell lines. Overall design: Treatment of various cell lines with saturating amounts of BCL6-inhibitors/degraders for 24 and 168 hours.	Co-expression
SRP097892	Rational targeting of RNA structure in SMN2 transcripts reverses Spinal Muscular Atrophy molecular phenotypes	Marine natural compound homocarbonyltopsentin PK4C9 is a small TSL2-binding molecule which was identified to increase exon 7 splicing to therapeutic levels and rescue downstream molecular alterations in SMA cells. To assess the functionality of the restored SMN protein, we studied whether PK4C9 could modify SMN-mediated splicing events using RNA sequencing data from PK4C9-treated (40 microM, 24 h) vs. DMSO-treated GM03813C fibroblasts. The data was also used to find shared motifs amongst PK4C9-sensitive splicing events, in order to contribute to the description of the mechanism of action of PK4C9 and to help identify off-targets. Overall design: Examination of 4 total-RNA replicates of DMSO-treated GM03813C fibroblasts (control) and 4 replicates of PK4C9-treated (40 microM, 24 h) GM03813C fibroblasts (GM03813C is a fibroblast cell line derived from a type I SMA patient).	Co-expression
SRP097912	Transcriptome-wide response to synthetic chromatin protein PcTF	The goal of this study was to identify genes that become upregulated in response to a synthetic transcription factor, PcTF. PcTF contains a conserved H3K27me3-binding chromodomain expressed in-frame with an mCherry fluorescent tag and a VP64 activation domain. Therefore, we expected genes with H3K27me3-associated promoters to become upregulated upon PcTF expression. We observed that hundreds of genes became up or downregulated. Overall design: Total RNA was extracted from PcTF-transfected U-2 OS, K562, or SK-N-SH cells, or from a stable U-2 OS cell line that carried a dox-inducible transgene that expressed either full-length PcTF or a truncated "delta-TF" peptide that lacked the histone-binding domain.	Co-expression
SRP097916	Analysis of UCA1 in Ovarian Cancer	UCA1 is an oncogene in ovarian cancer (OC). UCA1 was knocked down in OC cell lines and RNA-sequencing performed to profile the target genes.	Co-expression
SRP097979	Next Generation Sequencing of Gene expression changes in U2OS osteosarcoma cells with PML silencing	We used next generation sequencing to analyze the gene expression changes in U2OS osteosarcoma cells expressing shRNA targeting the promyelocytic leukemia (PML) gene transcripts Overall design: cDNA libraries of U2OS cells expressing control shRNA or shRNA targeting PML were generated from one biological replicate	Co-expression
SRP097980	RNA sequence method comparisons	Project comparing RNA prep and sequencing methods, as well as alignment and analysis methods.	Co-expression
SRP098089	Human Adult Sorted Live Cell Erythroblasts transduced with Sigma non-targeting shRNA negative control (SHC002V) with puromycin selection RNAseq	Erythroblasts cultured from mobilized CD34+ cells from six healthy adult human donors were used to generate an erythroblast transcriptome transduced with Sigma non-targeting shRNA negative control . Cellular maturation was maintained including enucleation.  On culture day 14 total RNA was isolated (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). We would like to thank Gerard Bouffard and the National Human Genome Research Institute for their expertise and assistance with RNA-seq. Overall design: Human CD34+ cells from health donor transduced with lentivirus expressing Sigma non-targeting shRNA negative control in serum free culture.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction.	Co-expression
SRP098102	Memory CD4+ T cell subsets show differential responses to HIV latency reversing agents [LARA]	HIV-1 persists in individuals on ART in infected central (CM), transitional (TM) and effector memory (EM) CD4+ T cells. We developed LARA (latency and reversion assay), which facilitates the examination of HIV latency reversal in CM, TM and EM subsets in a single assay. Studies with latency reversing agents (LRAs) revealed responses specific to each subset, including compounds that significantly reversed latency in all subsets but with a range of efficiency (bryostatin) to those that demonstrated subset specificity (IL-15). Significantly, LARA has allowed the demonstration that EM cells display a more activated profile compared to CM, which translated to enhanced efficiency in responsiveness to multiple LRAs and allowed the identification of mechanisms associated with the compounds that reactivate latent HIV in all subsets. Understanding the responsiveness of memory CD4+ T cells subsets to LRAs will accelerate the development of anti-latency therapy to interfering with viral persistence in vivo. Overall design: RNA-Seq was performed on samples generated in LARA from ex vivo (day 0) and in vitro culture (day 14) cells sorted on memory CD4+ T cell CM, EM and TM subsets.	Co-expression
SRP098103	Memory CD4+ T cell subsets show differential responses to HIV latency reversing agents [LRA stimulated]	HIV-1 persists in individuals on ART in infected central (CM), transitional (TM) and effector memory (EM) CD4+ T cells. We developed LARA (latency and reversion assay), which facilitates the examination of HIV latency reversal in CM, TM and EM subsets in a single assay. Studies with latency reversing agents (LRAs) revealed responses specific to each subset, including compounds that significantly reversed latency in all subsets but with a range of efficiency (bryostatin) to those that demonstrated subset specificity (IL-15). Significantly, LARA has allowed the demonstration that EM cells display a more activated profile compared to CM, which translated to enhanced efficiency in responsiveness to multiple LRAs and allowed the identification of mechanisms associated with the compounds that reactivate latent HIV in all subsets. Understanding the responsiveness of memory CD4+ T cells subsets to LRAs will accelerate the development of anti-latency therapy to interfering with viral persistence in vivo. Overall design: CD4 T cells were isolated from a cohort of Florida HIV-infected subjects that have been on successful ART for >36 months with a viral load =50 copies/mL. Three subjects in this cohort have previously been characterized according to their reservoir size (pDNA copies/million CD4) and relative distribution of the reservoir in memory CD4 T cell subsets namely central memory (TCM), transitional memory (TTM) and effector memory (TEM) CD4 T cells (R. Fromentin & N. Chomont unpublished data). We compared different classes of agents including PKC activators (Bryostatin), gamma-c cytokines (IL-15) and PMA+Ionomycin in their ability to induce viral transcription in the sorted memory CD4 T cell subsets. RNA from the sorted and 24h-stimulated subsets were purified. Unstimulated sorted cells from the same donors were included as pre-reactivation baseline controls.	Co-expression
SRP098104	RNA sequencing of erythroid and granulomonocytic colonies differentiated from transduced bone marrow CD34+ cells expressing U2AF1 S34F mutation, U2AF1 wild-type or empty vector control	Mutations of the splicing factor U2AF1 are frequent in the myeloid malignancy myelodysplastic syndromes (MDS) and in other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and increasing bone marrow blasts. We investigated the impact of the common U2AF1 S34F mutation on cellular function and mRNA splicing in the main cell lineages affected in MDS. We demonstrated that U2AF1 S34F expression in human hematopoietic progenitors impairs erythroid differentiation, and skews granulomonocytic differentiation towards granulocytes. RNA-sequencing of erythroid and granulomonocytic colonies revealed that U2AF1 S34F induced a higher number of cassette exon splicing events in granulomonocytic than erythroid cells, and altered mRNA splicing of many transcripts (expressed in both cell types) in a lineage-specific manner. The introduction of isoform changes identified in the target genes H2AFY and STRAP into hematopoietic progenitors recapitulated phenotypes associated with U2AF1 S34F expression in erythroid and/or granulomonocytic cells, suggesting a causal link. Importantly, we provided evidence showing that isoform modulation of the U2AF1 S34F target genes H2AFY and STRAP rescues the erythroid differentiation defect in U2AF1 S34F MDS cells, raising the possibility of using splicing modulators therapeutically. These data have critical implications for understanding MDS phenotypic heterogeneity, and for the development of new targeted therapies. Overall design: RNA sequencing was performed to identify the aberrant splicing events associated with U2AF1 S34F mutation (n=3) compared to U2AF1 wild-type (n=3) and empty vector control (n=3) in BFU-E and CFU-G/M colonies respectively.	Co-expression
SRP098107	A next generation sequencing based approach to identify extracellular vesicle mediated mRNA transfers between cells	Purpose: Exosomes and other extracellular vesicles (EVs) have emerged as an important mechanism of cell-to-cell communication. In this work, we present a novel next generation of sequencing (NGS) based approach to identify EV mediated mRNA exchanges between co-cultured adipocyte and macrophage cells. Methods:We performed molecular and genomic profiling and jointly considered data from RNA sequencing (RNA-seq) and genotyping to track the 'sequence varying mRNAs' transferred between cells. Results: We identified 8 mRNAs being transferred from macrophages to adipocytes and 21 mRNAs being transferred in the opposite direction. These mRNAs represented biological functions including extracellular matrix, cell adhesion, glycoprotein, and signal peptides. Conclusions: Our study sheds new light on EV mediated RNA communications between adipocyte and macrophage cells, which may play a significant role in developing insulin resistance in diabetic patients. This work establishes a new method that is widely applicable to examining genetic material exchanges in many other cellular systems. Overall design: Our main experiment was performed on an in-vitro co-culture cellular system, in which two types of human cells (adipocytes and macrophages) were cultured in the same dish but separated by a porous membrane to prevent them from being mixed together (see Methods). The porous membrane allows small particles (size less than 0.4 µm) to pass through, making EV mediated mRNA exchanges between the two cell lines possible. ADMO_qc_GRCH38.txt contains genotypes of genotype of Adipocytes and Macrohpages	Co-expression
SRP098166	Peptidomimetic blockade of MYB in acute myeloid leukemia [RNA-seq]	Aberrant gene expression is a hallmark of acute leukemias. However, therapeutic strategies for its blockade are generally lacking, in large part due to the pharmacologic challenges of drugging transcription factors. MYB-driven gene trans-activation with CREB-binding protein (CBP) is required for the initiation and maintenance of a variety of acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a prototypical peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP complex at ¼M concentrations and rapidly accumulates in the nuclei of AML cells. We found that treatment of AML cells with MYBMIM, but not with its inactive near-isosteric analogue TG3, led to the displacement and dissociation of MYB:CBP complex in cells, displacement of MYB from oncogenic enhancers and promoters enriched for MYB binding sites, and rapid downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes. Both human MLL-rearranged and non-rearranged AML cells, but not normal CD34+ umbilical cord blood progenitor cells, underwent sustained mitochondrial apoptosis in response to MYBMIM treatment, an effect that could be partially rescued by ectopic expression of BCL2. We observed that MYBMIM treatment impeded leukemia growth and extended survival of immunodeficient mice engrafted with primary patient-derived MLL-rearranged leukemia cells. These findings emphasize the exquisite dependence of human AML on MYB:CBP transcriptional dysregulation, and establish a pharmacologic approach for its therapeutic blockade. Overall design: RNA-sequencing of human leukemia cell line with MYB peptide mimic and controls.	Co-expression
SRP098484	Analysis of Fusobacterium persistence and antibiotic response in human colorectal cancers	Total RNA sequencing data from primary colorectal tumors, liver metastasis and patient derived xenographs. Persistence of Fusobacterium and co-occuring anaerobic bacteria in human colorectal cancer.	Co-expression
SRP098571	Regulation of Lipids is Central to Replicative Senescence	Cellular replicative senescence, a state of permanent cell-cycle arrest that occurs following an extended period of cell division in culture, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblast cells. We found that both the expression levels of lipid-regulating genes, as well as the abundance of specific lipid families, are actively regulated. We further found that 19 polyunsaturated triacylglycerol species showed the most prominent changes during replicative senescence. We argue that diversion of polyunsaturated fatty acids to glycerolipid biosynthesis could be responsible for the accumulation of specific triacylglycerols. This, in turn, could be one of the cellular mechanisms to prevent lipotoxicity under increased oxidative stress conditions observed during replicative senescence. Collectively, our results place regulation of specific lipid species to a central role during replicative senescence. Overall design: We sequence total RNA from 3 early PD and 3 senesent human BJ cell lines to detect the expressional differences between early PD and senescent cells.	Co-expression
SRP098574	Cancer-specific retargeting of BAF complexes by a prion-like domain [RNA-Seq]	Alterations in the function of transcriptional regulators can orchestrate oncogenic programs that are critical for the transformation and survival of cancer cells. Here we show that the BAF chromatin remodeling complex, which is mutated in over 20% of human tumors, interacts with EWSR1, a member of the FET family of proteins containing prion-like domains that are frequent partners in oncogenic fusions with transcription factors. In Ewing sarcoma, characterized by the EWS-FLI1 fusion, we find that the BAF complex is recruited by EWS-FLI1 to tumor specific enhancers at GGAA microsatellite repeats and contributes to the activation of target genes. This process depends on tyrosine residues that are necessary for the aggregation properties of the EWSR1 prion-like domain and is a neomorphic feature of EWS-FLI1 compared to the wild type ETS transcription factor FLI1. Furthermore, fusion of short fragments of the EWSR1 prion-like domain to FLI1 is sufficient to recapitulate EWS-FLI1-mediated gene expression. Our studies demonstrate that the aggregation properties of prion-like domains can retarget chromatin regulatory complexes to establish and maintain oncogenic gene expression and proliferation. Overall design: Ewing sarcoma cell lines (A673 and SK-N-MC) were analyzed by RNA-seq. EWS-FLI1 was depleted by infection with lentiviral shRNAs (shFLI1 and shGFP control).   Mesenchymal stem cells (MSCs) were analyzed by RNA-seq. EWS-FLI1, wild-type FLI1 and the mutant proteins EWS(YS37)-FLI1, SYGQ2-FLI1 and BAF47-FLI1 were expressed in MSCs with lentiviral expression vectors. In a separate experiment, MSCs were also co-infected with lentiviral shRNA targeting the BAF complex subunit BRG1/SMARCA4 and with a lentiviral vector expressing EWS-FLI1. Raw data not provided for primary cells due to patient privacy concerns. Submitter states that the raw data for these samples will be submitted to dbGaP.	Co-expression
SRP098649	Fatal Asthma and Non-Asthma Donor-Derived Airway Smooth Muscle Transcriptome Response to Glucocorticoid Treatment	Asthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity.  We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors. RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control.  Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads. Overall design: Transcriptome profiles obtained via RNA-Seq for airway smooth muscle cells from 9 fatal asthma and 8 non-asthma donors treated with budesonide (100nM for 24h) or vehicle control were compared	Co-expression
SRP098651	Leucegene: bone marrow sequencing from human normal tissue	Normal human  Bone marrow RNAseq Overall design: RNA-Seq of normal bone marrow from human	Co-expression
SRP098661	Hepatocyte maturation	We report the maintenance of mature metabolic function and their induction in primary and hepatic cell lines respectivvely Overall design: Screening of small molecule pathway inhibitors for hepatic maturation	Co-expression
SRP098688	Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [HCT RNA-Seq]	Growth factors (GFs) suppression by steroid hormones  recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids. Overall design: RNA-Seq – EGF treatemnt for 60 min of WT and DNMT1a and DNMT3b double-knockout HCT116 cells	Co-expression
SRP098694	Transcriptome characterization of human periodontal ligament cell clones (DMEM medium)	In this study, we purified periodontal ligament cell clones committed to osteoblastic/cementoblastic phenotype (C-O clones) and clones committed to fibroblastic phenotype (C-F clones), and employed RNA-seq to describe the differential transcriptional profile of osteoblastic/cementoblastic and fibroblastic cell clones from human periodontal ligament. The understanding of differences in periodontal ligament subpopulations can help to elucitade the favorable to formation of mineralizing and non-mineralizing tissues of periodontium.	Co-expression
SRP098695	Transcriptome characterization of human highly osteoblastic/cementoblastic periodontal ligament cell clones (OM medium)	In this study, we purified periodontal ligament cell clones committed to osteoblastic/cementoblastic phenotype (C-O clones) and clones committed to fibroblastic phenotype (C-F clones), and employed RNA-seq to describe the differential transcriptional profile of osteoblastic/cementoblastic and fibroblastic cell clones from human periodontal ligament. The understanding of differences in periodontal ligament subpopulations can help to elucitade the favorable to formation of mineralizing and non-mineralizing tissues of periodontium.	Co-expression
SRP098699	RNA sequencing of primary human platelets and in vitro cell lines	Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes. We use RNA sequencing of synchronized populations of in vitro derived platelet-like particles (PLPs) to show that mRNA decay strongly shapes the nascent platelet transcriptome. Our data suggests that the decay of platelet mRNAs is slowed by the natural loss of the mRNA surveillance and ribosome rescue factor Pelota (PELO). Overall design: Analysis of RNA sequencing data from primary human platelets and in vitro derived platelet-like particles; manipulation by overexpression of Pelota (PELO) in Meg01/platelet-like particles.	Co-expression
SRP098713	Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging	The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis. Overall design: mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate	Co-expression
SRP098715	Time-course RNA-sequencing of human induced regulatory T cell (iTreg) differentiation	Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first- in-man trials of Treg transfer achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by: a targeted shRNA screen confirming a functional role in FOXP3 induction; discriminant analyses classifying iTregs accordingly; and comparable expression in an independent novel iTreg RNA-Seq data set. The data generated by this novel approach facilitate understanding the molecular mechanisms underlying iTreg generation as well as the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune and inflammatory diseases. Overall design: We performed a time-course experiment including six time points and four iTreg differentiation conditions. We included also a control time series and unstimulated nTregs. Three biological replicates were included. The total sample count is 81. In detail, human naïve CD4+ T cells were magnetically negatively isolated from peripheral blood. Cells were stimulated in serum-free medium with anti-CD3/anti-CD28 antibodies plus IL-2, and samples were taken at 2h, 6h, 24h, 48h and 6d of stimulation. Mock stimulation control cells (sample group G02) received no further compounds, whereas induced regulatory T cells (iTregs) were either differentiated under addition of TGF-b (sample group G03), TGF-b + retinoic acid (sample group G04), TGF-b + retinoic acid + rapamycin (sample group G05) or TGF-b + butyrate (sample group G06). As control, naïve CD4+ T cells were left unstimulated (0h; sample group G01). Ex vivo isolated CD25-high cells were included as positive control for the Treg signature (“nTreg”; sample group G07). Tregs were defined by expression of FOXP3, the “master” transcription factor of Tregs.	Co-expression
SRP098730	Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [IMR90_MCF7_RNA-Seq]	Growth factors (GFs) suppression by steroid hormones  recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids. Overall design: RNA-Seq – EGF or dexamethasone (DEX) treatemnt for 60 min of MCf7 and IMR90 cells	Co-expression
SRP098735	Interrogation of functional cell surface markers identifies CD151 dependency in high-grade serous ovarian cancer	The high degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC. Overall design: 40 epithelial ovarian cancer cell lines and one immortalized line derived from ovarian surface epithelium (OE-E6/E7)	Co-expression
SRP098746	DND1 PAR-CLIP in human HEK293 and mouse germ line cells	DND1 destabilizes target mRNAs in germline development by recruitment of the CCR4-NOT deadenylation complex	Co-expression
SRP098757	Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate.	The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3''-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3''-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis. Overall design: RNA profiles of HeLa cells treated with PHAX, ZC3H18 and control siRNAs were generated by paired-end sequencing, in triplicated samples. iCLIP experiments were carried out on the CBP20, ARS2, PHAX, and ZC3H18 proteins in HeLa and HEK293 cells. Two replicates per protein were used.	Co-expression
SRP098758	A blood RNA signature for tuberculosis disease risk in household contact study - GC6 cohort.	Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis  infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic in the context of house hold contacts. Overall design: Samples are collected from subjects in a household contact study after a person comes back to the household, diagnosed with TB. Samples are collected every 6 months upto, 18 months. Some people go on to develop TB (cases)  where as some others do not (controls). Here we are trying to establish a gene signature to predict the occurance of TB.	Co-expression
SRP098761	Comprehensive analysis of gene expression in human retina and supporting tissues	Purpose: To identify the differences of gene expression between the macula and periphery of the eye. Methods: RNA Seq was performed on 8 normal postmortem eyes. Results: Significant differential expression was found between the layers of the posterior part of the eye and also between locations of a tissue layer. Conclusions: These results potentially provide a path to more rapidly elucidate not only the genetic basis of eye disease but also the impact of gene expression on molecular networks that in turn induce variations in disease associated traits. Overall design: Retinal and RPE/choroid/sclera RNA profiles from macula and periphery of each eye were generated by deep sequencing on an Illumina Hi-Seq. 32 biological samples were analyzed.	Co-expression
SRP098784	MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia [mutant MEF2C]	In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that transgenic Mef2cS222A/S222A mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, induced by MARK kinases in cells, and blocked by selective MARK inhibitor MRT199665, which caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C. These findings identify signaling-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease. Overall design: RNA-sequencing of human leukemia cell line with induction of wildtype or mutant MEF2C.	Co-expression
SRP098887	H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers [K562]	Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factors SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Although cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, clinical means to therapeutically target the spliceosome do not currently exist. Here, we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and selectively kills spliceosome-mutant epithelial and hematologic malignancies. The effects of H3B-8800 are entirely selective for the Sf3b complex, as evidenced by the identification of drug-resistant cells bearing mutations in Sf3b components. Although H3B-8800 modulates RNA splicing mediated by WT or cancer-associated SF3B1 mutants, its preferential effects on spliceosome-mutant cells is due to preferred retention of short, GC-rich introns, which are enriched in genes encoding a substantial number of spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers. Overall design: 12 samples, including both SF3B1 WT and mutant isogenic K562 cell lines with and without 13nM treatment with H3B-8800, in triplicate	Co-expression
SRP098903	Epigenetic repression via DNA methylation and trimethylation of H3K27 alters gene expression in esophageal adenocarcinoma [RNA-Seq]	Epigenetic modifications in the form of altered DNA or histone methylation can influence gene expression patterns critical for neoplastic initiation and progression. The fact that abnormal gene expression can be driven by epigenetic alterations led us to examine the correlation between DNA methylation, trimethylation of histone 3 lysine 9 (H3K9me3) and lysine 27 (H3K27me3), and gene expression in esophageal adenocarcinoma (EAC). Using genome-wide approaches (chromatin immunoprecipitation/sequencing (ChIP-Seq) and methylation arrays), we identified gene targets that were enriched with the chromatin-repressive marks H3K9me3, H3K27me3, and/or DNA hypermethylation across patients with EAC. Using RNA-Seq, we found genes involved in cellular morphology and movement, epithelial cell differentiation, epithelial junction signaling, as well as genes involved in epithelial-mesenchymal transition (EMT) were down-regulated in patients with poorly differentiated EAC. Additionally, comparative analyses of ChIP-Seq, DNA methylation, and RNA-Seq data allowed us to identify a group of genes downregulated in EAC is associated with aberrant H3K27me3 enrichment or a combination of H3K27me3 and DNA hypermethylation in the poorly differentiated EAC cases. Furthermore, by comparison to TCGA data sets, H3K27me3 enrichment is associated with aberrant DNA methylation across numerous EAC cases, suggesting that dysregulation of H3K27me3 and DNA methylation is crucial in the pathogenesis of EAC. Overall design: Total RNA was extracted using TRIzol reagent (Invitrogen/Life Technologies #15596-026) and sequencing libraries were generated with Illumina RNA-Seq library preparation kit with Ribozero. RNA deep-sequencing for paired-end 36 base pair reads was run at Illumina HiSeq2500; subsequently, 325 million pass filtered reads of each specimen were aligned to hg19. DESeq was used to normalize raw read counts. Cuffdiff was applied to analyze the differential gene expression between EAC and control (SQ) using a log2(fold change) of 1.0 as a cut-off for gene experssion.	Co-expression
SRP098905	Effect of MDK expressing Melanoma cells conditioned media in Human LEC	Gene expression analysis in hLECs treated with gain of function or loss of function of MDK in human melanoma cells. Overall design: Biological triplicates of hLEC treated for 3 days with EGM-2 MV conditioned media of melanoma cells. Cell line SK-Mel-147 KD for MDK (shMDK) and its corresponding control (shCtrl (LoF) and WM164 cell line overexpressing MDK (MDK)  or an empty vector (NEG) (GoF) were used to produce the conditioned media.	Co-expression
SRP098915	Single Cell RNA-Sequencing Identifies Diverse Roles of Epithelial Cells in Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease causing alveolar remodeling, inflammation, and fibrosis. We utilized single cell RNA-sequencing (scRNA-Seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of epithelial cells from normal human lung defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified three distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and, an additional atypical "transitional" cell that contribute to pathological processes in IPF. Individual IPF cells frequently co-expressed alveolar AT1, AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-ß, HIPPO/YAP, P53, and AKT-PI3 Kinase. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. Single cell transcriptomic analyses of respiratory epithelial cells identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. Present scRNA-seq transcriptomic analysis of normal and IPF respiratory epithelial cells provides a rich data source to further explore lung health and disease. Overall design: Dissociated single-cell preparations from peripheral lung of IPF patients (n = 3) and controls (n = 3) from cohort 2 were enriched for AT2 epithelial cells by FACS for CD326 (CD326) double positive, CD45 (hematopoietic) negative, CD31 (endothelial) negative cells, and HTII-280 after dissociation by proteases.	Co-expression
SRP098926	Identification of MELK-regulated genes in prostate cancer cells using next-generation sequencing	A cross-species analysis identified MELK as a potential therapeutic target in prostate cancer. To further elucidate the functional role of MELK in prostate cancer cells, we aimed to identify MELK-regulated genes. C4-2b cells were either treated with a small-molecule MELK inhibitor (OTSSP167), or transfected with siRNAs targeting MELK. Differentially expressed genes were identified using next-generation sequencing. Our results demonstrate that MELK promotes the expression of genes associated with tumour progression in prostate cancer cells. Overall design: Gene expression profiles of C4-2b cells by RNA-Seq following silencing or inhibition of MELK. Four independent biological replicates were performed for each treatment condition. Two different siRNAs directed against MELK were used to account for potential off-target effects of the siRNAs. Negative controls were cells transfected with AllStars Negative Control siRNA, and cells treated with DMSO (vehicle for OTSSP167).	Co-expression
SRP098939	Long ncRNA Landscape in the Ileum of Treatment Naïve Early Onset Crohn Disease	Objective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells	Co-expression
SRP098968	Transcriptome analysis revealed impaired cAMP responsiveness in PHF21A-deficient human cells	We performed RNA-Seq on PHF21A-deficient patient-dervied lymphoblasts as well as two unaffected individuals. Overall design: We performed RNA-Seq from patient-derived lymphoblast cells. Libraries were polyA-selected and strand-specific according to the protocol described in PMID: 25607527	Co-expression
SRP099002	Dedifferentiated Human Vascular Smooth Muscle Cells are a New Potential Cell Source for Endothelial Regeneration	Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional endothelial lineage facilitated by reprogramming.Human SMCs are first reprogrammed for 4 days to achieve a vascular progenitor state expressing CD34, by introducing transcription factors OCT4, SOX2, KLF4 and c-MYC. These SMC-derived progenitors are then induced along the endothelial lineage.	Co-expression
SRP099016	RNA-seq of Peripheral T-Cell Lymphoma cases and cell lines	Peripheral T-cell lymphoma (PTCL) consists of a group of rare and usually aggressive (fast-growing) non-Hodgkin lymphomas (NHLs) that develop from mature T-cells. This study investigated the transcriptome profiles of several PTCL patients and established cell lines.	Co-expression
SRP099053	RNA sequencing (RNA-SEQ) of 21 HBV-HCC patients with non-neoplastic liver and tumor tissues	Purpose: Chronic Hepatitis B virus (HBV) infection leads to liver fibrosis which is a major risk factor in Hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. HBV genome can be inserted into human genome, and chronic inflammation may trigger somatic mutations. Several studies characterized HBV integration sites in HCC patients with regard to frequently occurring hotspots. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regard to different degree of liver fibrosis is not clearly understood. In this study, we aim to find potential molecular mechanisms underlying tumor recurrence of HBV-associated HCC (HBV-HCC) with different degree of liver fibrosis. Methods: We performed RNA sequencing of 21 pairs of tumor and non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analysis of our RNAseq data and public available sequencing data related to HBV-HCC. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations with sequencing data showed that our method outperformed existing methods.  We also compared SNPs of each sample with SNPs in cancer census database and inferred patient's pathogenic SNP loads in tumor and non-neoplastic liver tissues. Conclusions: The HBV-integration and pathogenic SNP load patterns for HCC recurrence risk vary depending on liver fibrosis stage, suggesting potentially different tumorigenesis mechanisms for low and high liver fibrosis patients. Overall design: Total RNA (1-3µg/sample) extracted from surgical resection specimens were submitted to the Mount Sinai Genomic Core Facility for quality control analysis. The RNA quality was assessed using the Agilent 2100 Bioanalyzer, and the RNA integrity number for all 21 samples measured 8.2 ± 0.7 (mean ± SD). The poly(A)-RNA was captured using oligo-dT beads and used for cDNA library preparation using the standard TruSeq RNA Sample Prep Kit v2 protocol (Illumina, CA, USA). Briefly, total RNA was poly-A selected and then fragmented. The cDNA was synthesized using random hexamers, end-repaired and ligated with appropriate adaptors for sequencing. The library then underwent size selection and purification using AMPure XP beads (Beckman Coulter, CA, USA). The appropriate Illumina recommended 6 bp barcode bases are introduced at one end of the adaptors during PCR amplification step. The size and concentration of the RNAseq libraried was measured by Bioanalyzer and Oubit fluorometry (Life Technologies, NY, USA) before loading onto the sequencer. The mRNA libraries were sequenced on the Illumina HiSeq 2500 System with 100 nucleotide paired-end reads, according to the standard manufacturer's protocol (Illumina, CA, USA).	Co-expression
SRP099071	Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease	During S-phase of the cell cycle production of the core histone proteins is precisely balanced with DNA replication. Metazoan mRNAs encoding replication dependent (RD) histones lack polyA tail normally formed by 3' end cleavage and coupled polyadenylation of the pre-mRNA. Instead, they undergoes to endonucleolytic cleavage on the 3' side of an RNA hairpin (stem loop) producing mRNA with a 3´-stem loop (SL), which is exported from the nucleus for use in translation. The same endonuclease that is involved in normal protein-coding pre-mRNA cleavage, i.e. cleavage and poyladenylation specificity factor 73 (CPSF73), is proposed to catalyse RD pre-histone mRNA cleavage. Additional factors specific to RD pre-histone mRNA processing, including stem loop binding protein (SLBP) and the U7 small nuclear ribonucleoprotein (U7snRNP) that binds to a histone downstream element (HDE) are thought to be involved in CPSF73 targeting to RD pre-histone mRNA. We report that a different histone specific endonuclease (HSE), which like CPSF73 is a metallo ß lactamase (MBL) fold protein, is specific for RD pre-histone mRNA cleavage10,11. Crystallographic and biochemical studies reveal HSE has a di-zinc ion containing active site related to that of CPSF73, but which has distinct overall fold. Notably HSE depletion from cells leads to the production of unprocessed RD pre-histone mRNA due to inefficient 3' end processing. The consequent depletion of core histone proteins correlates with a cell cycle defect due to a delay in entering/progressing through S-phase. HSE thus may represent a new type of S-phase specific cancer target. Overall design: Examination of chromatin mRNA profiles in HeLa cells after depletion of HSE or CPSF73 by siRNA treatment.	Co-expression
SRP099073	Next Generation Sequencing Facilitates Quantitative Analysis of FoxO3 or Geminin/FoxO3 depletion on MDA-MB-231 cells Transcriptomes	We generated 2 Gb of high-quality sequencing data (~1 Gb per sample) and catalogued the expression profiles of 48,162 annotated human genes in each sample. The analysis showed differences of transcriptomes between Control and Geminin/FoxO3 co-depletion expression changes. We identified numerous differentially expressed genes that exhibited distinct expression patterns. These genes are appealing candidates for further investigation of the gene expression and associated regulatory mechanisms by Geminin and FoxO3 . Overall design: MDA-MB-231 mRNA profiles of Control, FoxO3 and Geminin/FoxO3 co-depletion were generated by deep sequencing,  using Illumina HiSeq4000.	Co-expression
SRP099127	The RNA helicase DDX39B regulates IL7R alternative splicing reducing the risk of Multiple Sclerosis	Purpose: The goal of this study is to investigate the role of DDX39B in RNA splicing Methods: RNA-Seq splicing analysis of HeLa cells with experimentally induced DDX39B expression knockdown Overall design: DDX39B expression is reduced in HeLa cells by siRNAs. Effects on alternative RNA splicing are compared between knockdown and control cells.	Co-expression
SRP099137	Global transcriptional profiling using RNA sequencing and DNA methylation patterns in highly enriched mesenchymal cells from young versus elderly women.	Purpose:  Identification of relevant genetic pathways that are altered with aging knowing that the precursors for bone-forming osteoblasts reside in the mesenchymal cell population of bone marrow. Method: harvested and characterized, without in vitro culture, mesenchymal cells form human bone marrow capable of osteogenic differentiation Results:  Identification of differentially regulated genes with aging in a highly enriched human bone marrow mesenchymal cell population. Conclusions:  we have for the first time identified age-related differential gene expression and DNA methylation patterns in a highly enriched human bone marrow mesenchymal cell populationprofiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: Examination of gene expression and DNA methylation patterns from a highly enriched bone marrow mesenchymal cell population from young (mean age, 28.7 years) versus old (mean age, 73.3 years) women	Co-expression
SRP099208	Trypanosoma cruzi mini-exon based mRNA amplification technique	We have developed a method of mRNA amplification based on T7 polymerase, where T7 promoter is attached to a oligonucleotide containing the mini-exon sequence, which will hybridize with cDNA molecules containing the anti-ME sequence Overall design: The method was tested on two different stages of T. cruzi (epimastigotes, Epi and cell-derived trypomastigotes, Trp) and for each one we have two biological replicates (A and B). Each mRNA sample was processed in three distinct ways: poly-A purification (polA), oligo-dT T7 (dT) amplification and oligo-ME T7 (ME) amplification. For the other analyzes, one biological replicate of epimastigotes (EpiA) was selected and processed for the following series of experiments:  mRNA quantity (100ng, 50ng, 25ng, 12.5ng, 6.25ng and 3.125ng); mixed sample with human mRNA (mRNA from HeLa cells, in the following masses (T. cruzi / Human): 100ng/0ng (100%), 100ng/900ng (10%), 10ng/990ng (1%), 5ng/4995ng (0.1%), 10ng/9990ng (0.1%). For the majority of the mixed sample series, Pfx was used as enzyme for 2nd strand synthesis. EpiB was used for mRNA extraction after cell sorting. All samples were processed in two technical replicates (1 and 2). For the cell sorting, there is three technical replicates. There is no technical replicates for the Poly-A samples	Co-expression
SRP099217	A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor	Approved drugs are invaluable tools to study biochemical pathways and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here, we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered the synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these two drugs modulates the stability of the androgen receptor (AR) and resensitizes AR mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for ?-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC might be repurposed to tackle resistance to antiandrogens in prostate cancer patients. Overall design: Two biological replicates were produced for each condition. Drug treatment was compared to vehicle-treated cells.	Co-expression
SRP099280	Human meiotic arrest	Molecular mechanism of human meiotic arrest	Co-expression
SRP099346	High-throughput sequencing of the B-cell receptor in African Burkitt Lymphoma reveals clues to pathogenesis	Endemic Burkitt lymphoma is an aggressive B cell non-Hodgkin lymphoma with the highest incidence in children of sub-Saharan Africa where its distribution is closely associated with Plasmodium falciparum malaria and Epstein Barr virus (EBV) infection. We used high throughput RNA sequencing to analyze human and EBV gene expression, extract immunoglobulin heavy and light chain sequences, and identify nucleotide variants in tumors from patients with histologically confirmed Burkitt lymphoma. Total RNA was extracted using the RNeasy Plus Mini Kit (Qiagen) from 18 cryopreserved tumor biopsies acquired from patients who presented to the Uganda Cancer Institute in Kampala, Uganda. PolyA-selected mRNA sequencing libraries were prepared using the TruSeq kit v2 kit (Illumina) and 50 bp, paired-end sequencing was performed on the Illumina HiSeq 2500 platform at a depth of 100 million reads per sample.	Co-expression
SRP099377	RED-ML: a novel, effective RNA editing detection method based on machine learning	To develop a highly accurate, speedy and general-purpose tool for RNA editing detection using RNA-seq data	Co-expression
SRP099405	A novel role for the EWS portion of EWS/FLI in binding GGAA-microsatellites required for oncogenic transformation in Ewing sarcoma [RNA-Seq]	Ewing sarcoma usually expresses the EWS/FLI fusion transcription factor oncoprotein. EWS/FLI regulates myriad genes required for Ewing sarcoma development.  EWS/FLI binds GGAA-microsatellite sequences in vivo and in vitro, and these sequences provide EWS/FLI-mediated activation to reporter constructs, suggesting that they function as EWS/FLI-response elements.  Genomic GGAA-microsatellites are highly variable and polymorphic.  Current data suggest that there is an optimal “sweet-spot” GGAA-microsatellite length (of 18-26 GGAA repeats) that confers maximal EWS/FLI-responsiveness to target genes, but the mechanistic basis for this was not known.  We now demonstrate the absolute necessity of an EWS/FLI-bound GGAA-microsatellite in regulation of the NR0B1 gene, as well as for Ewing sarcoma proliferation and oncogenic transformation.  Biochemical studies, using recombinant ?22 (a version of EWS/FLI containing only the FLI portion) demonstrated a stoichiometry of one ?22-monomer binding to every two consecutive GGAA-repeats on shorter GGAA-microsatellite sequences.  Surprisingly, the affinity for ?22 binding to GGAA-microsatellites significantly decreased, and ultimately became unmeasureable, when the size of the GGAA-microsatellite was increased to the “sweet-spot” length.  In contrast, a fully-functional EWS/FLI mutant (Mut9) that retains approximately half of the EWS portion of the fusion showed low affinity for smaller GGAA-microsatellites, but instead significantly increased its affinity at “sweet-spot” microsatellite lengths.  Single-gene ChIP and genome-wide ChIP-seq and RNA-seq studies extended these findings to the in vivo setting.  Taken together, these data demonstrate the absolute requirement of GGAA-microsatellites as EWS/FLI activating response elements in vivo and reveal an unsuspected novel role for the EWS portion of the EWS/FLI fusion in binding to optimal-length GGAA-microsatellites. Overall design: The treatments applied to our RNA-seq A673 samples were for EWS/FLI knockdown/rescue experiments. Briefly, A673 cells were stably infected and selected for expression of a control Luc-RNAi or the EF-2-RNAi to knock-down EWS/FLI. Following 4 days of selection, cells were infected with either an empty pMSCV-hygro vector or vector expressing full length type IV EWS/FLI, the Ä22 EWS/FLI mutant, or mut9 EWS/FLI mutant to rescue EWS/FLI (or respective mutant EWS/FLI) expression in these cells.	Co-expression
SRP099436	Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma	Multiple Myeloma (MM) is a frequently incurable hematological cancer in which over activity of MYC plays a central role, notably through upregulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small molecule library for anti-MM activity. The most potent hits identified were rocaglate-scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, our most promising rocaglate. Proteome-wide, reversion correlated with selective depletion of short-lived proteins key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF and MCL-1. The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic relevance of these findings in vivo and supports the feasibility of targeting the oncogenic MYC-driven translation program in MM with rocaglates. Overall design: RNA sequencing of 5 cell lines (NCI-H929, NAMALWA, U266, MM1S and OPM2) treated with CMLD010509 or vehicle control (DMSO)	Co-expression
SRP099457	RNA Sequencing of Pinometostat Sensitive and Resistant Paired Cell Lines	MLL-r cell lines KOPN-8 and NOMO-1 were cultured with pinometostat to derive treatment emergent resistant pools. RNA sequencing was performed on the resistant pools to generate hypotheses around mechanisms of resistance Overall design: RNA-sequencing of KOPN-8 and NOMO-1 cell lines treated long term (ie resistant) and short term (sensitive) with pinometostat, along with DMSO matched controls	Co-expression
SRP099470	RNAseq in sertoli cells infected with Zika virus	Because the Zika virus is sexually transmitted, and reduces fertility in mice, we wanted to know what are the transcriptional abnormalities associated with Zika virus infection in Sertoli cells. Sertoli cells are nurse cells that support spermatogenesis.	Co-expression
SRP099568	EOMES-expressing CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers	The presence of the PTPN22 risk variant (1858T) is associated to several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk variant on T cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve CD4+ T cells carrying two PTPN22 risk alleles overexpress a limited number of genes including CFLAR and 4-1BB important for cytotoxic T cell differentiation. Moreover, an increased number of cytotoxic EOMES+ CD4+ T cells were observed in PTPN22 risk allele carriers, which negatively correlated with a decreased number of naïve T cells in older individuals. No difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg) was observed in PTPN22 risk allele carriers and Treg suppressive capacity was not altered. Finally, in synovial fluids of RA patients, an accumulation of EOMES+ CD4+ T cells was observed with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, our data provide a novel mechanism of action of PTPN22 risk variant on CD4+ T-cell differentiation and identify EOMES+ CD4+ T cell as a relevant T cell subset in RA. Overall design: Healthy blood donors were selected based PTPN22 genotype, and RNA-sequencing was done on CD4 T cells	Co-expression
SRP099660	FUS mutant human motoneurons transcriptome analysis reveals altered pathways and impairment of microRNA function	Mutations in the RNA-binding protein FUS have been genetically linked to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease caused by the death of motoneurons (MNs). FUS is a ubiquitous protein and the mechanisms leading to selective MN loss downstream of FUS mutations are still largely unknown.   We report the first transcriptome analysis of human purified MNs, obtained from isogenic induced Pluripotent Stem Cells (iPSCs) with a FUS wild-type or mutant genetic background. Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to other neurological diseases and non-FUS ALS, suggesting a common pathological mechanism. We also found several microRNAs deregulated in FUS mutant MNs and focused on miR-375 and miR-125b. Notably, miR-125b is a neural-enriched microRNA with multiple functions in the nervous system and miR-375 had been previously associated to MN survival. We report that relevant targets of both microRNAs, including the neural RNA-binding protein ELAVL4 and apoptosis factors such as p53, are aberrantly increased in FUS mutant MNs. Characterization of FUS RNA targets in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS. Overall design: High-throughput sequencing of total RNA from human iPSC-derived motoneurons Hb9::GFP-positive (day12), 2 replicates; human iPSC-derived neural cells Hb9::GFP-negative (depleted of motoneurons, day12), 2 replicates; human iPSC-derived motoneurons FUS-WT (day12+7), 3 replicates;  human iPSC-derived motoneurons FUS-P525L/P525L mutant (day 12+7), 3 replicates. High-throughput sequencing of small RNA from human iPSC-derived motoneurons FUS-WT (day12+7), 3 replicates;  human iPSC-derived motoneurons FUS-P525L/P525L mutant (day 12+7), 3 replicates.	Co-expression
SRP099676	Transcriptome analysis for identification of novel biomarker for disease progression in Dengue patients	To study the early transcriptional signature in the peripheral blood mononuclear cells (PBMCs) in a large number of clinically and virologically well characterized patients with mild and severs dengue infection and establishes their correlation with disease progression Overall design: mRNA profiling of Dengue fever(DF), Dengue hemorrhagic fever [DHF], Dengue shock syndrome (DSS) and Disease control.	Co-expression
SRP099688	B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis	The clinical efficacy of B cell targeting therapies highlights the pathogenic potential of B cells in inflammatory diseases. Expression of Fc Receptor like 4 (FcRL4) identifies a memory B cell subset, which is enriched in the joints of patients with rheumatoid arthritis (RA) and in mucosa-associated lymphoid tissue. The high level of RANKL production by this B cell subset indicates a unique pathogenic role. In addition, recent work has identified a role for FcRL4 as an IgA receptor, suggesting a potential function in mucosal immunity. Here, the contribution of FcRL4+ B cells to the specific autoimmune response in the joint of patients with RA was investigated. Single FcRL4+ and FcRL4- B cells were sorted from synovial fluid and tissue from RA patients and their immunoglobulin genes characterized. Levels of hypermutation in the variable regions in both populations were largely consistent with memory B cells selected by an antigen- and T cell-dependent process. Recombinant antibodies were generated based on Ig variable region sequences and investigated for antigen specificity. A significantly larger proportion of the recombinant antibodies generated from the IgH and IgL variable regions of individual synovial FcRL4+ B cells showed reactivity towards citrullinated autoantigens. Furthermore, both in analyses based on heavy chain sequences and flow cytometric detection, these cells have significantly increased usage of the IgA isotype. Their low level of expression of immunoglobulin and plasma cell differentiation genes does not suggest current antibody secretion. We conclude that these activated B cells are a component of the local autoimmune response, and through their RANKL expression, can contribute to joint destruction. Furthermore, their expression of FcRL4 and their enrichment in the IgA isotype points towards a potential role in the link between mucosal and joint inflammation for these cells. Overall design: B cells were sorted from synovial fluid of 4 individuals with rheumatoid arthritis into FcRL4 positive and negative fractions, and RNA-seq was performed.	Co-expression
SRP099823	RNA profiling Analysis of the Serum Exosomes Derived from Active and Latent M.tuberculosis infectious Patients	We performed RNA-seq analysis on exosomes derived from the clinical specimens of healthy control (HC), active tuberculosis (ATB) and latent tuberculosis infection (LTBI) individuals. Our results revealed the distinguished gene expression panels and patterns of the exosomes for the LTBI and ATB patients: We identified many up-regulated and down-regulated differentially expressed genes (DEGs) in the LTBI and ATB samples, and further screened the top-20 DEGs, which might provide a clue to differentiate HC, LTBI and ATB;  We classified all the DEGs into six expression patterns, screened the top-20 genes in each pattern, and mainly focused on those highly expressed in LTBI and ATB; A lot of Mtb genes were only expressed and enriched in the exosomes of LTBI patients; Pathway and functional analysis further indicated the gradually increased deteriorated healthy signals in LTBI and ATB samples, including down-regulated signaling pathways/immune response, and up-regulated apoptosis/necrosis. Our findings not only add new data to tuberculosis clinical studies, but also facilitate the development of potential targets for the diagnosis, prevention and treatment of tuberculosis. Overall design: Examined three samples and each has two repeats	Co-expression
SRP099826	RNA-seq of H9-hESC derived human neural stem cells with combinations of mutant IDH1-R132H overexpression, P53 shRNA knockdown and/or ATRX shRNA knockdown	RNA-seq was performed to assess gene expression alterations by the addition of serial oncogenic hits (mutant-IDH1, P53 knockdown and ATRX knockdown) in human neural stem cells. Overall design: All RNA-seq was performed in duplicates, there are four conditions total. Vector NSCs are the control line and have an empty mCherry vector and a scramble shRNA vector. One hit NSCs express mutant-IDH1 and have a scamble shRNA vector. Two-hit NSCs express mutant IDH1 and have p53 knockdown. Three-hit NSCs express mutant-IDH1, P53 knockdown and ATRX knockdown.	Co-expression
SRP099844	Chemoprevention with COX2 and EGFR inhibition in FAP patients: mRNA signatures of duodenal neoplasia	RNA sequencing of duodenal polyps in FAP patients treated with plabebo or the drug combination, erlotinib + sulindac Overall design: 69 duodenal RNA sequencing datasets (17 baseline uninvolved from 17 FAP patients, 10 endpoint uninvolved and 16 polyp from 10 FAP patients on placebo, 10 endpont uninvolved and 16 polyp from 10 FAP patients on drug)	Co-expression
SRP099848	Generation of KRAS signatures using immortalized isogenic lung cells.	We generated RNAseq profiles from Small Airway Epithelial Cells (SALE) expressing either KRAS G12V or GFP control. Overall design: SALE stably expressing with KRAS G12V or GFP were harvested two weeks after infection.	Co-expression
SRP099922	Mitochondrial dsRNA triggers antiviral signalling in humans	Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts capable of forming long double-stranded RNA structures. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here, we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single cell level and identify keyroles for the degradosome components, mitochondrial dsRNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to  the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms evolved to protect vertebrates against microbial and viral attack. Overall design: We performed J2 IP dsRNA-seq from HeLa cell lysates by immunoprecipitation with anti-dsRNA (J2) mab. Untreated and siCntrl treated HeLa cells were used in the experiment.  Experiment was performed in duplicates from HeLa cells treated with siSUV3 and siPNPase.  Input RNA samples were ribodepleted with Ribo-Zero rRNA-removal kit. IPed RNA samples were not ribodepleted.	Co-expression
SRP100017	Human Adult Sorted Live Cell Erythroblasts transduced with Sigma shRNA Clone TRCN0000162889 targeting SLC25A39 with puromycin selection RNAseq.	Erythroblasts cultured from mobilized CD34+ cells from six healthy adult human donors were used to generate an erythroblast transcriptome transduced with Sigma shRNA Clone TRCN0000162889 targeting SLC25A39 gene. Cellular maturation was maintained including enucleation.  On culture day 14 total RNA was isolated (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). Preliminary screening data demonstrated a robust increase in fetal hemoglobin that may be due to off-target effects from this shRNA clone. See Series GSE94147 for Empty Vector Control dataset. Overall design: Human CD34+ cells from health donor transduced with lentivirus expressing Sigma shRNA Clone TRCN0000162889 to knockdown SLC25A39 gene expression in serum free culture.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction. Acknowledgement: We would like to thank Gerard Bouffard and the National Human Genome Research Institute for their expertise and assistance with RNA-seq.	Co-expression
SRP100037	RNA-Seq of TPP, IPTP Exposed Human Primary Preadipocites	Human primary preadipocites were treated for 6 days with TPP and IPTP. RNA was extracted and RNA-Seq was performed.	Co-expression
SRP100048	Poly(A)-ClickSeq resolves CF25-mediated alternative poly-adenylation, HeLa	Poly(A)-ClickSeq is a new methodology for the sequencing of the 3''UTR/poly(A) tail junction of RNA. We analysed both wild-type and CF25Im knock-down HeLa cells in culture using Poly(A)-ClickSeq to find the distribution of poly(A) sites in these samples and determine the role of CF25Im in poly(A) site selection (alternative poly-adenylation, APA). Overall design: RNA was extracted from HeLa cells with or without CF25Im Knock-down, each in triplicates, and sequenced using Poly(A)-ClickSeq and sequencing once on a HiSeq and once on a MiSeq	Co-expression
SRP100057	Single-cell RNA Sequencing as a tool for simultaneous shRNA detection and transcriptome analysis in the context of functional shRNA screens	Ectopic expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can reprogram somatic cells into induced pluripotent stem cells (iPSCs). These iPSCs are highly similar to embryonic stem cells and can be used for regenerative medicine, drug screening and disease modelling. Despite recent advances, reprogramming is a slow and inefficient process. This suggests that there are several safeguarding mechanisms to counteract cell fate conversion. Cellular senescence is one of these barriers, which is mediated through activation of the tumour suppressors p53/p21CIP1, p15INK4b and p16INK4a.   In this study, we have screened for shRNAs blunting reprogramming-induced senescence. To evaluate the feasibility of using single-cell RNA Sequencing (scRNA-Seq) in functional screens for simultaneous transcriptome and shRNA identification, we first assessed the accuracy of detecting shRNAs in single cells. To this end we performed a pilot experiment on a pool of OSKM-expressing IMR90 cells infected with the shRNA library. Overall design: 460 samples: 300 IMR90 cells expressing OSKM and shRNA library, 50 IMR90 cells expressing control vector, 50 K562 myeloid leukemia cells, 30 positive controls (RNA from IMR90 cells expressing control vector as input; RNA used as a control for the single cell processing, coming from RNA isolation of a bulk population of IMR90 cells expressing the control vector), 30 negative controls	Co-expression
SRP100068	Differential gene expression in Jagged1 treated human dental pulp cells.	The present study aimed to determine mRNA expression profilling of indirect immobilized Jagged1 treated human dental pulp cells. Human dental pulp cells were seeded on indirect immobilized Jagged1 surface for 24 h. Cells on hFc immobilized surface was employed as the control. RNA sequencing was performed using NextSeq500, Illumina. Data were processed on FastQC and FastQ Toolkit and subsequently mapped with Homo sapiens hg38 using TopHat2. Mapped data were processed through Cufflink2 and Cuffdiff2. Results demonstrated 1,465 differentially expressed genes in Jagged1 treated cells compared with the control. Enriched pathway analysis revealed that Jagged1 treated cells upregulated genes mainly involved in extracellular matrix organization, disease, and signal transduction categories. However, genes related to cell cycle, DNA replication and DNA repair categories were downregulated. In conclusion, Jagged1 activates Notch signaling and regulates cell cycle pathway in hDPs. Overall design: The mRNA profiles of human dental pulp cells treated with indirect immobilized Jagged1 (10nM) for 24 h was evaluated by next genereation RNA sequencing (NextSeq 500, Illumina) in triplicates. Cells on hFc immobilized surface was used as the control. In some condition, cells were pretreated with a gamma secretase inhibitor (DAPT; 20 uM) for 30 mins prior to Jagged1 exposure.	Co-expression
SRP100079	H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers [Nalm-6]	Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factors SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Although cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, clinical means to therapeutically target the spliceosome do not currently exist. Here, we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and selectively kills spliceosome-mutant epithelial and hematologic malignancies. The effects of H3B-8800 are entirely selective for the Sf3b complex, as evidenced by the identification of drug-resistant cells bearing mutations in Sf3b components. Although H3B-8800 modulates RNA splicing mediated by WT or cancer-associated SF3B1 mutants, its preferential effects on spliceosome-mutant cells is due to preferred retention of short, GC-rich introns, which are enriched in genes encoding a substantial number of spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers. Overall design: 9 samples, including SF3B1 mutant isogenic Nalm-6 cell lines with and without 13nM treatment with H3B-8800 or 15nM treatment with E7107	Co-expression
SRP100153	The cohesin release factor WAPL restricts chromatin loop extension. [RNA-Seq]	The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes. Overall design: RNAseq was performed in control, ?WAPL 3.3, ?WAPL 1.14, ?SCC4 and ?WAPL/?SCC4 cells in triplicate.	Co-expression
SRP100157	Coupling shRNA screening with single-cell RNA-Seq identifies mechanisms regulating senescence during reprogramming	Ectopic expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can reprogram somatic cells into induced pluripotent stem cells (iPSCs). These iPSCs are highly similar to embryonic stem cells and can be used for regenerative medicine, drug screening and disease modelling. Despite recent advances, reprogramming is a slow and inefficient process. This suggests that there are several safeguarding mechanisms to counteract cell fate conversion. Cellular senescence is one of these barriers, which is mediated through activation of the tumour suppressors p53/p21CIP1, p15INK4b and p16INK4a.   In this study, we have screened for shRNAs blunting reprogramming-induced senescence. We integrated single-cell RNA sequencing (scRNA-Seq) with shRNA screening to investigate the mechanism of action of the identified candidates. Overall design: 376 samples: 280 IMR90 cells expressing OSKM and shRNA library derived from the shRNA screen (bypassing senescence), 64 OSKM-expressing IMR90 cells (senescent), 32 IMR90 cells expressing control vector	Co-expression
SRP100164	ZNF131 suppresses centrosome fragmentation in Glioblastoma stem-like cells through regulation of HAUS5	To identify new Glioblastoma multiforme (GBM) therapeutic strategies, we previously performed genome-wide RNAi lethality screens in patient-derived GBM stem-like cells (GSCs) and neural progenitor cells (NPCs) to identify genes required for the self-renewal of GSC isolates, but which are dispensable for NPCs.  Here we report the retest of the GSC-lethal gene ZNF131, which encodes a novel vertebrate-specific BTB domain zinc finger transcription factor that is broadly required for GSC viability.  Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule (MT) nucleation along the mitotic spindle.  Of these genes only kd of HAUS5 displayed GSC-specific viability loss, and, critically, HAUS5 ectopic expression was sufficient to suppress viability defects of ZNF131 kd cells.  Moreover, ZNF131 and HAUS5 kd phenocopied each other in GSCs, each causing: mitotic arrest, centrosome fragmentation, loss of Augmin/HAUS complex on the mitotic spindle, and loss of GSC self-renewal and tumor formation capacity.  In control NPCs, we observed centrosome fragmentation and lethality only when HAUS5 kd was combined with kd of HAUS2 or HAUS4, two other Augmin complex members, demonstrating that the complex is essential in NPCs, but that GSCs have heightened requirement. Our results suggest that GSCs differentially rely on ZNF131-dependent expression of HAUS5 as well as the Augmin/HAUS complex activity to maintain the integrity of centrosome function and viability.  We speculate that this requirement likely arises from aneuploidy frequently observed in late stage GBM tumors, rather than supernumerary centrosomes. Overall design: ZNF131 suppresses centrosome fragmentation in Glioblastoma stem-like cells through regulation of HAUS5	Co-expression
SRP100261	Transcriptomic profiling of normal human cardiac fibroblast treated with halofuginone	Normal human cardiac fibroblast were treated with 200 nM halofuginone for 24 hours and the transcriptomic profile was measured by RNAseq. Overall design: Total of 6 samples analyzed, 3 treated with vehicle and 3 treated with halofuginone.	Co-expression
SRP100328	Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma	The introduction of novel therapeutic agents has considerably improved the median survival of patients with multiple myeloma (MM). However, the natural history of the disease is characterized by continuous relapses over time. As a consequence, the development of new drugs is still required to treat MM recurrence. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure. Amilorideinduced apoptosis was observed in a broad panel of MM cell lines and in xenograft mouse models. Moreover, amiloride also had a synergistic effect when combined with dexamethasone and melphalan. RNA-seq experiments showed that amiloride not only significantly altered the level of transcript isoforms and alternative splicing events, but also deregulated the spliceosomal machinery. Additionally, disruption of the splicing machinery in immunofluorescence studies was associated with the inhibition of myeloma cell viability after amiloride exposure. Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. On the other hand, the manageable toxicity profile of amiloride is well known and we did not find a significant systemic toxicity in mice treated with amiloride. Overall, our results provide a mechanistic rationale for the use of amiloride as an alternative treatment option for relapsed MM patients. Overall design: Poly A+ RNA from KMS12-BM and JJN3 cells untreated or treated with amiloride or TG003 (0.1 mM, 0.4 mM, and 0.4 mM respectively) for 24 h was isolated and prepared for RNA-seq.	Co-expression
SRP100364	The effect of Abl kinases,or Ponatinib challenging on breast cancer cells'' global transcriptome	To gain insight into the signaling pathway(s) required for ABL1/ABL2-kinase activity or effected by Ponatinib treatment, we evaluated the consequences of single or double inactivation of ABL1/ABL2 cells, or Ponatinib treated cells on the transcriptome of breast cancer cells. To examine the consequences of depleting the ABL kinases, or Ponatinib treatment on the transcriptome of lung metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 321 genes were significantly differently expressed in Ponatinib treated LM2 cells, and 73 genes were differently expressed in double inactivation of ABL1/ABL2 LM2 cells. However, only about 3.4 percent of Ponatinib affected genes can also be changed by ABL knocking down. Overall design: Samples were analyzed by pair of either control (DMSO) versus ABL Kinase inhibitor Ponatinib, Or using scrambled shRNA versus single or double inactivation of ABL1 and ABL2-specific shRNAs.	Co-expression
SRP100370	RNA-seq analysis revealed aberrant gene expression in motor neurons derived from ALS patient iPSCs bearing SOD1+/A272C mutation	The goal of this study is to gain insight into the early biomarkers and molecular pathways affected by the SOD1+/A272C mutation in human motor neurons. Isogenic control line was created by CRISPR/Cas9 mediated targeted gene correction. Motor neurons were derived from isogenic iPSC lines, and RNA sequencing was employed to determine differentially expressed genes. This study provides an isogenic platform to study ALS disease mechanism at the early stage. Overall design: wild type and mutant, 2 replicates.	Co-expression
SRP100394	Whole exome and transcriptome sequencing of DLBCL	To identigy different genomic alteration in DLBCL	Co-expression
SRP100404	novel patient-derived cell lines	novel patient-derived cell lines from primary human liver cancer and malignant liver metastasis	Co-expression
SRP100417	Gene expression in GBM with Cav3.2 inhibition	Glioblastoma stem cells (GSCs) have been implicated in tumor initiation, progression and resistance to therapy. We investigated the expression, function, mechanisms of action and therapeutic targeting of T-type calcium channels (Cav3.2) with the FDA approved and repurposed drug mibefradil in glioblastoma (GBM), and GSCs. We found that Cav3.2 is highly expressed in human GBM specimens and enriched in GCSs.  Analyses of TCGA and REMBRANDT databases confirmed the upregulation of Cav3.2 in a subset of tumors (TCGA) and showed that overexpression is associated with worse prognosis. Mibefradil and Cav3.2 knockdown inhibited the growth, survival and stemness of GSCs and sensitized them to temozolomide (TMZ) chemotherapy.  To investigate the mechanisms of action of Cav3.2 in GSC, we performed proteomic and transcriptomic screenings followed by functional rescue experiments. Inhibition of Cav3.2 altered cancer signaling pathways and gene transcription. Among other, inhibition of Cav3.2 suppressed GSC growth through inhibition of pro-survival pathways AKT/mTOR, and induction of apoptosis through upregulation of survivin, BAX and cleavage of caspase 9 and PARP.  Inhibition of Cav3.2 induced a decrease in the expression of oncogenes including PDGFA, PDGFB and TGFB1 and an increase in the expression of tumor suppressors including TNFRSF14 and HSD17B14. In vivo oral administration of Cav3.2 blocker mibefradil significantly inhibited GSC-derived xenograft growth, prolonged animal survival and sensitized the tumors to TMZ.  Our study represents the first comprehensive characterization of Cav3.2 in GBM tumors and GSC. The findings establish Cav3.2 inhibition with the repurposed FDA-approved drug mibefradil as a new strategy for GBM therapy. Overall design: Examination of gene expression after inhibition of Cav3.2 in GBM stem cells	Co-expression
SRP100426	The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in human cardiac stromal cells	Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic autosomal disease characterized by abnormal cell-cell adhesion, cardiomyocyte death, progressive fibro-adipose replacement of the myocardium, arrhythmias and sudden death. Several different cell types contribute to the pathogenesis of ACM, including, as recently described, cardiac stromal cells (CStCs). In the present study, we aim to identify ACM-specific expression profiles of human CStCs derived from endomyocardial biopsies of ACM patients and healthy individuals employing TaqMan Low Density Arrays for miRNA expression profiling, and high throughput sequencing for gene expression quantification. Results: We identified 5 miRNAs and 272 genes as significantly differentially expressed. Both the differentially expressed genes as well as the target genes of the ACM-specific miRNAs were found to be enriched in cell adhesion related biological processes. Functional similarity and protein interaction based network analyses performed on the identified deregulated genes, miRNA targets and known ACM-causative genes revealed clusters of highly related genes involved in cell adhesion, extracellular matrix organization, lipid transport and ephrin receptor signaling. Conclusions: We determined for the first time the coding and non-coding transcriptome characteristic of ACM cardiac stromal cells, finding evidence for a potential contribution of miRNAs to ACM pathogenesis or phenotype maintenance. Besides known pathways, we identified also deregulation of genes encoding ephrin receptors and ephrins, thus suggesting a potential involvement of Eph-ephrin signaling in CStCs from ACM hearts. Overall design: Expression profiles of cardiac stromal cells from 3 ACM patients were compared against those of cardiac stromal cells from 3 healthy individuals.	Co-expression
SRP100437	Priming and Activation of ERa Enhancers Through Ordered and Cooperative Interactions Between p300 and Mediator [GRO-seq]	Estrogen receptors alpha (ERa) converges estrogen signaling by orchestrating estrogen (E2)-dependent transcription regulation.  Upon binding to the chromatin, ERa serves as a nucleation site for de novo formation of transcription enhancer complexes.  Steroid receptor coactivators family proteins (SRCs, a.k.a p160) and Mediator complex are the two coregulators for ERa that directly interact with the receptors and control enhancer activity by regulating recruitment of other coregulators and transcription machinery.  Lysine acetyltransferase p300/CBP is also a critical coregulator for ERa that is recruited through SRCs in stable ERa enhancer complex.  ERa enhancers exhibit common enhancer features including enrichment of enhancer-specific histone modification (e.g. H3K4me1 and H3K27ac), coregulator recruitment, and active transcription.  Despite of recognition of those enhancer characteristics, the order of assembly and functions and the functional relationships among enhancer features during active enhancer complex formation is not well understood.  Using the time course genomics and molecular biology assays, we dissect the order of assembly and functions of ERa enhancer complex formation.  We describe the mechanism of SRC-independent p300 recruitment mediated by Mediator, leading to initial partial activation of the ERa enhancer for enhance priming.  Maturation of the enhancer in turn switches the p300 recruitment mechanism to an SRC-dependent manner, resulting in the maximum enhancer activity and transcription outcomes.  Thus, our results illustrate the role of SRC in enhancing the activity of primed enhancers.  Furthermore, we show that forced recruitment of p300 to inactive enhancers establishes active enhancer marks and induces ERa-target gene expression.  Together, we demonstrate the molecular mechanisms of ERa enhancer complex formation where p300 plays a pivotal role in enhancer activation and target gene expression controlled by distinctive mechanisms through different stages of ERa enhancer complex formation. Overall design: GRO-seq datasets were generated using E2-treated MDA-MB-231 cells expressing ERa wt and L540Q mutant to define ERa enhancers and to determine enhancer complex formation and activity.	Co-expression
SRP100445	Coding and noncoding transcriptome sequencing of KRAS mutated colorectal tumors and adjacent tissues from cancer patients and KRAS mutated Aberrant Crypt Foci and matching normal crypts from healthy individuals [RNA-Seq]	Colorectal cancer (CRC) is characterized by genome-wide alterations to DNA methylation that influence gene expression and genomic stability. Less is known about the extent to which methylation is disrupted in the earliest stages of CRC development. In this study we have combined laser-capture microdissection (LCM) with reduced representation bisulfite sequencing (RRBS) to identify cancer associated DNA methylation changes in human aberrant crypt foci (ACF), the earliest putative precursor to CRC. Using this approach, methylation profiles have been generated for 10 KRAS-mutant ACF and 10 CRCs harboring a KRAS mutation, as well as matched samples of normal mucosa. Of 811 differentially methylated regions (DMRs) identified in ACF, 537 (66%) were hypermethylated and 274 (34%) were hypomethylated. DMRs located within intergenic regions were heavily enriched for AP-1 transcription factor binding sites and were frequently hypomethylated. Furthermore, gene ontology (GO) analysis demonstrated that DMRs associated with promoters were enriched for genes involved in intestinal development, including homeobox genes and targets of the Polycomb repressive complex 2 (PRC2).Consistent with their role in the earliest stages of colonic neoplasia, 75% of the methylation changes identified in ACF were also present in the CRC samples. Together, these data demonstrate that DNA methylation changes, including significant hypomethylation, occur more frequently in early colonic neoplasia than previously believed, and identify epigenomic features of ACF that may provide new targets for cancer chemoprevention or lead to the development of new biomarkers for CRC risk. Overall design: 10 pairs primary tumor/matching normal colon tissue; 5 pairs Aberrant Crypt Foci/matching normal crypt. 30 samples in total. Two technical replicates of the library preparation for sample 165S (165S1 and 165S2)	Co-expression
SRP100477	BEARscc: robustness of single-cell clusters determined using simulated technical replicates	Technical variance is a major confounding factor in single-cell RNA sequencing, not least because measurements on the same cell are not replicable. We developed BEARscc, a tool that simulates experiment-specific technical replicates based on a probabilistic model of technical variance trained on RNA spike-in measurements. We demonstrate that the tool improves the unsupervised classification of cells and aids the interpretation of single-cell RNA-seq experiments. Overall design: scRNA-seq was performed on dilute whole brain tissue and water samples in order to assess BEARscc as cluster robustness tool.	Co-expression
SRP100507	GCTM-5 positive and negative cells in pancreatic adenocarcinoma cell lines	Analysis of GCTM-5 positive and negative cells sorted from CFPAC-1 and SW1990 human pancreatic adenocarcinoma cell line. Results provide insight into molecular characteristics of GCTM-5 positive cells. Overall design: Gene expression analysis of CFPAC-1 and SW1990 human pancreatic adenocarcinoma cells presenting GCTM-5 antigen or not (each 3 replicates).	Co-expression
SRP100509	Nickel exposure induces persistent mesenchymal phenotype in human lung epithelial cells through epigenetic activation of ZEB1	Purpose: Environmentally induced diseases, including cancer typically develop long after the exposure has occurred. However, most of the toxicological studies are conducted during active exposure. Therefore, environmental exposure-induced adverse effects that persist after cessation of exposure is poorly understood. Methods: Immortalized human bronchial epithelial cells (BEAS-2B) were cultured in Dulbecco's Modified Eagle's Medium (DMEM, Cellgro) supplemented with 1% Penicillin Streptomycin and 10% Fetal Bovine Serum (FBS, Atlanta Biologicals) at 37 degree C and 5 % CO2. For Ni exposure, various concentrations of NiCl2 (Sigma N6136) was added to the media and the cells were cultured for 6 weeks. Following exposure, the cells were washed and cultured in Ni-free medium for 2 weeks to obtain the Ni-washed-out cells. To obtain homogenous populations of Ni-exposed cells, the cells exposed to 100 mM NiCl2 for 6 weeks were plated in 15 cm plates in Ni-free medium at the rate of 1000, 500, 100 and 50 cells per plate. Nicely separated single colonies were picked and the populations were expanded in Ni-free medium. Results: Here we report that Ni, an environmentally prevalent, low-mutagenic carcinogen causes epithelial-mesenchymal transition (EMT) that persists even after the exposure has ceased. Ni-induced persistent EMT induction is dependent on the upregulation of ZEB1, an EMT master regulator. We found that Ni exposure resolved the bivalent chromatin environment of ZEB1 gene, thereby keeping it in a permanent 'on' state. The continuously expressing ZEB1 downregulated its negative regulators, thus establishing a self-sustaining positive regulatory loop. Given the importance of EMT in a number of diseases including asthma, pulmonary fibrosis, development of premalignancy, carcinogenesis and metastasis, we believe that persistent EMT induction through epigenetic activation of ZEB1 is a major step in Ni-induced human diseases. Overall design: RNA Seq gene expression comparison done in replicates	Co-expression
SRP100570	Gene expression profiling of ISWI chromatin remodeler mutants before and after DNA damage	Gene expression profiling of ISWI chromatin remodeler mutants before and after DNA damage BAZ1A is a regulatory subunit within the ISWI family of chromatin remodelers in humans. We and others have shown that BAZ1A is required for efficient recovery from DNA damage.  The DNA damage hypersensitivity caused by BAZ1A* is as severe as the deletion of the entire gene. This is striking given that BAZ1A* contains only two substitutions (K1181A and K1183Y) within a poorly characterized domain of BAZ1A. We find that this domain can interact with DNA, and that the mutations present in BAZ1A* hinder DNA binding. We used transcriptional profiling to identify molecular events leading to the DNA damage hypersensitivity of BAZ1A* cells. Overall design: HeLa cells (CL132529) were subjected to genome editing using the Cas9 technology to abrogate expression of the chromatin regulator BAZ1A. Lentiviral transduction was then used to re-express either BAZ1A wild-type or the BAZ1A* mutant in BAZ1A knockout cells. All genome edited cell lines have been cloned and passed in-house QC (mycoplasma-free and cell line authenticated). Cells were either unchallenged (control) or subjected to UVC irradiation (200 J/m2) to cause DNA damage.  One hour after irradiation, total RNA was extracted in triplicate.  Gene expression was measured by RNA-sequencing. In total there are 8 conditions: 4 cell lines (parental (HeLa), BAZ1A knockout, re-express BAZ1A, re-express BAZ1A* mutant), with or without DNA damage. Each condition includes triplicate RNA extractions, for a total of 24 samples.	Co-expression
SRP100585	RNAseq changes in human fibroblasts after treatment with E16.5 skin extract	To identify the cellular processes upregulated in fibroblasts after treatment with E16.5 skin extract	Co-expression
SRP100620	H3.3K27M cooperates with p53 loss and Pdgfra gain in mouse embryonic neural progenitor cells to induce invasive high-grade gliomas [Human RNA-Seq]	Gain-of-function mutations in histone 3 (H3) variants are found in a large proportion of pediatric high-grade gliomas (pHGG) and are often associated with p53 loss and PDGFRA amplification. However, a lack of faithful models has hampered investigation of disease mechanisms and preclinical development. Here, we describe a somatic mouse model of H3.3K27M-driven HGG, which faithfully recapitulates human H3.3K27M pHGG. H3.3K27M and p53 loss are sufficient for neoplastic transformation but only within a specific window of brain development. In this model, H3.3K27M primes the PDGFRA pathway during transformation, and accordingly gain of wild-type PDGFRA decreases latency and increases invasion. Finally, we reveal a previously underappreciated dynamic regulation of H3K27 trimethylation at specific loci. Overall, this experimental model provides key insights into oncohistone-driven pHGG pathogenesis and will enable investigations of future therapies. Overall design: We performed genome-wide transcriptome profiling (RNAseq) of 12 samples derived from human patients: matched normal brain controls (normal brain tissue from pediatric brain tumor patients; n = 3), pediatric high-grade gliomas (pHGG) that are wild-type for H3.3 and TP53 (n = 4), pHGG with H3.3K27M and loss-of-function TP53 mutations (n = 5).	Co-expression
SRP100632	KDM4 inhibition targets breast cancer stem cells [RNA-Seq]	We treated breast cancer stemm cells (BCSC) with a KDM4 inhibitor Overall design: BCSC1 cells were cultured in the presence and absence of KDM4(i)	Co-expression
SRP100639	Be1 and Be2 B cells are transcriptionally distinct	B cells cultured in the presence of Th1 CD4 T cells (Be1) or Th2 CD4 T cells (Be2) lead to distinct phenotypic outcomes.  To determine when the phenotypic differences emerged, IgD positive and IgD negative Be1 and Be2 cells were isolated from cultures derived from 3 independent donors and RNA-seq performed.  These data define the transcriptional differences of Be1 and Be2 cells ad distinct differentiation stages and show that Be1 B cells contain a pre-ASC signature that is absent from Be2 B cells. Overall design: Be1 and Be2 cells that were IgD positive and IgD negative from three different donors were analyzed by RNAseq.	Co-expression
SRP100643	Dynamics of HIV Latency and Reactivation in a Primary CD4+ T Cell Model	HIV latency is a major obstacle to curing infection. Current strategies to eradicate HIV aim at increasing transcription of the latent provirus. In the present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed to produce viral particles upon ex vivo exposure to SAHA (vorinostat), despite effective inhibition of histone deacetylases. To identify steps that were not susceptible to the action of SAHA or other latency reverting agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing, and a viral-encoded reporter. This model served to investigate the characteristics of latently infected cells, the dynamics of HIV latency, and the process of reactivation induced by various stimuli. During latency, we observed persistence of viral transcripts but only limited viral translation. Similarly, the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data. This study highlights the importance of post-transcriptional blocks as one mechanism leading to HIV latency that needs to be relieved in order to purge the viral reservoir. Overall design: Establishment and maintenance of HIV latency+ reactivation with different agents. RNAseq was performed for both HIV infected and mock infected cells at: Week 0,2,4,6,8 and 10 of latency and at 8, 24 and/or 72 hours post reactivation with vorinostat (SAHA), disulfiram (disu), azacytidine (aza), interleukin-7 (IL-7), anti-CD3/anti-CD28 (antiCD3) or DMSO).	Co-expression
SRP100645	Systematic Functional Perturbations Uncover a Prognostic Genetic Network Driving Human Breast Cancer [RNA-Seq]	Gene-expression patterns of primary breast cancers aid clinicians in predicting the risk of metastatic disease. Some prognostic signatures have recently been prospectively validated, highlighting their clinical value. Such classifiers conceivably comprise biomarker genes that, in fact, functionally contribute to the oncogenic and metastatic properties of the tumors, but this has not been investigated systematically. We previously reported that the transcription factor Fra-1 not only has an essential role in breast cancer, but also drives the expression of a highly prognostic gene set. Here, we systematically perturbed the function of 31 individual Fra-1-dependent poor-prognosis genes and examined their impact on breast cancer growth in vivo. Because of the considerable number of genes in this gene set, we anticipated that the contribution of single genes to breast cancer progression would be limited. In contrast, we find that stable shRNA depletion of each of nine individual signature genes strongly inhibits breast cancer growth and aggressiveness. Several factors within this nine-gene set regulate each other's expression, suggesting that together they form a network. The nine-gene set is regulated by estrogen, ERBB2 and EGF signaling, all established breast cancer factors. We also uncover three transcription factors, MYC, E2F1 and TP53, which act alongside Fra-1 at the core of this network. ChIP-Seq analysis reveals that a substantial number of genes are bound, and regulated, by all four transcription factors. The nine-gene set retains significant prognostic power and includes several potential therapeutic targets, including the bifunctional enzyme PAICS, which catalyzes purine biosynthesis. Depletion of PAICS largely cancelled breast cancer expansion, exemplifying a prognostic gene with breast cancer activity. Our data uncover a core genetic and prognostic network driving human breast cancer. We propose that pharmacological inhibition of components within this network, such as PAICS, may be used in conjunction with the Fra-1 prognostic classifier towards personalized management of poor prognosis breast cancer. Overall design: RNA-Seq experiment to examine mRNA levels in metastatic breast cancer cell line (MDA-MB-231 LM2) after treatment with shRNA for scrambled control or shRNA for transcription factors for FOSL1 (Fra-1), E2F1, TP53, MYC, or EZH2 (two biological replicates for each gene and control)	Co-expression
SRP100652	Gene and isoform expression of aminopeptidases ERAP1 and ERAP2 from RNASeq data	This goal of this study was to investigate the gene expression effect of disease associated polymorphisms in the endoplasmic reticulum aminopeptidase genes ERAP1 and ERAP2. The enzymes ERAP1 and ERAP2, encoded on chromosome 5q15, function by trimming endogenously derived peptides for human leukocyte antigen (HLA) mediated presentation to the immune system. Polymorphisms in ERAP1 and/or ERAP2 have been observed in several immune-mediated diseases with specific HLA associations, implicating altered peptide handling and presentation as a prerequisite for immune autoreactivity. Evidence for the elevated expression or altered transcriptional profile of these genes in diseases characterised by immune autoreactivity provides grounds for the development of aminiopeptidase inhibitors for the therapeutic treatment of such conditions.	Co-expression
SRP100664	The transcriptional characterization of different states of cancer stem cells in triple-negative breast cancer	Breast cancer stem cells (BCSCs) are thought to be responsible for tumor initiation, metastasis and relapse. The biomarkers of BCSCs were widely recognized as Aldehyde dehydrogenase positive (ALDH+) and CD24-CD44+. Previous studies showed that tumor populations expressing ALDH+ and CD24-CD44+ represented epithelial-like BCSCs and mesenchymal-like BCSCs, respectively. However, the overlapped population of ALDH+CD24-CD44+, which have greatest tumor-initiating and invasive capacity, is lack of transcriptional characterization. Here we used biomarker combinations ALDH and CD24/CD44 to sort four populations from two triple-negative breast cancer patient-derived xenografts (PDXs), and performed whole-transcriptome sequencing on each population. We systematically compared three states of BCSCs with differentiated tumor cell population, as well as characterization of the ALDH+CD24-CD44+ BCSCs compared with other three populations at the first time. By the pair-comparisons, we identified 90 unique differential expressed genes (DEGs) in ALDH+CD24-CD44+ BCSCs of two PDXs, 32 upregulated and 58 downregulated DEGs. We proposed that P4HA2, PTGR1 and RAB40B were potential prognostic genes in TNBC.	Co-expression
SRP100681	mRNAseq of Huntington''s disease and control patient iPSC-derived neural cells	Purpose: The goals of this study are to compare the transcriptomic profile (mRNA-seq) of HD  and control patient iPSC-derived neural cells to identify alterations in gene expression Methods:  RNA were isolated from HD and control iPSC-derived neural cells. mRNAseq using Illumina Truseq mRNA PolyA+ v2 lib prep and Hiseq 2000. Statistical difference in mRNA levels were calculated with subsequent GO and pathway analysis Results: mRNAseq and statistical analysis revealed 1869 differentially expressed genes between HD and control iPSC-derived neural cells. Conclusions: Our study shows 1869 differentially expressed genes between HD and control iPSC-derived neural cells, and reveals gene networks that relevant to the mechanism of HD pathogenesis. Overall design: mRNA profiles of HD and control iPSC-derived neural cells were generated by mRNAseq, in duplicate, using Illumina Truseq mRNA PolyA+ v2 and Illumina Hiseq 2000.	Co-expression
SRP100686	Novel SF3B1 Deletion Mutations Result in Aberrant RNA Splicing in CLL Patients	Recurrent mutations in RNA splicing factors SF3B1, U2AF1, and SRSF2 have been reported in hematologic cancers including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). However, SF3B1 is the only splicing associated gene to be found mutated in CLL and has been shown to induce aberrant splicing. To investigate if any other genomic aberration caused similar transcriptome changes, we clustered RNASeq samples based on an alternative 3' splice site (ss) pattern previously identified in SF3B1-mutant CLL patients. Out of 215 samples, we identified 37 (17%) with alternative 3' ss usage, the majority of which harbored known SF3B1 hotspot mutations. Interestingly, 3 patient samples carried previously unreported in-frame deletions in SF3B1 around K700, the most frequent mutation hotspot. To study the functional effects of these deletions, we used various minigenes demonstrating that recognition of canonical 3' ss and alternative branchsite are required for aberrant splicing, as observed for SF3B1 p.K700E. The common mechanism of action of these deletions and substitutions result in similar sensitivity of primary cells towards splicing inhibitor E7107. Altogether, these data demonstrate that novel SF3B1 in-frame deletion events identified in CLL result in aberrant splicing, a common biomarker in spliceosome-mutant cancers. Overall design: 13 CLL samples, 5 SF3B1 WT, 5 SF3B1 p.K700E, and 3 with in-frame deletions around the K700 position of SF3B1	Co-expression
SRP100726	Global transcriptome profiling of triple-negative breast cancer cell lines treated with small-molecules targeting Bromodomain and Extra Terminal (BET) proteins	Triple negative breast cancer (TNBC) represents the most clinically challenging subtypes of breast cancer for which targeted therapeutics are still lacking. Bromodomain and Extra Terminal (BET) proteins, including ubiquitously expressed BRD2, BRD3, BRD4 and testis-specific BRDT, are epigenetic “readers” and play a major role in epigenetic regulation of gene transcription. BET proteins have emerged as new therapeutic targets for human cancer and other diseases. Based upon a new class of BET bromodomain (BRD) inhibitor, BETi-211, we have developed a highly selective and potent BET protein degrader, BETd-246. In comparison, BETd-246 is much more potent and effective than the corresponding BET inhibitor BETi-211 in growth inhibition and apoptosis induction in TNBC cell lines, indicating critical differences between these two different BET targeting approaches in their regulation of gene transcription. To understand the mechanisms of actions of BETi-211 and BETd-246 in TNBC, we performed RNA-seq analysis on MDA-MB-157, MDA-MB-231 and MDA-MB-468. These cell lines were treated for 3 h to capture the early transcriptional responses to BETi-211 or BETd-246. RNA-seq analysis reveals that BETd-246 predominantly down-regulates the expression of a large number of genes whereas BETi-211 up- and down-regulates an approximately equal number of genes in TNBC cells. Critically, transcriptomic analysis uncovers that a set of proliferation and survival-related genes, including MCL1 and BRD2, were oppositely regulated by BETd-246 and BETi-211 in these TNBC cell lines. Overall design: Global gene transcription profiling was performed in MDA-MB-157, MDA-MB-231 and MDA-MB-468 cell lines treated with DMSO, Thalidomide (1000 nmol/L), BETi-211 (1000 nmol/L) or BETd-246 (100 nmol/L) for 3 hours. Independent biological replicates (such as DMSO1 and DMSO2) were analyzed for each cell line under each condition. Both DMSO- and Thalidomide-treated samples were used as controls.	Co-expression
SRP100755	Genome-wide transcriptional targets of KLF15 in human airway smooth muscle	We previously demonstrated that the transcription factor, KLF15, is a glucocorticoid-regulated gene that represses primary human airway smooth muscle (ASM) proliferation. Here, we show that KLF15 also represses ASM hypertrophy. To uncover the mechanistic basis for these effects, we integrated transcriptome data from KLF15 over-expression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq). This led us to identify PLCD1 as both a KLF15-regulated gene and a repressor of ASM hypertrophy. Overall design: Genome-wide transcriptional targets of KLF15 in human airway smooth muscle cells were determined by RNA-seq in cells transduced with a KLF15-expressing adenovirus (Ad-KLF15) compared to a control adenovirus (Ad-GFP).	Co-expression
SRP100771	Identification of diverse target RNAs that are functionally regulated by human Pumilio proteins	We used RNA-seq to measure transcript levels in human cells with the PUM1 and PUM2 proteins knocked down; by analyzing the differences in transcript abundances between those conditions, we were able to identify 927 targets showing significant changes in the presence of the PUM knockdown. Overall design: Comparative expression profiling via RNA seq between cells undergoing shRNA-mediated PUM knockdown and cells treated with a non-target control	Co-expression
SRP100786	Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [1]	Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic epithelial cells from 3 healthy donors. 92 single cell libraries, 3 bulk controls, 1 empty well control. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 2500 lane).	Co-expression
SRP100787	The transcription start site and enhancer landscape of the descending colon in inflammatory bowel disease	Inflammatory bowel disease (IBD) is a common and chronic gut disorder, with two subtypes: Crohn''s disease (CD) and ulcerative colitis (UC), which are challenging to diagnose. The molecular pathology IBD is not well understood, and the underlying gene regulatory regions have not been comprehensively investigated. Relatedly, most IBD-associated SNPs are located in non-coding regions, and may effect gene regulation. Here, we profiled genome-wide promoter and enhancer activity in the descending colon of IBD patients. IBD-induced enhancer and promoters are highly enriched for IBD-associated SNPs, and can predict IBD diagnosis with an accuracy of 85% in an external cohort. Overall design: This experiment includes a total of 94 patients: 25 patients with active UC(UCa), 17 patients with UC in remission(UCi), 20 patients with active CD(CDa), 3 patients with CD in remission(CDi) and 29 healthy controls (Ctrl).	Co-expression
SRP100793	Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [2]	Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic lamina propria mesenchymal cells from 3 healthy donors. 183 single cell libraries, 6 bulk controls, 3 empty well controls. Individual donors processed as separate batches with Fluidigm C1 IFCs and pooled for sequencing (2 x Illumina HiSeq 2500 lanes).	Co-expression
SRP100795	Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease [3]	Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Ulcerative colitis colonic lamina propria mesenchymal cells from 3 donors. 178 single cell libraries, 7 bulk controls, 7 empty well controls. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 4000 lane).	Co-expression
SRP100803	DNA methylation signature defines genes modulated by stromal cell contents of human breast tumors [RNA-seq]	Using genome-wide approaches, we have identified groups of genes modulated by CAF-secreted factors from human breast cancer cell lines grown in different CAF-conditioned medium. The genes modulated by CAF secreted factors were characterized by a specific DNA methylation pattern: hypermethylation at transcription start site (TSS) and shore regions. Approximately 60% of them exhibited a methylation-dependent expression level and 20% of them were also dependent on the methyl-CpG-binding protein domain 2. Thus, these specific DNA methylation patterns were linked to an epigenetic control of their expression, upon CAF-secreted factors. We have therefore identified some molecular events defining the responsiveness of groups of genes to stromal cell contents in human breast tumors. Overall design: RNAseq of untreated SKBR3 cells and AU565 cells, CAF-conditionned medium treated cells, DAC treated cells, siMBD2 treated cells, siCtrl, in duplicates or in quadriplicates for untreated SKBR3 cells	Co-expression
SRP100825	Homo sapiens Raw sequence reads	HITS-CLIP experiments provide the state-of-the-art means of identifying RNA-binding sites for typical and atypical RNA binding proteins (RBPs) in living cells, which are crucial for understanding the increasingly recognized complexity of RNA regulation. However, current CLIP technology was limited to small amounts of CLIP RNA and complicate procedures with high experimental failure rates. Here we describe an easy-operating CLIP (eoCLIP) protocol. While maintaining high quality and precision, eoCLIP omits the RNA radioactive labeling by 32P and the followed autoradiographic visualization steps. It also applied the commercially available small RNA library preparation kit to simplify the efficiency of RBP-bound RNA recovery. By incorporating paired IgG as a crucial control, eoCLIP improves signal-to-noise in identifying authentic binding sites. The easy-operation and efficiency of the eoCLIP protocol offers a unique opportunity for large-scale generation of transcriptome-wide binding maps for RBPs.	Co-expression
SRP100829	Transcriptome analysis of immature and matured human oocytes from patients of young and advanced maternal age	Study Question: What effects do maternal age and oocyte maturation stage have on the human oocyte transcriptome that may be associated with oocyte developmental potential? Summary Answer: Although polyadenylated transcript abundance changes during human oocyte maturation irrespective of age, young (YNG) and advanced maternal age (AMA) metaphase II (MII) oocytes exhibit divergent transcriptomes. What is known already: Maternal age and maturation stage affect oocyte polyadenylated transcript abundance in human oocytes. Although RNA-Seq analysis of single human MII oocytes has been conducted, comparison of the germinal vesicle (GV) and MII oocyte transcriptomes has not been investigated using RNA-Seq, a technique that could provide novel insight into oocyte maturation and age-associated aberrations in gene expression. Participants / materials, settings, methods: Patients undergoing infertility treatment at the Colorado Center for Reproductive Medicine (Lone Tree, CO, USA) underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ultrasound guided egg retrieval. Unused GV oocytes obtained at retrieval were donated for transcriptome analysis. Single oocytes were stored (at -80°C in PicoPure RNA Extraction Buffer; Thermo Fisher Scientific, USA) immediately upon verification of immaturity or after undergoing in vitro oocyte maturation (24 hour incubation), representing GV and MII samples, respectively. After isolating RNA and generating single oocyte RNA-Seq libraries (SMARTer Ultra Low Input RNA HV kit; Clontech, USA), Illumina sequencing (100 bp paired-end reads in HiSeq 2500) and bioinformatics analysis (CLC Genomics Workbench, DESeq2, Weighted Gene Correlation Network Analysis (WGCNA), 3'UTR motif analysis, Ingenuity Pathway Analysis) were performed. Main results and the role of chance: Within the 12,770 expressed genes in human oocytes (reads per kilobase per million mapped reads (RPKM) > 0.4 in at least 3 of 5 replicates for a minimum of one sample type), 458 and 3,506 genes significantly (adjusted p < 0.05 and log2 fold change > 1) increased and decreased in polyadenylated transcript abundance during oocyte maturation, respectively. The differentially expressed genes were enriched (FDR < 0.05) for biological functions and canonical pathways related to cell cycle and mitochondrial function. The majority (76%) and minority (25%) of up- and down-regulated transcripts with a complete 3'UTR were predicted to be targets of cytoplasmic polyadenylation (910 total genes), respectively. Differential gene expression analysis between young and advanced maternal age oocytes (within stage) identified 1 and 255 genes that significantly differed (adjusted p < 0.1 and log2 fold change > 1) in polyadenylated transcript abundance for GV and MII oocytes, respectively. These genes included CDK1, NLRP5, and PRDX1, which have been reported to affect oocyte developmental potential and be markers of oocyte quality. Despite similarity in transcript abundance between GV oocytes irrespective of age, divergent expression patterns emerged during oocyte maturation. These age-specific differentially expressed genes were enriched (FDR < 0.05) for functions and pathways associated with mitochondria, cell cycle, and cytoskeleton. Gene modules generated by WGCNA (based on gene expression) and patient traits related to oocyte quality (e.g. age and blastocyst development) were determined to be correlated (p < 0.05) and enriched (FDR < 0.05) for functions and pathways associated with oocyte maturation. Limitations, reasons for caution: The human oocytes used in the current study were obtained from patients with varying causes of infertility (e.g. decreased oocyte quality and oocyte quality-independent factors), possibly affecting oocyte gene expression. Oocytes in this study were retrieved at the GV stage following hCG administration and the MII oocytes were derived by in vitro maturation of patient oocytes, which has the benefit of identifying intrinsic differences between samples, but may not be completely representative of in vivo matured oocytes. Thus, these factors should be considered when interpreting the results. Wider Implications of the findings: Transcriptome profiles of young and advanced maternal age oocytes, particularly at the MII stage, suggest aberrant transcript abundance contributes to the age-associated decline in fertility. Overall design: Study design, size, and duration: The effect of oocyte maturation (cross-sectional analysis) and age (longitudinal analysis) on polyadenylated transcript abundance were analyzed by examining single GV and single in vitro matured MII oocytes derived from five young (<30 years; average age 26.8; range 20-29) and five advanced maternal age (=40 years; average age 41.6 years; range 40-43 years) patients. Thus, a total of 10 young (5 GV and 5 MII) and 10 advanced maternal age (5 GV and 5 MII) oocytes were individually processed for RNA-Seq analysis.	Co-expression
SRP100833	Assessing the impact of loss of MORC2 on the transcriptome	By comparing HeLa cells lacking MORC2 generated through CRISPR/Cas9-mediated gene disruption to wild-type HeLa cells, the goal of the experiment was to determine the effect of loss of MORC2 on the transcriptome. Overall design: Total RNA-seq of three independent knockout HeLa clones lacking MORC2.	Co-expression
SRP100834	Hyper-repression of HUSH target genes by over-expression of the R252W Charcot-Marie-Tooth disease mutant MORC2	By comparing wild-type SK-N-SH neuroblastoma cells to cells over-expressing either wild-type or R252W mutant MORC2, the goal of the experiment was to assess the effect of MORC2 over-expression on the transcriptome. Overall design: Total RNA-seq of SK-N-SH cells in triplicate, either 1) mock transduced, 2) transduced with lentiviral vector encoding wild-type MORC2 or 3) transduced with lentviral vector encoding R252W MORC2.	Co-expression
SRP100835	Assessing the impact of the R252W Charcot-Marie-Tooth disease mutation in MORC2 on HUSH-mediated repression	HeLa cells lacking MORC2 generated through CRISPR/Cas9-mediated gene disruption were reconstituted with either wild-type or R252W mutant MORC2, and re-repression of HUSH target genes assessed by RNA-seq Overall design: Total RNA-seq of MORC2 knockout cells, either 1) mock transduced, 2) transduced with lentiviral vector encoding wild-type MORC2 or 3) transduced with lentviral vector encoding R252W MORC2.	Co-expression
SRP100849	Stem cell functionality is microenvironmentally defined during tumor expansion and therapy response in colon cancer	Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically but entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts (CAFs). Hence, stem cell properties change in time depending on the cell location. Furthermore, although chemotherapy enriches for cells with a CSC phenotype, also in this context functional stem cell properties are fully defined by the microenvironment. To conclude, we identified osteopontin (OPN) as a key CAF-produced factor that drives in situ clonogenicity in colon cancer. Overall design: RNA-Seq was performed to compare gene expression between the edge and the centre of tumors, derived from human colorectal cancer cell lines grown as PDX in nude mice.	Co-expression
SRP100857	Identification of differential expressed genes of JQ1 or JQ1+Bortezomib in colorectal cancer cells	The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors including MYC. However, only a subset of CRC cells response to BETi, suggesting an intrinsic resistance to BETi in CRC. We investigated the effect of JQ1 on cell proliferation, apoptosis, angiogenesis and MYC expression in a panel of 11 CRC cells in vitro and in vivo. JQ1-resistant CRC cells were used for the screening for the effective combination therapies with JQ1. RNA-seq of single drug or combined drugs treatment was performed to explore the mechanism of action. Overall design: RKO cells were treated with  JQ1 (1 µM) for 6 h. HCT116 cells were treated with DMSO, JQ1 (1 µM) , Bortezomib (5nM), JQ1 (1 µM)+Bortezomib (5nM) for 6h. RNA was extracted for RNA-seq.	Co-expression
SRP100878	Expression of TGFß-inducible myosin-X predicts survival and chemotherapy resistance in squamous cell lung cancer	Squamous cell lung carcinoma (SCC) corresponds to about 25% of all lung cancers. Therapeutic approaches are very limited and platinum-based chemotherapy remains the main treatment option. Despite multiple studies, there are no generally accepted predictive biomarkers for SCC. Transforming growth factor-ß (TGFß) signaling was shown to be implicated in numerous pro-tumorigenic processes, including immune evasion, inflammation and cancer metastasis. In the context of SCC epithelial-to-mesenchymal transition phenotype that is commonly mediated by TGFß was widely observed in surgically resected specimens. However, the relation between TGFß-induced changes and SCC progression remains to be elucidated. In the presented work, we combined phenotypic and transcriptome-wide approaches to identify novel predictive biomarkers for SCC. We show that TGFß treatment activated Smad-mediated signal transduction and resulted in increase of migratory and invasive properties of SK-MES1 cells. Multiple actin cytoskeleton-related proteins, including myosin motor proteins such as Myosin-X, were up-regulated upon TGFß stimulation. siRNA-mediated knockdown of Myosin-X completely abrogated TGFß-induced collagen gel invasion. Finally, analysis of mRNA expression in paired surgically resected tissues of 151 SCC patients with corresponding 80-month clinical follow-up, showed that the mRNA expression ratio of Myosin-X in tumor and adjacent non-tumor tissue is predictive for overall survival and chemotherapy resistance independently of tumor stage. Given Myosin-X role in cellular motility and invasion, it can represent a new biomarker for aggressive disease and serve as a potential molecular target for therapeutic intervention in patients with SCC. Overall design: SK-MES-1 cells were treated with TGFb or left untreated and mRNA isolated at t=[0h, 8h, 24h, 48h] in biological triplicates.	Co-expression
SRP100883	Integrin-b4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells	We report the gene expression profiles of normal epithelial and carcinoma cell populations that differ in their relative levels of integrin-beta 4 expression. ITGB4 high, mesenchymal subtype, triple-negative breast cancer cells were found to be more epithelial than related ITGB4 low cells. Overall design: RNA-seq was used to compare the expression of mesenchymal-like carcinoma cell subtypes isolated from polyclonal cell populations. Isolated cell populations that had high levels of ITGB4 were found to be more epithelial than those with low levels, despite the fact that they were within the mesenchymal-like cell state spectrum.	Co-expression
SRP100900	Isolation and Functional Interrogation of Adult Human Prostate Epithelial Stem Cells at Single Cell Resolution	Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was confirmed using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 expression without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to separate stem and progenitor cells, RNA-seq identified unique gene signatures for the separate populations which may serve as biomarkers. Pathways enrichment in stem cells identified ribosome biogenesis and membrane estrogen-receptor signaling with NF?B signaling enriched in progenitors and these were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified cancer stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Overall design: Comparing RNA-seq gene profiles in label-retaining prostate stem cells and non-retaining progenitor cells	Co-expression
SRP100928	Lineage specific differentiation is influenced by state of human pluripotency [RNA-seq]	Human pluripotent stem cells (hPSCs) have been reported in naïve and primed states. However, the ability of human PSCs to generate mature cell types is the only imperative property for translational utility. Here, we reveal that the naïve state enhances self-renewal capacity while restricting lineage differentiation in vitro to neural default fate. Gene expression analyses indicate expression of multiple lineage associated transcripts in naïve hPSCs and thus failed to predict biased functional differentiation.  Naïve hPSCs can be converted to primed allowing recovery of multilineage differentiation over long serial passage or immediately through suppression of OCT4 but not NANOG. To this end, we identified chemical inhibitors of OCT4 expression that acutely restore naïve hPSC differentiation. Our study identifies unique cell fate features and critical restrictions in human pluripotent states, and provides an approach to overcome these barriers that harness both efficient naïve hPSC growth whilst maintaining in vitro differentiation capacities essential for hPSC applications. Overall design: hPSC lines were transduced with shRNA lentiviruses in order to assess the effects of reducing NANOG and OCT4 gene expression on differention in the naïve state.  shRNA expressing cells were sorted and then total RNA was extracted in order to perform transcriptome profiling by RNA-seq. Each experimental condition involves 2 technical replicates of 2 biological replicates (2 tech X 2 biol = 4 reads).	Co-expression
SRP100936	Whole transcriptome analysis of PBMCs stimulated with either a P. aeruginosa phage PNM lysate or with its bacterial host  P. aeruginosa	The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile, by means of whole transcriptome analysis, of peripheral blood mononuclear cells (PBMCs) derived from a healthy human donor and stimulated with a Pseudomonas aeruginosa phage PNM lysate, or P. aeruginosa strain 573. The PBMCs were stimulated for 20 h, followed by lysis of the cells and RNA extraction. In total, three stimulations were performed: control sample (i.e. not stimulated), P. aeruginosa phage PNM lysate and P. aeruginosa strain 573. Each stimulation was conducted in triplicate. The transcriptome analysis showed that the phage induce a clear immunological responses. Both pro- and anti-inflammatory genes were up-regulated in the PBMCs in the presence of the phage or its bacterial host. Our results indicate that bacteriophages might play a bigger role in the  immune response then previously described and might have a broader effect than the clearing of bacterial infections alone, such as the suppression of the immune response to benefit their own survival. Overall design: The transcriptome analysis showed that the phage induce a clear immunological responses. Both pro- and anti-inflammatory genes were up-regulated in the PBMCs in the presence of the phage or its bacterial host. Our results indicate that bacteriophages might play a bigger role in the	Co-expression
SRP100948	Heterogeneity in neurodegenerative disease	RNA was purified from fusiform gyrus tissue sections of autopsy-confirmed Alzheimer''s cases and neurologically normal age-matched controls. The "SAM.ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007261 Overall design: RNA from fusiform gyrus of Alzheimer''s or Neurologically Normal post-mortem tissue.	Co-expression
SRP100953	JUN-Mediated downregulation of EGFR signaling is associated with resistance to gefitinib in EGFR-mutant NSCLC cell lines [RNA-seq]	The Epidermal Growth Factor Receptor (EGFR) regulates a diverse set of biological processes including cell growth, proliferation, and differentiation.  Deregulation of the EGFR pathway has been implicated in a variety of human diseases including cancer.  Gefitinib and erlotinib are tyrosine kinase inhibitors (TKIs) that have demonstrated clinical benefit for patients with Non-small cell lung cancer (NSCLC) and EGFR activating mutations.  However, patients invariably acquire resistance to TKI treatment through a number of mechanisms.  We utilized in vitro models of NSCLC with EGFR activating mutations and derived three isogenic cell lines with acquired resistance to gefitinib. We next studied genomewide mRNA expression in resistance  and wild type cells  and their effect in the  reprogramming of  pathways in lung cancer cell line models.. Overall design: Differntial expresssion profile of transcripts of  parental (HCC827) and EGFR-TKI (HCC827 ZDR3) resistance cells	Co-expression
SRP100982	SLC25A25-AS1 knockdown data of two colorectal carcinoma cell lines (HT29 and SW480)	We identified that SLC25A25-AS1 was a lncRNA influencing radiation response. Therefore, we aimed to explore more biological roles of SLC25A25-AS1 in this process. Towards this end, we used RNA interference (RNAi)-mediated knockdown of SLC25A25-AS1 in HT29 and SW480 to explore the changes of mRNA expression profiles and explore the phenotype outcomes. Overall design: A four sample study using total RNA collected from three cell lines (HT29 and SW480) with or without knockdown of SLC25A25-AS1.	Co-expression
SRP100993	RNA transcriptome analysis during HSV-1 infection	For Samples 1-8 and 11-18: The innate immune sensor retinoic acid-inducible gene-I (RIG-I) detects double-stranded RNA derived from RNA viruses, and recent studies have demonstrated that RIG-I also plays a role in the antiviral response to DNA viruses. To identify the physiological RNA species that are recognized by RIG-I during HSV-1 infection, we purified the RNAs that co-immunoprecipitated with FLAG-tagged RIG-I in transfected human embryonic kidney (HEK) 293T cells that had been infected with a recombinant HSV-1 (hereafter referred to as HSV-1 mut) containing a mutation (K220A) in the viral serine/threonine protein kinase US3 that abolishes its catalytic activity, as the viral kinase is known to antagonize type-I IFN responses. As controls, RNA species bound to FLAG-RIG-I in uninfected cells and RNA bound to FLAG-GFP from both HSV-1 mut-infected and uninfected cells were also purified. RIG-I-bound RNA and total RNA extracted from uninfected and HSV-1 mut-infected cells were analyzed by RNAseq, and the resulting sequences were mapped to both the HSV-1F-strain and human genome (hg38). This analysis revealed that several human transcripts were highly enriched in the RIG-I-bound fraction from infected cells; in contrast, the enrichment of viral sequences was low. The cellular transcripts that were most abundant in the RIG-I fraction were predominantly non-coding RNAs from different subclasses, as well as some coding RNAs. For Samples 9 and 10: HSV-1 infection is known to induces changes in the transcriptional profile of the infected cell. To analyze global changes in RNA transcript levels in infected cells, total RNA was extracted from HEK 293T cells that were infected with wild-type (WT) HSV-1. For comparison, total RNA was extracted from HEK 293T cells that remained uninfected. Next, RNAseq analysis was performed. The resulting sequences were mapped to the human genome, and gene inductions were calculated and normalized to uninfected samples to determine changes in gene expression upon infection. Overall design: Cells, which were not infected or infected with either wildtype HSV-1 or mutated HSV-1 were either subjected to a pulldown isolating RLR/GFP associated RNA (8 samples) or the corresponding total RNA (8 samples) was extracted from the infected cells and sequenced. Additionally, non-transfected cells were infected and total RNA extracted and sequenced (2 samples)	Co-expression
SRP101286	Global transcriptome analysis of BJAB cells that are modulated by EBV infection or (and) EBV BART6-3p mimics.	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are using transcriptome profiling (RNA-seq) to evaluate the effects of EBV infection or (and) EBV BART6-3p mimics on the global transcriptome of the BJAB cells. Methods: BJAB cells were transfected with negative control mimics or BART6-3p mimics for 48 h and then infected with EBV virons for 2h. RNAs were extracted by Trizol and sequenced by Solexa high-throughput sequencing service (Oebiotech, Shanghai, China). Data were extracted and normalized according to the manufacturer's standard protocol. Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05. There are 408 mRNAs were up-regulated and 263 were down-regulated in “EBV infection” group cells comparing to “Mock” group cells. There are 385 mRNAs were up-regulated and 246 were down-regulated in “EBV infection + Bart6-3p mimics” group cells comparing to “EBV infection + negative control mimics” group cells. Conclusions: Our study describes the global transciptome changes of BJAB cells induced by EBV infection or (and) EBV 6-3p mimics. Overall design: BJAB cells mRNA profiles of “mock” (no infection, no treatment), “EBV infection”, “EBV infection + negative control mimics”, and “EBV infection + BART6-3p mimics” were generated by RNA sequecning, using Solexa high-throughput sequencing service (Oebiotech, Shanghai, China).	Co-expression
SRP101290	Tracing the temporal-spatial transcriptomic landscapes of the human fetal digestive tract by single cell RNA-seq analysis [fetal tissues]	The development of digestion tract is critical for proper digestion of food and absorbance of nutrient for an individual. It includes the spatial segregation into esophagus, stomach, small and large intestine. The temporal-spatial gene expression profiles of human digestion tract in vivo have never been analyzed at single-cell resolution.Here we analyzed esophagus, stomach, small intestine (SI) and large intestine (LI) from multiple human embryos between 6 and 25 weeks of gestation by single cell RNA-seq analyses.We firstly identified 51 clusters of different types of cells using t- Distributed Stochastic Neighbor Embedding (t-SNE) analysis.Moreover,cell type of each organ were identified according to the known marker genes and new cell types were further analyzed.The dynamic change of each cell type were tracked during the human embryonic digestive tract development.We found HOX family geens paly different roles in the regulation of digestion tract developemnt. In addition, Hedgehog,TGFß and BMP signaling pathway are essential for SI and LI development in human fetal. The function of nutrient digestion and absorption was increased as the SI development in human fetal.Finally, we demonstrated that the immune system was established at late stage of human fetal and verified the immune-like cells,such as T cell, B cells and macrophage. In summary, by using single cell RNA seq technique, we identified the waves of signaling pathways and critical cell types for the human digestion tract development. Overall design: Single cell transcriptome profiles of four main human organs (esophagus, stomach, small and large intestine) from 6 week to 25 week gestation of digestion system were generated by next generation sequencing using Illumina HiSeq X Ten	Co-expression
SRP101294	Transcriptome profiling from adipose tissue during low-caloric diet reveals predictors of long-term weight and glycemic outcomes in obese, non-diabetic subjects	Background: Low-caloric diet (LCD) reduces fat mass excess, improves insulin sensitivity, and alters adipose tissue (AT) gene expression. Yet the relationship with long-term clinical outcomes remains unclear. Objective: We evaluated transcriptome alterations in AT during LCD and association with weight and glycemic outcomes both at LCD termination and 6-month after the LCD. Results: Upon LCD, we identified 1'173 genes differentially expressed; with 350 and 33 genes associated respectively with changes in BMI and Matsuda. Twenty-nine genes were associated with both endpoints. Pathway analyses highlighted enrichment in lipid and glucose metabolism. Models were constructed to predict weight maintainers. A model based on clinical baseline parameters could not achieve any prediction (validation's AUC= 0.50 [0.36, 0.64]), while a model based on clinical changes during LCD yielded to good performance (AUC=0.73 [0.60, 0.87]). Incorporating baseline expression from the 18 genes outperformed the best clinical model (AUC=0.87 [0.77, 0.96], Delong's p=0.012). Similar analyses were made to predict subjects with good glycemic improvements. Both baseline- and LCD-based clinical models yielded to similar performance (with best AUC=0.73 [0.60, 0.85]). Addition of expression changes during LCD improved substantially the performance (AUC=0.80 [0.69, 0.92], p=0.058). Conclusions: This study investigated AT transcriptome alterations following LCD in a large cohort of obese, non-diabetic patients. The identified genes enabled to significantly improve clinical models and predict long-term clinical outcomes. These biomarkers may help clinicians understanding the large inter-subject variability and better predict the success of dietary interventions. Overall design: Design: Using RNAseq, we analyzed transcriptome changes in AT from 191 obese, non-diabetic patients within a multi-center controlled dietary intervention. Expression changes were associated with outcomes after 8-week LCD (with 800-1000kcal/d) and 6-month after LCD. Results were validated using RT-qPCR in 350 subjects from the same cohort. Statistical models were constructed to predict subjects considered as weight maintainers or glycemic improvers 6-month after LCD.	Co-expression
SRP101296	CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [RNA-Seq]	CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth.  However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored.  Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models.  The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner.  CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155.   Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers. Overall design: CARM1 wild type and knockout samples assayed by RNA-seq	Co-expression
SRP101298	RNAseq of CCRF-CEM, a T-cell acute lymphoblastic leukemia cell line, after knockdown with 2 control hairpins and 6 hairpins targeting the PRC2 complex.	The data was used to study mechanisms of apoptosis resistance induced by loss of PRC2. Overall design: CCRF-CEM cells infected with shLuciferase, shGFP, shEZH2.1, shEZH2.4, shEED2, shEED5, shSUZ12.2, shSUZ12.3 were harvested, RNA isolated, and RNAsequencing performed on HiSeq 2000.	Co-expression
SRP101380	Homo sapiens Raw sequence reads	The effect of Yao Tu Ke Li on whole transcriptome in prevention and treatment for lumbar disc degeneration	Co-expression
SRP101418	Triple-negative breast cancer  RNA-Seq from matched fresh-frozen versus formalin-fixed paraffin-embedded tissue	RNA-seq performed on 21-paired fresh-frozen and formalin fixation and paraffin-embedded triple-negative breast cancer specimens and evaluated genome alignment, transcript coverage and differential transcript enrichment.	Co-expression
SRP101420	mRNA expression data from ESCs derived by polar body transfer reconstructed embryos (PBTESCs)	Here we report the derivation of human PBTESCs from polar body transfer resconstructed embryos. We used RNA-seq to compare the gene expression levels among human parthenogenetic haploid ESCs (hPGES)?normal human ESCs (H9) and human forskin fibroblasts and identified that these cells express conventional ESCs pluripotent markers and most maternally imprinted genes were down-regulated. Overall design: We collected fresh ESCs samples of 3 cell lines from PB1 transfer and 3 cell lines from PB2 transfer each at around 10^6 cells in similar passage. All the sample was lysised by 1 mL Trizol directly and stored at -80?. DNA libraries building and sequencing was performed at the same time to reduce systematic error. Gene expression profiles of all the cell lines were analysed on illumina Hiseq 2500.	Co-expression
SRP101458	Super-Enhancers Promote Transcriptional Dysregulation in  Nasopharyngeal Carcinoma [RNA-seq]	Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high  incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC,  particularly those involving epigenetic dysregulation, remain largely elusive,  hampering the clinical management of this malignancy. To identify novel druggable  targets, we carried out an unbiased high-throughput chemical screening and observed  that NPC cells were highly sensitive to cyclin-dependent kinases (CDKs) inhibitors,  especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced  anti-neoplastic activities both in vitro and in vivo. An integrative analysis using both  whole-transcriptome sequencing (RNA-Seq) and chromatin-immunoprecipitation  sequencing (ChIP-Seq) pinpointed oncogenic transcriptional amplification mediated  by Super-Enhancer (SE) as a key mechanism underlying the vulnerability of NPC  cells to THZ1 treatment. Further characterization of SE-mediated network identified  many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR,  TBC1D2 and a long non-coding RNA, TP53TG1. These transcripts were highly and  specifically expressed in NPC, and functionally promoted NPC malignant phenotypes.  Moreover, DNA-binding motif analysis within the SE segments suggest that several  transcription factors (including ETS2, MAFK and TEAD1) may help establish and  maintain SE activity across the genome. Our data together established the landscape  of SE-associated oncogenic transcriptional network in NPC, which can be exploited  for the development of more effective therapeutic regimen for this disease. Overall design: RNA-seq in three NPC cell lines – C666-1, HK1 and HNE1	Co-expression
SRP101524	ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (RNA-seq)	We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing. Overall design: Samples used in this study correspond to B-lymphoblastoid cell lines (B-LCL) derived from peripheral blood of individuals affected by ICF1 syndrome and healthy individuals	Co-expression
SRP101621	TimeLapse-seq: adding a temporal dimension to RNA sequencing through nucleoside recoding	RNA sequencing (RNA-seq) offers a snapshot of cellular RNA populations, but not temporal information about the sequenced RNA. Here we report TimeLapse-seq, which uses oxidative-nucleophilic-aromatic substitution to convert 4-thiouridine into cytidine analogs, yielding apparent U-to-C mutations that mark new transcripts upon sequencing. TimeLapse-seq is a single-molecule approach that is adaptable to many applications and reveals RNA dynamics and induced differential expression concealed in traditional RNA-seq. Overall design: RNA isolated from cells +/- s4U feed was subjected to oxidative-nucleophilic-aromatic-substitution chemistry and sequenced. All sequencing was performed in duplicate per condition assessed.	Co-expression
SRP101697	Gene Expression In Blood From an Individual With ß-Thalassemia: an RNA Sequence Analysis	Background: The thalassemias are highly diverse at both the molecular and clinical levels. Many of the HBB mutations that result in ß-thalassemia are missense mutations in the coding region of the ß-globin gene, but a few cause alternative splicing, and interfere with normal processing of the ß-globin transcripts. Transcriptome profiling in individuals affected with ß-thalassemia, especially in individuals who carry novel mutations in the HBB, may improve our understanding of the heterogeneity and molecular mechanisms of the disease. Methods: Members of a family with a daughter affected with thalassemia intermedia, although her mother was not clinically affected, were examined for physical characteristics, hematological parameters and ß-globin gene sequences. We also characterized genome-wide gene expression in the family using RT-qPCR and high-throughput RNA-sequencing mRNA expression profiling of blood. Results: Clinical findings, hematological indices, DNA and RNA sequence analysis of individuals with ß-thalassemia, including the description of a novel mutation in the ß-globin gene, which introduces a cryptic donor splice site. More than 300 genes are differentially expressed in ß-thalassemic blood with many of the DEGs involved in pathways relevant to the clinical management of ß-thalassemia. ß-thalassemia shows important similarities and differences with sickle cell disease at the transcriptome level. Conclusions: We described the down-regulation of the ß-globin gene in ß-thalassemia by RNA-sequencing analysis using a sample from an affected individual and her mother, who have a novel mutation in the HBB that creates a cryptic donor splice site. The daughter has a typical ß-thalassemia allele as well, and an unexpectedly severe phenotype. The DEGs are enriched in pathways that are directly or indirectly related to ß-thalassemia such as hemopoiesis, heme biosynthesis, response to oxidative stress, inflammatory responses, immune responses, control of circadian rhythm, apoptosis, and other cellular activities. We compare our findings with published results of RNA-Sequencing analysis of sickle cell disease (SCD) and erythroblasts from a KLF1-null neonate with hydrops fetalis, and recognize similarities and differences in their transcriptional expression patterns. Overall design: Total RNA was isolated from blood using EDTA as an anticoagulant and Trizol reagent (Sigma-Aldrich, Germany). 500ng of the total RNA from each of the daughter (sample D), mother (sample M), and a control individual with normal hematological indices (sample N) was used for RNA-Sequencing library preparation, and the quality of RNA was determined with Bioanalyzer 2100. Libraries for RNA-sequencing were prepared with a KAPA Stranded RNA-sequencing Kit (Illumina), following the manufacture's instructions. Sequencing was performed on an Illumina HiSeq 2500 system for pair-ended reads with a length of 100 bp (2x100 bp). Pre-processing and data quality control were performed using Illumina proprietary software.	Co-expression
SRP101719	Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer	In order to identify the processes altered in T regulatory cells (Treg) by Zoledronic acid (ZA), we examined RNA expression by RNA-seq in Treg treated with and without ZA. We identified gene expression alterations in ZA-treated Treg that were essential to Treg function. Overall design: Human T regulatory cells isolated from healthy donors (n=6) were cultured overnight with IL-2 and OKT3 (anti-CD3) in the presence or absence of ZA. RNA sequencing (Illumina HiSeq2500) was performed to identify differential gene expression induced by ZA treatment of Treg.	Co-expression
SRP101726	Genome Scale Analysis of miRNA and mRNA regulation during preterm labor [monocytes]	The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort.  We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL.  Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age	Co-expression
SRP101731	Transcriptional profiles of CD8+ T cells from peripheral blood of melanoma patients before and after anti-PD1 therapy	RNA-Seq analysis was used to study the profile of CD8 t cells from melanoma patients before and after treatment to detect transcriptional changes in peripheral blood	Co-expression
SRP101737	Genome Scale Analysis of miRNA and mRNA regulation during preterm labor [whole blood]	The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort.  We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL.  Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age	Co-expression
SRP101750	Single cell RNA-sequencing of day 15 cells derived from the directed differentiation of human iPSCs towards lung epithelium	It has been postulated that during human fetal development all cells of the lung epithelium derive from an embryonic endodermal NKX2-1+ precursor, however, this hypothesis has not been formally tested due to an inability to purify or track this theorized cell for detailed characterization. Progress has been made in deriving lung epithelial cells from human induced pluripotent stem cells (iPSCs). However, little is known about the heterogeneity or genetic programs of the cells generated using these lung differentiation protocols. We engineered and differentiated NKX2-1GFP reporter iPSCs in vitro, recapitulating the major developmental milestones of lung development, to generate and isolate human primordial lung progenitors (day 15 of differentiation) that expresses NKX2-1 but are initially devoid of markers of differentiated lung lineages. To further characterize the cells generated in the lung directed differentiation protocol we performed single cell RNA-seq analysis of cells on day 15 of lung directed differentiation. We analyzed sorted NKX2-1GFP+ cells for the iPSC line C17 and cells from the iPSC line BU3. Overall design: We sorted C17NKX2-1GFP+ and BU3 cells on day 15 of the lung directed differentiation and loaded into separate Fluidigm C1 integrated fluidics circuits (IFCs).  Lysis, conversion polyA+RNA into full length cDNA and amplification of cDNA was performed using the Fluidigm C1 according to the manufacturer’s protocol. After sequencing on an Illumina Hiseq2500 80 single cell transcriptional profiles from BU3 and 65 from ips17 cell line were compared after filtering and normalization.	Co-expression
SRP101761	RNA-seq identifies ß-estradiol treatment in U2OS osteosarcoma cell	This study was to identify gene expression profile change associated withß-estradiol treatment in osteosarcoma cells by high-throughput RNA sequencing	Co-expression
SRP101765	Whole transcriptome analysis after treatment with NCT	A naphthyridine carbamate tetramer (NCT) is a synthetic compound, which selectively binds to nucleic acids containing CGG/CGG sequence. Although NCT is a promising compound for a wide range of DNA and RNA based biotechnology such as modulation of specific gene expression, little is known about its behavior in human cells. In the present study, we investigated the changes induced in the gene expression by NCT. The genes differentially expressed in the presence of NCT in HeLa cells are evaluated through whole-transcriptome analysis.	Co-expression
SRP101784	Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3	Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by: a targeted shRNA screen confirming a functional role in FOXP3 induction; discriminant analyses classifying iTregs accordingly; and comparable expression in an independent novel iTreg RNA Seq data set. Conclusion: The data generated by this novel approach facilitate understanding the molecular mechanisms underlying iTreg generation as well as the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune and inflammatory diseases Overall design: Comparing the gene expression in activated CD4+ cells and iTreg differentiated cells in human. 10 time points, 3 biological replicates for each time point.	Co-expression
SRP101793	Expression analysis of Mebendazole treated THP-1 cells in three paired samples	Mebendazole treatment of MLL rearanged cell line THP-1 Overall design: 3 pairs of THP-1 cells were either treated with Mebendazole or vehicle control	Co-expression
SRP101809	Single cell RNA-seq reveals expansion of IGRP-reactive CD4+ T cells in recent onset type I diabetes (single-cell RNA-seq of T-cell clone)	Islet-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects are thought to be involved in disease pathogenesis, but full understanding of their role is complicated by their presence also in blood of in healthy subjects. To elucidate their role in T1D, we have combined flow cytometry and single cell RNA sequencing (RNA-seq) techniques to link prior antigen exposure, inferred from expanded TCR clonotypes, and functional capacities of islet antigen-reactive CD4+ memory T cells. We find that cells activated by pooled peptides from immunodominant islet antigens showed significantly higher clonotype sharing within recent onset T1D subjects than in healthy individuals, consistent with in vivo T cell expansion during disease progression. There was no clonotype sharing between donors, indicating a predominance of TCRs with distinct or “private” specificities. Expanded clonotypes could be stable, as one was detected at repeat visits by spanning more than a year by one subject. We identified distinct IGRP peptides as the targets of expanded TCR clonotypes from two T1D subjects, thereby implicating this molecule as a trigger for CD4+ T cell expansion during T1D. Transcriptome profiles of cells from T1D and healthy subjects differed, particularly in cells having the most highly expanded TCR clonotypes. As a group, cells with the most highly expanded TCR clonotypes showed Th2-like phenotypes, but at the single cell level there was phenotypic heterogeneity within and between donors. Our findings demonstrate unique specificities and phenotypes of individual islet-reactive CD4+ memory T cells that have expanded during disease progression. Overall design: This project contains RNA-seq files from four cell types: 1) T cell clone (N=149 single cell profiles); 2) T cell clone (N=9 bulk cell profiles); 3) CD8+ influenza-reactive T cells (N=45 single cell profiles); and 4) CD4+ pooled islet antigen-reactive T cells (N=246 single cell profiles).	Co-expression
SRP101810	Single cell RNA-seq reveals expansion of IGRP-reactive CD4+ T cells in recent onset type I diabetes (bulk RNA-seq of T-cell clone)	Islet-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects are thought to be involved in disease pathogenesis, but full understanding of their role is complicated by their presence also in blood of in healthy subjects. To elucidate their role in T1D, we have combined flow cytometry and single cell RNA sequencing (RNA-seq) techniques to link prior antigen exposure, inferred from expanded TCR clonotypes, and functional capacities of islet antigen-reactive CD4+ memory T cells. We find that cells activated by pooled peptides from immunodominant islet antigens showed significantly higher clonotype sharing within recent onset T1D subjects than in healthy individuals, consistent with in vivo T cell expansion during disease progression. There was no clonotype sharing between donors, indicating a predominance of TCRs with distinct or “private” specificities. Expanded clonotypes could be stable, as one was detected at repeat visits by spanning more than a year by one subject. We identified distinct IGRP peptides as the targets of expanded TCR clonotypes from two T1D subjects, thereby implicating this molecule as a trigger for CD4+ T cell expansion during T1D. Transcriptome profiles of cells from T1D and healthy subjects differed, particularly in cells having the most highly expanded TCR clonotypes. As a group, cells with the most highly expanded TCR clonotypes showed Th2-like phenotypes, but at the single cell level there was phenotypic heterogeneity within and between donors. Our findings demonstrate unique specificities and phenotypes of individual islet-reactive CD4+ memory T cells that have expanded during disease progression. Overall design: This project contains RNA-seq files from four cell types: 1) T cell clone (N=149 single cell profiles); 2) T cell clone (N=9 bulk cell profiles); 3) CD8+ influenza-reactive T cells (N=45 single cell profiles); and 4) CD4+ pooled islet antigen-reactive T cells (N=246 single cell profiles).	Co-expression
SRP101844	Extensive overlap of the STAT6 and RXR cistromes in the active enhancer repertoire of human CD14+ monocyte-derived differentiating macrophages	Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) ? or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via several members of the nuclear hormone receptor superfamily, including retinoid X receptors (RXRs). It has been documented that cytokines are able to modulate macrophage responses to lipid signals but the underlying mechanisms of these events at the genomic level are not well understood. Previous work suggested that STAT6 is a facilitator of nuclear receptor mediated events acting likely at the genome level, which prompted us to investigate genome-wide DNA binding events (cistromes) in human CD14+ monocyte-derived macrophages in the presence and absence of IL-4. We determined the impact of IL-4 on the PU.1, RXR and STAT6 cistromes within the active enhancer regions marked by H3K27 acetylation using chromatin immunoprecipitation followed by deep sequencing and integrated bioinformatic analyses. We found that about 2/3rd of the IL-4-induced STAT6 peaks co-localized with RXR peaks. These binding sites had a distinct motif enrichment profile as compared to the non-overlapping RXR peaks. Interestingly, short-term IL-4 exposure did not change RXR-binding on the STAT6/RXR co-bound enhancers. The functional consequences of the uncovered cistromic interaction between IL-4/STAT6 and RXR signaling pathways include additive and synergistic gene expression events.	Co-expression
SRP101856	Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells	Purpose: The goal of this study is to investigate the effect on gene exression of mutations in Ebola virus inate immune response antagonizing  domains (IRAD). Methods: RNA-Seq transcriptome analysis of dendritic cells 8 and 24 hours post infection Overall design: Human dendritic cells are infected with wild-type Ebola viruses and viruses  harboring mutations in IRADs. Gene expression levels at 8 and 24 hours post infections were compared to mock infected cells.	Co-expression
SRP101868	RNAseq of IL-36 stimulated primary human keratinocytes	Keratinocytes isolated from one healthy donor were stimulated in triplicate for 24h with IL-36a, IL-36ß or IL-36? Overall design: Gene expression profile of IL-36 stimulated keratinocytes	Co-expression
SRP101882	Effect of BET bromodomain inhibition with JQ1 in stressed human derived iPS cardiomyocytes	Gene expression profile of endothelin-1 (ET-1) stressed human derived iPS cardiomyocytes (from Cellular Dynamics) with or without the BET bromodomain inhibitor JQ1 Overall design: Human derived iPS cardiomyocytes from Cellular Dynamics were cultured according to manufacturers protocol with a 4 day serum starvation following by pre-treatment with either JQ1 ( ) or DMSO for 3 hours then stimulation with endothelin-1	Co-expression
SRP101890	Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability [RNA-Seq]	We analyzed differential methylation (via WGBS) between four distinct human brain regions (NAcc-nucleus accumbens, BA9-dorsolateral prefrontal cortex, BA24-anterior cingulate cortex, and HC-hippocampus) in both sorted nuclei and intact tissues. We isolated neuronal and non-neuronal (glial) nuclei from the same six individuals for each tissue via FACS using the neuronal marker, NeuN. Additionally, we performed WGBS from non-sorted tissues from these same brain regions in a total of 12 individuals (BA9 n = 9; BA24 n = 5; HC n = 6; NAcc n = 7). To complement our DNA methylation analyses, we measured gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) in neuronal and non-neuronal nuclei from the nucleus accumbens and dorsolateral prefrontal cortex from six more individuals. We then performed an integrative analysis to understand how the epigenome contributes to brain region-specific function. Overall design: 72 WGBS libraries were sequenced (from intact tissue (27 libraries) and NeuN+ and NeuN- flow sorted nuclei (45 libraries)) from hippocampus, nucleus accumbens, prefrontal cortex (BA9), and anterior cingulate gyrus (BA24). RNA-seq (20 libraries) and ATAC-seq (23 libraries) data from NeuN+ and NeuN- flow sorted nuclei from the nucleus accumbens and prefrontal cortex (BA9) were also obtained.	Co-expression
SRP101894	Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression	We studied the molecules involved in downstream signaling induced by interferons to regulate PD- L1 and PD-L2 expression using a shRNA screen, Western blot, mRNAexpression profiling, promoter truncation analysis and chromatin immunoprecipitation.These studies revealed that the interferon gamma-JAK1/2-STAT1-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter. PD-L2 responded equally to interferon beta and gamma, and shared regulation through IRF1 and alsoSTAT3, which bind to the PD-L2 promoter. Analysis of biopsies from patients with melanoma confirmed interferon signature enrichment and upregulation of gene targets for STAT1/2/3 and IRF1 in anti-PD-1 responding tumors. Therefore, these studies map the signaling pathway of interferon-inducible PD-1 ligand expression Overall design: Melanoma biopsies pre and on- anti-PD-1 treatment were sent for transcriptomic analysis by paired end RNAseq analysis	Co-expression
SRP101904	Epigenetically repressing human cytomegalovirus lytic infection and reactivation from latency in THP-1 model by targeting H3K9 and H3K27 histone demethylases	Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes. During this process, a number of histone modification enzymes, including histone demethylases (HDMs), play important roles in driving IE expression, but the mechanisms involved are not fully understood. To get a better understanding of these mechanisms, we profiled this well-established CMV experimental latency-reactivation model based on TPA (12-O-Tetradecanoylphorbol-13-acetate) induced THP-1 differentiation, which recapitulates many key features of CMV latency and reactivation in vivo, including the important role of viral chromatin in controlling viral IE gene expression.	Co-expression
SRP101934	Knock-down of Ror1 in MDA-MB-231 cell line decreases cell invasiveness	RNA-Seq profiling of triple-negative MDA-MB-231 cell line with know-down of non-canonical WNT signaling receptor Ror1. The MDA-MB231 cells were either transfected with a non-sense control shRNA (shCTL) or with a ROR1 shRNA (shROR1) construct. The objective was to find expression-responsive targets of these perturbations as potential drivers of MDA-MB231 cell invasiveness. Overall design: Two conditions of  MDA-MB-231 cells each in 3 replicates:  1. non-sense control shRNA (shCTL),  2. ROR1 shRNA (shROR1)	Co-expression
SRP101938	Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing [RNA-Seq]	Purpose: DNA methyltransferase 3A (DNMT3A) mediates de novo DNA methylation. Mutations in DNMT3A are associated with hematological malignancies, most frequently acute myeloid leukemia. DNMT3A mutations are hypothesized to establish a pre-leukemic state, rendering cells vulnerable to secondary oncogenic mutations and malignant transformation. However, the mechanisms by which DNMT3A mutations contribute to leukemogenesis are not well-defined. Methods: mRNA profiles of wild-type (WT) and DNMT3A mutated k562 cell lines were generated by deep sequencing, using Illumina HiSeq2500. Sequence reads were trimmed to remove possible adapter sequences and nucleotides with poor quality at the ends. Remaining sequence reads were then aligned to the human reference genome (hg19) using Tophat2. Gene read counts were measured using FeatureCounts and FPKM values were calculated with cufflinks. edgeR was used to identify differentially expressed genes between conditions, and topGO was used for annotation (Alexa, Rahnenfuhrer, and Lengauer, 2006). Sample comparison for differential gene expression was as follows: WTblk and WT1 versus MT2, MT3, MT4, and MT5. Gene enrichment set analysis (GSEA) was conducted with KEGG, Biocarta, and Reactome pathway datasets (Subramanian et al., 2005). Results: DNMT3A-mutated cells displayed impaired differentiation capacity. RNA-seq was used to compare transcriptomes of DNMT3A-mutated and WT cells; DNMT3A ablation resulted in downregulation of genes involved in spliceosome function, causing dysfunction of RNA splicing. Unexpectedly, we observed DNMT3A-mutated cells to exhibit marked genomic instability and an impaired DNA damage response compared to WT. Conclusions: CRISPR/Cas9-mediated DNMT3A-mutated K562 cells may be used to model effects of DNMT3A mutations in human cells. Our findings implicate aberrant splicing and induction of genomic instability as potential mechanisms by which DNMT3A mutations might predispose to malignancy. Overall design: mRNA profiles of wild type (WT) and DNMT3A mutated K562 cell lines were generated by deep sequencing using Illumina HiSeq2500	Co-expression
SRP101952	RNA_seq and Ribo_seq analyses of control and CPT-treated MCF7 cells	We used RNA-seq and Ribo-seq analyses to examine the effect of CPT treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) using biological duplicates of control and CPT-treated (5 hrs) MCF7 cells	Co-expression
SRP101959	Novel transcriptional networks regulated by CLOCK in human neurons	The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin-immunoprecipitation sequencing for endogenous CLOCK in adult neocortex and RNA-sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts co-expressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks are driven by hub genes with human-specific patterns of expression. Thus, these data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. Overall design: We carried out RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) in differentiated human neural progenitor cells and ChIP-sequencing (ChIP-seq) in both differentiated human neural progenitor cells and BA10 and BA40 of adult human neocortex. For the Chip-seq, five replicates were used for each of the two Brodmann areas (BA10 and BA40) of adult human frozen brain tissue (i.e. the five replicates of BA10 and BA40 came from the same five individuals). For the RNA-seq, three independent replicates of control and CLOCK knockdown samples were used each time point analyzed. For the ATAC-seq, three independent replicates of control and CLOCK knockdown samples were used.	Co-expression
SRP101987	Prospective Isolation and Comparison of Human Germinal Matrix and Glioblastoma EGFR+ Populations with Stem Cell Properties	Characterization of non-neoplastic and malignant human stem cell populations in their native state can provide new insights into gliomagenesis. Here we developed a purification strategy to directly isolate EGFR+/– populations from human germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de-novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF ligand (LBEGFR+), and uniquely compared their functional and molecular properties. LBEGFR+ populations in both GM and GBM encompassed all sphere-forming cells and displayed proliferative stem cell properties in vitro. In xenografts, LBEGFR+ GBM cells showed robust tumor initiation and progression to high-grade, infiltrative gliomas. Whole transcriptome sequencing analysis confirmed enrichment of proliferative pathways in both developing and neoplastic freshly isolated EGFR+ populations, and identified both unique and shared sets of genes. The ability to prospectively isolate stem cell populations using native ligand-binding ability opens new doors into understanding both normal human progenitors and tumor cell biology. Overall design: We performed full transcriptome sequencing by RNA-seq on freshly isolated EGFR+ and EGFR– populations from human brain germinal matrix (GM, n=3) and from human glioblastoma (GBM, n=3) resections. Three biological replicates were sequenced for each group: GM EGFR+, GM EGFR–, GBM EGFR+, and GBM EGFR–. Sequencing was performed on Illumina HiSeq 2500 (125bp pair-end sequencing, 38-50mil paired-end reads/sample).	Co-expression
SRP101998	RNA-seq detects pharmacological inhibition of Epstein-Barr virus late transcription during spontaneous reactivation.	The stepwise and sequential expression of viral genes underlies progression of the infectious life cycle. The Epstein-Barr virus (EBV) is both a tractable model for elucidating principles of transcription as well as a global health threat. We describe an experimental protocol and bioinformatics pipeline for functional identification of EBV true late genes, the last step of transcription prior to virion packaging and egress. All data have been uploaded to the Gene Expression Omnibus under accession code GSE96689. The key improvement over previous approaches is leveraging the sensitivity of RNA-seq to detect gene expression changes during spontaneous reactivation. Overall design: Examination of late gene expression in 2 cell types after acyclovir treatment. Please note that the wig files are a slightly modified format in that they display a viral genome not available as a chromosome on the UCSC genome browser. The wig files are readable by the IGV browser (as described in the associated publication).	Co-expression
SRP102019	Time-dependent regulation of cellular programming of monocytes by NCOR2 [RNASeq_TK]	Whole transcriptome profiling (RNA-Seq) of a time kinetics experiment containing human monocyte-derived cells, which were activated with IL4 either directly at the start of the culture, or at different hours after an initial activation with GMCSF alone. Cells being activated solely with GMCSF were added as controls Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with either GMCSF alone for 72 hours to obtain Mo-GMCSF[IL4 (0h)] cells as controls, with the combination of GMCSF and IL4 for 72 hours or 144 hours to obtain Mo-GMCSF[IL4 (0-72h)] or Mo-GMCSF[IL4 (0-144h)] cells, respectively, or with first GMCSF and then with the combination of GMCSF and IL4 for different durations. For the latter, monocytes were first activated with GMCSF for either 12, 24, 48 or 72 hours, and then with GMCSF plus IL4 until a total activation time of 144 hours. This resulted in Mo-GMCSF[IL4 (12-144h)], Mo-GMCSF[IL4 (24-144h)] , Mo-GMCSF[IL4 (48-144h)]  and Mo-GMCSF[IL4 (72-144h)] cells, respectively.	Co-expression
SRP102020	RNA_seq and Ribo_seq analyses of control and Nutlin3a-treated MCF7 cells (20 hrs)	We used RNA-seq and Ribo-seq analyses to examine the effect of Nutlin3a (activator of p53) treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in control and Nutlin3a-treated (20 hrs) MCF7 cells	Co-expression
SRP102021	RNA_seq and Ribo_seq analyses applied to PC9 and H1933 human cancer cell lines	We used RNA-seq and Ribo-seq analyses to examine translation efficiency (TE) in PC9 and H1933 cells Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in PC9 and H1933 cell lines	Co-expression
SRP102031	mitoCPR - a surveillance pathway that protects mitochondria in response to mitochondrial import stress [human]	Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Physiological perturbations and disease conditions can lead to mitochondrial import defect. We find that in budding yeast, mitochondrial import defects result in activation of a surveillance mechanism, which we termed mitoCPR. The mitoCPR is aimed at ameliorating mitochondrial import and protecting mitochondria during import stress. This is mediated by the mitoCPR effector, Cis1, which associates with mitochondria to reduce the accumulation of mitochondrial preproteins at the organelle's surface. Clearance of preproteins depends on the AAA-ATPase Msp1 and the proteasome, suggesting that Cis1 facilitates the degradation of unimported proteins that accumulate at the mitochondrial surface. We further show that mitoCPR is critical for maintaining mitochondrial functions during mitochondrial import stress and provide evidence that it is an ancient, conserved mitochondrial protection mechanism. Overall design: Three replicates each of WT control, rho0 (lacking mitochondrial DNA) and CCCP-treated (to induce mitochondrial protein import stress) were compared.	Co-expression
SRP102077	H-STS NET cell line perturbed with small molecule compounds	Expression profile of H-STS NET cell line at 6h and 24h after perturbation with small molecule compounds. Overall design: H-STS cells were perturbed with small molecule compounds at isopotent concentrations, corresponding to ED20 and 1/10 of it, as measured by cell viability assays at 60h, or vehicle control (DMSO, ethanol and methanol). The cells were lysed at 6h and 24h after perturbation and total RNA isolated. Libraries for RNA-seq were generated with the TruSeq protocol (Illumina) and sequenced in a Hi-Seq 2500 instrument (Illumina).	Co-expression
SRP102092	Time-dependent regulation of cellular programming of monocytes by NCOR2 [RNASeq_KD]	Whole transcriptome profiling (RNA-Seq) was performed on human Mo-GMCSF[IL4 (0-72h)] cells with either NCOR2 being knocked down or corresponding WT cells Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with the combination of GMCSF and IL4 for 72h to obtain Mo-GMCSF[IL4 (0-72h)] cells. During the last 24 hours of activation, either siRNAs targeting NCOR2 or scrambled RNAs were added to obtain NCOR2 knock down cells and corresponding WT cells, respectively	Co-expression
SRP102096	ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator [RNA-seq]	Here we show that ZBTB48 binds directly both to telomeric as well as to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism. Overall design: ZBTB48 WT clones were generated by single sorting parental cells (HeLa & U2OS pools) into 96 well plates. ZBTB48 KO clones were generated by transiently transfecting a ZBTB48 TALEN pair (H12250; from TALEN library Resource, Seoul National University) into HeLa and U2OS cells, followed by single sorting into 96 well plates. Clones were first phenotypically screened for absence of ZBTB48 IF staining and subsequently verified by sequencing the exact genomic alterations across the TALEN cut site. Counts provided are not normalized.	Co-expression
SRP102105	Gene expression alterations of pancreatic intraepithlial neoplasia	Gene expression data from the RNA sequencing of laser microdissected pancreatic intraepithelial neoplasia and pancreatic normal ducts. Overall design: All RNA samples were isolated from laser microdissected tissues.  Samples were prepared in two sets.  13 samples (1 normal duct, 2 PanIN-1s, 3 PanIN-2s, and 7 PanIN-3s) were sequenced on an ABI SOLiD 5500 instrument.  8 samples (2 normal duct, 2 PanIN-1s, 2 PanIN-2s, and 2 PanIN-3s) were sequenced on an Illumina HiSeq instrument.  Datasets were combined using ComBat batch removal.	Co-expression
SRP102139	Osteogenic programming of adipose-derived mesenchymal stem cells using a fungal metabolite that suppresses the Polycomb protein EZH2	We report genome-wide expression changes that occur in adipose-derived mesenchymal stem cells upon treatment with CytoD cytoskeletal drug. mRNA-Seq analysis shows that CytoD-treated samples cluster together. In addition, we also see that cells treated with CytoD show upregulation of osteogenic markers, epiregulators, and a number of key molecular function pathways including extracellular matrix, cell membrane gene expression. Overall design: Adipose MSCs were cultured in Advanced-MEM base (Life Technologies), 5% platelet lysate, and 1% non-essential amino acids (Life Technologies), and 2U/ml heparin. Cells used for experiments were of passage 6. Adipose MSCs were seeded at 3,000 cells per cm2 in maintenance medium in 6-well plates and incubated under standard culture conditions for 24 hours before being changed to osteogenic medium containing vehicle (DMSO) or 0.1 µg/ml cytochalasin D (Sigma). Osteogenic medium maintenance media supplemented with 10 nM dexamethasone, 25 µg/ml ascorbic acid, and 10 mM ß-glycerophosphate. Cells in culture were prepared for RNA isolation by lysing with Qiazol. Purified RNA was then submitted for RNA-sequencing.	Co-expression
SRP102140	mRNA expression profile of A549 cells and MSR-A549 cells with or without JQ1 treatment	To establish effective multitargeted KRAS pathway therapy, we analyzed mediators of acquired resistance to chronic momelotinib and MEK inhibitor exposure in A549 cells. Since inhibitor resistance was completely reversible after drug withdrawal for several passages, suggesting epigenetic reprogramming, we investigated whole mRNA expression profiles in A549, momelotinib and selumetinib resistant (MSR)-A549 cells and MSR-A549 cells following drug withdrawal for 10 days. In parallel, we also examined mRNA expression profiles of MSR-A549 cells treated with the BET inhibitor JQ1, to identify specific targets regulated by H3K27 acetylation. Overall design: mRNA profile of MSR-A549 cells with or without JQ1 treatment.	Co-expression
SRP102181	Enhancement of Arterial Specification in Human Pluripotent Stem Cell Cultures Promotes Definitive Hematoendothelial Program with Broad Myelolymphoid Potential	Identification of the regulators that lead to arterial specification with definitive hematopoietic potential should help to design strategies to recapitulate HSC development from human pluripotent stem cells (hPSCs). Here, using ETS1 conditional H1 hESC line, we found that ETS1 induction at the mesodermal stage of differentiation dramatically enhances the arterial specification in hPSC cultures and formation of DLL4+CXCR4+/- arterial HE with lymphoid potential and the capacity to produce red blood cells with high expression of BCL11a and b-globin. ETS1 effect was mediated through upregulation of NOTCH signaling. Together, these findings demonstrated that promotion of arterial specification in cultures could aid in generation of definitive hematopoiesis from hPSCs. Overall design: We engineered H1 human embryonic stem cells (hESC) carrying doxycycline (DOX)-inducible ETS1-P2A-EGFP transgene (iETS1-hESCs) and differentiated them to endothelial and hematopoietic cells in chemically defined conditions	Co-expression
SRP102182	Global transcriptional analysis of different HT1080 cell phenotypes induced by cell proliferation and density	Following uncontrolled proliferation, a subset of primary tumor cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized to be the initiations of metastasis. This study reveals a novel adaptive mechanism that harnesses synergistic paracrine signaling via IL-6/8, which is amplified by cell proliferation and cell density, to directly promote cell migration. This effect occurs in metastatic human sarcoma and carcinoma cells - but not in non-metastatic cells-, through the downstream signaling of WASF3 and Arp2/3. Our RNA-seq based global transcriptional analysis showed that the transcriptional phenotype of high-density cells that emerges due to proliferation resembles that of low-density cells treated with a combination of Il-6/8. Simultaneous inhibition of IL-6/8 receptors significantly decreases the expression of WASF3 and Arp2/3 in a mouse xenograft model and consequently reduces metastasis. Overall design: Population-level RNA sequencing on five different HT1080 cell phenotypes induced by varying microenvironment. HT1080 cells were embedded in type I 3D collagen matrices in increasing cell densitieis from 10 cells/mm3 to 150 cells/mm3. RNA-seq performed on matrix embedded cells with cell densities of 10 cells/mm3 (low-density) and 50 cells/mm3 (high-density). Recombinant IL-6, IL-8 (both R&D systems), or both reconstituted in DPBS were added to matrix embedded cells with a cell density of 10 cells/mm3 (low-density with IL-6/IL-8/IL6+IL8). One collagen matrices without cells was sequenced and analyzed as a negative control. All data is obtained from single sequencing experiment. RNA-seq performed on these cell populations. All populations were incubated for 24h at 37°C, 5% CO2. The collagen matrices were exposed to cell lysis buffer and mechanically broken down using a syringe. The lysates of matrices were centrifuged and the supernatant was separately collected. Total RNA isolation was performed with RNA MiniPrep Kit (Zymo Research). Since the cells were embedded in the collagen matrices at the low cell density, the RNA-seq protocol (modified from Pan et al PNAS 2013) was implemented to capture uniformly distributed, full-length coverage sequences from low-quality and low-quantity cells. The cDNA libraries were sequenced using 50 bp single-ended reads. Data was processed using Bowtie2 for read alignment and RSEM for quantification of gene expression.	Co-expression
SRP102186	RNA sequencing of Amygdala in schizophrenia	We used RNA sequencing to investigate gene expression profiling in the amygdala tissues of 22 schizophrenia patients and 24 non-psychiatric controls.	Co-expression
SRP102193	Multiplexed engineering and analysis of endogenous enhancer activity in single cells: Mosaic-Seq of 10 enhancers in combination	Transcriptional enhancers orchestrate cell-type specific gene expression programs critical to eukaryotic development, physiology, and disease. However, despite the large number of enhancers now identified, only a small number have been functionally assessed. Here, we develop MOsaic Single-cell Analysis by Indexed CRISPR Sequencing (Mosaic-seq), a method that measures one direct phenotype of enhancer repression: change of the transcriptome, at the single cell level. Using dCas9-KRAB to suppress enhancer function, we first implement a multiplexed system to allow the simultaneous measurement of the transcriptome and detection of sgRNAs by single cell RNA sequencing. We validate this approach by targeting the HS2 enhancer in the well-studied beta-globin locus. Next, through computational simulation, we demonstrate strategies to robustly detect changes in gene expression in these single cell measurements. Finally, we use Mosaic-seq to target 71 hypersensitive regions belonging to 15 super-enhancers in K562 cells by utilizing a lentiviral library containing 241 unique-barcoded sgRNAs. Our results demonstrate that Mosaic-seq is a reliable approach to study enhancer function in single cells in a high-throughput manner. Overall design: The overall design consists of RNA sequencing in bulk and in single K562 cells. As a control, we performed single-cell RNA sequencing of K562 cells expressing dCas9-KRAB and a control sgRNA targeting the non-expressed HSBP1 gene in two biological replicates. As a pilot project, we performed single cell RNA-Seq of dCas9-KRAB K562 cells after pooled infection of a library of 10 sgRNA viruses targeting promoters and enhancers in the beta-globin locus. As controls for this experiment, we individually infected these 10 sgRNAs and either performed 1) bulk RNA sequencing or 2) single cell RNA sequencing after pooling the separately infected cells. Finally, we scaled this single-cell approach to measure transcriptome changes for a library of 241 sgRNAs spanning 71 hypersensitive sites from 15 super-enhancers in K562 cells. The data in this GEO series relate to the application of Mosaic-Seq for combinatorial repression of enhancers. Four experiments are performed with low MOI, and one is performed at high MOI.	Co-expression
SRP102239	Enhancer Transcription Reveals Subtype-Specific Transcription Programs Controlling Breast Cancer Pathogenesis [RNA-Seq]	Noncoding transcription is a defining feature of active enhancers, linking transcription factor (TF) binding to the molecular mechanisms controlling gene expression.  To determine the relationship between enhancer activity and biological outcomes in breast cancers, we profiled the transcriptomes (using GRO-seq and RNA-seq) and epigenomes (using ChIP-seq) of 13 different breast cancer cell lines representing the five major molecular subtypes of breast cancer.  In addition, we developed a robust and unbiased computational pipeline that simultaneously identifies putative subtype-specific enhancers and their cognate TFs by integrating the magnitude of enhancer transcription, TF mRNA expression levels, TF motif p-values, and enrichment of H3K4me1 and H3KK27.  When applied across the 13 different breast cancer cell lines, the Total Functional Score of Enhancer Elements (TFSEE) identified key breast cancer subtype specific transcription factors that act at transcribed enhancers to dictate gene expression patterns determining growth outcomes. Overall design: To determine the relationship between enhancer activity and biological outcomes in breast cancers, we profiled the transcriptomes (using GRO-seq and RNA-seq) and epigenomes (using ChIP-seq) of 13 different breast cancer cell lines representing the five major molecular subtypes of breast cancer.	Co-expression
SRP102251	Methylation of Transcription Factor YY2 Regulates its Transcriptional Activity and Cell Proliferation	Yin Yang 1 (YY1) is a multifunctional DNA-binding transcription factor shown to be critical in a variety of biological processes, and its activity and function have been shown to be regulated by multitude of mechanisms, which include but are not limited to post-translational modifications (PTMs), its associated proteins and cellular localization. YY2, the paralog of YY1 in mouse and human, has been proposed to function redundantly or oppositely in a context specific manner compared to YY1. Despite its functional importance, how YY2's DNA binding activity and function is regulated, particularly by PTMs, remains completely unknown. Here we report the first PTM with functional characterization on YY2, namely lysine 247 mono-methylation (K247me1), which was found to be dynamically regulated by SET7/9 and LSD1 both in vitro and in cultured cells. Functional study revealed that SET7/9-mediated YY2 methylation regulated its DNA-binding activity in vitro and association with chromatin examined by ChIP-seq (chromatin immunoprecipitation coupled with sequencing) in cultured cells. Knockout of YY2, SET7/9 or LSD1 by CRISPR (clustered, regularly interspaced, short palindromic repeats) /Cas9-mediated gene editing followed by RNA-seq revealed that a subset of genes was positively-regulated by YY2 and SET7/9, but negatively-regulated by LSD1, which were enriched with genes involved in cell proliferation regulation. Importantly, YY2-regulated gene transcription, cell proliferation and tumor growth were dependent, at least partially, on YY2 K247 methylation. Finally, somatic mutations on YY2 found in cancer, which are in close proximity to K247, altered its methylation, DNA binding activity and gene transcription it controls. Our findings revealed the first PTM with functional implications imposed on YY2 protein, and linked YY2 methylation with its biological functions. Overall design: The RNA-seq in this study was designed to reveal YY2, SET9 and LSD1 regulated genes in HeLa cells.	Co-expression
SRP102295	Splicing Modulators Act at the Branch Point Adenosine Binding Pocket Defined by the PHF5A-SF3b Complex	Developing small-molecule splicing modulators represents a promising therapeutic approach for various diseases.  Natural products such as pladienolide, herboxidiene, and spliceostatin have been identified as potent splicing modulators that target SF3B1 in the SF3b subcomplex. Using integrated chemogenomic, structural and biochemical approaches, we show that PHF5A, another core component of the SF3b complex, is also targeted by these compounds. Mutations in PHF5A-Y36, SF3B1-K1071, SF3B1-R1074, and SF3B1-V1078 confer resistance to these modulators, suggesting a common site of interaction.  Whole-transcriptome RNA-seq analysis reveals that PHF5A-Y36C has minimal effect on basal splicing but alters the action of splicing modulators from inducing intron-retention to exon-skipping.  Relative intron strength to splicing inhibition correlates with the differential in GC content between adjacent introns and exons, leading to this differential global splicing pattern. We determine the crystal structure of human PHF5A and find that Y36 is located on the surface in a region of high sequence conservation. Structural analysis of the cryo-EM spliceosome Bact complex shows that these mutations cluster in a well-defined pocket surrounding the branch point adenosine suggesting a possible competitive mode of action for these splicing modulators, which interact with the aromatic side-chain of PHF5A-Y36. Collectively, we propose that PHF5A-SF3B1 forms a central node for binding to these small-molecule splicing modulators, offering insights to modulate splicing. Overall design: 24 samples, including HCT-116 cells +/- treatment with E7107 with and without PHF5A Y36C mutation. Each condition has 6 replicates.	Co-expression
SRP102361	Analysis of Combined Transcriptomes Identifies Gene Modules Differentially Responding to Pathogenic Stimulation in Vascular Smooth Muscle and Endothelial Cells	Smooth muscle cells (SMCs) and endothelial cells (ECs) constitute vasculature media and endothelium, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but also damage the protective endothelial lining, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMCs versus ECs) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFa or IL-1ß, both established inducers of SMC hyperplasia and EC dysfunction. To analyze combined SMC/EC transcriptomes we developed customized algorithms. Induced by TNFa or IL-1ß, 212 and 263 genes respectively showed greater up-regulation in SMCs than in ECs (SMC-enriched), while 140 and 204 genes showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene interaction networks identified 5 common hubs and 4 common bottlenecks in the two SMC-enriched gene sets, and 8 hubs and 3 bottlenecks shared in the EC-enriched gene sets. Significantly, four gene modules were formed with these hubs and bottlenecks. While the JUN module (including JUN, KLF5, HIF1A, CXCL8, FOSL1) and FYN module (FYN, JAK2, MAP2, PIK3R3, DAB2, ASAP2) were SMC-enriched, the SMAD3 (SMAD3, CDKN1A, TRAF1, BCL6, CEBPD, TRIB3, ANK3) and XPO1 (XPO1, ETS2, SSH2, NDRG1, GFPT2?) modules were EC-enriched. As these core subnetworks respond to pathogenic stimulation in a SMC-versus-EC differential manner, they may inform potential intervention targets for selective mitigation of SMC hyperplasia without endothelial damage. Overall design: In this study, we performed RNA sequencing (RNA-seq) and global analyses of differential SMC-versus-EC transcriptomic responses, to the same pathogenic cytokine stimulant under stringently controlled conditions. The objective was to identify the gene modules (or subnetworks) that are highly up-regulated in SMCs yet little affected or regulated toward the opposite direction in ECs	Co-expression
SRP102374	Integrated target discovery screens identify IL11 as novel therapeutic target for fibrosis [human]	Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. IL11 signals in cis and trans via the ERK cascade to activate a programme of fibrosis primarily at the level of protein translation. Injection of IL11 to mice causes fibrosis of the heart, kidney, lung, skin and liver whereas genetic ablation of the IL11 receptor prevented fibrosis across tissues. These data define a new non-canonical fibrogenic pathway and prioritise IL11 as a novel therapeutic target for fibrosis of the heart and other organs Overall design: 24 human cardiac fibroblasts. 10 basal, 10 IL11 induced, 4 TGFB1 induced. Cardiac fibroblasts were cultured in serum-free media for at least 16 hours prior to treatment with either TGFB1 or IL11.	Co-expression
SRP102427	Multilineage communication regulates human liver bud self-organization from pluripotency II	Conventional 2-D differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. 3-D organoids generate complex organ-like tissues, however it is unclear how heterotypic interactions impact lineage identity. Here we use single-cell RNA-seq to reconstruct hepatocyte-like lineage progression from pluripotency in 2-D culture. We then derive 3-D liver bud (LB) organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during LB development. We find that LB hepatoblasts diverge from the 2-D lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark 3-D LBs against fetal and adult human liver scRNA-seq data, and find a striking correspondence between the 3-D LB and fetal liver cells. We use a receptor-ligand pairing analysis and a high-throughput inhibitor assay to interrogate signaling in LBs, and show that VEGF crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development. Overall design: Single-cell transcriptomes from multiple time points during hepatocyte-like lineage progression from pluripotency in 2-D culture, from 3-D liver bud (LB) organoids that self-organized after reconstituting hepatic, stromal, and endothelial interactions, and from adult, fetal, and mouse primary liver tissue.	Co-expression
SRP102429	Single-cell RNAseq analysis of the empty and i8TF cell lines after 3 days of BL-CFC culture	The aim of the experiment was to assess the cell heterogeneity after the doxycycline treatment and the subsequent induction of the 8 transcription factors in the BL-CFC culture. Overall design: A2lox.empty and A2lox.i8TFs cell lines were used for this experiment. A2lox.empty is used a negative control while the doxycycline is inducing the expression of Erg, Fli1, Tal1, Lyl1, Lmo2, Runx1, Cbfb and Gata2 in the A2lox.i8TFs  cell line. Cells were cultured in BL-CFC culture for 1 day before doxycycline treatment and were cultured for an additional 48hours with (i8TFs_plus and E_plus) or without doxycycline (i8TFs_minus and E_minus). As additional controls of the single cell RNA seq experiment, bulk A2lox.i8TFs cells were collected at the same time point from the condition without doxycycline (Pos_Ctrl), also buffer only was used as negative control (Neg_Ctrl) and a human cell line as other control (K562).	Co-expression
SRP102430	AmpliSeq analysis of human iPSC-derived cardiomyocytes	Analysis of human iPSC-derived cardiomyocytes unstimulated or stimulated with endothelin-1 in the presence of either vehicle (DMSO), Ivermectin, Importazole, IPA-3, or verapamil. Results provide insight into the pathways regulated by the treatments. Overall design: AmpliSeq of human iPSC-derived cardiomyocytes untreated or treated with endothelin-1 in the presence of either vehicle (DMSO), Ivermectin, Importazole, IPA-3, or verapamil for 18 hours, in quadruplicate, using Ion Proton System.	Co-expression
SRP102433	Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state	The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. We present TRAPeS, a publicly available tool that can efficiently extract TCR sequence information from short-read scRNA-seq libraries. We apply it to investigate heterogeneity in the CD8+ T cell response in humans and mice, and show that it is accurate and more sensitive than existing approaches. Coupling TRAPeS with transcriptome analysis of CD8+ T cells specific for a single epitope from Yellow Fever Virus (YFV), we show that the recently described “naive-like” memory population have significantly longer CDR3 regions and greater divergence from germline sequence than do effector-memory phenotype cells. This suggests that TCR usage is associated with the differentiation state of the CD8+ T cell response to YFV. Overall design: We applied and tested TRAPeS to scRNA-seq data from a range of CD8+ T cell responses. These data sets were selected to include both mouse and human CD8+ T cells as well as those expected to have a range of TCR complexities. In mice, we used the lymphocytic choriomeningitis virus (LCMV) infection model, and profiled CD8+ T cells responding to either acute or chronic infection (using the Armstrong and Clone 13 strains of LCMV, respectively). In healthy human subjects we profiled naive CD8+ T cells, effector memory CD8+ T cells, and antigen-specific CD8+ T cells elicited by CMV infection; vaccination with the live attenuated yellow fever virus infection (YFV-17D); or by vaccination with adenoviral and modified vaccinia Ankara vectors encoding HCV proteins. We sorted up to 128 single CD8+ T cells from each dataset to a total of 565 cells, and generated scRNA-seq libraries with short (25-30bp) paired-end reads. To evaluate the accuracy of TRAPeS, we compared its output with that of directly sequencing the TCR sequence using long reads (in which reconstruction is not required). To that end, we sequenced libraries of epitope-specific cells for Clone 13, Armstrong and CMV, and naive T cells from the CMV donor with both short (25-30bp) paired-end and 150bp single-end sequence reads.	Co-expression
SRP102440	Altered Hydroxymethylation is seen at regulatory regions in pancreatic cancer and regulates oncogenic pathways [RNA-seq]	Transcriptional deregulation of oncogenic pathways is a hallmark of cancer, and can be due to epigenetic alterations. 5-hydroxymethylcytosine is a recently discovered epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC enriched loci with hmC-seal was conducted in low-passage pancreatic cancer cell lines and primary patient-derived xenografts and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers. Furthermore, base pair resolution analysis of methylation and hydroxymethylation with oxidative bisulfite sequencing was conducted and correlated with chromatin accessibility by ATAC-seq in pancreatic cancer and control samples. 5hmC was specifically enriched at open regions of chromatin and gain of 5-hmC was correlated with upregulation of the cognate transcripts, including many oncogenic pathways implicated in pancreatic neoplasia, such as myc, KRAS, VEGF and BRD4. Specifically, BRD4 was overexpressed and acquired 5hmC at enhancer regions in majority of neoplastic samples. Functionally, acquisition of 5hmC at BRD4 promoter regulated increase in transcript expression. Furthermore, blockade of BRD4 inhibited pancreatic cancer growth in vivo. In summary, redistribution of 5-hmC and preferential enrichment at oncogenic enhancers is a novel regulatory mechanism in human cancer. Overall design: Gene expression profiling using RNAseq was performed to assess transcriptomic profiles of pancreatic controls and pancreatic cancer cells	Co-expression
SRP102441	High-throughput and site-specific identification of 2''-O methylation sites using Ribose Oxidation sequencing (RibOxi-Seq)	We report our newly developed method for high-throughput sequencing of 2''-O methylation sites using positive signal and site specific approach. The pilot experiment using MiSeq generated ~2.5 million reads per sample. The 2''-O methylation site identification produced a promising distribution pattern matching known sites. For accurate and sensitive base call, >10 million reads are required per sample as evidenced in the NextSeq experiment. Overall design: Total RNA extracted are aliquoted either as control or oxidized samples. The control RNAs are digested and subjected to custom small RNA sequencing library preparation, while the oxidized group has additional steps after digestion to oxidize RNA ends to selectively enrich fragments with 2''-O methylated terminal base for subsequent library preparation.	Co-expression
SRP102444	Widespread activation of antisense transcription of the host genome during Herpes simplex virus 1 infection	We show that Herpes simplex virus 1 (HSV-1) induces the expression of about 1000 antisense transcripts from the human host cell genome. Overall design: Human WI-38 and HeLa cells were infected with Herpes simplex virus 1, and antisense transcripts on the host cell genome defined using a custom algorithm.	Co-expression
SRP102483	Effects of arsenic and Pseudomonas aeruginosa infection on gene expression in human airway epithelial cells	Purpose: To determine effects of arsenic on gene expression in polarized primary human bronchial epithelial (HBE) cells and impact on transcriptional response to Pseudomonas aeruginosa infection Methods: mRNA profiles of HBE cells from 6 donors exposed to 0, 5, 10 or 50 ug/L total arsenic +/- Pseudomonas aeruginosa (48 samples) were generated using Illumina sequencing, aligned in CLC Genomics workbench and analyzed for DE in EdgeR Findings: 20-30 million reads were mapped per sample and transcripts were identifed that were significantly differentially expressed in response to arsenic and Pseudomonas aeruginosa Overall design: Gene expression profiles of HBE cells from 6 donors exposed to three concentrations of arsenic +/- Pseudomonas were generated using mRNA sequencing	Co-expression
SRP102487	Identification of a Cell-of-Origin for Fibroblasts Comprising the Fibrotic Reticulum in Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with a prevalence of one million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli, creating a reticular network that leads to death by asphyxiation. Lung fibroblasts from patients with IPF have phenotypic hallmarks, distinguishing them from their normal counterparts: pathologically activated Akt signaling axis, increased collagen and a-smooth muscle actin expression, distinct gene expression profile, and ability to form fibrotic lesions in model organisms. Despite the centrality of these fibroblasts in disease pathogenesis, their origin remains uncertain. Here, we report the identification of cells in the lungs of patients with IPF with the properties of mesenchymal progenitors. In contrast to progenitors isolated from nonfibrotic lungs, IPF mesenchymal progenitor cells produce daughter cells manifesting the full spectrum of IPF hallmarks, including the ability to form fibrotic lesions in zebrafish embryos and mouse lungs, and a transcriptional profile reflecting these properties. Morphological analysis of IPF lung tissue revealed that mesenchymal progenitor cells and cells with the characteristics of their progeny comprised the fibrotic reticulum. These data establish that the lungs of patients with IPF contain pathological mesenchymal progenitor cells that are cells of origin for fibrosis-mediating fibroblasts. These fibrogenic mesenchymal progenitors and their progeny represent an unexplored target for novel therapies to interdict fibrosis. Overall design: RNA-seq of lung fibroblasts from IPF or healthy control patients at day 0 or day 21 of culture.	Co-expression
SRP102516	Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [human RNA-seq]	The lung alveolus is the primary site of gas exchange in mammals. Within the alveolus, the alveolar type 2 (AT2) epithelial cell population generates surfactant to maintain alveolar structure and harbors a regenerative capacity to repair the alveolus after injury. We show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the AT2 cell population is critical for regenerating the alveolar niche. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a majority of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome, and functional phenotype with specific responsiveness to Wnt and FGF signaling that modulates differentiation and self-renewal, respectively. Importantly, human AEPs (hAEPs) can be isolated and characterized through a conserved surface marker and are required for human alveolar self-renewal and differentiation using alveolar organoid assays. Together, our findings show that AEPs are an evolutionarily conserved alveolar progenitor lineage essential for regenerating the alveolar niche in the mammalian lung. Overall design: Examination of open chromatin in 2 subtypes of alveolar epithelial cell populations	Co-expression
SRP102524	Effect of PKN1 inhibition on androgen responsive genes	1. Human LNCaP prostate cancer cells were transfected with siRNA SmartPools targeting PKN1 or a non-targeting siRNA SmartPool.  Forty hours after transfection, cells were treated with synthetic androgen R1881 (5nM) or vehicle.  Three biological  replicates were generated per treatment group.  Forty-eight hours later, total RNA was isolated and processed for RNA-Seq analysis.   2. Human LNCaP prostate cancer cells were treated with synthetic androgen R1881 (5nM) or vehicle and CEP701 (50nM)  or DMSO.  Three biological replicates were generated per treatment group.  Forty-eight hours later, total RNA was isolated and processed for RNA-Seq analysis.	Co-expression
SRP102528	Epigenetic and transcriptional analysis of mesoderm progenitor cells identifies HOPX as a novel regulator of hemogenic endothelium	We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from cardiogenic or hemogenic mesoderm. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified novel candidate regulators of mesodermal lineage determination. HOPX, a non-DNA binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. We used HOPX reporter and knockout hESCs, as well as hopx loss of function studies in zebrafish, to show the requirement of HOPX in vivo and in vitro in hemato-endothelial lineage specification. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis acting at least in part through suppression of Wnt/ß-catenin signaling. Single cell RNA-seq data during mouse hematopoietic development in vivo confirm a role for HOPX in hematopoietic fate. Taken together, we show that HOPX is a novel regulator of hemato-endothelial fate specification in vitro and in vivo that functionally regulates Wnt signaling to modulate primitive hematopoiesis. Overall design: 2 biological replicates were isolated from cardiac progenitor cells (CPCs) and endothelial populations derived from cardiogenic mesoderm (C-ECs) and hemogenic mesoderm (H-ECs). RNA-seq and ChIP-seq (H3K4me3 and H3K27me3) was performed for each replicate.	Co-expression
SRP102542	Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans	The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages. Overall design: The prospective exercise training study was approved by the Mayo Clinic Institutional Review Board, registered at https://clinicaltrials.gov (#NCT01477164) and conducted in accordance with the Declaration of Helsinki. All participants provided informed written consent. Participants were recruited into two distinct age groups: young (18–30 years) or older (65–80 years) with a goal of an equal number of men and women. The final groups were approximately balanced for sex, and all women in the older group were post-menopausal. Exclusion criteria were structured regular exercise (>20 min, twice weekly), cardiovascular disease, metabolic diseases (type 2 diabetes mellitus, fasting blood glucose > 110 mg/dL, and untreated hypothyroidism or hyperthyroidism), renal disease, high body mass index (BMI > 32 kg/m2), implanted metal devices, pregnancy, smoking, and history of blood clotting disorders. Exclusionary medication included anticoagulants, insulin, insulin sensitizers, corticosteroids, sulfonylureas, barbiturates, peroxisome proliferator-activated receptor ? agonists, ß blockers, opiates, and tricyclic antidepressants. Following baseline measurements, the participants were randomized to three groups (HIIT, RT, or CT) using gRand (v1.1, Peter A. Charpentier) following a permuted block strategy with block length of 15 and 2 factors (age and sex). HIIT was 3 days per week of cycling (4 × 4 min at >90% of peak oxygen consumption [VO2 peak] with 3 min pedaling at no load) and 2 days per week of treadmill walking (45 min at 70% of VO2 peak). RT consisted of lower and upper body exercises (4 sets of 8–12 repetitions) 2 days each per week. CT participants first underwent a 12-week sedentary period (SED) and wore accelerometers to record any structured activity. Following SED, participants underwent metabolic studies and began CT of 5 days per week cycling (30 min at 70% VO2 peak) and 4 days per week weight lifting with fewer repetitions than RT. Both baseline and post-training studies were performed in all participants.	Co-expression
SRP102549	RNAseq data of 81 liver cancer cell lines	A large panel of 81 liver cancer cell models, designated as LIver cancer MOdel REpository (LIMORE) was constructed. These cell lines include 31 public cell lines and 50 new cell models establishend from Chinese liver cancer patients. Whole genome sequencing (WGS), exome sequencing (WES) and RNA sequencing (RNAseq) were performed to obtain the genetic information for these cell lines. These cell lines and associated data provide new models and also a rich resource for liver cancer. Overall design: RNAseq for 81 liver cancer cell models was performed to analyze the gene expression of these lines. SK-Hep1 was also sequenced, though not considered as HCC cell line.	Co-expression
SRP102550	mRNAseq of Huntington''s disease and control patient iPSC-derived brain microvascular endothelial cells	Purpose: The goals of this study are to compare the transcriptomic profile (mRNA-seq) of HD and control patient iPSC-derived brain microvascular endotheial cells to identify alterations in gene expression. Methods: RNA were isolated from HD and control iPSC-derived brain microvascular endothelial cells. mRNAseq using Illumina TruSeq mRNA PolyA+ v2 lib prep and HiSeq 2500. Statistical difference in mRNA levels were calculated with subsequent GO and pathway analysis. Results: mRNAseq and statistical analysis revealed differentially expressed genes between HD and control iPSC-derived brain microvascular endothelial cells. Conclusions: Our study shows differentially expressed genes between HD and control iPSC-derived brain microvascular endothelial cells, and reveals gene networks that are relevant to the mechanism of HD pathogenesis. Overall design: mRNA profiles of HD and control iPSC-derived brain microvascular endothelial cells were generated by mRNAseq, in duplicate, using Illumina TruSeq mRNA PolyA+ v2 and Illumina HiSeq 2500.	Co-expression
SRP102557	Molecular transitions in early progenitors during human cord blood hematopoiesis	Hematopoietic stem cells give rise to diverse cell types in the blood system, yet our molecular understanding of the earliest fate decisions that generate this enormous diversity in humans remains incomplete. Here we leverage Drop-seq to individually profile more than 20,000 progenitors cells from human cord blood, without prior enrichment or depletion for individual lineages based on surface markers. Our data reveal a transcriptional ''atlas'' of progenitor states in human cord blood, which we leverage to reconstruct differentiation trajectories from HSC to four downstream lineages. And we also demonstrate that Drop-seq data can be utilized to identify new heterogeneous markers of cell state. Overall design: CD34+ cells were enriched from human cord blood mononuclear cells, and mRNA profiles were generated by paired-end sequencing in Illumina HiSeq, with cDNA being amplified using the Drop-seq protocol, or a modified SMART-Seq2 protocol. Generally, 2-3 replicates were performed per biological sample.	Co-expression
SRP102662	RNAseq of SUN knockdown cells	investigation of SUN role in nuclear export	Co-expression
SRP102683	Transcriptional responses induced by controlled human malaria infection (CHMI)	Whole blood RNA-Seq was applied to investigate gene expression kinetics in Tanzanian males who underwent controlled malaria infection by intradermal injection with aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Overall design: 10 volunteers injected intradermally with a total of 25'000 infectious Plasmodium falciparum sporozoites (PfSPZ).	Co-expression
SRP102685	RNAseq study of synovial biopsies after triple DMARD treatment	Total RNA sequencing was performed on samples isolated from joint synovial biopsies from subjects with rheumatoid arthritis before and after 6 months of triple DMARD treatment Overall design: One biopsy sample per subject/time point was analyzed without replicates	Co-expression
SRP102688	Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses	We perform massively parallel single cell RNA-seq (MARS-Seq) on non-lymphocytic immune cells sorted from a human stage IA lung adenocarcinoma lesion and from the adjacent non-involved lung. With an unbiased single cell transcriptomic analysis of non-lymphocyte cells accumulating in these tissues, we sought to capture the heterogeneity of the tumor-infiltrating myeloid (TIM) compartment. Using a previously described unbiased expectation-maximization algorith (Paul et al., 2015), we identified clusters that were then named according to literature-reported marker profiles. This revealed a CD141+ DC subets, a CD1c+ DC subset, and a macrophage subset that clustered separately and was found to be enriched in the lesion as compared to other macrophage subsets. Overall design: Using singlet, CD45+ DAPI- CD3- CD19- gating, over 1100 cells from a human stage IA lung adenocarcinoma lesion and over 700 cells from the non-involved lung were sorted into individual wells of a 384-well plate, then processed by MARS-Seq.	Co-expression
SRP102707	Effect of selective glucocorticoid receptor modulation (SGRM) on gene expression in human prostate cancer cell lines	Human prostate cancer cell lines treated with androgen receptor (AR) agonists/antagonists and concurrent glucocorticoid receptor (GR) agonist/antagonists Overall design: Human prostate cancer cell lines in charcoal-stripped FCS-containing media were treated for 3 days with AR agonists (R1881 1nM) +/-antagonist (enzalutamide 10uM) and then pulsed with 2 or 6 hour treatment with GR agonist (Dex 100nM)  +/- antagonist (SGRM, 335 1uM and 297 1uM) after which RNA was collected and sequenced	Co-expression
SRP102710	De novo reconstruction of human adipose reveals conserved lncRNAs as regulators of brown adipogenesis	Obesity has emerged as a formidable health crisis due to its association with metabolic risk factors such as diabetes, dyslipidaemia and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but its implication in human adipocytes remain largely unknown at least partially due to the lack of a comprehensive lncRNA catalog, particularly those specifically expressed in brown adipose tissue (BAT).  In this study, we performed deep RNA-seq on adult subcutaneous, omental and fetal brown adipose tissues to de novo construct a catalog of 3,149 adipose active lncRNAs of which 1,351 are specifically detected in BAT. We further identified 318 lncRNAs conserved between human and mouse which, compared with non-conserved ones, are more broadly expressed in multiple cell types. One of these, lnc-dPRDM16, is transcribed divergently from Prdm16, tightly correlated with Prdm16 (R = 0.7) in both mouse and human, and co-expressed (R = 0.7) with protein-coding genes enriched in lipid and fatty acid catabolic processes. Loss of function of lnc-dPRDM16 led to a down-regulation of Prdm16 and an obvious reduction of adipogenesis in brown adipocyte culture. Together, our work has provided a comprehensive human adipose catalog built from diverse fat types, which when applied to our roadmap, identifies lnc-dPRDM16 as a promising modulator of adipose development for future clinical research. Overall design: Transcriptome profiling of BAT, OME and SUB samples	Co-expression
SRP102722	Transcriptome sequencing identify a recurrent CRYL1-IFT88 chimeric transcript in hepatocellular carcinoma	We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. Further RT-PCR and Sanger sequencing experiments were performed to validate potential recurrent fusion transcripts in other 54 pairs of tumor and adjacent non-tumor samples. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways, especially cell cycle, DNA replication, p53 and complement and coagulation cascades. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9.52% (6/63). The full length of CRYL1-IFT88 was obtained by 3'' and 5'' RACE. The function of the fusion transcript is closed to CRYL1 because it contained most of domain of CRYL1. According to the bioinformatics analysis, IFT88, reported as a tumor suppressor, might be seriously depressed in the tumor cell with this fusion because the transcript structure of IFT88 was totally changed. The function depression of IFT88 caused by gene fusion CRYL1-IFT88 might be associated with tumorigenesis or development of HCC. Overall design: RNA-Seq for tumor and adjacent non-tumorous tissues from nine hepatocellular carcinoma (HCC) patients.	Co-expression
SRP102725	Genetic-to-epigenetic Therapy for Pancreatic Cancer	We utilized RNA-Seq to define molecular markers for the effect of chaetocin and MLN8237 combination. PDAC cells were treated with individual drugs or their combination and compared to vehicle. Treatment was limited to 24 hours to extract RNA before significant mitotic catastrophe occurred to capture the transcriptional effect. Overall design: PANC-1 mRNA profiles following 24 hrs of treatment with vehicle (DMSO), chaetocin (30nM), MLN8237 (90nM) or a combination of chaetocin(30nM)+MLN3237(90nM). Each condition was performed in triplicate.	Co-expression
SRP102731	Transcriptome analysis of immortalized and transformed human IMR90 fibroblasts	No description.	Co-expression
SRP102735	Expression profiles of restoration of BAP1 in a BAP1 deficient cell line	RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins. Cell line UPMM3 contains a frameshift mutation in BAP1. Overall design: RNA-seq of UPMM3 with restoration of BAP1 and BAP1 mutant proteins	Co-expression
SRP102746	Polyamide Efficacy in Enzalutamide-Resistant Prostate Cancer	We report the biological activity of a Py-Im polyamide targeted to the sequence 5'-WGWWCW-3', which is found in a subset of ARE half-sites. This molecule reduces the growth of enzalutamide-resistant LREX' cells, both in vitro and in vivo. Gene expression changes associated with polyamide treatment in both settings are deposited here.	Co-expression
SRP102769	Gene expression profiles of eighteen hepatocellular carcinoma (HCC) cell lines with definite metastatic potentials and tropisms	In this study we investigate the gene expressed profiles in 18 HCC cell lines with different metastatic potentials and organ-tropisms. Among them, HCC cell lines Huh7, Hep3B, SNU398, SMMC-7721,Bel-7402,HepG2,PLC-5 exhibit low metastasis abilities in nude mice model, while MHCC-97L, MHCC-97H, CSQT-1, CSQT-2, HCCLM3, LM1-S3, LM1-S4, LM1-S5, LM1-S11, LnM1-S11, LnM1-S13 exhibit high metastasis abilities in nude mice.LM1-S3, LM1-S4, LM1-S5, LM1-S11 derived from the parent cell line HCCLM3 have higher metastasis abilities specific to lung, and LnM1-S11, LnM1-S13 are specific to lymph node metastasis. We aim to explore differentially expressed genes involved in the process of HCC metastasis and organ-specific metastasis, and identify their biological functions.	Co-expression
SRP102798	High-throughput RNA sequencing on circular RNA profiles of human bladder cancer tissues and normal bladder tissues	In order to find out circular RNAs profiles in human bladder cancer tissues and normal bladder tissues, we characterized circuclar RNA transcripts by performing RNA-Seq on ribosomal RNA-depleted total RNA from three pairs of human bladder cancer tissues and paired normal bladder tissues.A computational pipeline based on the anchor alignment of unmapped reads was used to identify circular RNAs. Collectively, we identified16,535 distict circular RNAs, most of them origined from exons (88.96%), others from introns, linc RNA, intergenic region, 3'UTR and 5'UTR. Among all these circRNAs, 571 circRNAs were differentially expressed between bladder cancer tissues and normal bladder tissues, and 524 circRNAs were downregulated in bladder cancer tissues (91.2%), others were upreguluated. These significantly differential expressed circular RNA might have regulatory function in bladder cancer, and worth to be further explored. Overall design: Circular RNAs profiles of thredd pairs of bladder cancer tissues and paired adjacent normal bladder tissues were generated by RNA deep-sequencing, using HiSeq2000, Illumina.	Co-expression
SRP102804	Determination of tRNA aminoacylation levels by high throughput sequencing	Here we develop a high throughput sequencing method that enables accurate determination of charged tRNA fractions at single base resolution (Charged tRNA-seq). Our method takes advantage of the recently developed DM-tRNA-seq method, but includes additional chemical steps that specifically remove the 3''A residue in the uncharged tRNA. Charging fraction is obtained by counting the fraction of A-ending reads versus A+C-ending reads for each tRNA species. In HEK293T cells, most cytosolic tRNAs are charged at >90% levels, whereas tRNASer and tRNAThr are generally charged at lower levels. These low charging levels were validated using acid denaturing gels. Our method should be widely applicable for investigations of tRNA charging as a parameter for biological regulation. Overall design: 3 biological replicates of tRNA from HEK293T cells are analyzed; each biological replicate is also demethylase treated/untreated	Co-expression
SRP102811	Transcriptome analysis of normal human lung fibroblasts (NHLFs) following TBX4 knockdown.	TBX4 is a transcription factor unique to lung fibroblasts and is associated with super-enhancer. RNA-sequencing analysis on NHLFs following TBX4 knockdown revealed a broad array of genes possibly regulated by TBX4. Overall design: NHLFs were transfected with siRNAs for TBX4, and RNA-sequencing was performed using Illumina HiSeq.	Co-expression
SRP102818	The head and neck cancer cell oncogenome: A platform for the development of precision molecular therapies	We performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. These genetically-defined experimental HNSCC cellular systems may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.	Co-expression
SRP102918	RNA-sequencing analysis of non silencing or ILF2 shRNA-transduced H929 cells	To understand whether ILF2 is required to ensure the alternative splicing and processing of specific pre-mRNAs in Multiple Myeloma (MM) in physiological conditions, we performed RNA sequencing (RNA-Seq) analysis of ILF2-  and  non-silencing shRNA  transduced  H929 cells. Overall design: Total RNA from H929 cells transduced with a non-silencing or ILF2 shRNA (two independent replicates per condition) were isolated with the RNeasy Mini kit (Qiagen). Libraries were constructed using the TruSeq® Stranded Total RNA LT - (with Ribo-Zero TM Gold) - Set A (Illumina) according to the manufacturer's instructions. Transcriptomic RNA-Seq was performed on the Illumina 2000 HiSeq platform using the standard paired-end protocol. In total, 60-160 million 76-bp reads were generated per sample. An initial sequence-level quality assessment was performed using FastQC (version 0.10.1, Simon Andrews). The RNA-Seq reads were then mapped to the reference human genome (GRCh37) using Tophat2, allowing a maximum of two mismatches per 76-bp sequencing end. Differential splicing was assessed by multivariate analysis of transcript splicing (MATS) using an FDR<0.05. Pathway enrichment analysis was performed with Pathway Studio.	Co-expression
SRP102945	Global gene expression profile of dasatinib-resistant RCH-ACV cells	Purpose: Several ALL subtypes have been described depending on their karyotype, cell type, immunophenotype and gene-expression profile. Recently, a novel ALL subtype has been described and is characterized by expression of the pre-B cell receptor (pre-BCR). Interestingly, half of the cases is associated with the chromosomal translocation t(1:19), coding for the chimeric fusion protein E2A-PBX1, which is present in about 5% of pediatric and adult ALL. Using preclinical models, we and other groups have shown very promising preclinical activity of dasatinib in pre-BCR+ ALL and early clinical evidence supports our observations. To study mechanism of acquired dasatinib resistance, we generated dasatinib-resistant pre-BCR+/E2A-PBX1+ cell lines through multiple passages in the presence of increasing drug concentrations. Whole transcriptome analysis of dasatinib-sensitive and resistant ALL cells were performed to detect systematically differentially expressed genes and enriched pathways involved in dasatinib resistance. Overall design: RNA was isolated at three different time points (replicates) from two independent generated dasatinib-resistant RCH-ACV sublines. Replicates from control dasatinib-sensitive RCH-ACV cell sublines were used as controls.	Co-expression
SRP102952	Integrated target discovery screens identify IL11 as novel therapeutic target for fibrosis [168 human cardiac fibroblasts]	Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. IL11 signals in cis and trans via the ERK cascade to activate a programme of fibrosis primarily at the level of protein translation. Injection of IL11 to mice causes fibrosis of the heart, kidney, lung, skin and liver whereas genetic ablation of the IL11 receptor prevented fibrosis across tissues. These data define a new non-canonical fibrogenic pathway and prioritise IL11 as a novel therapeutic target for fibrosis of the heart and other organs Overall design: 168 human cardiac fibroblasts. 84 control, 84 TGFB1 induced. Cardiac fibroblasts were cultured in serum-free media for at least 16 hours prior to treatment with TGFB1.	Co-expression
SRP102989	RNA-seq data from somatic tissues and gonads from Anolis, human, mouse, opossum, platypus, chicken and xenopus Raw sequence reads	No description.	Co-expression
SRP102999	Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study	The gene expression approach has provided promising insights into the pathophysiology of PTSD. However, few studies used hypothesis-free transcriptome-wide expression approach. Transcriptome-wide expression study using RNA sequencing (RNA-Seq) of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current and 42 past PTSD). The current and never PTSD samples were randomly split to form both discovery (N=195) and replication (N=87) cohorts. Differentially expressed genes identified in RNA-Seq were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, and 5 (FKBP5, NDUFA1, CCDC85B, SNORD54, SNORD46) showed >1.2-fold difference in expression consistently between the discovery and replication cohorts. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but were not significant following FDR correction. The gene expression score achieved sensitivity of 0.917 and specificity of 0.508 for identifying PTSD cases in the replication cohort. It was similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls. We confirmed the role of FKBP5 in PTSD and identified four additional differentially expressed genes that may constitute biomarkers for this condition. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations. Overall design: 324 human samples; 201 never,  82 current, 41 past with PTSD. Gene expression profiling by high throughput sequencing	Co-expression
SRP103009	mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4	The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5'' UTR. mTORC1 also controls ATF4 translation through uORFs, but independent of changes in eIF2a phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery. Overall design: RNA-seq analysis of wild-type and ATF4-null HEK293T cells treated with Torin 1 or tunicamycin for 6 h, and ribosome profiling analysis of HEK293T cells treated with Torin 1 for 24 h.	Co-expression
SRP103018	In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells	Understanding the unique mechanisms of human oogenesis necessitates the development of an in vitro system of stem cell differentiation into oocytes. Specialized cell types and organoids have been derived from human pluripotent stem cells in vitro, but generating a human ovarian follicle remains a challenge. Here we report that human embryonic stem cells (hESCs) can be induced to differentiate into ovarian follicle-like cells in vitro. First, we find that two RNA-binding proteins specifically expressed in germ cells, DAZL and BOULE, regulate the exit from pluripotency and entry into meiosis. By expressing DAZL and BOULE with recombinant human GDF9 and BMP15, these meiotic germ cells are further induced to form ovarian follicle-like cells (FLCs), including oocytes and granulosa cells. This robust in vitro differentiation system will allow the study of the unique molecular mechanisms underlying human pluripotent stem cell differentiation into late PGCs, meiotic germ cells, and ovarian follicles. Overall design: Including 6 samples,4 controls: ES_1, ES_2, SDE_1, SDE_2; 2 samples: FLC_1 (HSF6), FLC_2 (H9)	Co-expression
SRP103021	Circadian networks in human embryonic stem cell-derived cardiomyocytes	Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs. Recent in vivo findings in the heart demonstrate that the circadian clock controls oscillatory gene expression programs in the adult myocardium. However, whether in vitro human embryonic stem (ES) cell-derived cardiomyocytes can establish circadian rhythmicity is unknown. Here we report that while undifferentiated human ES cells do not possess a functional clock, oscillatory expression of known core clock genes emerges during directed cardiac differentiation, with robust rhythms in day 30 cardiomyocytes. Our data reveal a stress related oscillatory network of genes that underlies a time-dependent response to doxorubicin, a frequently used anti-cancer drug with cardiotoxic side effects. These results provide a set of oscillatory genes that is relevant to functional cardiac studies and that can be deployed to uncover the potential contribution of the clock to other processes such as cardiac regeneration. Overall design: Human embryonic stem cells (ES cells) were differentiated via a directed differentiation protocol in vitro towards cardiomyocytes for a period of 30 days. Cardiomyocytes were synchronized with dexamethasone and triplicate samples for RNA extraction and sequencing were taken every 4 hours for 48 hours in total. RNA was then extracted using TRIzol, barcoded and amplified following the CEL-Seq protocol.	Co-expression
SRP103065	Transcriptomic insights into human decidual and peripheral blood CD4 T cells	We performed the analysis of transcriptional and alternative splicing landscapes for paired decidual and peripheral blood CD4 T cells during human pregnancy by high-throughput mRNA sequencing. Overall design: Healthy women during early pregnancy were recruited, and FACS was performed to isolate and purify the CD4+ T cells from the decidua and peripheral blood. We sequenced the RNA samples on an Illumina HiSeq 2500 platform.	Co-expression
SRP103099	Patient derived xenograft models of leukemia and lymphoma whole transcriptome sequencing	To facilitate preclinical translational science, this cohort of patient-derived xenograft (PDX) models of leukemia and lymphoma has undergone molecular characterization with whole transcriptome sequencing, targeted exon sequencing of genes recurrently altered in leukemia and lymphoma, and other approaches. Here we provide the whole transcriptome sequencing data for these PDX models. Related molecular data and de-identified clinical information can be obtained at http://www.proxe.org.	Co-expression
SRP103115	RNA-seq in acute myeloid leukemia (AML) cells with and without knockdown of METTL14	To dissect the mechanism underlying the oncogenic function of METTL14 in AML, we performed deep sequencing for mRNA isolated from MM6 and NB4 cells with and without knockdown of METTL14 Overall design: We lentivirally transduced pLKO.1-based lentiviral shRNA targeting METTL14 (i.e., shM14-#2) or scramble shRNA (i.e., shNS) into human MM6 and NB4 AML cells. After selected with puromycin (0.5 µg/mL) for two passages, cells were collected and RNA was extracted using TRIzol reagent (Invitrogen, Carlsbad, CA). PolyA RNA was subsequently purified from100 ng total RNA using NEBNext Poly(A) mRNA Magnetic Isolation Module. NEBNext Ultra Directional RNA Library Prep Kit (New England BioLabs, Ipswich, MA) was used for library preparation. Each group was sequenced in duplicate by Illumine Hiseq 1000 with single end 50-bp read length.	Co-expression
SRP103188	Somatic to Naive direct reprogramming	Here we propose the direct conversion of human somatic cells into naive induced pluripotent cells (niPSC). Dataset: 7 expanded niPSC lines (4 from BJ cells, 1 from HFF-1, 1 from WI38, 1from IMR90), 1 freshly-isolated primary colonies of niPSC from BJ, 1 established naive embryonic line H9, 1 primed induced pluripotent cell line (from BJ), 1 sample of BJ fibroblasts, 1 sample of WI38 fibroblasts, 1 sample IMR90 fibroblasts.	Co-expression
SRP103200	Enhancer landscape of AML patient samples	AML patient samples and a few normal blood sample were assayed for H3K27ac ChIP-seq and RNA-seq. We discovered subtypes of AML based on these enhancer landscapes.	Co-expression
SRP103222	Differentially expressed genes from RNA-Seq and functional enrichment results are affected by the choice of single-end versus paired-end reads and stranded versus non-stranded protocols	We undertook four mammalian transcriptomics experiments to compare the effect of read mapping, feature counting and differential expression analysis using single-end (SE) and paired-end (PE) protocols. For three of these experiments we also compared a non-stranded (NS) and a strand-specific approach to mapping the paired-end data. Overall design: Each of the four RNA-Seq experiments had a simple but typical design, comprised of three biological controls and three treated samples. The six samples in each of the experiments were independent biological replicates. Experiments 1 and 2 were from mouse tissue or primary cells whereas Experiments 3 and 4 involved human primary cells and a cell line respectively.  In all four experiments sequencing was performed on both ends of the cDNA fragment (paired-end reads). We mapped both ends (see Methods) to produce our paired-end data set (PE data). We also mapped only the first read to produce our single-end read datasets for each experiment (SE data).  Sequencing for Experiment 1 occurred in 2012 and used a non-strand-specific protocol for library preparation (Illumina TruSeq kit). The other three experiments were sequenced more recently with the Illumina TruSeq Standed library preparation kit [13]. For these three experiments we looked at the effect of analyzing the paired-end data with a protocol that recognizes the strand-specific nature of the reads (PE data) and also with a protocol that does not recognize this (NS data). In this way we could assess the difference that a strand-specific protocol makes to gene expression analysis.	Co-expression
SRP103225	Transcriptomics of human-Helicobacter co-cultures	This study looked at the transcriptomics of human gastric epithelial cells co-cultured with either wild type or Tip-a knockout Helicobacter pylori SS1.	Co-expression
SRP103305	Whole transcriptome sequencing of human U937 cell line	RNA editing signature during myeloid leukemia cell differentiation.	Co-expression
SRP103454	Homo sapiens isolate:HEK293T Epigenomics	CBX7-RIP-Seq data for HEK293T cells	Co-expression
SRP103588	Functional studies of rare genetic variants causally connected with Alzheimer''s disease in the Polish population	The main objective of the project is to determine the physiological function of rare variants of sequence of genes causally associated with Alzheimer''s disease (AD). The analyzed rare genetic AD variants are mutations in PSEN1 gene in patients with familial early-onset AD (fEOAD). The research group is recruited from among patients with causative mutations of EOAD and FAD, which are under hospital care of neurodegenerative disease diagnostic centers from all over Poland. As a research material primary skin fibroblasts were derived from fEOAD patients and age- and sex- matched controls.	Co-expression
SRP103737	Expression analysis of genes modulated after knock-down of lncRNA CHROME.	Thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome, many of which are not conserved in lower mammals. The majority of these lncRNAs remain functionally uncharacterized and may have important implications in human physiology and disease. Here, we identify a primate-specific lncRNA, CHROME, which is increased in the plasma and atherosclerotic plaques of individuals with coronary artery disease compared to healthy controls. Using a loss-of-function approach, we show that CHROME functions as a competing endogenous RNA of microRNAs  and regulates the concentration and biological functions of target genes. Overall design: We used three replicate samples of HEPG2 cells that were treated with shRNA for CHROME compated to three replicate control samples.	Co-expression
SRP103767	Quantitative analysis of primary human and pluripotent stem cell-derived brain microvascular endothelial cells transcriptomes via next generation sequencing	Next-generation sequencing (NGS) has significantly facilitated the analysis of the gene profile and elucidated the molecular mechanisms important for specific cell lineage differentiated from human pluripotent stem cells (hPSCs). Here we report the application of RNA-sequencing technology for transcriptome profile of primary human brain microvascular endothelial cells (BMECs) and hPSC-derived BMECs, and comparison of transcriptomes among cells, including hPSCs, mesodermal progenitors, ectodermal progenitors, endodermal progenitors, hBMECs and hPSC-derived BMECs from hPSCs. Four different BMEC samples differentiated from hPSCs by two different methods and hBMECs were performed in IIIumina HiSeq2500. The resulting sequence reads (about 20 million reads per sample) were mapped to human genome (hg19) using HISAT, and the RefSeq transcript levels (FPKMs) were quantified using the python script rpkmforgenes.py. We next analyzed the expression of a subset of genes that regulate key BBB attributes, including tight junctions and molecular transporters. The gene set comprises 20 tight junction-related genes and an unbiased list of all 25 CLDN genes, all 407 solute carrier (SLC) transporters, and all 53 ATP-binding cassette (ABC) transporters regardless of prior knowledge of BBB association. Primary human BMECs expressed 234 of these genes. BMECs differentiated from hPSCs via the defined method expressed many of these same genes (206 of 234 (88%)) as did BMECs differentiated via the UM method (208 of 234 (89%), indicating a close similarity between hPSC-derived BMECs and primary human BMECs with respect to transcripts having likely relevance to BBB function. RNA sequencing was used to compare global gene expression profiles in the hPSC-derived BMECs with BMECs generated from our previously reported co-differentiation system and primary human BMECs. As expected, hPSC-derived BMECs from three independent differentiations clustered closely and were similar to those generated from the undefined UM platform. Moreover, the hPSC-derived BMECs clustered with primary human BMECs and were distinct from undifferentiated hPSCs and hPSC-derived ectoderm, endoderm and mesodermThis study provides detailed transcriptome comparison between hBMECs and hPSC-derived BMECs and unveils important genes related BMEC phenotypes. Overall design: Transcriptome profiles of human primary brain microvascular endothelial cells and hPSC-derived brain microvascular endothelial cells were generated by RNA-seq technology using IIIumina HiSeq2500	Co-expression
SRP103772	Next Generation Sequencing RNA Seq data from UKE Phase I rVSV ZEBOV vaccine clinical trial, from full blood samples on Days 0,1,3,7	10 adult participants of dose group 3x10^6 pfu, and 10 participants of dose group 20x10^6 pfu. Reads were aligned to the human reference assembly (GRCh38.p7) using STAR software (v2.4.2a; option ''--quantMode GeneCounts''). Gene annotation was obtained from Ensembl (release 79, ensemble.org). VOOM+Limma analysis (R software, version 3.2.2) was used to assess differential gene expression at each post-vaccination day (d1, d3 and d7) against baseline (d0). Next, we intergreted gene expression data and antibody response using an sPLS algorithm, in order to down-select genes correlating with multivariate antibody responses at days 28, 54, 84,180. Overall design: 56 samples from D0, D1, D3 and D7 were analysed. Data from samples with low RIN (RIN <8, 17 samples), low RNA or library concentration (2 samples), missing samples (5 samples)  were set to missing.	Co-expression
SRP103779	Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and PVT1 Knockdown by CRISPRi in MDA-MB-231 human breast cancer cell line	Induced MYC expression by CRISPRi targeting PVT1 was validated by RNA-seq Overall design: total RNA profiles were sequenced by two independent viral infection	Co-expression
SRP103786	Human Oral and Cutaneous Wound Healing Transcriptomes	Comparative analysis between oral and cutaneous wound healing in humans using paired and sequential biopsies during the repair process. Overall design: mRNA profiles of Oral/Skin Wound Healing human sample  were generated by sequencing using Illumina	Co-expression
SRP103787	Human normal oral keratinocytes (NOK) siRNA and Human epidermal keratinocytes (HEK) overexpression RNA-Seq	Transcriptome of si-RNA transfected NOK  cells and adenovirus-transduced HEK cells Overall design: mRNA profiles of HEK (human epidermal keratinocytes) transduced with adenoviruses and NOK (human normal oral keratinocytes) transfected with siRNAs.	Co-expression
SRP103803	Glucose impairs tamoxifen sensitivity modulating CTGF in breast cancer cells	Metabolic diseases, including type 2 diabetes and obesity are relevant negative prognostic factor in patients with breast cancer (BC). We have investigated the mechanisms through which elevated glucose levels affect tamoxifen sensitivity of estrogen receptor positive (ER+) BC cells. We found that MCF7 BC cell sensitivity to tamoxifen was 2-fold reduced in 25mM glucose (HG), a concentration mimicking hyperglycaemia, compared to 5.5 mM glucose (LG), resembling normal fasting glucose levels in humans. Shifting MCF7 cells from HG to LG ameliorated their responsiveness to tamoxifen. RNA-Sequencing revealed that glucose modified the transcriptome of MCF7 cells. In particular, cell cycle-related genes were affected by glucose. Combining gene specific knockdown and treatment with human recombinant proteins, we identified the Connective Tissue Growth Factor (CTGF) as glucose-induced factor able to reduce MCF7 cell sensitivity to tamoxifen. Moreover, we found that both CTGF expression levels and tamoxifen responsiveness were enhanced co-culturing MCF7 cells with human adipocytes through an Interleukin-8 (IL8)-mediated mechanism. Indeed, IL8 inhibition reduced CTGF levels and rescued tamoxifen sensitivity in MCF7 cells. Interestingly, CTGF immuno-detection in bioptic specimens obtained from women with ER+ BC correlated with distant metastases (P-value = 0.000), hormone therapy resistance (P-value = 0.000), reduced overall (P-value = 0.051) and disease free survival (P-value = 0.000). Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting the adipocytes’ release of IL8. Both CTGF and IL8 may represent potential targets in novel therapeutic strategies to increase tamoxifen sensitivity. Overall design: The gene expression profile of MCF7 cells grown in high glucose and then shifted in low glucose (HG?LG; n=1) were compared to MCF7 cells grown in high glucose (HG; n=1).	Co-expression
SRP103811	Single-cell transcriptomics of East-Asian pancreatic islets cells	Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on a- and ß-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between a- and ß-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 a, 105 ß, 6 d endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between a- and ß-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian ß-cells. We report on East-Asian a- and ß-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian ß-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis. Overall design: 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. 223 islet-cells remained after samples QC, and these cells were used for subsequent analyses. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. We identified 118 a and 105 ß endocrine cells in our dataset.	Co-expression
SRP103819	Rhinovirus infection results in stronger and more persistent genomic dysregulation: evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence	Background: Rhinovirus (HRV) is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined. Methods: Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis. Results: At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation. At 36 hours (before the emergence of peak symptoms), 1329 genes were significantly altered from baseline in the asthmatics compared to 62 genes in the controls. At this time point, asthmatics lacked an increase in IL-10 signaling observed in the controls. At 7 days following HRV inoculation, 222 genes were significantly dysregulated in the asthmatics, whereas only 4 genes were dysregulated among controls. At this time point, the controls but not asthmatics demonstrated upregulation of SPINK5. Conclusions: As judged by the magnitude and persistence of dysregulated genes, asthmatics have a substantially different host response to HRV-A16 infection compared with non-asthmatic controls. Gene expression differences illuminate biologically plausible mechanisms that contribute to a better understanding of the pathogenesis of HRV-induced asthma exacerbations. Overall design: Comparison of gene dysregulation in adult asthmatics and healthy controls at baseline and following human Rhinovirus inoculation.	Co-expression
SRP103821	Human monocyte-derived macrophage (MDM) cell transcriptome response to infection with H1N1, H3N2, and H5N1 influenza virus.	Human monocyte-derived macrophages (MDM) serve as a model for resident alveolar macrophages (AM) in the human respiratory tract. mRNA-Seq analysis was used to profile the cellular transcriptome of MDM cells at multiple time points in response to infection with influenza A/California/04/09 (H1N1), A/Wyoming/03/03 (H3N2), and A/Vietnam/1203/04 (H5N1) HALo virus.  The Influenza A/Vietnam/1203/04 (H5N1) HALo mutant virus is an attenuated H5N1 virus generated from wild-type Influenza A/Vietnam/1203/04 (H5N1) virus as described in Steel, J., et al. J Virol. 2009 Feb; 83(4):1742-53. Overall design: Human monocyte-derived macrophages (MDM), obtained from healthy donor blood, were infected with influenza A/California/04/09 (H1N1), A/Wyoming/03/03 (H3N2), or A/Vietnam/1203/04 (H5N1) HALo virus. Infected samples and time-matched mock-infected samples were collected in duplicates at 3, 6, 12, and 18 hrs post infection for mRNA-Seq analysis.	Co-expression
SRP103828	Gene expression signature of vemurafenib resistance in WM989 and WM983B melanoma cells	Therapies targeting signaling molecules mutated in cancers can often have striking short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures. Resistance can sometimes result from a secondary mutations in rare cells, but other times, there is no clear genetic cause, raising leaving the possibility of non-genetic rare cell variability. Here, we show that melanoma cells can display profound transcriptional variability at the single cell level that predicts which cells will ultimately resist drug treatment. This variability involves semi-coordinated transcription of a number of resistance markers at high levels in a very small percentage of cells. The addition of drug then induces an epigenetic reprogramming in these cells, converting the transient transcriptional state to a stably resistant state. This reprogramming begins withis a progressive process consisting of a loss of SOX10-mediated differentiation followed by activation of new signaling pathways, partially mediated by activity of Jun-AP-1 and TEAD. Our work reveals the multistage nature of the acquisition of drug resistance and provides a framework for understanding resistance dynamics. We find that other cell types also exhibit sporadic expression of many of these same marker genes, suggesting the existence of a general rare-cell expression program. Overall design: We performed RNA sequencing on WM989 cells without vemurafenib, after 48 hours of treatment, and upon the development of resistance.	Co-expression
SRP103839	Single-cell Multi-omics Sequencing and Analyses of Human Colorectal Cancer	Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multi-omics sequencing together with multi-regional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sub-lineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single-cell multi-omics sequencing. Overall design: Single cell RNA-seq and Bisulfite-seq on whole cells or by TrioSeq2. [scTrioSeq2Rna and scTrioSeq2Met Samples] Sample Title structure: Library_PatientID_SamplingPositions_CellID SamplingPositions abbreviations: PT:  Primary Tumor LN:  Lymph Node metastasis ML:  Liver Metastasis MP:  Post-treatment Liver Metastasis	Co-expression
SRP103842	Plasma transcriptome profiling in patients with chronic kidney disease and end-stage renal disease	Cardiovascular disease is the major cause of morbidity and death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Patients with CKD and ESRD are at high risk for myocardial dysfunction, ischemia and heart failure. The mechanisms linking impaired renal function and increased risk for cardiovascular diseases, however, remain elusive. In addition, conventional therapeutics proven effective in reducing cardiovascular events in general population fail to provide similar benefits in uremic patients. There is a clear need to identify novel mediators of cardiovascular complications in uremic patients to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to develop new therapeutic strategies.  It has become increasingly clear that the transcription of the eukaryotic genome is far more pervasive and complex than previously appreciated. While the expression of messenger RNAs (mRNAs) and microRNAs (miRNAs) account for only ~1% of all transcribed species, up to 90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be functional and involved in specific physiological and pathological processes through epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cardiovascular complications in patients with renal dysfunction.   In this proposal, we seek to apply next-generation sequencing technology to investigate circulating (plasma) lncRNA expression in control subjects and in patients with CKD and ESRD. We will test the hypothesis that circulating lncRNA expression signature can reflect the underlying kidney disease states in patients with CKD and ESRD. In addition, we will determine if circulating lncRNA expression signature could be a sensitive and specific biomarker to predict adverse cardiovascular events in patients with ESRD. Overall design: During the initial exploratory phase, plasma total RNA was isolated from 48 study subjects (28 ESRD, 8 CKD and 12 controls), followed by amplicon-based RNA sequencing (AmpliSeq TranscriptomeTM, Thermo Fisher), which allows simultaneous quantification of 20812 human transcripts, including 2228 lncRNAs. Differential expression analyses following RNASeq identified lncRNAs that were altered with ESRD, compared to control/CKD, as well as lncRNAs that were linked to adverse CV outcomes in uremic patients. The prognostic role of plasma lncRNAs in patients with ESRD were then validated in an independent cohort of 111 subjects.	Co-expression
SRP103851	Transcriptome sequencing wide functional analysis of human mesenchymal stem cells (LPS)	Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs LPS (1ug/ml). Overall design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500(101 cycles PE lane).	Co-expression
SRP103852	Transcriptome sequencing wide functional analysis of human mesenchymal stem cells (Poly(I:C))	Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs Poly(I:C) (10ug/ml) Overall design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500(101 cycles PE lane).	Co-expression
SRP103854	Cooperativity between EMT and non-EMT cells promotes breast cancer metastasis via paracrine GLI activation	Recent fate mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that it failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumor cells in a paracrine manner in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI-926, a Smoothened inhibitor, blocks this effect, and inhibits growth in PDX models. In human breast tumors, the EMT-TFs strongly correlate with activated Hedgehog/GLI signaling, but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis in part via non-cell autonomous effects that activate the Hh pathway. While all Hh inhibitors may act against tumors with canonical Hh/GLI signaling, only GLI inhibitors would act against EMT-induced GLI activation. In recent years, immunohistochemical analyses and multiplex high-throughput single cell sequencing of human tumor cells have shown that tumors are composed of diverse cell subpopulations containing different driver mutations, gene and protein expression profiles, growth rates, and responses to chemotherapeutics. Such heterogeneity is exacerbated by cellular plasticity, where some cells may undergo oncogenic epithelial-to-mesenchymal transition (EMT), resulting in loss of cell-cell adhesion and polarity, reduced epithelial and elevated mesenchymal protein expression, increased migration and invasion, and enhanced dissemination from the primary tumor. Because metastases in patients appear epithelial, the reverse process, mesenchymal-to-epithelial transition (MET), may occur to allow tumor cell colonization in secondary metastatic sites, establishing cellular plasticity as an important aspect of tumor progression. However, the role of EMT in carcinoma metastasis is controversial. Recent lineage tracing studies argue against the requirement of EMT for metastasis, as reporter-tagged cells that underwent a previous EMT were not found at the secondary site. However, these studies did not address the potential cooperation between EMT and non-EMT cells during the metastatic process, as EMT cancer cells may enable non-EMT cells to gain access to the secondary site, leading to macrometastatic growth. Thus, metastasis can be influenced by intratumoral heterogeneity: where a small proportion of primary tumor cells that have undergone an EMT may influence neighboring, non-EMT tumor cells. Twist1, Snail1, and Six1 are EMT-inducing transcription factors (EMT-TFs) that have all been associated with breast cancer metastasis. All three EMT-TFs regulate critical developmental processes such as cell survival, migration and invasion; in part by influencing EMT. In addition, they are downregulated post-embryogenesis, but re-expressed in various cancers where they cell autonomously induce EMT, resulting in increased percentages of tumor initiating cells (TICs) and enhanced metastasis. In carcinomas, Twist1 and Snail1 transcriptionally repress E-Cadherin (E- Cad) and upregulate mesenchymal genes. Similarly, Six1 overexpression induces EMT by regulating E-Cad localization and altering other EMT markers. During development and cancer, EMT-TFs act in concert with several signaling networks including TGFß, Wnt, and Hedghog (Hh). The Hedgehog (Hh) signaling pathway is a prominent regulator of embryonic development, where Hh ligands function as morphogens to control numerous developmental processes. Interestingly, in Drosophila eye development, hh is a direct target of sine oculis (the homolog of Six1) and Six1 regulates Hh/GLI signaling during lung development and in fibroblasts. Additionally, Twist1 and Hh/GLI signaling are intimately linked during development, and recently Twist1 and Snail1 were associated with the Hh pathway in TICs. In mammals, canonical activation of Hh/GLI signaling involves binding of one the Hh ligands such as(either, Desert (DHH), Indian (IHH), or Sonic Hedgehog (SHH) to Patched-1 (PTCH1) or Patched-2 (PTCH2) receptors, relieving the inhibitory activity of PTCH on Smoothened (SMO). When inhibition is relieved, levels of the transcriptional activator forms of one or more GLI transcription factors (GLI1, 2, or 3) increase in the nucleus, resulting in activation of Hh target genes 12. Non-canonical activation of the GLI TFs can occur in a Hh- or SMO-independent manner via secreted factors like TGF-ß19. Importantly, autocrine and paracrine Hh-mediated crosstalk between tumor cells and the tumor microenvironment 20 results in increased proliferation, stem cell self-renewal and metastasis in various cancers 21. In basal cell carcinoma (BCC) and medulloblastoma, activated Hh signaling is often due to mutations in pathway components such as PTCH and SMO, while in other tumor types including breast, mutations are not observed at high frequency. Instead there is evidence for Hh ligand-dependent pathway hyperactivity. Because numerous studies link Hh signaling to progression in multiple tumor types, derivatives of cyclopamine (e.g. GDC-0449 and IPI926), a naturally occurring plant-derived steroidal alkaloid which targets SMO, are in clinical trials for select patients with BCC and medulloblastoma with promising efficacy. However, these inhibitors have not shown promise in breast cancer despite evidence for activation of this pathway. Herein, we demonstrate that EMT-TFs Twist1, Snail1 and Six1 influence neighboring carcinoma cells in a non-cell autonomous manner, by increasing EMT features and aggressive properties of cells not expressing these TFs. Six1 is a key mediator of the non-cell autonomous effects downstream of Twist1 and Snail1, and can induce metastasis of non-Six1, non-EMT cells. All three EMT-TFs function non-cell autonomously by activation of GLI-mediated transcription in non-EMT cells, but employ different mechanisms of pathway activation, some of which are Hh ligand and SMO-independent. We find that pharmacological inhibition of GLI, but not SMO, in the non-EMT cells efficiently inhibits the non-cell autonomous phenotypes imparted by all three EMT-TFs. Importantly, we demonstrate that in selected patient derived breast cancer xenograft (PDX) models endogenously expressing high levels of these EMT-TFs (but not Hh ligands), GANT61 (a GLI1/2 inhibitor) inhibits tumor growth whereas IPI926 (a SMO inhibitor) did not. Our data suggest that upstream SMO inhibitors may not prove efficacious in tumors where a proportion of cells activate GLI-TF via EMT-TFs, and instead argue that inhibitors directly targeting GLI may be more effective. Overall design: Human breast cancer xenograft RNA sequencing. Mice were untreated.	Co-expression
SRP103856	HIV-1 perturbs homeostatic ILCs, unmasks ILC1 plasticity, and boosts TCF7+ memory NK cells	Bulk RNA-seq, and single cell RNA-Seq using inDrops methodology, were used to compare two populations of cells that had been sorted by flow cytometry from human peripheral blood mononuclear cells (PBMCs) from two donors, G27 and G33. To sort the cells, PBMCs were stained with antibodies to 11 lineage markers (FITC), anti-CD56 (PE), and anti-CD94 (APC). The 11 lineage marker positive cells were excluded to identify the innate lymphocyte cell (ILC) population. Then we sorted the Lin-CD56+CD94- cells (CD127-ILC1s, 'neg') from the Lin-CD56+CD94+ cells (NK cells, 'pos') with a BD FACSAria IIu. Libraries were generated from each of these two populations. Overall design: Quantification and analysis of FACS-sorted human ILC cells from two donors.	Co-expression
SRP103878	RNA sequencing data for 30 bladder cancer cell lines	RNA-sequencing of a panel of urothelial cancer cells. The goal of the study is to examine the genome-wide expression profile in each of the 30 urothelial cancer cells tested in our laboratory. Overall design: Each of the 30 cell lines was DNA fingerprinted to confirm its real identity. Total RNA was obtained from each cell line and subjected to Illumina RNA sequencing.	Co-expression
SRP103934	Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy	Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp) disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to reversion to specific fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease. Analysis of alternative splicing (AS) transitions during human myogenesis reveals hundreds of AS events that undergo prenatal isoform transitions and both AS and alternative polyadenylation abnormalities are prominently detectable in infant CDM muscle biopsies. While the majority of RNA targets are also mis-regulated in adult-onset DM1, splicing dysregulation is significantly more severe in CDM. Since many of these mis-processing events are MBNL-regulated, we generated mouse Mbnl double (Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models that recapitulate the congenital myopathy, gene expression and spliceopathy defects characteristic of CDM. This study demonstrates RNA mis-processing is a major pathogenic factor in CDM and provides novel mouse models to further examine roles for co/post-transcriptional gene regulation during tissue development. Overall design: Disease-control (SMA type 1) and CDM skeletal muscle (biceps brachii) was used for RNA-seq and polyA-seq and transcriptome analysis (gene expression, alternative splicing, and alternative cleavage and polyadenylation) was performed to identify RNA mis-processing associated with disease. Newborn (P0) quadriceps muscle from wild-type, double (Mbnl1; Mbnl2) knockout (DKO), and TKO (Mbnl1; Mbnl2; Mbnl3) knockout (TKO) muscle and wild-type and Mbnl3 knockout (3KO) myoblasts were also used for transcriptome analysis to test the contribution of MBNL loss-of-function to disease features.	Co-expression
SRP103944	DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A [RNA-Seq]	We demonstrate that dCas9-SunTag-DNMT3A dramatically increased CpG methylation at the HOXA5 locus in human embryonic kidney 293T cells (HEK293T). Furthermore, using a single sgRNA, dCas9-SunTag-DNMT3A was able to methylate a 4.5 kb genomic region and repress HOXA5 gene expression. Reduced representation bisulfite sequencing (RRBS) and RNA-seq showed that dCas9-SunTag-DNMT3A methylated regions of interest with minimal impact on the global DNA methylome and transcriptome. Overall design: I)PCR amplicon deep sequencing of dCas9-SunTag-DNMT3A treated HEK2937 samples  using Illumina Nextseq sequencing system. II) Reduced representation bisulfited sequencing (RRBS) of plasmid transfected HEK 293T cells using Illumina Hiseq2000 sequencing system. III)  Whole genome bisulfite sequencing of dCas9-SunTag-DNMT3A treated HEK2937 samples. IV) RNA sequencing of dCas9-SunTag-DNMT3A treated HEK2937 samples	Co-expression
SRP103945	RNA-seq and ChIP-seq analysis of BMI1 or RING1B-silenced prostate cancer cells C4-2	Purpose: Study of the role of BMI1 dependent and indpendent of PRC1 in castration-resistant prostate cancer(CRPC)   Method: The expression of BMI1 or RING1B was silenced by 2 independent siRNA strands targeted at BMI1 or RING1B in C4-2 cells, scramble RNA as control. mRNA profiles and genome-wide chromatin-state maps were generated by deep sequencing. AR, BMI1 and IgG ChIP was conducted in C4-2 cells.  Results: AR-induced genes were significantly down regulated by BMI1 knockdown but not RING1B. higher expression levels of BMI1 activated genes (those downregulated by BMI1 knockdown) were significantly associated with poorer disease-free  and poorer overall survival. Overall design: Expression profiling by RNA-seq, profiling of BMI1 and RNF2 (wildtype and  knockdown) from C4-2 cell lines.  DNA was purified from chromatin immunoprecipitates for AR, BMI1 or IgG using the phenol/chloroform extraction. IgG was used as a negative control for ChIP. Then, DNA was amplified by quantitative PCR and normalized to input.	Co-expression
SRP103997	RNA sequencing of 6 individual clones of THP-1 cells resistant to NSC-370284	Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is a potent oncogene in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high level expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML. NSC-311068 and especially NSC-370284 significantly repressed TET1-high AML progression in vivo. UC-514321, an optimized derivative of NSC-370284, exhibited an even more potent therapeutic effect and prolonged the median survival of TET1-high AML mice over three folds. NSC-370284 and its derivative showed strong synergistic effects with standard chemotherapy. NSC-370284 directly targeted STAT3/5, transcriptional activators of TET1, and thus repressed TET1 expression. Our results highlight the therapeutic potential of targeting the STAT/TET1 axis by selective inhibitors in AML treatment.	Co-expression
SRP104118	Modeling the pathogenesis of Charcot-Marie-Tooth disease type 1A using patient-specific iPSCs	Here, human induced pluripotent stem cells (control-hiPSCs, CMT1A-hiPSCs, and PMP22-hiPSCs) were induced to differentiate to Schwann cells  (control-SCs, CMT1A-SCs, and PMP22-SCs) through neural crest stage (control-NCSCs, CMT1A-NCSCs, and PMP22-NCSCs). We sequenced mRNA samples from Schwann cell differentiation of human pluripotent stem cells at 3 different stage to generate the gene expression profiles of these cells. Overall design: 7 samples, including undifferentiated hiPSCs (control-hiPSCs and CMT1A-hiPSCs), freshly isolated p75+/HNK1+ NCSCs  (control-NCSCs and CMT1A-NCSCs), and SCs (control-SCs, CMT1A-SCs, and PMP22-SCs) were analyzed.	Co-expression
SRP104120	Cell-cycle-resolved analysis of RNA expression in neuroblastoma cells upon MYCN knockdown	Previous studies of c-MYC or MYCN effects on the cellular transcriptome have been performed with unsynchronized tumor cell populations. We reasoned that these results might have been influenced by different cell-cycle profiles of cells with high or low MYC levels  as the expression of a large part of the genome varies with cell-cycle phase. To correct for this potentially confounding effect, we performed RNA sequencing in cell-cycle-synchronized neuroblastoma cells and then compared the transcriptomes of cells with high and low MYCN in equivalent cell-cycle phases. Overall design: IMR5/75 neuroblastoma cells with tetracycline-inducible MYCN shRNA were arrested at G1:S transition by thymidine treatment for 18 h. After washout, transcriptome was measured at 11 time points over 22h (2 biological replicates).	Co-expression
SRP104137	Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq]	Organoid techniques provide unique platforms to model brain development and neurological disorders. While organoids recapitulating corticogenesis were established, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, remains to be developed. Here, we describe a system to generate MGE or cortex-specific organoids from human pluripotent stem cells. These organoids recapitulate the developments of MGE and cortex domains respectively. Population and single-cell transcriptomic profiling revealed transcriptional dynamics and lineage productions during MGE and cortical organoids development. Chromatin accessibility landscapes were found to be involved in this process. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, we applied fusion organoids as a model to investigate human interneuron migration. Together, our study provides a new platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development. Overall design: mRNA profiles of hMGEOs and hCOs were generated by deep sequencing	Co-expression
SRP104148	Next Generation Sequencing Facilitates Differential Expression Analysis of miRNA Expression In the Whole Blood Samples Obtained From Prostate Cancer Patients vs. Controls	Research conducted using the novel approach of Next Generation Sequencing to determine the differentially expressed microRNAs in whole blood samples from prostate cancer patients. Overall design: The whole blood miRNA  samples from both controls and patients were sequences and a differential expressional analysis was conducted to identify possible biomarkers to distinguish patients from controls.	Co-expression
SRP104149	Functional astrocytes differentiated from hiPSCs	Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate.  Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ~90% S100ß-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. Overall design: 6 hiPSC-derived astrocyte lines were generated. Total RNA were extracted from these hiPSC-astrocytes as well as 2 primary astrocyte lines and analyzed by RNA sequencing.	Co-expression
SRP104161	Enhancer profiling in metastatic cancer [RNA-Seq]	Metastases cause the majority of cancer-related deaths. Yet, the origins of metastatic cancer phenotypes remain poorly understood. Few metastasis-specific driver mutations have been identified [1-3], raising the possibility that metastatic transcriptional programmes may emerge from perturbations in the oncogenic signalling cascades that support the development of primary tumours. Here, using genome-wide histone modification profiling, high-throughput chromatin conformation capture by Hi-C and functional analysis in human-derived metastasis models of renal and breast cancers, we identify transcriptional enhancers that drive metastatic cancer progression. We demonstrate that specific enhancers and enhancer clusters are activated in metastatic cancer cell populations. The activation status of these enhancers is associated with gene expression patterns predictive of poor patient outcome in clinical samples. CRISPRi-mediated inhibition of enhancer activity and genetic ablation of enhancer sequences demonstrated the requirement of metastasis-associated regulatory elements for metastatic colonization in vivo. We further show that metastatic cancer clones co-opt evolutionarily conserved enhancers that converge on shared metastasis driver genes, such as CXCR4. Thus, we provide functional evidence for the requirement of specific enhancers for metastatic colonization and show that metastatic traits can arise through tissue-specific commissioning of distal gene regulatory elements. Overall design: mRNA profiling in experimental models of metastasis.	Co-expression
SRP104165	Endometrial cell-type specific RNA-seq	Cell-type specific RNA-seq is a powerful approach for unravelling molecular processes of endometrial receptivity, and to detect novel sensitive biomarkers of receptivity. Overall design: 16 paired endometrial tissue samples from pre-receptive (defined as LH2) and receptive phase endometria (defined as LH8) from Estonia (defined as E) and Spain (defined as S) were collected. CD9-positive epithelial cells (defined as epithelium) and CD13-positive stromal cells (defined as stroma) were isolated with fluorescent activated cell sorting (FACS) and full transcriptome analysis was performed by RNA-seq.	Co-expression
SRP104166	Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain [snDrop-seq]	Detailed characterization of the cell types in the human brain requires scalable experimental approaches to examine multiple aspects of the molecular state of individual cells, as well as computational integration of the data to produce unified cell-state annotations. Here we report improved high-throughput methods for single-nucleus droplet-based sequencing (snDrop-seq) and single-cell transposome hypersensitive site sequencing (scTHS-seq). We used each method to acquire nuclear transcriptomic and DNA accessibility maps for >60,000 single cells from human adult visual cortex, frontal cortex, and cerebellum. Integration of these data revealed regulatory elements and transcription factors that underlie cell-type distinctions, providing a basis for the study of complex processes in the brain, such as genetic programs that coordinate adult remyelination. We also mapped disease-associated risk variants to specific cellular populations, which provided insights into normal and pathogenic cellular processes in the human brain. This integrative multi-omics approach permits more detailed single-cell interrogation of complex organs and tissues. Overall design: Single DAPI+ nuclei (according to the Samples list) were isolated from the visual cortex (BA17), frontal cortex (BA6 or BA10), and cerebellar hemisphere from 6 different postmortem adult human brains and were processed for single-nucleus Drop-seq (snDrop-seq). This series contains data only for snDrop-Seq.	Co-expression
SRP104232	Homo sapiens Transcriptome or Gene expression	transcriptomic study of changes in normal (spontaneously) immortalised keratinocytes upon infection with human papillomavirus type 16 and upon keratinocyte differentiation	Co-expression
SRP104287	Perturbation-response genes reveal signaling footprints in cancer gene expression	Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike existing methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression. Overall design: HEK293?RAF1:ER cells were treated with different stimuli (4OHT, Ly29002, TNFa, TGF1b, IFNg) for different periods of time (1h, 4h).	Co-expression
SRP104300	Intrinsic Immunity Shapes Viral Resistance of Stem Cells	Numerous studies have demonstrated that stem cells are more resistant to virus infection than their differentiated progenies; however, the nature of this differential virus resistance remains a mystery. Here we analyzed gene expression in both mammalian stem cells and cells at various stages of differentiation. We found that stem cells intrinsically express a subset of interferon stimulated genes (ISGs) and that this property is conserved across species. We show that ISG expression is truly intrinsic, as stem cells are refractory to interferon (IFN). Further, ISG expression varies in a cell type-specific manner and decreases as cells differentiate. We show that once cell differentiate they become IFN-responsive and a broad spectrum of ISGs are then induced by canonical IFN signaling. Importantly, we also show that intrinsically expressed ISGs protect stem cells from virus infection. Finally, we performed in vivo experiments to show that protecting stem cells from virus infection is critical because stem cells are needed to regenerate tissues damaged by virus infection. Our findings have important implications for understanding both stem cell biology and the evolution of innate immunity. Overall design: mRNA profiles for hESC-derived cells and primary cells were generated by deep sequencing, in duplicate or triplicate, using IlluminaHiSeq 2000.	Co-expression
SRP104301	Gene expression changes in Hutchinson Gilford Progeria Syndrome (HGPS) are counteracted by calcitriol	RNA expression was measured using RNA-seq Overall design: RNA levels of normal human primary fibroblasts and HGPS patient-derived fibroblasts subjected to short (4 days) and long (3 months) treatment with calcitriol (1,25D). RNA levels were compared among all different samples.	Co-expression
SRP104304	5hmC dynamically correlated with enhancer''s activities during hES-to-Pancreatic endoderm cell differentiation (RNA-Seq)	We generated 5hmC, WGBS and RNAseq of the cells in 5 stages during hES-to-pancreatic endoderm cell differantiation, and investigated the 5hmC correlation with 4 histones (H3K4me1, H3K4me3, H3K27ac and H3K27me3) during this process. Our results showed that 5hmC is dynamically correlate with enhancers'' activities. Overall design: Purpose: Determine the roles of 5hmC during hES to pancreatic endoderm cell differentiation process. The whole genome bisulfite sequencing, CMS-IP, ATAC-seq and RNAseq for the 5 stages (ES,DE,GT,FG,PE) have been sequenced.	Co-expression
SRP104390	Comparison of expression profiles of APP-depleted prostate cancer cells (LNCaP)	This analysis determines the relevanve of APP in prostate cancer as potential novel redox-regulator in androgen-responsive and castration-refractory prostate cancer Overall design: LNCaP cells either expressing empty vector (pcDNA3.1) or overexpressing wild-type androgenreceptor (AR) were stably transduced with shRNA against APP	Co-expression
SRP104391	Retinoic acid suppresses MYB in adenoid cystic carcinoma [RNA-seq]	Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor. Surgical resection, whenever possible, is the standard therapy for ACC, but there are no available therapeutic options available if surgery fails. Here we performed a chemical genetic screen using a zebrafish embryo culture system and identified retinoic acid agonists as potent suppressors of c-myb. Retinoic acid treatment strongly decreased c-myb gene expression in U937 cells and suggested a direct transcriptional mechanism of regulation. Retinoic acid agonists strongly inhibited tumor growth in vivo in different ACC patient derived xenograft models. Analysis of the xenografts revealed a significant decrease in MYB binding at translocated enhancers, thereby disrupting the MYB positive feedback loop that drives ACC. Our findings identify an important role of retinoic acid in MYB regulation and as a potential new effective therapy for ACC. Overall design: RNA-seq analysis of ACC xenograft samples treated with vehicle or ATRA	Co-expression
SRP104402	Mapping the human DC lineage through the integration of high dimensional techniques	Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the dendritic cell precursors within the peripheral blood.	Co-expression
SRP104405	Transcriptome analysis on TDP43 and SRSF3 downstream genes and binding RNAs in MDA-MB231 cells by Next Generation Sequencing	TDP43 and SRSF3 has been reported to be RNA-binding proteins; however their roles in breast cancer progression has not been  examined previously. Here, we performed RNA-seq on MDA-MB231 cells stably expressed sh-control, shTDP43, shSRSF3 or sh-TDP43 and sh-SRSF3 using lentivirus in duplicates. In addition, MDA-MB231 cells with stable expression of flag-TDP43 or flag-SRSF3 were also generated by using lentivirus. RIP-seq was also applied to identify binding RNA against Flag antibodies. Overall design: Kncoking down TDP43 or SRSF3 in these cells was achieved using stable expression of shRNA specific for TDP43 or SRSF3 gene using lentivirus. Stable infected cells were selected and harvested for RNA isolation in duplicates. RNA-seq was performed to study the effect of TDP43 or TDP43-knowdown in MDA-MB231. Examination of RNA immunoprecipitation in Flag-TDP43 and Flag-SRSF3 wtih Flag antibodies.	Co-expression
SRP104418	RNASeq_Fibroblasts_Rapamycin&MethionineRestriction	old and young human cardiac fibroblasts plus those treated with rapamycin and methionine restriction or a combination of both	Co-expression
SRP104694	mRNA profiles of U251 cells with endogenous Gcn5 depletion and reconstituted expression of WT Flag-rGcn5 or Flag-rGcn5 Y645A / endogenous DLST depletion and reconstituted expression of WT V5-rDLST or V5-rDLST R224A/K226E	Purpose: The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) of U251 cells with endogenous Gcn5 depletion and reconstituted expression of WT Flag-rGcn5 or Flag-rGcn5 Y645A / endogenous DLST depletion and reconstituted expression of WT V5-rDLST or V5-rDLST R224A/K226E Transcriptomes. And quantitatively analyze the cell signaling pathways that regulated by the studied mutants. Methods: total mRNA was extracted from U251 cells with endogenous Gcn5 depletion and reconstituted expression of WT Flag-rGcn5 or Flag-rGcn5 Y645A / endogenous DLST depletion and reconstituted expression of WT V5-rDLST or V5-rDLST R224A/K226E.llumina compatible libraries were prepared by using the KAPA Stranded mRNA-Seq Library Preparation Kit for Illumina® platforms (KAPA Biosystems). In brief, 250 ng of total RNA was enriched for poly-A-tailed mRNA by using Kapa's mRNA Capture beads. Poly-A-enriched RNA was fragmented to a median size of 150 bp by using chemical fragmentation and converted into double-stranded cDNA with dUTP incorporated into the second cDNA strand. The ends of the double-stranded cDNA were polished, 5'-phosphorylated, and 3'-A-tailed for the ligation of indexed adapters. Adapter-ligated DNA fragments were amplified by 8 cycles of PCR. The strand with incorporated dUTP was not amplified. The resulting libraries were quantified by qPCR and assessed for size distribution by using the 4200 TapeStation (Agilent Technologies), and then multiplexed, 4 per pool, and sequenced on the Illumina's NextSeq500 by using the mid-output, 75-bp paired-end read format. Results: Using an optimized data analysis workflow, we mapped about 50 million sequence reads per sample to the human genome and quantified the expression of protein coding genes in the U251 cells of WT Gcn5 and Gcn5 Y645A mutant/WT DLST and DLST R224A/K226E mutant.  Altered expression of 3 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Conclusions: Our study represents the first detailed analysis of U251 cells with endogenous Gcn5 depletion and reconstituted expression of WT Flag-rGcn5 or Flag-rGcn5 Y645A / endogenous DLST depletion and reconstituted expression of WT V5-rDLST or V5-rDLST R224A/K226E Transcriptomes. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that Gcn5 Y45A mutant and DLST R224A/K226E mutant, which reduce histone H3 K79 succinylation, can regulate several cell signaling pathways that important for cancer cell proliferation. Overall design: mRNA profiles of U251 cells with endogenous Gcn5 depletion and reconstituted expression of WT Flag-rGcn5 or Flag-rGcn5 Y645A / endogenous DLST depletion and reconstituted expression of WT V5-rDLST or V5-rDLST R224A/K226E	Co-expression
SRP104697	Mapping the human DC lineage through the integration of high dimensional techniques	Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: single-cell RNA Seq of human dendritic cells	Co-expression
SRP104720	RNA expression profiles from HUVECs overexpressing adenovirally delivered HIF1a and HIF2a proteins	RNA-Seq analysis was performed from human umbilical vein endothelial cells exposed to constitutively active HIF1a and HIF2a overexpression Overall design: RNA expression profiles from HUVECs overexpressing adenovirally delivered HIF1a and HIF2a proteins	Co-expression
SRP104749	BET Bromodomain Inhibition Blocks the Function of a Critical AR-Independent Master Regulator Network in Lethal Prostate Cancer	BET bromodomain inhibitors are known to block prostate cancer cell survival through suppression of c-Myc and androgen receptor (AR) function. However, little is known about other transcriptional modulators whose function is blocked by these drugs and the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency may be increasing. In this study we determined that BET bromodomain inhibition suppresses survival of a diverse set of CRPC cell models, including those that do not express the AR or in which c-Myc is not suppressed. To identify additional transcriptional regulators whose suppression contributes to the anti-tumor effects of BET bromodomain inhibition, we treated multiple CRPC cell lines with the BET bromodomain inhibitor JQ1, measured genome-wide gene expression changes, and then used the Master Regulator Inference Algorithm (MARINa). This approach identified transcriptional regulators whose function is blocked by JQ1 and whose suppression recapitulates the effects of BET bromodomain inhibition. High Expression of these Master Regulators in aggressive human CRPC demonstrates their clinical relevance. Overall design: RNA-seq profiles of multiple prostate cancer cell lines to understand gene expression changes associated with JQ1 treatment; ChIP-seq profiles of BET bromodomain protein BRD4 binding in the PC3 prostate cancer cell line to understand changes in BRD4 chromatin occupancy associated with JQ1 treatment.	Co-expression
SRP104789	Culture of Human embryonic stem cells in different media	No description.	Co-expression
SRP105013	Dexamethasone (DXM)  have a critical influence on the birth weight of infant	Trophoblast cells of human placenta were treated (DXM group) or un-treated (control group) by DXM, and then were performed with RNA-sequencing.	Co-expression
SRP105047	An integrative analysis of non-coding regulatory DNA variations associated with autism	A number of genetic studies have identified rare protein-coding DNA variations associated with autism spectrum disorder (ASD), a neurodevelopmental disorder with significant genetic etiology and heterogeneity. In contrast, the contributions of functional, regulatory genetic variations that occur in the extensive non-protein-coding regions of the genome remain poorly understood. Here we developed a genome-wide analysis to identify rare single nucleotide variants (SNVs) that occur in non-coding regions and determined regulatory function and evolutionary conservation of these variants. Using publicly available datasets and computational predictions, we identified SNVs within putative regulatory regions in promoters, transcription factor binding sites, microRNA genes and their target sites. Overall, we found regulatory variants in the ASD cases were enriched in autism-risk genes and genes involved in fetal neurodevelopment. As with previously reported coding mutations, we found an enrichment of regulatory variants associated with dysregulation of neurodevelopmental and synaptic signaling pathways. Among these were rare inherited non-coding SNVs found in the mature sequence of a number of microRNAs predicted to affect the regulation of autism-risk genes. We show a paternally inherited miR-873-5p variant, with reduced NRXN2 binding affinity, overlays a maternally inherited NRXN1 putative loss-of-function coding variation to likely increase genetic liability in an idiopathic ASD case. Our analysis pipeline provides a new resource for identifying loss-of-function regulatory DNA variations that may contribute to the genetic etiology of complex disorders. Overall design: This data is RNAseq of tagged-microRNA mRNA-pulldown assays for wild-type and mutant miR-873-5p. Four replicates each, with paired control (con) and pulldown (PD) samples for each replicate.	Co-expression
SRP105050	Transcriptomic analysis of the HOTAIR-regulated genes	An integrated RNA sequencing transcriptomic and quantitative proteomic analysis were employed to systematically explore the regulatory role of HOTAIR in HCC. A total of 673 transcripts and 298 proteins were identified to be dysregulated after HOTAIR inhibition. Overall design: Examine the overall transcriptomic changes in HepG2 cells after HOTAIR knockdown by RNA sequencing, in triplicate, using Illumina Hiseq 2000 platform.	Co-expression
SRP105066	CRISPR/Cas9-mediated ASXL1 mutation in U937 cells perturbs myeloid differentiation	Purpose: Recurrent ASXL1 mutations are frequently observed in all spectrums of myeloid malignancies and published data suggests that ASXL1 mutations may be involved in leukemic transformation as a tumor suppressor. Yet the molecular mechanisms of cell desitiny regulated by ASXL1 are  to be further delineated. Methods: mRNA profiles of wild-type (WT) and CRISPR/Cas9 induced ASXL1 mutated U937 cell lines were generated by next generation sequencing, using Illumina HiSeq2500. Sequence reads were trimmed to remove possible adapter sequences and nucleotides with poor quality at the ends. Remaining sequence reads were then aligned to the human reference genome (hg19) using Tophat2. Gene read counts were measured using FeatureCounts and FPKM values were calculated with cufflinks. edgeR was used to identify differentially expressed genes between conditions, and topGO was used for annotation (Alexa, Rahnenfuhrer, and Lengauer, 2006). Sample comparison for differential gene expression was as follows: WTblk and WT1 versus MT2, MT3, MT4, and MT5. Gene enrichment set analysis (GSEA) was conducted with KEGG, Biocarta, and Reactome pathway datasets (Subramanian et al., 2005). Results: ASXL1-mutated cells displayed impaired differentiation capacity. RNA-seq was used to compare transcriptomes of ASXL1-mutated and WT U937 cells. Transcriptom analysis revealed that ASXL1 mutations decreased the expression of genes essential to myeloid differentiation, including CYBB and CLEC5A genes, which manifested in ASXL1-MT U937 cells as perturbed potential of differentiation compared with WT cells. Also, gene set enrichment analysis revealed that ASXL1 mutations masively affected gene sets relating to cell death and survival. Conclusion: By introduction of mutations into genome using the CRISPR/Cas9 system, we established ASXL1-mutated U937 cell lines. Our results indicated that ASXL1 mutations perturbed monocytic/phagocyte differentiation, which is a hallmark of myeloid malignancies, by down regulating genes essential to myeloid differentiation, including CYBB and CLEC5A, also massively affected multiple gene sets involving in cell survival. Overall design: mRNA profiles of wild type (WT) and ASXL1 mutated U937 cell lines were generated by deep sequencing using Illumina HiSeq2500	Co-expression
SRP105113	DNA damage signaling mediates the functional antagonism between replicative senescence and terminal muscle differentiation	The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescentfibroblasts DDR precluded MYOD-mediated activation of the myogenic program. A DDR-resistant MYOD mutant could overcome this barrier by resuming cell cycle progression. Likewise, DDR inhibition could also restore MYOD ability to activate the myogenic program in human senescent fibroblasts. Of note, we found that cell cycle progression is necessary for DDR-resistant MYOD mutant to reverse senescence-mediated inhibition of the myogenic program. These data provide the first evidence of DDR-mediated functional antagonism between senescence and MYOD-activated gene expression, and indicate a previously unrecognized requirement of cell cycle progression for the activation of the myogenic program. Overall design: RNASeq	Co-expression
SRP105199	Chromosomal instability promotes metastasis through a cytosolic DNA response	Chromosomal instability (CIN) is a hallmark of cancer, and it results from ongoing errors in chromosome segregation during mitosis. While CIN is a major driver of tumor evolution, its role in metastasis has not been established. Here we show that CIN promotes metastasis by sustaining a tumor-cell autonomous inflammatory response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose envelopes frequently rupture exposing their DNA content to the cytosol. This leads to the activation of the cGAS-STING cytosolic DNA-sensing pathway and downstream noncanonical NF-kB signaling.  Genetic suppression of CIN significantly delays metastasis in transplantable tumor models, whereas inducing chromosome segregation errors promotes cellular invasion and metastasis in a STING-dependent manner. In contrast to primary tumors, human and mouse metastases strongly select for CIN, in part, due to its ability to enrich for metastasis-initiating mesenchymal subpopulations, offering an opportunity to target chromosome segregation errors for therapeutic benefit. Overall design: To determine whether CIN is causally involved in metastasis, we devised a genetic approach to alter the rate of chromosome missegregation in transplantable tumor models of human TNBC (MDA-MB-231); cont: Control sample. Part of the CIN-medium group. Ka; Overexpression of Kif2a, which does not affect the number of chromosome segregation errors during anaphase and serves as an additional control. Part of the CIN-medium group. Kb; Overexpression of Kif2b, which leads to suppressed chromosome segregation errors during anaphase. Part of the CIN-low group. MK; Overexpression of MCAK which leads to suppressed chromosome segregation errors during anaphase. Part of the CIN-low group. MKH; Overexpression of dominant-negative form of MCAK, leading to increased number of chromosome segregation errors during anaphase. Part of the CIN-high group.	Co-expression
SRP105203	Transcription of bovine milk and meat factors (BMMFs) in HEK293TT cells	We analyze the transcription of these bovine milk and meat factors (BMMFs) and MS isolates in human HEK293TT cells. While all analyzed DNA agents are readily transcribed, one of the MS brain isolates (MSBI1.176), sharing homology with a transmissible spongiform encephalopathy (TSE)-associated DNA molecule, is transcribed at highest levels. Our results support the transcription of an open reading frame (ORF) encoding a replication-associated protein, which is highly conserved among all isolated BMMFs. In the case of the cow milk isolate CMI1.252, transcription also occurs in a second large ORF. Transcriptome profiling upon BMMF expression identified host cellular gene expression changes related to cell cycle progression and cell viability control, indicating potential pathways for a pathogenic involvement of BMMFs. Overall design: The BMMFs CMI1.252, CMI3.168, MSBI1.176 and MSBI2.176 were transfected into HEK293TT cells. RNA-Seq was performed in triplicates per isolate at day 3 post transfection	Co-expression
SRP105219	Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq2]	Organoid techniques provide unique platforms to model brain development and neurological disorders. While organoids recapitulating corticogenesis were established, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, remains to be developed. Here, we describe a system to generate MGE or cortex-specific organoids from human pluripotent stem cells. These organoids recapitulate the developments of MGE and cortex domains respectively. Population and single-cell transcriptomic profiling revealed transcriptional dynamics and lineage productions during MGE and cortical organoids development. Chromatin accessibility landscapes were found to be involved in this process. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, we applied fusion organoids as a model to investigate human interneuron migration. Together, our study provides a new platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development. Overall design: mRNA profiles of hMGEOs and hCOs with single-cell level were generated by deep sequencing	Co-expression
SRP105222	MALT1 Inhibition Is Efficacious in Both Naïve and Ibrutinib-Resistant Chronic Lymphocytic Leukemia.	The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged by the frequent emergence of resistant clones. The ibrutinib target, Bruton''s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK. Recent findings show that MI-2, a small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another type of BCR pathway-dependent lymphoma. We therefore studied the activity of MI-2 against CLL and ibrutinib-resistant CLL. Treatment of CLL cells in vitro with MI-2 inhibited MALT1 proteolytic activity reduced BCR and NF-?B signaling, inhibited nuclear translocation of RelB and p50, and decreased Bcl-xL levels. MI-2 selectively induced dose and time-dependent apoptosis in CLL cells, sparing normal B lymphocytes. Furthermore, MI-2 abrogated survival signals provided by stromal cells and BCR cross-linking and was effective against CLL cells harboring features associated with poor outcomes, including 17p deletion and unmutated IGHV Notably, MI-2 was effective against CLL cells collected from patients harboring mutations conferring resistance to ibrutinib. Overall, our findings provide a preclinical rationale for the clinical development of MALT1 inhibitors in CLL, in particular for ibrutinib-resistant forms of this disease. Cancer Res; 77(24); 7038-48. ©2017 AACR. Overall design: To investigate the effect targeting MALT1 with MI-2 on tumor biology, 1 µg of total RNA from purified CLL cells treated for 8h with 2 µM MI-2 in vitro (N=3) was subject to RNA sequencing (by next-generation sequencing) and compared to untreated controls (N=3).	Co-expression
SRP105225	RNA-sequencing in immortalized human mammary epithelial cells	The epithelial-to-mesenchymal transition (EMT) contributes to tumor heterogeneity and has been implicated in tumor initiation and metastasis. To systematically identify genes involved in EMT, we performed a genome-scale expression screen in human mammary epithelial cells and found a striking enrichment in RNA splicing factors. In particular, the RNA-binding proteins QKI and RBFOX1 were necessary and sufficient to promote EMT and stem-like states. Among the transcripts cooperatively regulated by both factors, we found that alternative splicing of the actin-binding protein FLNB plays an essential role in the regulation of EMT. The skipping of FLNB exon 30 and the elevated expression of QKI were strongly associated with EMT gene signatures in both basal B subtype breast cancer cell lines and basal-like breast cancer patient samples. These observations demonstrate that alternative splicing regulated by QKI and RBFOX1 plays an active role in promoting EMT in basal-like breast cancers. Overall design: RNA-sequencing libraries were generated from immortalized human mammary epithelial cells (HME) overexpressing negative control proteins EGFP or HcRed, or candidate ORFs QKI, RBFOX1 or SNAI1. For each ORF, two to three replicates were sequenced.	Co-expression
SRP105227	A third generation therapeutic vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: first-in-human trial of ChAd63-KH	Whole  blood transcriptomic profiling indicated that CHAd63-KH induced innate immune responses  characterized by an interferon signature and the presence of activated dendritic cells. Overall design: Whole transcriptome using paired RNA samples with a high dose of the vaccine, pre vaccination and 24 hour post vaccination, and a subsequent experiment showing RNAseq from a low dose of the vaccine pre vaccination, 2hours post, 24 hours post and 14 days post vaccination.	Co-expression
SRP105266	RNA-Seq of treatment response of platinum sensitive and platinum resistant ovarian cancer cells	Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2''-deoxy-5-fluorouridine (5-FdU) and 3''-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis. Overall design: Platinum-sensitive A2780 and platinum resistant-cells A2780cis were treated with 5-FdU-Ecyd for 6h and 12h, there are also 6h and 12h untreated controls, all groups are in triplicates	Co-expression
SRP105292	Mapping the chemotherapy-induced RNA interactome in Glioblastoma [RNA-Seq]	Long non-coding RNAs (lncRNAs) are increasingly recognized as important players in transcription and epigenetic-driven cell diversification. So far, lncRNA function in more dynamic transcriptional reprogramming, i.e drug response, has been largely unexplored. Here, we investigated the regulatory circuits induced by chemotherapy in glioblastoma, the most aggressive and clinically refractory brain cancer. We performed a detailed characterization of the cellular and transcriptional response of glioblastoma stem-like cells to the alkylating agent temozolomide (TMZ). We found that in addition to mRNAs, TMZ affects the expression of a large number of non-coding RNAs (miRNAs, snoRNAs, lncRNAs). Our global transcriptome analysis provides a comprehensive characterization of regulatory circuits involving transcription factors, mRNAs, miRNAs and lncRNAs. To analyse the putative functions of these largely unknown RNA molecules, we developed a pipeline to integrate small and large RNA-seq data from multiple public databases and our own experiments. This led to the identification of the RNA interactome of glioblastoma and allowed us to define regulatory loops mediated by lncRNAs. We identified 22 key lncRNAs involved in transcriptional regulatory motifs, and three lncRNAs associated with patient prognosis, independent of other known response predictors. The investigation of TMZ-induced molecular networks in glioblastoma highlights novel coding and non-coding RNA-based predictors of glioblastoma chemoresistance, as well as potential targets to counteract such resistance. Overall design: RNA and small RNA profiling of 3 GBM stem-like cells and neural stem cells under TMZ treatment or vehicle in triplicate. This Series represents the RNA profiling dataset.	Co-expression
SRP105312	Homo sapiens Transcriptome or Gene expression	Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys, serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss of function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination of brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.	Co-expression
SRP105325	BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against Mantle Cell Lymphoma cells	Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1, and the NFkB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the level of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared to ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Co-treatment of ARV-771 with ibrutinib or the BCL2-antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior pre-clinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or resistant MCL. Overall design: Twelve samples in biologic triplicates	Co-expression
SRP105329	RNA-Seq of SHEP TET21N cells upon Doxorubicin treatment	MYCN-high and MYCN-low neuroblastoma cells differ in their responses to Doxorubicin treatment. To explain this difference we compared the global trancriptomes of MYCN-high and MYCN-low cells before, during and after treatment. Overall design: MYCN-high cells without doxycyline and MYCN-low cells with doxycycline were treated with 0.1µg/ml Doxorubicin.  Transcriptome was measured for the following time points: in untreated cells,  in cells which were treated with Doxorubicin for 72 hours, and in cells collected three, eight and fourteen days after Doxorubin washout.  Experiment was performed in biological duplicate.	Co-expression
SRP105333	RNA-sequencing in MDA-231-D cells transfected with ZEB1 or ZEB2 siRNAs	We searched for roles of ZEB1and/or ZEB2 during EMT by RNA-seq in breast cancer cells. Overall design: Expression of mRNA in a basal type breast cancer cell line MDA-231-D transfected with ZEB1 or ZEB2 siRNAs.	Co-expression
SRP105348	Post-transcriptional remodelling is temporally deregulated during motor neurogenesis in human ALS models	Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate regulators of RNA-processing that are ubiquitously expressed throughout development. To understand the molecular impact of ALS-causing mutations on early neuronal development and disease, we performed transcriptomic analysis of differentiated human control and VCP-mutant induced pluripotent stem cells (iPSCs) during motor neurogenesis. We identify intron retention (IR) as the predominant splicing change affecting early stages of wild-type neural differentiation, targeting key genes involved in the splicing machinery. Importantly, IR occurs prematurely in VCP-mutant cultures compared with control counterparts; these events are also observed in independent RNAseq datasets from SOD1- and FUS-mutant motor neurons (MNs). Together with related effects on 3'UTR length variation, these findings implicate alternative RNA-processing in regulating distinct stages of lineage restriction from iPSCs to MNs, and reveal a temporal deregulation of such processing by ALS mutations.  Thus, ALS-causing mutations perturb the same post-transcriptional mechanisms that underlie human motor neurogenesis. Overall design: Bulk RNA-seq at different timepoints throughout a 35-day differentiation protocol that converted iPSC cells to highly enriched motor neurons.	Co-expression
SRP105349	Progressive  motor  neuron  pathology  and  the  role  of  astrocytes  in  a  human  stem  cell model of VCP-related ALS	Motor   neurons (MNs)   and   astrocytes   (ACs) are   implicated   in   the   pathogenesis   of amyotrophic  lateral  sclerosis  (ALS),  but  their  interaction  and  the  sequence  of  molecular events leading to MN death remain unresolved. Herewe optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (>85%) functional populations of  spinal  cord  MNs  and  ACs.  We  identifysignificantlyincreased  cytoplasmic  TDP-43  and  ER stress as  primary  pathogenic  events in patient-specific  valosin-containing  protein  (VCP)-mutant MNs, with  secondary  mitochondrial  dysfunction  and  oxidative  stress.  Cumulatively these  cellular  stresses  result  in  synaptic  pathology  and  cell death  in  VCP-mutant  MNs. We additionallyidentify  a  cell-autonomous VCP-mutant  AC  survival  phenotype, which   is   not attributable  to  the  same  molecular  pathology  occurring in VCP-mutant MNs. Finally, through iterative  co-culture  experiments,  we  uncover  non-cell-autonomous  effects  of  VCP-mutant ACs  on  both  control  and  mutant  MNs.  This  work  elucidates  molecular  events  and  cellular interplay thatcould guide future therapeutic strategies in ALS. Overall design: Bulk RNA-seq at different timepoints throughout a 35-day differentiation protocol that converted iPSC cells to highly enriched motor neurons.	Co-expression
SRP105369	Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets	Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups. Overall design: Total healthy bone marrow was sorted to isolate distinct cell populations. RNA-Seq analysis was performed on sorted cells to determine gene expression profile of healthy bona marrow subpopulations.	Co-expression
SRP105671	Liver maturation	Gene expression of human liver cells at different developmental stages.	Co-expression
SRP105756	A gene expression study of the developing human eye	There is a vast range of tools with which to study the cells and tissues of the human body, however the scarcity of human embryonic material as a resource for direct study means that there is still limited data on the specific expression patterns which exist during human development. While embryonic studies are common place in other mammalian organisms and these have contributed greatly to our knowledge, characterising the events which occur during human development specifically is crucial in order to extrapolate the differences which exist between humans and other organisms and understand the human situation more completely. Establishing and maintaining collections of human developmental tissue for direct study requires significant time and resources, and is not a viable option for all. For this reason the creation of an atlas defining the key events which occur during human eye development would be of great value to the field. Through the Human Developmental Biology Resource we have collected human developmental eye tissue from post conception week 4 to 19 and performed gene expression studies using RNA sequencing. This study begins to reveal the spatiotemporal gene expression patterns which occur during normal human eye ontogenesis and represents a benchmark for comparison with development, disease and cellular differentiation studies. Overall design: 32 samples, which include 10 embryonic, 19 foetal and 3 adult samples	Co-expression
SRP105765	Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy [RNA-Seq]	Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2- deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML. Overall design: Fold change analysis between treatment and control	Co-expression
SRP105769	Expression profile of early and mid-secretory healthy human endometrium revealed by RNA-seq	Inner uterine lining or endometrium is a unique constantly self-renewed adult tissue that is vital for embryo implantation. As the footrace for universal endometrial receptivity markers continues, RNA-seq remains the most powerful tool for transcriptomic marker discovery. In this study, we aimed to elucidate endometrial maturation mechanisms at transcriptomic level and identify novel robust biomarker candidates for endometrial receptivity. Overall design: The differential gene expression profiles of early secretory and mid-secretory phase endometrial biopsies obtained from 20 healthy fertile women across one menstrual cycle were analysed using paired sample study design.	Co-expression
SRP106008	Identification of long noncoding RNA RP11-2B6.2 as a positive regulator of type I interferon pathway in lupus nephritis	Methods and Materials  The high throughput RNA sequencing (RNA-seq) data from kidney biopsies of LN patients and controls was applied studied to screen for candidate lncRNAs. Quantitative real-time polymerase chain reaction(RT-qPCR) was used to detect the expression of lncRNAs and individual IFN-stimulated genes (ISGs). Western blotting and dual-luciferace luciferase reporter assay was  adopted to explore the specific function of the candidate lncRNA.     Results  The expression of lncRNA RP11-2B6.2 was significantly increased in the kidney tissues from LN patients compared with those from healthy controls, and positive correlated with the degree of disease activity and renal injuryinjuries. Additionally, expression of LncRNA RP11-2B6.2 could be stimulated by type I IFN. Silencing it RP11-2B6.2 significantly reduced the expression of a group of interferon-stimulating genes(ISGs) including IFIT1, OAS1, etc., Furthermore, it lncRNA RP11-2B6.2 affected the expression of IFN alpha and beta receptor subunit 1 (IFNAR1), phosphorylation of Jak1 and Stat1, and the luciferase activity induced by interferon stimulated response element(ISRE).    Conclusion  Long noncoding RNA RP11-2B6.2 is a positive regulator of the type I IFN signaling pathway in LN. It LncRNA RP11-2B6.2 may contribute to the pathogenesis of LN and provide served as a potentially therapeutic target. Overall design: RNA-seq data from kidney biopsies of LN patients and controls was used to screen for candidate lncRNAs	Co-expression
SRP106011	Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation	We set out to identify molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. Gene expression changes unequivocally discriminated benign versus malignant states, and a dual epigenetic and immune signature emerged defining this transition. We discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was discriminated by a 122-epigenetic gene signature ('epigenetic' cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of 'viral mimicry' were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures ('immune' clusters) were identified.  TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of RNA transcripts may be better predictors for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell's epigenome with the immune milieu with potential for future therapeutic targeting. Overall design: Examination of transcriptome changes from benign states to early-, intermediate-, and late-category tumors using a unique set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions.	Co-expression
SRP106033	mRNA Sequencing of Human PromoCells Using Random Primed mRNA-Sequencing Technique	The differential gene expression of human cardiomyocytes induced by kinase inhibitors sorafenib and sunitinib is measured by a high-throughput mRNA-sequencing approach called 3''-DGE, that is based on a 3'' end-focused reference sequence library and a transcript molecule counting method with unique molecular identifiers (UMI) for correcting PCR bias. Overall design: Cells were treated with sunitinib, sorafenib, or vehicle control for 48 hours, and gene expression levels of all samples were measured by 3''-DGE and conventional random-primed mRNA-sequencing methods using paired-end reading to obtain the genome-wide expression profiles for each sample.	Co-expression
SRP106034	mRNA Sequencing of Human PromoCells Using 3''-directed Digital Gene Expression (3''-DGE) Technique	The differential gene expression of human cardiomyocytes induced by kinase inhibitors sorafenib and sunitinib is measured by a high-throughput mRNA-sequencing approach called 3''-DGE, that is based on a 3'' end-focused reference sequence library and a transcript molecule counting method with unique molecular identifiers (UMI) for correcting PCR bias. Overall design: Cells were treated with sunitinib, sorafenib, or vehicle control for 48 hours, and gene expression levels of all samples were measured by 3''-DGE and conventional random-primed mRNA-sequencing methods using paired-end reading to obtain the genome-wide expression profiles for each sample.	Co-expression
SRP106038	Topological demarcation by HMGB2 is disrupted early upon senescence entry and induces CTCF clustering across cell types [RNA-seq]	We hypothesized that entry into senescence of different primary human cells can be triggered by one early molecular event affecting the spatial organization of chromosomes. To test this, we combined whole-genome chromosome conformation capture, population and single-cell transcriptomics, super-resolution imaging, and functional analyses applied on proliferating and replicatively-senescent populations from three distinct human cell types. We found a number of genes involved in DNA conformation maintenance being suppressed upon senescence across cell types. Of these, the abundant high mobility group (HMG) B1 and B2 nuclear factors are quantitatively removed from cell nuclei before typical senescence markers appear, and mark a subset of topologically-associating domain (TAD) boundaries. Their loss coincides with obvious reorganization of chromatin interactions via the dramatic spatial clustering of CTCF foci. HMGB2 knock-down recapitulates this senescence-induced CTCF clustering, while also affecting insulation at TAD boundaries. Overall design: Gene expression profiles generated by sequencing total (ribodepleted) RNA from HUVEC (D1-D3), polyA-selected or nascent (factory) RNA from IMR90 (I10 and I79), polyA-selected RNA from MSC (donors A-D), or polyA-selected RNA from control (NTC) and HMGB2-knockdown (HMGB2-KD) HUVEC.	Co-expression
SRP106049	Pluripotent stem cell models of Blau syndrome reveal an IFN-<gamma>-dependent inflammatory response in macrophages	Background: Blau syndrome, or early-onset sarcoidosis, is a juvenile-onset systemic granulomatosis associated with a mutation in Nucleotide-binding oligomerization domain 2 (NOD2). The underlying mechanisms of Blau syndrome leading to autoinflammation are still unclear, and there is currently no effective specific treatment for Blau syndrome. Objectives: To elucidate the mechanisms of autoinflammation in Blau syndrome, we sought to clarify the relation between disease associated-mutant NOD2 and the inflammatory response in human samples. Methods: Blau syndrome-specific induced pluripotent stem cells (iPSCs) lines were established. To precisely evaluate the in vitro phenotype of iPSC-derived cells, the disease-associated NOD2 mutation of iPSCs was corrected using a CRISPR/Cas9 system. We also introduced the same NOD2 mutation into a control iPSC line. These isogenic iPSCs were then differentiated into monocytic cell lineages, and the status of NF-?B pathway and proinflammatory cytokine secretion were investigated. Results: We focused on the signals that upregulate the expression of NOD2, especially IFN-? signaling. IFN-? treatment of NOD2-mutant macrophages induced ligand-independent NF-?B activation and proinflammatory cytokine production. IFN-? treatment acted as a priming signal through the up-regulation of NOD2 protein and recruitment of NOD2 on the basement membrane. Conversely, the production of proinflammatory cytokines by MDP, a ligand of NOD2, was decreased in mutant macrophages. Conclusions: Our data support the significance of ligand-independent autoinflammation in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific iPSC panel provides a useful platform for probing therapeutic and diagnostic clues for the treatment of Blau syndrome patients. Overall design: RNA-sequencing was conducted to identify the genes expressed in reponse to stimulation in different manners between WT and MT cells	Co-expression
SRP106050	RNA-seq of TRRAP knock-down HBEC ALI cultures	Gene expression for shNT, shTRRAP-a, and shTRRAP-b expressing cells at ALI day 4 and day 14 was measured using RNA sequencing technology. Each experimental condition was performed in duplicate with two independent donors. Cells expressing the shRNA constructs (RFP+) were sorted by FACS, and the RNA was isolated and prepared for next generation sequencing analysis.	Co-expression
SRP106077	YY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunction [RNA-seq]	Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth retardation, feeding problems, and various congenital malformations. Our combined clinical and molecular data define the 'YY1 syndrome' as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from person-derived cells, using antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding, with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators. Overall design: Individuals with mutations or deletion in YY1 were identified among patients with idiopathic intellectual disability. LCLs were established from 4 of these patients (1 deletion, 2 missense mutations, and 1 non-sense mutation undergoing non-sense-mediated decay) as well as from unrelated controls, and their transcriptome were compared.	Co-expression
SRP106148	p63 controls the enhancer landscape during keratinocyte differentiation	Here we characterized the transcriptome and epigenome of control keratinocytes during differentiation. Epigenomic analyses showed that the temporal enrichment of p63 motifs in dynamic enhancers underscores the key role of p63 in orchestrating the enhancer landscape during keratinocyte differentiation. The cooperation between p63 and its co-regulating factors, such as RUNX1, is important for the finetuning of gene expression. Overall design: RNA-Seq, H3K4me3 ChIP-Seq and H3K27me3 ChIP-Seq of keratinocytes during differentiation on day0(proliferation), day2(early differentiation), day4(mid differentiation) and day7(late differentiation). RUNX1 ChIP-Seq of keratinocytes at the proliferation stage(day0).	Co-expression
SRP106195	A SRp55-regulated alternative splicing network controls pancreatic beta cell survival and function	Progressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes. Overall design: Five independent preparations of EndoC-ßH1 cells exposed to control (siCTL) or SRp55 (siSR#2) siRNAs	Co-expression
SRP106204	Homo sapiens Transcriptome or Gene expression	Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.	Co-expression
SRP106341	Next Generation Sequencing Analysis of control and siSRSF1 treated RKO cell Transcriptomes	We treated the RKO cells with siSRSF1 or control siRNA for 48 hours. Then we extracted the RNAs and performed the next generation sequencing. By comparing sequcing data from siSRSF1 and contron siRNA treated samples, we profiled the gene expression regulated by siRNA. Overall design: RKO cells mRNA profiles of Control and siSRSF1 treated samples were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP106349	Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD	The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands.  The AHR is expressed in all breast cancer subtypes and it can switch the aggressiveness of breast cancer cells from low to high depending on the ligand that it binds.  Jagged 1 (JAG1) is a NOTCH receptor ligand that is overexpressed in basal-like breast cancer.  JAG1 promotes breast cancer progression in part by increasing the migratory and invasive activity of breast cancer cells (BCCs).  The regulation of JAG1 by AHR in MCF-7 and MDA-MB-231 BCCs by two AHR ligands (TCDD and ITE) was investigated in this report.  TCDD is the prototype AHR ligand, and ITE is a non-toxic endogenous AHR ligand with anti-cancer activity.  Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and cell movement.  Short interfering RNA (siRNA)-directed knockdown of AHR confirmed TCDD-stimulated decreases in JAG1 required AHR expression.  TCDD-induced reductions in JAG1 were inhibited by the AHR antagonist CH-223191.  The endogenous non-toxic AHR ligand ITE also reduced JAG1 by activating AHR in BCCs.  MDA-MB-231 are basal-like BCCs that are highly migratory and invasive, and these cancer cell attributes were significantly inhibited by ITE.  We reduced JAG1 with targeting siRNA, and the outcome mirrored ITE, it suppressed TNBC cell migration and invasive activity.  Collectively, these findings are the first showing that ITE is a tumor-suppressing AHR ligand in TNBC cells in part because it reduces JAG1 expression Overall design: Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq	Co-expression
SRP106453	RNA-seq of MCF7 cell lines after EPIC1 siRNA knockdown	In an integrated analysis of long noncoding RNA (lncRNA) epigenetic alterations in 6475 tumor samples and 781 cancer cell lines, we characterized the epigenetic landscape for 1,006 epigenetically activated and 1,117 epigenetically silenced lncRNAs across 20 cancer types. Combining bioinformatics analyses and functional validation, we identified epigenetically induced lncRNA 1 (EPIC1) as a potential oncogene. EPIC1 is epigenetically activated in 15 cancer types and correlated with poor survival of breast cancer. In EPIC1 hypermethylated cancer cell lines, its expression can be induced by demethylating agent in a time- and dose-dependent manner. Knockdown of EPIC1 inhibits MYC targets expression, leads to cell cycle arrest, inhibits colony formation, and decreases cancer cell growth in vitro and in vivo. Mechanistically, EPIC1 directly interacts with MYC 148-220 aa region through its 5' end. Overexpression of EPIC1 increases MYC targets expression and promotes cell proliferation, which can be abolished by the MYC knockdown. Overall design: MCF-7 cells were transfected with 40 nM siRNAs targeting EPIC1 or a control gene luciferase.  After transfection for 72 hours, total RNA was isolated and RNA libraries were prepared for sequencing.	Co-expression
SRP106457	RNA-seq analysis of scaffold attachment factor A (SAF-A) knockdown in RPE1 cells	Analysis of gene expression by RNA-seq upon siRNA mediated knockdown of scaffold attachment factor A (SAF-A) versus control siRNA in RPE1 cells at 24 hour and 48 hour time points post transfection reveals SAF-A loss does not impact on gene transcription Overall design: Two control RNA-seq libraries where produced (24h and 48h) to compare to the two SAF-A siRNA knockdown RNA-seq libraries, each was a single experimental replicate.	Co-expression
SRP106476	A versatile approach for assessing human stem cell-derived retinal progeny using single cell transcriptomics	To study photoreceptor (PR) production in human pluripotent stem cells (hPSCs), we created a reporter line that robustly labels PRs throughout differentiation. We then performed scRNAseq to define the molecular signature of hPSC-PRs Overall design: We employed both a genetically engineered reporter line and scRNAseq to examine PRs and other NR cell types in serum-free cultures of differentiating hPSC-Ovs (D070* and  D218* samples). Adult* samples are from adult retinal tissue.	Co-expression
SRP106480	Expression Profiling of Cisplatin Resistant SKOV3 Cell Lines vs. Wild Type SKOV3 Cell Lines	Ovarian cancer SKOV3 cells were studied to profile the expression of wild type (WT, Cisplatin Susceptible) cells and Cisplatin Resistant (CR) cells. The goal was to gain insights or to build hypotheses into the mechanisms of Cisplatin resistance in this cell-based model. Overall design: The study included two experimental groups, SKOV3 wild-type cells and SKOV3 Cisplatin resistant cells.  Each group had two biological replicate samples.	Co-expression
SRP106481	Comprehensive single cell transcriptional profiling of a multicellular organism by combinatorial indexing	We developed a combinatorial indexing strategy to profile the transcriptomes of large numbers of single cells or nuclei (Single cell Combinatorial Indexing RNA-seq or sci-RNA-seq). We applied sci-RNA-seq to profile nearly 50,000 cells from C. elegans at the L2 stage, effectively ~56-fold “shotgun cellular coverage” of its somatic cell composition. Overall design: human and mouse cell lines, C.elegans.	Co-expression
SRP106522	High capacity of the endoplasmic reticulum to prevent secretion and aggregation of amyloidgenic proteins	Protein aggregation is associated with neurodegeneration and various other pathologies. How specific cellular environments modulate the aggregation of disease proteins is not well understood. Here we investigated how the endoplasmic reticulum (ER) quality control system handles ß-sheet proteins that were designed de novo to form amyloid-like fibrils. While these proteins undergo toxic aggregation in the cytosol, we find that targeting them to the ER (ER-ß) strongly reduces their toxicity. ER-ß is retained within the ER in a soluble polymeric state, despite reaching very high concentrations exceeding those of ER-resident molecular chaperones. ER-ß is not removed by ER-associated degradation (ERAD) but interferes with ERAD of other proteins. These findings demonstrate a remarkable capacity of the ER to prevent the formation of insoluble ß-aggregates and the secretion of potentially toxic protein species. Our results also suggest a generic mechanism by which proteins with exposed ß-sheet  structure in the ER interfere with proteostasis. Overall design: We have performed RNA-sequencing (RNA-seq) in HEK293 cells transfected with ER-ß or empty vector (EV) control plasmids in triplicate.	Co-expression
SRP106526	Homo sapiens_Cell line_Raw sequence reads	No description.	Co-expression
SRP106527	RNA-seq for 30 HapMap CEU samples	Along with phased genotype data for 30 family trios from HapMap project the data from this experiment allows to perform joint estimation of both genetic and parent-of-origin effects in RNA-seq data of 30 children. This framework allows confirming existing imprinted genes as well as finding additional imprinted genes, including partially imprinted genes. Data was collected from 15 males and 15 females in five runs: 10 individuals sequenced in November 2014 with 150 bp paired-end reads, 10 sequenced twice in December 2014 with 150 bp paired-end reads and 10 sequenced twice in January 2015 with most of the reads sequenced with 150bp paired-end reads and another smaller run with 75bp paired-end reads.	Co-expression
SRP106609	Human RELA haploinsufficiency results in autosomal dominant chronic mucocutaneous ulceration: the transcriptional profile of RelA haploinsufficient patients	The treatment of chronic mucocutaneous ulceration is challenging and only some patients respond selectively to inhibitors of tumor necrosis factor-alpha (TNF-a). TNF-a activates opposing pathways leading to caspase-8-mediated apoptosis as well as NF-kB-dependent cell survival. We investigated the etiology of autosomal dominant mucocutaneous ulceration in a family whose proband was dependent on anti-TNF-a therapy for sustained remission. A heterozygous mutation in RELA (NM_021975: c.559+1G>A), encoding the NF-kB subunit RelA (p65), segregated with the disease phenotype and resulted in RelA haploinsufficiency. The patients' fibroblasts exhibited increased apoptosis in response to TNF-a, impaired NF-kB activation, and defective expression of NF-?B-dependent anti-apoptotic genes. We show that Rela+/- mice have similarly impaired NF-kB activation, develop cutaneous ulceration from TNF-a exposure, and exhibit severe dextran sodium sulfate-induced colitis ameliorated by TNF-a inhibition. These findings demonstrate an essential contribution of biallelic RELA expression in protecting stromal cells from TNF-a-mediated cell death, thus delineating the mechanisms driving the effectiveness of TNF-a inhibition in this disease. Overall design: Total RNA was obtained from human dermal fibroblasts from two patients with RelA haploinsufficiency  (in duplicates) as well as three healthy controls after they were treated with TNF-a for 24 hours and the transcriptional profile of the samples was determined.	Co-expression
SRP106621	Homo sapiens Raw sequence reads	Esophageal squamous cancer cells KYSE30 and KYSE 30 Taxol resistant cells.	Co-expression
SRP106651	Defining a microRNA-mRNA targetome for calcineurin inhibitor induced nephrotoxicity	MicroRNAs have been implicated in the molecular pathogenesis of calcineurin inhibitor nephrotoxicity. However, identification of bona fide physiologically relevent miRNA/mRNA targeting interactions remains a challenge. To define a comprehensive miRNA/mRNA targetome and determine the role of miRNAs in cyclsporine-induced nephrotoxicity, we performed PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) against endogenous Argonaute 2 (AGO2) protein in human proximal tubule cells treated with cyclosporine A (CsA) or vehicle control. Statistically significant mRNA targets of miRNAs in the RNA Inducing Silencing Complex (RISC) complex were identified by PIPE-CLIP, a bioinformatic framework based on a zero-truncated negative binomial model. Further, we determined the total cellular differential expression of miRNAs and mRNAs by conventional deep sequencing methods. Our data indicate that CsA causes specific changes in miRNAs and mRNAs associated with the RISC complex.  A relatively small fraction of the miRNAs and mRNAs identified by total cell RNA-seq were also found in the RISC complex suggesting that changes in targeting by miRs are not necessarily reflected in changes observed in total cellular RNA. Pathway enrichment analysis after integrating miRNA-seq, mRNA-seq, and PAR-CLIP datasets identified canonical pathways specifically under regulation by miRNAs following CsA treatment. Our analysis indicates that miRNAs play an integral role in regulating widespread dysregulation of the proximal tubule cell gene program, contributing to alterations in cell-cell adhesion, integrin-cytoskeleton signaling, and calcium signaling. Analysis of high confidence 3''UTR targets revealed a specific role for miR-101-3p in regulating MAPK signaling which may contribute to the pathogenesis of cyclosporine-induced nephrotoxicity in a calcineurin-independent manner. Overall design: AGO2-PAR-CLIP, mRNA-seq, and miRNA-seq of a human kidney proximal tubule cell line (HK-2) treated with cyclosporine A or vehicle control was performed and sequenced by Illumina HiSeq 2500. Two replicate AGO2-PAR-CLIP samples in each condition and four replicates in each condition for mRNA-seq and miRNA-seq were obtained.	Co-expression
SRP106659	The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks	The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigantype (FPLD2), a lipodystrophic syndrome complicated by early-onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2. Genome modeling in fibroblasts from patients with FPLD2 caused by the lamin A R482W mutation reveals repositioning of the mesodermal regulator T/Brachyury locus towards the nuclear center relative to normal fibroblasts, suggesting enhanced activation propensity of the locus in a developmental model of FPLD2. Addressing this issue, we report phenotypic and transcriptional alterations in mesodermal and endothelial differentiation of induced pluripotent stem cells we generated from a patient with R482Wassociated FPLD2. Correction of the LMNA mutation ameliorates R482W-associated phenotypes and gene expression. Transcriptomics links endothelial differentiation defects to decreased Polycomb-mediated repression of the T/Brachyury locus and over-activation of T target genes. Binding of the Polycomb repressor complex PRC2 to T/Brachyury is impaired by the mutated lamin A network, which is unable to properly associate with the locus. This leads to a deregulation of vascular gene expression over time. By connecting a lipodystrophic hotspot lamin A mutation to a disruption of early mesodermal gene expression and defective endothelial differentiation, we propose that the mutation rewires the fate of several lineages, resulting in multitissue pathogenic phenotypes. Overall design: RNA-seq data pertain to examination of expression profiles of 1) iPS cells derived from patients with Familial Partial Lipodystrophy of Dunnigan-type (FPLD2) with the LMNA p.R482W mutation and 2) FPLD2 patient-derived iPS cells in which the LMNA mutation has been repaired -- both during mesodermal differentiation from day 0 to day 4. ChIP-seq data pertain to ChIP of lamin A/C (LMNA) and lamin B1 (LMNB1) from cultured FPLD2 patient fibroblasts.	Co-expression
SRP106689	Impact of DNA demethylation agents (5-azacytidine or vitamin C) on gene expression in glioblastoma HSR-GBM1 cells	Glioblastoma HSR-GBM1 cells have low mitochondrial DNA copy numbers which is associated with the abnormal DNA methylation patterns. By inducing DNA demthylation using 5azacytidine and vitamin C, HSR-GBM1 cells modulate their mitochondrial copy number and capability of differentiation. Overall design: HSR-GBM1 cell line with three conditions: untreated control group, treated with 5 azacitidine and treated with vitamin C.  3 biological replicates of each condition.	Co-expression
SRP106712	An in vitro human liver model by iPSC-derived parenchymal and non-parenchymal cells	We have established culture systems to generate liver progenitor cells (LPCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) from hiPSCs. Then, we established co-culture system of hiPSC-derived liver cells and performed RNA-seq of hiPSC-derived liver model. Overall design: Liver progenitor cells (LPCs), Liver sinusoidal endothelial cells (LSECs, and hepatic stellate cells (HSCs) were generated from human iPS cells. Expression profile of hiPSC-derived liver model (co-culture system of LPCs and NPCs, N=2) was compared with hiPSC-derived LPCs (N=2) and primary human hepatocytes (N=2) by RNA-seq.	Co-expression
SRP106788	A practical solution for preserving single cells for RNA sequencing	We present a method for histological tissue fixation using dithio-bis(succinimidyl propionate) (DSP), or Lomant''s Reagent, to stabilise cell samples for single-cell transcriptomic applications. Overall design: Single-cell RNAseq from 2,3 and 7 day old DSP fixed cells were compared with RNAseq from fresh cells	Co-expression
SRP106817	Therapeutic targeting of KDM1A/LSD1 in Ewing sarcoma engages the ER-stress response I	The purpose of this study was to define biomarkers of  sensitivty and mechanisms of resistance to the KDM1A/LSD1 inhibtor SP-2509 (HCI-2509) in Ewing sarcoma cell lines. We report that regardless of drug sensitivity all cell lines engage the UPR and ER-stress response following treatment with SP-2509 resulting in apoptotic cytotoxicity. In addition hypersentsitive cell lines shared a common basal transcriptnomic profile, with hypersensitive cell lines signficantly inducing ETS1  which was not observed in sensitive cell  lines. Overall design: 6 Ewing sarcoma cell lines were treated with either vehicle control (DMSO) or the reversible LSD1/KDM1A inhibitor SP-2509 (2uM) for 48hrs. Three SP-2509 hypersensitive (IC50< 300nM)(A673, TC32, TC252) and three SP-2509 sensitive (IC50>900nM) (EWS-502, ES-2 and TC71) cell lines were investigated. Paired RNA from three indpendent experiments per cell line was analyzed.	Co-expression
SRP106846	RBM10 promotes transformation-associated processes in small cell lung cancer and is directly regulated by RBM5	Lung cancers are the leading cause of cancer-related deaths worldwide, with small cell lung cancer (SCLC) being the most aggressive type. At the time of diagnosis, SCLC has usually already metastasized, and an astonishing 95% of patients eventually succumb to the disease. This highlights the need for more effective SCLC screening and treatment options. Interestingly, the earliest and most frequent genetic alteration associated with lung cancers involves a lesion in the region to which the RNA binding protein RBM5 maps. We have recently shown that a decrease in RBM5 expression may be a key step in SCLC development, as RBM5 regulated many transformation-associated processes in SCLC cells. RBM5 is structurally and functionally similar to another RNA binding protein, RBM10. Both proteins have tumor-suppressor properties in a variety of cancer cell lines, and it has been suggested that RBM5 expression can influence RBM10. Due to their similarities, and the recent evidence that RBM10 is mutated in up to 21% of lung cancers, we hypothesized that RBM10 would share RBM5’s tumor-suppressor properties in SCLC. Using transcriptome analysis and functional assays, we show, however, that RBM10’s function was significantly opposite to what we hypothesizedaltered by RBM5; in the endogenously RBM5-null GLC20 SCLC cell line, RBM10 actually promoted cell proliferation and other transformation-associated processes. Using RNA immunoprecipitation followed by next generation sequencing (RIP-Seq) and Western blotting, we demonstrate that RBM5 post-transcriptionally regulated RBM10 expression via direct interaction with specific RBM10 splice variants. We propose a model describing the impact of this interaction on cellular processes. Our results provide evidence that RBM10 expression, in RBM5-null tumors, may contribute to tumor growth and metastasis. Measurement of both RBM10 and RBM5 expression in clinical samples may therefore hold prognostic and/or potentially predictive value.	Co-expression
SRP106855	Chronophin regulates metabolic and transcriptomic features of glioblastoma stem-like cells	High throughput sequencing of poly-A RNA Overall design: Two-condition experiment: Control- and Chronophin shRNA (CIN/PDXP) in glioblastoma stem-like cells	Co-expression
SRP106874	RNA-seq of head and neck cancer cell lines	Transcriptome analysis in head and neck cancer cell lines, FaDu and UMSCC47  with and without 5-aza''2-deoxycytidine(Aza)/trichostatin A(TSA) treatment. Overall design: FaDu and UMSCC47 with and without 5-aza''2-deoxycytidine(Aza)/trichostatin A(TSA) treatment transcriptomes were analyzed by RNA-sequencing.	Co-expression
SRP106875	Integrated time course omics analysis distinguishes immediate therapeutic response from acquired resistance (RNA-Seq)	BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors. To determine the dynamics of these molecular changes, we obtained high throughput omics data weekly during the development of cetuximab resistance in a head and neck cancer in vitro model. RESULTS: An unsupervised algorithm, CoGAPS, was used to quantify the evolving transcriptional and epigenetic changes. Applying a PatternMarker statistic to the results from CoGAPS enabled novel heatmap-based visualization of the dynamics in these time course omics data. We demonstrate that transcriptional changes result from immediate therapeutic response or resistance, whereas epigenetic alterations only occur with resistance. Integrated analysis demonstrates delayed onset of changes in DNA methylation relative to transcription, suggesting that resistance is stabilized epigenetically. CONCLUSIONS: Genes with epigenetic alterations associated with resistance that have concordant expression changes are hypothesized to stabilize resistance. These genes include FGFR1, which was associated with EGFR inhibitor resistance previously. Thus, integrated omics analysis distinguishes the timing of molecular drivers of resistance. Our findings provide a relevant towards better understanding of the time course progression of changes resulting in acquired resistance to targeted therapies. This is an important contribution to the development of alternative treatment strategies that would introduce new drugs before the resistant phenotype develops. Overall design: RNA isolation and sequencing were performed for 23 samples including 2 replicates of parental SCC25 cetuximab sensitive cell line, generations of SCC25 cell lines treated with either cetuximab or PBS over weeks (each week of treatment labeled C1 to C11), and a set of 11 stable cetuximab resistant clones derived from SCC25. Sequencing was performed at the Johns Hopkins Medical Institutions (JHMI) Deep Sequencing & Microarray Core Facility. Total RNA was isolated from a total of 1x106 cells using the AllPrep DNA/RNA Mini Kit (Qiagen, Hilden, Germany) following manufacturer's instructions. The RNA concentration was determined by the spectrophotometer Nanodrop (Thermo Fisher Scientific, Waltham, MA) and quality was assessed using the 2100 Bioanalyzer (Agilent, Santa Clara, CA) system. An RNA Integrity Number (RIN) of 7.0 was considered as the minimum to be used in the subsequent steps for RNAseq. Library preparation was performed using the TrueSeq Stranded Total RNAseq Poly A1 Gold Kit (Illumina, San Diego, CA), according to manufacturer's recommendations, followed by mRNA enrichment using poly(A) enrichment for ribosomal RNA (rRNA) removal. Sequencing was performed using the HiSeq platform (Illumina) for 2X100bp sequencing. Reads were aligned to hg19 with MapSplice16 and gene expression counts were quantified with RSEM17. Gene counts were upper-quartile normalized and log transformed for analysis following the RSEM v2 pipeline used to normalize TCGA RNA-seq data.	Co-expression
SRP106905	The expression of genes encoding palmitoylated proteins in axonal and synaptic compartments is affected in CLN1/PPT1 transfected neuronal cells	CLN1 disease (OMIM #256730) is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product (PPT1) is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 is also related to specific functions in the synaptic compartment. The aim of this study was to recognize molecular signatures and functional modules connected with CLN1. We utilized differentiated SH-SY5Y neuroblastoma cells to overexpress wild type CLN1 (SH-p.wtCLN1) and introduced selected mutations previously detected in CLN1 patients. wtCLN1 and two mutant CLN1- harbouring cell lines were characterized by whole transcriptomic profiling using RNA-seq, to subsequently identify differentially expressed genes (DEGs) and alterations in related neuronal functions. Overall design: Examination of transciptomic profiles of three transfected SH-SY5Y neuroblastoma cell lines, which over-expressed either wtCLN1 or two mutated CLN1 constructs	Co-expression
SRP106948	Single cell RNA sequencing of peanut-responsive T cells	Peanut-responsive T cells from peanut allergic subjects were identified and selected based on CD154 expression after stimulation of peripheral blood mononuclear cells with crude peanut extract for 18h. As controls, polyclonally activated CD4+ T cells from peanut allergic subjects were selected. Additional controls included CD4+CD25+CD127- Tregs from peanut allergic or healthy controls. Single cells were obtained using the C1 system from Fluidigm, and a barcoded library constructed. Sequencing (Illumina) was performed using 100 nt paired end reads. Data on a total of 431 cells was available. The goal of the study was to understand the heterogeneity of the peanut-specific T cell response. Overall design: 212 peanut-responsive T cells from 5 peanut allergic subjects, 122 polyclonally activated T cells from 3 peanut allergic subjects, and 97 Tregs from 4 peanut allergic and 4 healthy controls were obtained.	Co-expression
SRP106954	N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis	RNA modifications are integral to regulation of RNA metabolism. One such abundant mRNA modification is m6A, which impacts various aspects of RNA metabolism including splicing, transport and degradation. Current knowledge about proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe a comprehensive and systematic mass spectrometry-based screening of m6A interactors in various cell types and species. Amongst the main findings, we identified G3BP1 as a protein, which is repelled by m6A and which positively regulates mRNA stability in an m6A regulated manner.  Furthermore, we identified FMR1 as a novel, RNA sequence context dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represents a rich resource for the community and sheds further light on the complex interplay between m6A, m6A interactors and mRNA homeostasis. Overall design: Transcriptome wide profiling of G3BP1 and G3BP2 binding sites and mRNA half-live measurement after G3BP1 overexpression or knockdown.	Co-expression
SRP106993	Downregulation of DDX5/DDX17 and REST	We aimed at analysing the effect of RNA helicases DDX5 and DDX17 and of the transcription factor REST on gene expression in the human SH-SY5Y neuroblastoma cell line (European Collection of Cell Cultures, ECACC), which was cultured as recommended by the supplier. Overall design: siRNA control (2 replicates) + siRNA DDX5/DDX17 (2 replicates) + siRNA REST (2 replicates) + siRNA REST/DDX5/DDX17 (2 replicates)	Co-expression
SRP107004	Anti-inflammatory effect of indoleacrylic acid (IA)	Host factors in the intestine, such as mucus secretion, play an important role in selecting for the colonization of bacteria that contribute to intestinal health. Here we characterized the capability of commensal species to cleave and transport mucin-associated monosaccharides and found that several members of the Clostridiales order can utilize intestinal mucins as an energy source. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster that enables the production of the tryptophan metabolite indoleacrylic acid (IA), which we show has a beneficial effect on intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples revealed that the genetic capability of microbes to utilize mucins and metabolize tryptophan was diminished in patients with inflammatory bowel disease. Our data suggest that stimulating the production of IA to promote anti-inflammatory responses could have therapeutic benefit. Overall design: Isolated hPBMCs treated with IA or 0.1% DMSO followed by LPS stimulation. Comparisons of interest: 490_DMSO_vs_490_IA 1685_DMSO_vs_1685_IA 406_DMSO_vs_406_IA ALL_DMSO_vs_ALL_IA	Co-expression
SRP107025	Expression profile of Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP-NET)	Expression profile of human GEP-NET tumors, including 113 fresh frozen biopsies of primary and metastatic tumours originating from pancreas (P-NET, 83 primary and 30 metastasis), 81 from small intestine (SI-NET, 44 primary and 37 metastasis), and 18 from rectum (RE-NET, 3 primary and 15 metastasis). Overall design: 212 GEP-NET samples with cellularity >70% were analyzed. Total RNA was isolated and RNA integrity assayed by a 2100 Bioanalyzer (Agilent Technologies). High-quality total RNA samples, with RIN (RNA integrity number) above 7, were processed by TruSeq library preparation for RNA-Seq profiling (Illumina). For each sample, a minimum of 30 million 100bp single-end reads or 90 million 100bp paired-end reads were sequenced on the Illumina HiSeq2500 platform. RNA-Seq reads were mapped to the Homo sapiens assembly 19 reference genome, using Bowtie. Reads mapping to known genes, based on Entrez Gene identifiers, were then counted using the GenomicFeatures R-system package (Bioconductor).	Co-expression
SRP107042	Gene expression changes upon drug withdrawal (A375/451Lu cell lines)	In this study we investigate the mechanism of drug addiction Overall design: Drug was withdrawn from several cell lines, and gene expression profiling was performed over time	Co-expression
SRP107043	Gene expression changes upon drug withdrawal (Mel888 cell line)	In this study we investigate the mechanism of drug addiction Overall design: Drug was withdrawn from wt / MAPK1 KO / JUNB KO double drug resistant mel888 (DR Mel888) cells, and gene expression profiling was performed upon drug withdrawal	Co-expression
SRP107072	IsoHD RNA-sequencing	Transcriptomic profiling using a human isogenic Huntington disease (IsoHD) pluripotent stem cell allelic panel	Co-expression
SRP107094	Homo sapiens Transcriptome or Gene expression	The goal of the study is to study how ADAR1 and the ADAR1 isoform ADAR1p150 edit mRNAs and what the functional consequences on gene expression is.	Co-expression
SRP107119	Transcriptome analysis of HPV transfected human trophoblast cells (JAR)	HPV is known to infect trophoblast cells. Downstream effects are however not studied well. This study aimed to investigate changes in the transcriptome of human trophoblasts after transfection of HPV16 E6 and E7, both seperately and in combination. The chorioncarcinoma cell line JAR was used as a model system. The overall goal was to investigate possible effects of HPV on pregnancy outcome after placental infection with HPV.	Co-expression
SRP107129	Human salivary adenoid cystic carcinoma cell line raw sequence reads with NOTCH1 upregulation	To explore the molecular mechanism underlying the effects of NOTCH1 on salivary adenoid cystic carcinoma cell growth and metastasis.	Co-expression
SRP107189	Whole transcriptome profile of citrulline-specific B cells from patients with rheumatoid arthritis	Although the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. By utilizing whole transcriptome profiling of human citrulline-specific B cells, we identified diverse inflammatory pathways, cytokines and transcriptional programs that define the biological role of B cells in RA and identify targets for drug intervention. Significantly, we identified the restricted expression of IL15Ra on citrulline-specific B cells and also demonstrated that B cells can express the epidermal growth factor amphiregulin (AREG) under inflammatory conditions. Mechanistically, we demonstrate that AREG has a direct impact on the cellular effectors of RA; it increases the proliferation and invasiveness of RA fibroblast-like synoviocytes (FLS) and synergizes with ACPA to enhance differentiation of osteoclasts. Overall, we present the first comprehensive transcriptome profile of autoreactive B-cell in an autoimmune disease, which can serve as a foundational dataset for studying the multi-faceted roles of B cells in autoimmune diseases Overall design: Whole transcriptome profile of CCP-specific B cells (RA-CCPPOS) with that of CCP-negative B cells (RA-CCPNEG) from the same donor and hemagglutinin-specific (HAPOS) B cells from healthy individuals elicited upon vaccination with seasonal influenza virus	Co-expression
SRP107198	Synergistic activity and heterogeneous acquired resistance of combined MDM2 and MEK inhibition in KRAS mutant cancers	There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers and colorectal carcinomas that harbor wild-type TP53. The combination of pimasertib (MEK inhibitor) + SAR405838 (MDM2 inhibitor) was synergistic and induced the expression of PUMA and BIM, led to apoptosis and growth inhibition in vitro, and tumor regression in vivo. Acquired resistance to the combination commonly resulted from the acquisition of TP53 mutations, conferring complete resistance to MDM2 inhibition. In contrast, resistant clones exhibited marked variability in sensitivity to MEK inhibition, which significantly impacted sensitivity to subsequent treatment with alternative MEK inhibitor-based combination therapies. These results highlight both the potential promise and limitations of combining MEK and MDM2 inhibitors for treatment of KRAS mutant NSCLC and CRC. Overall design: A427, DV-90, H1944, H358, LU-99A, SW1573 cells treated with 10 nM, 100 nM, 1000 nM pimasertib, SAR405838 or combination (3 replicates each)	Co-expression
SRP107224	Treatment of SW480 colon cancer cell induced xenografts with AZD and DBZ	RNASeq data from replicates with and without treatment of SW480 colon cancer cells Overall design: 3 biological replicates of xenografts treated with vehicle, AZD or DBZ	Co-expression
SRP107230	Identification of PAX7-induced transcriptional changes and PAX7 genomic binding during skeletal myogenic differentiation of H9 embryonic stem cells	Skeletal myogenic commitment of human pluripotent cells can be achieved by doxycycline-inducible expression of the transcription factor PAX7. To gain further insights on PAX7 function during this process, we performed a time course whole transcriptome analysis of differentiating H9 human embryonic stem cells from doxycycline-treated and untreated cultures. In addition, we identified the genomic binding of PAX7 in one of the selected time point (referred as PAX7+ proliferating myogenic progenitors). Overall design: Gene expression profiling was performed on biological replicates from differentiating H9 cells at the following time points: PAX7+ mesodermal cells (day 14), PAX7+ proliferating myogenic progenitors (approximately day 23), and differentiated myocytes (differentiation stage – around day 30; 7 days in the absence of PAX7 induction). Since PAX7 expression is doxycycline inducible, we also collected uninduced control samples at the same time points (termed mesodermal cells for day 14 and proliferating cells for day 23). PAX7 genomic binding was assessed in day 23 dox-treated cultures.	Co-expression
SRP107257	RNA_sequencing in HMECs model	Understanding the transcriptome change in early breast carcinogenesis	Co-expression
SRP107319	Transcriptomic analysis in breast cancer cell lines after CDK4/6 inhibition	We measured changes in expression of 20,812 genes in human breast cancer cell lines after treatment with abemaciclib Overall design: Examination of changes in gene expression in 3 cell lines, in triplicate	Co-expression
SRP107321	Transcriptomic analysis in PDX mammary carcinoma after CDK4/6 inhibition	We measured changes in expression of 20,812 human genes PDX tumors growing in mice after treatment with abemaciclib Overall design: Examination of changes in gene expression	Co-expression
SRP107322	ARS2 is a general suppressor of pervasive transcription [RNAseq]	Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome-wide. We show that ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II (RNAPII) at protein-coding (pc) genes, Moreover, our results reveal a general role of ARS2 in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication dependent histone (RDH)-, promoter upstream transcript (PROMPT)- and enhancer RNA (eRNA)-loci. Depletion of the ARS2 interaction partner ZC3H18 mimics the ARS2 depletion, although to a milder extent, whereas depletion of the exosome core subunit RRP40 only impacts RNA abundance post-transcriptionally. Interestingly, ARS2 is also involved in transcription termination events within first introns of pc genes. Our work therefore establishes ARS2 as a general suppressor of pervasive transcription with the potential to regulate protein-coding gene expression. Overall design: RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control), ARS2(SRRT), ZC3H18 and CBP80. Total RNA was collected for each condition in triplicates.	Co-expression
SRP107324	Simultaneous detection and relative quantification of coding and non-coding RNA using a single sequencing reaction	The ability to compare the abundance of one RNA molecule to another is a crucial step for understanding how gene expression is modulated to shape the transcriptome landscape. However, little information is available about the relative expression of the different classes of coding and non-coding RNA or even between RNA of the same class. In this study, we present a complete portrait of the human transcriptome that depicts the relationship of all classes of non-ribosomal RNA longer than sixty nucleotides. The results show that the most abundant RNA in the human rRNA-depleted transcriptome is tRNA followed by spliceosomal RNA. Surprisingly, the signal recognition particle RNA 7SL by itself occupied 8% of the ribodepleted transcriptome producing a similar number of transcripts as that produced by all snoRNA genes combined. In general, the most abundant RNA are non-coding but many more protein coding than non-coding genes produce more than 1 transcript per million. Examination of gene functions suggests that RNA abundance reflects both gene and cell function. Together, the data indicate that the human transcriptome is shaped by a small number of highly expressed non-coding genes and a large number of moderately expressed protein coding genes that reflect cellular phenotypes. Overall design: RNA was isolated from SKOV3ip1 and INOF human cell lines and selected with different methods. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.	Co-expression
SRP107327	IL-6/Stat3-Dependent Induction of Distinct, Obesity-Associated Natural Killer Cells Deteriorates Energy and Glucose Homeostasis	Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes the expansion of interleukin-6 receptor (IL6Ra)-expressing NK cells, which also express a number of other myeloid lineage genes such as the colony-stimulating-factor 1 receptor (Csf1r). Selective ablation of Csf1r- expressing NK cells prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of myeloid signature NK cells, protects from obesity, insulin resistance and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity, correlate with markers of systemic low-grade inflammation and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on IL-6/Stat3-dependent formation of distinct NK cells, which may provide a novel target for the treatment of obesity, metaflammation-associated pathologies and diabetes. Overall design: RNA sequencing of two types of NK cells from mouse and human (IL6Ra negative NK cells vs. IL6Ra positive NK cells) and mouse organs (IL6Ra_NKdel vs. IL6Ra_NKflox)	Co-expression
SRP107337	Transcriptomic analysis of purified human cortical microglia reveals age-associated changes	Purpose: Microglia are essential for central nervous system (CNS) homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here, we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. We identified an age-associated gene signature in human microglia that was enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression, and actin disassembly. Methods: mRNA profiles of 39 human microglia samples isolated from subjects with intact cognition, 16 corresponding superior parietal cortex tissue and 10 epilepsy surgical samples were generated in a Illumina HiSEQ 2500 sequencer. mRNA profiles of 6 parietal cortex from mice were prepared with a Quantseq 3'mRNA-Seq kit (Lexogen, USA). Reads were aligned to the hg38 assembly of the human genome using STAR and quantified at the gene level by featureCounts. Differential expression between whole brain tissue, surgical samples and isolated microglia was assessed with limma. Results: Overall, genes expressed by human microglia are similar to those in mouse, including established microglia genes CX3CR1, P2YR12, and ITGAM/CD11B. However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fc-gamma? and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression, and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently. Conclusions: Here we present the an extensive human microglia gene expression profile. Critical differences with mouse microglia, especially in the context of aging, were observed which highlight the necessity to independently study human microglia. These data and analyses serve as a starting point to address human-specific microglia genes and functions under physiological and neuropathological conditions. Overall design: mRNA profiles of 39 human microglia samples isolated from subjects with intact cognition, 16 corresponding superior parietal cortex tissue and 10 epilepsy surgical samples were generated in a Illumina HiSEQ 2500 sequencer. mRNA profiles of 6 parietal cortex from mice were prepared with a Quantseq 3'mRNA-Seq kit (Lexogen, USA).	Co-expression
SRP107366	RNA sequencing results for liver	Quantitative prediction algorithm of the differentiation status in liver-specific cultures	Co-expression
SRP107383	Human serum and heparin-free platelet lysate as appropriate xeno-free alternatives for production of human MuStem cell batches	Purpose: The population of muscle-derived stem cells called MuStem cells is presented as promising candidate for cell-based therapy of muscle diseases. To validate if this agent can be really presented as therapeutic product and so to be eligible to a future clinical use, it is now required to demonstrate beforehand an efficacy with cells prepared in compliance with good manufacturing practices (GMPs). The aim of the current study was to evaluate the use of two xeno-free blood derivatives corresponding to human serum (HS) and human platelet lysate (hPL) as alternatives to controverted but until now used fetal bovine serum (FBS) for isolation and expansion of human MuStem (hMuStem) cells. Methods: A comparative study was performed with hMuStem cells isolated and in vitro expanded by using commercially available HS and hPL to determine its impact on their proliferation rates, clonogenicity, myogenic commitment level and oligopotency with regard to results obtained under FBS-based medium. Also, their respective phenotype and global gene expression patterns were investigated by flow cytometry and high throughput 3' digital gene expression RNA-sequencing in order to define a possible differential impact of the human nutrients tested. Results: Comparatively to FBS-based medium, use of HS- and hPL-supplemented ones efficiently supported long-term proliferation of hMuStem cells and enhanced clonogenicity, without main modification of their expression profile and allowing besides limiting the supplementation in growth factors. In vitro differentiation assay combined to transforming growth factor ß1 (TGF-ß1)-depletion experiments showed a lower myogenic commitment level as well as fusion ability of hMuStem cells when cultured with hPL-based medium according to a TGF-ß1-independent process. Use of hPL-derived 3D hydrogel or fibrinogen-depleted hPL demonstrated that heparin-free hPL derivatives maintain consequent myogenic differentiation potential. In addition, the reduced myogenicity was shown to be rapidly reversible following replacement of hPL by HS or fibrinogen-depleted hPL. Conclusions: All together, our original findings position HS and hPL as efficient and suitable alternatives to FBS for preparation of hMuStem cell batch in compliance with GMPs. Overall design: mRNA profile of hMuStem cells cultured in hPL was compared to the mRNA profile of hMuStem cells cultured in HS. The profiles were generated in triplicates using the 3''DGE-Seq technology.	Co-expression
SRP107388	Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency [RNA-Seq]	Recently, we reported that bacterial incorporation induces cellular transdifferentiation of human fibroblasts. However, the bacterium-intrinsic cellular- transdifferentiation factor remained unknown. Here, we found that cellular transdifferentiation is caused by ribosomes. Ribosomes, isolated from both prokaryotic and eukaryotic cells, induce the formation of embryoid body-like cell clusters. Numerous ribosomes are incorporated into both the cytoplasm and nucleus through trypsin-activated endocytosis, which leads to cell-cluster formation. Although ribosome-induced cell clusters (RICs) express several stemness markers and differentiate into derivatives of all three germ layers in heterogeneous cell populations, RICs fail to proliferate, alter the methylation states of pluripotent genes, or contribute to teratoma or chimera formation. However, RICs express markers of epithelial–mesenchymal transition without altering the cell cycle, despite their proliferation obstruction. These findings demonstrate that incorporation of ribosomes into host cells induces cell transdifferentiation and alters cellular plasticity. Overall design: RNA-seq was conducted for ribosome-induced cell clusters (RICs) at day 0, 2, 5, 8, 11, 14.	Co-expression
SRP107747	Specific labeling of stem cell activity in human colorectal organoids using an ASCL2-responsive minigene	Organoid technology provides the possibility to culture human colon tissue and patient-derived colorectal cancers (CRC) while maintaining all functional and phenotypic characteristics. Labeling of human colon stem cells (CoSCs), especially in normal and benign tumor organoids, is challenging and therefore limits usability of multi-patient organoid libraries for CoSC research. Here, we developed STAR (STem cell Ascl2 Reporter), a minimal enhancer/promoter element that reports transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC fate. Among others via lentiviral infection, STAR minigene labels stem cells in normal as well as in multiple engineered and patient-derived CRC organoids of different stage and genetic make-up. STAR revealed that stem cell driven differentiation hierarchies and the capacity of cell fate plasticity (de-differentiation) are present at all stages of human CRC development. The flexible and user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research on human adult stem cell biology. Overall design: Cells from different colon organoid types were FACS sorted for stem STemness Ascl2 Reporter activity for transcriptome profiling by RNA-seq.	Co-expression
SRP107780	UPF1/SMG7-dependent MicroRNA-mediated Gene Regulation	A majority of metazoan mRNAs are under microRNA (miRNA)/Argonaute (Ago)-mediated control of RNA stability at the post-transcriptional level. Although the molecular mechanism of the miRNA-mediated repression of target mRNAs through Ago/TNRC6 pathway have been largely elucidated, however, the existence of alternative TNRC6-independent miRNA-mediated post-transcriptional gene regulation pathway remains unknown. Here, we suggest that endogenous miRNAs (endo-miRNAs) can downregulate the target mRNAs via the alternative molecular pathway, Ago-associated UPF1/SMG7, core mediators of nonsense-mediated mRNA decay. Global analyses of mRNAs in a response to UPF1 RNA interference in miRNA-deficient cells reveal that 3'UTR-length-dependent mRNA decay by UPF1 requires endo-miRNA targeting via CUG motif. The repression of miRNA targets is more additively or synergistically accomplished by combination of Ago2 and UPF1 through UPF1-associated SMG7, recruiting CCR4-NOT deadenylase complex, in TNRC6-independent manner. We expect that the new miRNA-mediated mRNA decay pathway enables the miRNA targeting to become more predictable and expand the miRNA-mRNA regulatory network. Overall design: Examination of 11 different knockdown condition in HeLa cell type	Co-expression
SRP107789	RNA-seq transcriptonal profiling in human K562 cells with or without dCas9 and sgRNAs	Cis-regulatory elements (CREs) are commonly recognized by correlative chromatin features, yet the molecular composition of the vast majority of CREs in chromatin remains unknown. Here we describe a CRISPR affinity purification in situ of regulatory elements (CAPTURE) approach to unbiasedly identify locus-specific chromatin-regulating protein complexes and long-range DNA interactions. Using an in vivo biotinylated endonuclease-deficient Cas9 protein and sequence-specific guide RNAs, we show high-resolution and selective isolation of chromatin interactions at a single copy genomic locus. Purification of human telomeres using CAPTURE identifies known and new telomeric factors. In situ capture of individual constituents of the enhancer cluster controlling human ß-globin genes establishes evidence for composition-based hierarchical organization of enhancer structure. Furthermore, unbiased analysis of chromatin interactions at disease-associated cis-elements and developmentally controlled super-enhancers reveals spatial features causally regulate gene transcription. Thus, comprehensive analysis of locus-specific regulatory composition provides mechanistic insight into genome structure and function in development and disease. Overall design: RNA-seq was performed to determine the effects on global gene expression in K562 cells stably expressing Flag-bio-tagged dCas9 and sgRNAs targeting several regulatory elements within the ß-globin cluster (sgHS2, sgHBG and sgHS1-5) or the non-targeting sgRNA (sgGal4).	Co-expression
SRP107791	CD133hi, Notchhi, DP (double positive) and DN (double negative) in GBML8 and GBML20, both patient-derived glioblastoma tumorsphere cultures	CD133hi, Notchhi, DP and DN cells were FACS-isolated from GBML8 and GBML20 cultures and analyzed with RNA-seq, in order to find cell type-specific gene signatures. Overall design: CD133hi, Notchhi, DP and DN cells were FACS-isolated and subjected to RNA isolation and RNA-seq. The experiment represents averaged data of 2 independent FACS isolations from GBML8 and 1 isolation from GBML20.	Co-expression
SRP107802	Selectively targeting bromodomain and extraterminal proteins for degradation as a novel anti-glioblastoma strategy [RNA-seq (time course)	Purpose: Characterization of mechanism and vulnerability of BET protein dependency in GBM cells.  Methods: ChIP-seq and RNA-seq were performed on GBM cells at different time points following treatment with dBET6, a novel BET protein degrader. The transcriptome responses of parental and JQ1-resistant U87 cells to JQ1 and dBET6 were compared as well.     Result: This study reveals crucial functions of BET proteins and provides the rationale and therapeutic merits of targeted degradation of BET proteins by dBET6 in GBM. Overall design: RNA-Seq of U87 cells in response to dBET6 at different time points; RNA-Seq of NNI24 patient-derived GBM propagating cells in response to dBET6.	Co-expression
SRP107817	A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts	Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs) has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.	Co-expression
SRP107853	Microvesicle-mediated delivery of miR-1343: impact on markers of fibrosis	We previously identified miR-1343 as a potent repressor of TGF-b signaling and fibrosis through the direct attenuation of both canonical TGF-b receptors. Here, we build upon our previous findings to better characterize the function of endogenous miR-1343 in normal biology. CRISPR/Cas9 techniques were used to delete the miR-1343 locus in A549 lung epithelial cells. Loss of miR-1343 was found to impact several processes and genes implicated in fibrosis and known to be TGF-b pathway effectors. These responses are opposite to those we observed previously when miR-1343 was overexpressed in the same cell type. Overall design: mRNA profiles of 3 independent deletion clones and 3 non-targeted (NT) clones from the same experiment, as well as 3 replicates of non-clonal A549 cells.	Co-expression
SRP107857	TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency	Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naive and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency. Furthermore, we discovered that TRIM28 regulates paternal ICR methylation and chromatin accessibility in the primed state, with no effects on maternal ICRs. Taken together, our study shows that abnormal TE expression is tolerated by self-renewing human pluripotent cells, whereas germline competency is not. Overall design: Examination of transcription, DNA methylation and chromatin accessibility of human ES cells for wild type and Trim28 knockout.	Co-expression
SRP107867	MDA5 effect during HRV and RSV infection in respiratory epithelial cells.	A549 cells that had been transfected 48 hours earlier with siRNA to MDA5 or non-specific negative control siRNA, were uninfected or infected for 6, 12, 24, and 48 hours with HRV-B14 or RSV. For each time point, infections were performed in triplicate. Total cellular RNA were isolated using RNeasy Mini Kit (Qiagen). Multiplexed RNA libraries were prepared using the Truseq RNA sample prep kit (Illumina). Libraries were sequenced on a HiSeq 2000 Sequencing System (Illumina) to produce 50 bp single end reads. Sequencing reads were aligned with ELAND to the human reference genome version hg19.	Co-expression
SRP107875	ZFR coordinates crosstalk between RNA decay and transcription in innate immunity	Identification of RNAs differentially expressed upon ZFR knockdown in THP1 and HEK-293TO cells. Overall design: Paired-end RNA-Seq on THP1 cells treated with ZFR-specific or control shRNAs and HEK-293TO cells treated with ZFR-specific or control siRNAs.	Co-expression
SRP107901	Identification of reference genes for normalizing the levels of circulating RNA transcripts in pregnant women based on whole-transcriptome data	For quantification of RNA transcript using RT-qPCR data, normalization of the data by the internal control reference genes is often required. However, it has been demonstrated that a proper choice of reference genes is highly dependent on the tissues or cells being investigated. It has also been known that reference genes are highly specific for a particular experimental model, and validation for each situation, on an individual basis, is essential. Currently, there is a lack of data on reference genes that are suitable for normalization of RT-qPCR data in the blood circulation of pregnant women. The objective of this study is to identify reference genes in maternal blood based on the whole-transcriptome data of 19 maternal whole blood samples, sequenced on the HiSeq-4000 platform in two libraries (technical replicates) per sample.	Co-expression
SRP107921	Preliminary Report of Transplantation of Human Fetal Retinal Pigment Epithelial Cells on Age-related Macular Degeneration Patients	Background:  Different sources of retinal pigment epithelial cells (RPE) were transplanted to treat Age-related Macular Degeneration. But the mechanisms of therapeutic effect are unclear till now, and GMP level fetal RPE (fRPE)   need further evaluation for treatment. Methods: Modified GMP fRPE primary culture system was founded. These RPE were tested on Mer-/- mice and sodium iodate induced retinopathy primate model for safety and feasibility. Five dry-AMD patients and one Stargardt's Disease patient were enrolled, and received sub retinal transplantation of hfRPE with three dosage cohorts(1×105,2×105,5×105). ETDRS, optic coherent tomographic imaging (OCT), color fundus (CF), fluorescent angiography (FFA), autofluorescence, microperimetry examination were conducted before surgery, and during follow-up period. The studies are registered with ClinicalTrials.gov, numbers NCT02868424. Findings: GMP level fRPE from modified primary culture system has good proliferative capacity and full functions of RPE in vitro. Human fetal RPE can survive long period in sub-retinal space in mice and monkey models of RPE degeneration, and showed therapeutic effect on Mer-/- mice. During our nine-months follow-up of six clinical cases, no endophthalmitis, no vitreous hemorrhage, no proliferative vitreoretinopathy was observed, and epiretinal memrbrane was the only complication. Among the patients, four of them achieved increase in  ETDRS visual acuity (VA), of which the greatest improvement was 18 letters, and one kept steady while the other had 9 letters decreased VA. Color fundus photos and OCT demonstrated the existence of the fRPE cells, and improved retinal sensitivity as well as the changes observed in auto fluorescence also can tell the situation of grafted cells to some extent. Interpretation: GMP level fRPE from modified culture system exhibited satisfactory results on in vitro and preclinical experiments. Preliminary clinical trial proved safety of the fRPE subretinal transplantation, and substantiated it a promising therapy for dry AMD including the converted from exudative AMD. Overall design: Retinal mRNA profiles of human fetal RPE cells cultured in xeno-free medium were conducted from 3 aborted fetus.	Co-expression
SRP107927	Interleukins 12 and 15 induce cytotoxicity and early natural killer cell differentiation in type 3 innate lymphoid cells	Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. While their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines IL-12 and IL-15, and correlates with expression of the master transcription factor of cytotoxicity eomesodermin (Eomes). As revealed by transcriptome analysis and flow cytometric profiling, differentiated ILC3s express CD94, NKG2A, NKG2C, CD56 and CD16 among other NK cell receptors, and possess all components of the cytotoxic machinery. These characteristics allow them to recognize and kill leukemic cells. Therefore, ILC3s can be harnessed for cytotoxic responses via differentiation under the influence of proinflammatory cytokines. Overall design: Expression profiling (RNA-Seq) of NKp44+ innate lymphoid cells (ILC) derived from pediatric tonsils and spleens of NOD SCID-/-?c-/- mice reconstituted with human hematopoietic progenitor cells.  Three experiental groups were compared: not cultured ILCs, ILCs cultured with IL-2 and IL-7, and ILCs cultured with IL-12 and IL-15.	Co-expression
SRP107943	Dual inhibition of HDMX and HDM2 as a Therapeutic Strategy in Leukemia	The p53 protein is the most frequently inactivated tumor suppressor in human cancer. While p53 mutations are found in 50% of all cancers, the p53 pathway can also be suppressed by its interaction with endogenous inhibitors HDMX and HDM2, which are frequently overexpressed in patients with acute myeloid leukemia and other cancers. Thus, pharmacological disruption of both these interactions is an attractive strategy to restore p53-dependent tumor suppressor activity in AML with wild type P53. Strategies targeting HDM2 have recently generated promising results; however, cancer cells are still left vulnerable to p53 inhibition by HDMX, particularly in cancers such as leukemia that overexpress HDMX. In this study, we demonstrate that dual HDMX/HDM2 inhibition using a stapled alpha-helical peptide (ALRN-6924), which has recently entered clinical testing, leads to striking anti-leukemic effects.  ALRN-6924 robustly activates p53-dependent transcription at the single cell and single molecule level, and exhibits biochemical and molecular biological on-target activity in leukemia cells in vitro and in a patient who received ALRN-6924 treatment. Dual HDMX/HDM2 inhibition by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and apoptosis in cell lines and primary AML patients' cells, including in leukemic stem cell-enriched populations, and disrupts functional clonogenic and serial replating capacity. Furthermore, ALRN-6924 leads to significantly improved survival in an AML xenograft model in vivo. At the molecular level, dual HDMX/HDM2 inhibition leads to global transcriptional activation of p53-dependent pathways in leukemia cells. Our study provides insight into the effects of dual HDMX/HDM2 inhibition and proof-of-concept for ALRN-6924 as a novel therapeutic approach in AML and other cancers with high HDMX levels. Overall design: Total mRNA expression profiles of vehicle (1:10 DMSO) or 1 uM ALRN-6924 treated AML cells (6 hours) were generated by deep sequencing, in triplicates, using the Illumnia HiSeq 2500 instrument.	Co-expression
SRP108020	Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment	The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes.  In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.  Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models.  Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects.  Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects.  RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals.  Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis.  As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients. Overall design: Single-end 50 bp RNA-seq of MM.1S myeloma cell line either grown alone in monoculture, MM.1S isolated after 24 hr co-culture with immortalized HS5 bone marrow stromal cells, or HS5 bone marrow stromal cells grown alone	Co-expression
SRP108025	Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses	Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the pediatric, elderly, and immune compromised populations. A gap in our understanding of hRSVdisease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralog of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 WT or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I IFN responses, suppression of dendritic cell maturation, and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV associated morbidity and mortality. Overall design: 12 samples where analysed. A549 cell line was infected with mock, hRSV or mutated hRSV virus. Samples are: control mock-infected (2 replicas), hRSV wild-type NS1 infected (3 replicas), hRSV NS1 1-118 infected (3 replicas), hRSV NS1 L132A/L133A infected (2 replicas) and hRSV NS1 Y125A infected (2 replicas). Libraries was prepared for 96 h.p.i.	Co-expression
SRP108032	Cytokine Stimulation of PTPN2-deleted cancer cells	PTPN2 was deleted from a selection of murine and human cancer cells using CRISPR/Cas9. The loss-of-function phenotype was assessed in vitro with cytokine stimulation or vehicle control. Overall design: In order to determine the effect of PTPN2-inhibition of interferon signalling, Cas9-expressing murine (B16 melanoma) and human (A375, A549, HT29, MelJuSo) cancer cells were infected with lentivirus containing guide RNA (sgRNA) against Ptpn2 or a non-targeting sequence. After Ptpn2 deletion was verified, the cell lines were treated with vehicle control (PBS with 0.1% BSA), interferon-beta (IFNb), interferon-gamma (IFNg), or tumor necrosis factor (TNFa), alone or in combination, and transcriptionally profiled by directional, paired-end RNAseq after a 48 hour stimulation.!Series_overall_design = Please note that ''Bro3'' and ''Bro4''  refer to non-targeting guides provided by the Broad Institute. Please note that ''Bro3'' and ''Bro4''  refer to non-targeting guides provided by the Broad Institute.	Co-expression
SRP108035	Subtle asymmetry of gene expression in embryonic and foetal human brains	Note: this project is a combination of the data deposited here in  GEO and data made available by HDBR in ArrayExpress under E-MTAB-4840. Summary: Brain asymmetry in humans, both structurally and functionally, is observed very early during development, and is important for healthy development. Using RNA sequencing, we investigated gene expression profiles of left and right sides of various brain structures in human foetuses aged 5 to 13 weeks post conception. All brain structures showed significant differences between the expression profiles of left and right sides. The differences partly correlated with gene expression changes with age, suggesting left/right differences in maturation rate. In particular on the faster side (right for cerebral cortex, left for all other investigated tissues), different tissues were lateralised for tissue-specific processes. In the youngest forebrain (5.5 weeks), KCTD12, SNAI1 and GATA1 were significantly right-lateralised. SNAI1 is involved in visceral asymmetry in vertebrates, and KCTD12 is important in lateralisation of fish brains. In the youngest midbrain, SOX1 was significantly left-lateralised. Overall design: For the part of the project for which data are deposited here, six human embryos in Carnegie stage 15 or 16 were studied. Left and right side of the midbrain and left and right side of the forebrain were dissected, and RNA sequenced. Differential expression analysis per tissue to find left/right differences (paired analysis by embryo).	Co-expression
SRP108038	The stress granule transcriptome reveals principles of mRNA accumulation in stress granules.	Stress granules are mRNA-protein assemblies formed on nontranslating mRNAs. Stress granules are important in the stress response, related to neuronal mRNP granules, and aberrant stress granules contribute to some degenerative diseases.  By RNA-Seq and single molecule FISH, we describe the stress granule transcriptome in both yeast and mammalian cells. This reveals that while essentially every mRNA, and some ncRNAs, can be targeted to stress granules, the efficiency of targeting can vary from <1% to 73%. mRNA accumulation in stress granules is increased by longer coding regions, poor translatability, and correlates with some RNA binding proteins. Standardizing the RNA-Seq analysis by single molecule FISH allows a quantitative description of the general and stress gra­nule transcriptome. Approximately 15% of the bulk mRNA molecules accumulate in stress granules suggesting their effect will be limited primarily to subsets of mRNAs highly accumulating in stress granules Overall design: To determine the RNAs in mammalian stress granules, we purified and performed RNA-Seq in triplicate on SG cores from U-2 OS cells isolated following 60' of arsenite exposure, referred to as SGRNA. For each sample, 5% of the lysate was extracted for RNA-Seq on the total RNA population, referred to as TotalRNA.  To determine the RNAs in yeast stress granules, we purified and sequenced the mRNAs within SG cores from Saccharomyces cerevisiae after induction of SGs by sodium azidefor 30 minutes. SGRNA and TotalRNA were isolated from three independent biological replicates and sequenced.	Co-expression
SRP108039	Single-cell RNA-seq following APE1/Ref-1 knockdown in Pancreatic Ductal Adenocarcinoma	APE1 was knocked down using siRNA in low passage patient-derived PDAC cells and the resulting cells, along with control cells were analysed using scRNA-seq to identify differentially expressed genes and pathways as a result of APE1 knock-down. Overall design: siRNA APE1 knock-down versus scrambled control, The SMARTer system was used to generate cDNA from 96 captured single cells.  Unstranded 2x100bp reads were sequenced using a HiSeq2500 on rapid run mode in 1 lane.	Co-expression
SRP108059	Maturing an Enteric Nervous System in Human Intestinal Organoid-derived Tissue-Engineered Small Intestine	Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIO). However, HIO-TESI fails to develop an ENS. In a previous report of combined HIO with additional human enteric neural crest cells (ENCC), an ENS was established but lacked maturity. The purpose of our study is to establish a mature ENS derived exclusively from hPSC in HIO-TESI. hPSC-derived ENCC supplementation of HIO-TESI generates ENCC-HIO-TESI with mature submucosal and myenteric ganglia, repopulates excitatory, inhibitory, and sensory neurons, and restores the neuroepithelial circuit and neuron-dependent contractility and relaxation. Our findings validate a novel approach to restoring a functional hPSC-derived ENS in ENCC-HIO-TESI and implicate their potential for the treatment of enteric neuropathies. Overall design: Examination of HIO-TESI growth with and without the addition of HESC-derived ENCC.	Co-expression
SRP108065	RNA-sequencing of pediatric idiopathic dilated cardiomyopathy patients and healthy controls	We used NGS of rna to understand transcriptome wide changes that occur in the left ventricles of pediatric idiopathic dilated cardiomyopathy patients. Overall design: Left ventricles were harvested from failed or healthy control patients and rna was sequenced	Co-expression
SRP108070	Gene expression data from the HCT-116 colon cancer cell line in the presence or absence of siRNA targeting APC	Gene expression data were collected by RNA-seq from HCT-116 cells in the presence or absence of siRNA targeting APC and 1,376 transcripts changed in expression following APC silencing were identified relative to scrambled siRNA-transfected and untreated controls. Overall design: Examination of gene expression under 3 different transfection conditions	Co-expression
SRP108120	Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder	total RNA-sequencing on dlPFC neurons from 19 human cocaine addicts (1-19) and 17 healthy controls (21-40) Overall design: Total RNA-seq on FACs isolated neuronal nuclei from human post-mortem dorsolateral prefrontal cortex	Co-expression
SRP108121	A Signaling and Transcription Architecture for the Specification of Human Germ Cell Lineage	The mechanism for human germ-cell specification, which sets out a complex program generating spermatozoa or oocytes, remains largely unknown.  We established a system for inducing human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) via incipient mesoderm-like cells (iMeLCs).  Here, we show that EOMESODERMIN (EOMES) elevates in iMeLCs through WNT signaling and is essential for activating SOX17, a key driver for hPGC(LC) specification, with the duration/dosage of the WNT signaling/EOMES expression dictating the germ-cell competence.  Upon hPGCLC induction, BMP signaling activates TFAP2C independently from SOX17, and SOX17 and TFAP2C instate the hPGCLC program, including BLIMP1 expression, in an interdependent fashion.  The hPGC(LC) specification program is highly consistent with the monkey program, but is divergent from the mouse one regarding key transcription factors and their hierarchy of actions.  These findings delineate evolutionary divergence of mammalian germ-cell specification, providing a foundation for further human germ-cell development in vitro. Overall design: RNAseq analysis of hiPSCs, iMeLCs and hPGCLCs in multiple knockout/rescued lines	Co-expression
SRP108182	The role of FAM46C in myeloma cells [sequencing]	FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis is not determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity indicating a MM survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. Furthermore, pathway analysis suggests that enforced FAM46C expression activates the unfolded protein response (UPR) pathway and induces mitochondrial dysfunction. In contrast, endogenous CRISPR FAM46C depletion enhanced MM cell growth and notably decreasing Ig light chain and BIP expression, activating of ERK and anti-apoptotic signaling and conferring relative resistance to dexamethasone and lenalidomide treatment. The genes altered in FAM46C depleted cells are enriched for signaling pathways regulating estrogen, glucocorticoid, B cell receptor signaling and ATM signaling. Together these results implicate FAM46C in myeloma cell growth and survival. FAM46C mutation contributes to myeloma pathogenesis and disease progression by perturbation in plasma cell differentiation and endoplasmic reticulum homeostasis. Overall design: Two myeloma cell lines (MM1.S and KMS11) were infected with lentivirus harboring either vector (pCDH or vec) or FAM46C-expressing cassette. At day 3 after infection, cells were harvested for mRNA sequencing analysis. A total of 8 samples were analyzed, including replicates of two controls (vector) and FAM46C overexpression from each cell line.	Co-expression
SRP108209	Genomic and transcriptomic characterization of acute myeloid leukemia cases with MYC amplification as double minutes (AML-dmin)	Double minutes (dmin) are rare in acute myeloid leukemia (AML) and the mechanism underlying their genesis as well as their transcriptional implications are still unclear. Here, we applied the Illumina next-generation sequencing technology to investigate these structures in a collection of AML cases with MYC amplification in form of dmin. By whole genome sequencing (WGS), we dissected the molecular heterogeneity of 8q24 amplicon structures in our dataset and reconstructed their internal organization at single nucleotide resolution level. In parallel, by performing the transcriptome sequencing (RNA-seq) of the same cases, we profiled gene expression signature, fusion transcripts and mutational patterns associated with dmin presence. The same cases were analyzed also by SNP array technology for genomic profiling (Affymetrix CytoScan HD platform, raw data available in Array Express repository under Accession Number E-MTAB-5372).	Co-expression
SRP108222	AR-independent prostate cancer is sustained through FGF signaling	Androgen receptor (AR) signaling is a distinctive feature of prostate cancer (PC) and represents the major therapeutic target for the treatment of metastatic disease. Though highly effective, AR antagonism has the potential to generate tumors that bypass a functional requirement for AR activity. We show here that a phenotypic shift has occurred in metastatic PCs with the emer-gence of a double-negative AR-null neuroendocrine-null phenotype that is notable for MAPK and FGF pathway activity. To identify mechanisms capable of sustaining PC survival, we gener-ated a model system designated AR program-independent prostate cancer (APIPC) which re-sists AR-targeted therapeutics, lacks neuroendocrine features, expresses high levels of FGF8 and the ID1 oncogene, and activates MAPK signaling. Pharmacological blockade of MAPK or FGF signaling inhibited APIPC tumor growth, supporting FGF/MAPK as a therapeutic avenue for treating AR-null PC. Overall design: RNA sequencing of human prostate tumor cell lines using the Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.	Co-expression
SRP108237	Transcriptome analysis of CD4+ T cells infected with Ebolavirus	Evaluating the transcriptome profiles of CD4+ T cells that were cultured with mock, LPS, or recombinant Ebolavirus strain Mayinga (EBV) with a particular interest in characterizing the T lymphocyte cell death-associated pathways. Overall design: Transcriptome profiles of CD4+ T cells cultured with three treatments, mock, LPS, and Ebolavirus.  For each treatment, samples were taken from four donors on two separate days, day 1 and day 4 post-infection.	Co-expression
SRP108244	PGE2 mediated gene expression changes in human cervical stromal cells	The cervix represents a formidable structural barrier for successful induction of labor. Approximately 10% of pregnancies undergo induction of cervical ripening and labor with prostaglandin (PG) E2 or PGE analogs, often requiring many hours of hospitalization and monitoring. On the other, preterm cervical ripening in the second trimester predicts preterm birth. The regulatory mechanisms of this paradoxical function of the cervix are unknown. Here, we show that PGE2 utilizes cell-specific EP2 receptor-mediated increases in Ca2+ to dephosphorylate and translocate HDAC4 to the nucleus for repression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH). The crucial role of 15-PGDH in cervical ripening was confirmed in vivo. Although PGE2 or PGDH inhibitor alone did not alter gestational length, treatment with PGDH inhibitor+PGE2 or metabolism-resistant dimethyl-PGE2 resulted in preterm cervical ripening and delivery in mice. The ability of PGE2 to selectively auto-amplify its own concentrations in stromal cells by signaling transcriptional repression of 15-PGDH elucidates long-sought-after molecular mechanisms that govern prostaglandin action in the cervix. This is the first report detailing unique mechanisms of action in the cervix and serves as a catalyst for (i) the use of PGDH inhibitors to initiate, or amplify low-dose PGE2-mediated cervical ripening, or (ii) EP2 receptor antagonists, HDAC4 inhibitors, and 15-PGDH activators to prevent preterm cervical ripening and preterm birth. Overall design: human cervical stromal cells were treated with DMSO (vehicle) or PGE2 (100 nM) for 1 h or 24 h followed by RNA sequencing	Co-expression
SRP108251	RNA-seq of GM15850 and GM15851 cells treated with synthetic transcription elongation factors.	Switching a paused RNA polymerase II into productive elongation is tightly-regulated, especially at genes involved in human development and disease. To exert control on this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that binds a component of the transcription elongation machinery. The resultant bifunctional molecules convert constituent modules from broad-spectrum inhibitors of transcription into a gene-specific stimulator of transcriptional elongation. Here, we present Syn-TEF1, a molecule that actively facilitates transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a debilitating and ultimately lethal neurodegenerative disease with no effective therapy. Overall design: The global effect on expression of synthetic transcription elongation factor (Syn-TEF1) and its constituent parts was examined in cells from a patient with FRDA (GM15850) and a healthy sibling control patient (GM15851).	Co-expression
SRP108264	Role of XRN2 ribonucleolytic activity in RNA metabolism	We analysed the effect of depriving the human cell of the catalytic activity of the nuclear 5' to 3' exoribonuclease XRN2. Catalytic amino acids in this protein had been defined previously, so it was possible to design a mutated catalytically inactive form of the protein (XRN2D233A-D235A) (PMID: 19194460). We created 293 Flp-In T-REx stable cell lines that induciby silence endogenous XRN2, and concomitantly express wild-type or inactive XRN2 in fusion with EGFP at the C-terminus. Thus, complementation of silencing of endogenous XRN2 with the expression of mutant version of the protein allows to directly link potential phenotypes with the lack of XRN2 enzymatic activity. To this end we isolated total RNA from tetracycline-treated cells, depleted it from rRNA and conducted strand-specific deep sequencing. Overall design: 6 samples were analysed. 3 replicates of control cells (endogenous copy of XRN2 gene is silenced and catalytically active exogenous XRN2-EGFP is expressed) and 3 replicates of cells deprived of XRN2 ribonucleolytic activity (endogenous copy of XRN2 gene is silenced and catalytically inactive exogenous XRN2(D233AD235A)-EGFP is expressed)	Co-expression
SRP108292	Cellular responses to human cytomegalovirus infection.	Here we perform a systems analysis of the HCMV host-cell transcriptome across two cell-types. Overall design: Total RNA profiles of mock- and HCMV-infected MRC-5 and ARPE-19 cells in biological duplicate, at three time-points.	Co-expression
SRP108341	TrapSeq: An RNA Sequencing-based pipeline for the identification of genetrap insertions in mammalian cells	Current pipelines used to map genetrap insertion sites are based on inverse- or splinkerette-PCR methods, which despite their efficacy are prone to artifacts and do not provide information on the impact of the genetrap on the expression of the targeted gene. We developed a new method, which we named TrapSeq, for the mapping of genetrap insertions based on paired-end RNA sequencing. By recognizing chimeric mRNAs containing genetrap sequences spliced to an endogenous exon, our method identifies insertions that lead to productive trapping. Overall design: We conducted two independent screenings for sensitivity against 6-thioguanine (6TG) and an ATR inhibitor (ATRi). We applied our RNAseq-based  pipeline (TrapSeq) to identify mutations that provide resistance to these reagents. Importantly, and besides its use for screenings, when applied to individual clones our method provides a fast and cost-effective way that not only identifies the insertion site of the genetrap but also reveals the impact of the insertion on the expression of the trapped gene. Please note that HAP1, haploid for all chromosomes, derives from near-haploid KBM7 parent line which was in turn obtained from a chronic myeloid leukemia patient in blast crisis phase (Carette et al. Nature 477:340-343, 2011).	Co-expression
SRP108348	Transcriptome analysis of the Golgi stress response	We explore the transcriptional response of mammalian cells undergoing various insults to Golgi homeostasis. HEK293 cells (Flp-In T-REx 293 cells) stably containing a doxycycline-inducible Golgi-localized HaloTag2 construct (GA-HT2) were treated with the ionophore nigericin, the glycosylation inhibitor xyloside, or were induced by doxycycline and treated with the hydrophobic tag HyT36 to induce destabilization of GA-HT2. We found that while nigericin and xyloside induce global transcriptional changes, destabilization of GA-HT2 induces a Golgi-specific response. Overall design: HEK293/GA-HT2 cells were treated in duplicate with nigericin, xyloside, HyT36, or the vehicle DMSO in the absence of doxycycline. In addition, cells were treated with DMSO or HyT36 in the presence of doxycyline.	Co-expression
SRP108358	Mixed-species RNAseq analysis of human lymphoma cell adhesion to mouse stromal cells identifies a core gene set that is also differentially expressed in the lymph node microenvironment of MCL and CLL patients.	Background:A subset of hematological cancer patients is refractory to treatment or suffer relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment via microenvironment interaction. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Results: Using RNAseq and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma (MCL) cells stably adhered to stromal cells or in suspension within a co-culture and in separate culture as well as mouse MS-5 stromal cells in co-culture or in separate culture. 1050 differentially expressed transcripts in adherent MCL cells identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. Comparison with previous MCL and chronic lymphocytic leukemia (CLL) patient data identified 116 genes that are differentially regulated in all three studies. From these genes we suggest a gene signature (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion mediated microenvironment signaling in MCL/ CLL cells. Conclusions: The model system developed and characterized here together with suggested signature genes can be used in future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms. Overall design: RNA-seq; four conditions in quadruplicates, 16 samples in total.	Co-expression
SRP108363	Effect of TUNAR silencing and GSK3 inhibition on human b-cell transcriptome	The aim of the study is to identify the target genes of long noncoding RNA TUNAR in human EndoC-ßH1 cells with or without treatment of GSK3 inhibitor. Overall design: Human EndoC-ßH1 cells were treated with negative siRNA or TUNAR siRNA, and then subjected to GSK3 inhibitor 1-AKP or not. Differentially expressed genes were identified by quantifying transcriptome by RNA-seq.	Co-expression
SRP108388	Homo sapiens Raw sequence reads	To study significant different expressed genes in GBM, we squenced 3 GBM and 3 normal brain tissue using RNA-Seq	Co-expression
SRP108393	A transcriptionally und functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade	Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic, and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1-) from non-small cell lung cancer patients. We observed that, PD-1T T cells show a markedly different transcriptional and metabolic profile as compared to PD-1N and PD-1- lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes are impaired in classical effector cytokine production, they produce CXCL13 that mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1 bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides novel potential avenues for therapeutic intervention. Overall design: Intratumoral CD8+ T cells from 11 non-small cell lung cancer patients that were sub-sorted into PD1-high (PD-1T), PD1-intermediate (PD-1N) and PD1-negative (PD-1-) cells, were sequenced using Illumina HiSeq4000. In addition, peripheral blood effector memory T cells from 4 healthy donors were sequenced using Illumina HiSeq4000.	Co-expression
SRP108397	CLIP-seq dataset for eIF4A3	CLIP-seq dataset of FLAG-eIF4A3 T163 variants in HeLa cells	Co-expression
SRP108414	Effect of low-dose sorafenib and alkylating agents in inflammation and angiogenesis in breast cancer	Molecular targeted compounds are emerging as important component to improve the efficacy of classical chemotherapeutics. In this study, we tested whether using low dose sorafenib to reduce off target inhibitions of kinases impacts the antitumor effect of alkylating agents in breast cancer models. Overall design: MDA-MB231 cells were treated with 1 µM sorafenib, 40 µg/mL MMS, or pre-incubated with 1 µM sorafenib for 12 h followed by 40 µg/mL MMS, each in two independent experiments. RNA was harvested 8 and 24 h, or post MMS treatment for combination treatment.	Co-expression
SRP108449	Homo sapiens Transcriptome or Gene expression	Antibiotics-treated liver cell line	Co-expression
SRP108472	SIRT7 Antagonizes TGF-ß Signaling and Inhibits Breast Cancer Metastasis	Protein deacetylase SIRT7 is significantly downregulated in lung metastases of human patient and mouse tissues, and predicted metastasis-free survival. To explore the roles of SIRT7 in breast cancer, we analysed the gene expressions in breast cancer BT549 cells with SIRT7 knockdown or not. Overall design: The mRNA profiles of breast cancer BT549 cells with SIRT7 knockdown or not were generated by deep sequencing using Illumina HiSeq-2000	Co-expression
SRP108496	Comparative Transcriptomic Profiling of Normal-Appearing and Scarred Areas of the Lungs Reveals Pathobiological Clues to Idiopathic Pulmonary Fibrosis	RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with overtly scarred peripheral and basilar lung regions and macroscopically unaffected central lung areas. OBJECTIVES: To gain better insight into IPF pathobiology by comparing transcriptomic profiles of normal-appearing and scarred regions of IPF lung. METHODS: Lung tissue samples from macroscopically unaffected (normal-appearing, IPFn) and scarred (IPFs) regions of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. RT-qPCR and immunohistochemistry were used to confirm selected findings. MEASUREMENTS AND RESULTS: Numerous previously reported IPF-associated gene expression disturbances as well as additional differentially expressed mRNAs were observed. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of extracellular matrix-, immunity- and inflammation-related mRNAs. The magnitude and statistical significance of these changes were comparable or greater than those in the IPFs-to-HC comparison. When directly compared with IPFn, IPFs tissues demonstrated elevated expression of epithelial mucociliary mRNAs. Compared with HC, both IPFn and IPFs tissues demonstrated reduced expression of mRNAs related to solute carrier membrane transport and metabolic processes. Primary fibroblast cultures from IPFn and IPFs tissues were transcriptomically identical. CONCLUSIONS: Macroscopically normal-appearing IPF tissues demonstrate profound disease activity and substantially similar transcriptomic profiles to scarred areas. Differences between these tissues are due to cell types other than fibroblasts and notably include enhanced expression of mucociliary genes in scarred areas. Deranged epithelial homeostasis or possibly non-transcriptomic factors may thus explain the marked architectural differences between normal-appearing and terminally scarred lung in end-stage IPF. Overall design: RNASeq of 26 lung tissue samples from patients with IPF, including affected and unaffected areas of the lung, and from healthy controls	Co-expression
SRP108505	Gene Expression Analysis of Melanoma Cells Treated with 6-Thio-dG In Vitro	Telomerase promoter mutations are highly prevalent in human tumors including melanoma. Telomere transcriptional signatures are enriched in a subset of therapy-naïve melanomas associated with worse overall survival, in BRAF-mutant intrinsically resistant melanoma cells that evade MAPK inhibitors (MAPKi), as well as in a subset of post-treatment tumor biopsies derived from patients who have disease progression on MAPKi or the immune checkpoint inhibitors, anti-CTLA-4 or anti-PD1. We demonstrate the efficacy of a telomerase-directed nucleoside, 6-thio-2''-deoxyguanosine (6-thio-dG) that results in telomere dysfunction and cell death in various models of therapy-resistant cells. Furthermore, 6-thio-dG significantly inhibits tumor growth of primary tumor biopsy cultures derived from patients who had disease progression on multiple therapies including anti-CTLA-4 or anti-PD1. Overall design: A375 and LOX-IMVI BR melanoma cells were treated with the control, 6-Thio-dG and BIBR 1532. RNA was purified from two biological replicates for RNA sequencing.	Co-expression
SRP108507	SQSTM1/p62-directed metabolic reprogramming is essential for normal neurodifferentiation	Neurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the ageing population, but their aetiology and disease mechanisms are poorly understood. Studying monogenic neurodegenerative diseases, with known genetic cause, provides an opportunity to understand cellular mechanisms also affected in more complex disorders. We recently reported that loss-of-function mutations in the autophagy adaptor protein, SQSTM1/p62, lead to a slowly progressive neurodegenerative disease presenting in childhood. To further elucidate the neuronal involvement, we studied the cellular consequences of loss of p62 in a neuroepithelial stem (NES) cell model and differentiated neurones, derived from reprogrammed p62 patient cells, or by CRISPR/Cas9-directed gene editing in NES cells. Transcriptomic and proteomic analyses suggest that p62 is essential for neuronal differentiation by controlling the metabolic shift from aerobic glycolysis to oxidative phosphorylation required for neuronal maturation. This shift is blocked by the failure to sufficiently downregulate lactate dehydrogenase expression due to the loss of p62, possibly through impaired Hif-1a downregulation and increased sensitivity to oxidative stress. The findings implicate an important role for p62 in neuronal energy metabolism and particularly in the regulation of the shift between glycolysis and oxidative phosphorylation, required for normal neurodifferentiation. Overall design: Transcriptomes of neuroepithelial stem cells in an undifferentiated (0d) and differentiated state (4d) were generated in triplicates on an Illumina HiSeq 2500.	Co-expression
SRP108531	Universal alternative splicing of noncoding exons	The human transcriptome is so large, diverse and dynamic that, even after a decade of investigation by RNA sequencing (RNA-Seq), we are yet to resolve its true dimensions. RNA-Seq suffers from an expression-dependent bias that impedes discovery of low-abundance transcripts and has prevented a complete census of gene expression. Here we performed targeted single-molecule and short-read RNA-Seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome and identifies a fundamental distinction between the architecture of protein-coding and noncoding gene content. Unlike their coding counterparts, noncoding exons undergo universal alternative splicing to produce a seemingly limitless variety of isoforms. Targeted RNA-Seq analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse. Despite this divergence, human alternative splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a local splicing code that is more strongly conserved than the noncoding isoforms themselves. We propose that noncoding exons are functionally modular, with combinatorial alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution. Overall design: Duplicate or triplcate tissue samples from adult human, mouse or Tc1 mouse (carries human chromosome 21), anaylsed by RNA CaptureSeq targeted to Chr21 and syntentic regions of the mouse genome	Co-expression
SRP108538	Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor Alpha Bound Enhancers [RNA-Seq]	Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to impact gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that can prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor a binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine tune the expression of target genes. Overall design: The effects of Enhancer interference (Enhancer-i) and control guide RNA treatment on the transcriptome before and after estrogen treatment, with 2 replicates per condition.	Co-expression
SRP108543	Gene expression profiling of human iPSC kidney organoid-derived proximal tubules	The kidney organoid differentiation protocol takes induced pluripotent stem cells through to kidney organoid via directed differentiation in approximately 25 days. The cells are grown in a monolayer in a dish for seven days and are subjected to growth factors before being pelleted on day seven. The organoids then continue to differentiate as a 3D structure, with at least 8 distinct kidney cell types identifiable around day 18. Here proximal tubules were isolated from day 25 kidney organoids and RNA-sequencing libraries generated. Overall design: RNA-Seq of three replicates of proximal tubules isolated from human kidney organoids	Co-expression
SRP108544	Human iPSC derived glomeruli facilitate accurate modelling of podocytopathy	Podocytes are the highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria. Studies into podocyte biology and disease has been hampered by a paucity of in vitro models of this non-proliferative cell type. Here we characterise sieved glomeruli from kidney organoids derived from human pluripotent stem cells. Compared to conditionally immortalised podocytes, organoid-derived glomeruli show superior podocyte-specific gene and protein expression, morphology and functional properties. Using CRISPR-derived MAFB reporter iPSC lines, homozygous MAFB mutant organoids recapitulated the anticipated disease related transcriptional changes. Culture of kidney organoids on chicken chorioallantoic membrane resulted in glomerular vascularisation, glomerular filtration barrier assembly, formation of slit diaphragms and fenestrated endothelial cells. This definitively demonstrates that human iPSC kidney organoid-derived glomeruli can serve as an accurate model of human podocytopathies and glomerular disease in vitro. Overall design: Gene expression profiling of three immortalised podocyte line samples at 33 degrees celsius, three immortalised podocyte line samples at 37 degrees celsius and three day 25 kidney organoid derived glomeruli	Co-expression
SRP108551	Effects of WCE herbal extract on hormone-refractory PC-3 tumors	Genome-wide transcriptomic analysis of the tumor gene expression following by WCE treatment in PC-3 orthotopic xenograft model	Co-expression
SRP108559	RNA sequencing data from tissue degradation in DLPFC	These RNA-seq data are from dorsolateral prefrontal cortex (DLPFC) tissue from 5 individuals left off ice at room temperature for 0, 15, 30, and 60 minutes. Resulting RNA was extracted and sequenced with both polyA+ and RiboZero protocols.	Co-expression
SRP108577	RNA-sequencing of shSRC-1 and shNT tamoxifen treated LY2 cells	The steroid co-activator protein SRC-1 plays an important role in endocrine therapy resistant breast cancer. Its expression is associated with large high grade tumours, HER2 positivity, disease recurrence and resistance to endocrine therapy. SRC-1''s role in affecting the transcriptome of the breast cancer endocrine resistant setting is uncovered through this RNA-seq analysis of LY2 cells grown with or without the presence of SRC-1 Overall design: We report the RNA-sequencing of tamoxifen treated LY2 breast cancer cells treated with non-targeting shRNA or SRC-1 (NCOA1) targeting shRNA and examine the gene expression differences.	Co-expression
SRP108597	Pain-driven transcriptome changes in synovium of knee osteoarthritis patients	Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA. Overall design: RNA-seq of mRNA and small non-coding RNA of 10 patients with high and low knee pain	Co-expression
SRP108624	CDK4/6 inhibitor resistance in prostate cancer	CDK4/6 kinase inhibitors have shown great promise in clinical trials in various cancer types and have recently entered clinical trial for advanced prostate cancer. Although patients are expected to respond well to this class of drugs, development of resistance in some patients is anticipated. To pre-empt this and study how prostate cancer may evade CDK4/6 inhibition, new resistance models were generated from LNCaP and LAPC4 prostate cancer cells cells by prolonged culturing in presence of 0.5uM palbociclib. RNA sequencing data was integrated with phospho-proteomics to unravel the molecular underpinnings of acquired resistance to palbociclib and resultant broad CDK4/6 inhibitor resistance. Overall design: Thirty total sample: three biological replicates of vehicle control and PD treated parental and Palbociclib (PD) resistant cells (PDR) that were generated from LAPC4 and LNCaP cells.	Co-expression
SRP108628	Smad5 acts as an intracellular pH messenger and maintains bioenergetic homoeostasis	we report here that Smad5 acts as a pHi messenger and maintains bioenergetic homeostasis of a cell by regulating cytoplasmic metabolic machinery Overall design: Reads Per Kilobase of exon per Megabase of library size (RPKM) were calculated using a protocol from Chepelev et al., Nucleic Acids Research, 2009. In short, exons from all isoforms of a gene were merged to create one meta-transcript. The number of reads falling in the exons of this meta-transcript were counted and normalized by the size of the meta-transcript and by the size of the library.	Co-expression
SRP108638	Iron response of HepG2 cells	RNA-seq of HepG2 cells in response to iron Overall design: RNA-seq experiment conducted in two biological replicates. Total RNA samples were submitted to the Otago Genomics and Bioinformatics Facility at the University of Otago (Dunedin, New Zealand) under contract to the New Zealand Genomics Limited for library construction and sequencing. The libraries were prepared using TruSeq stranded mRNA sample preparation kit according to the manufacturer's protocol (Illumina) and pair-end sequenced on one lane of HiSeq 2000 (Illumina), generating 100-bp reads.	Co-expression
SRP108685	Gene expression activation in CLL mediated by MSCs contact	Survival of primary CLL cells is mediated by mesenchimal stromal cells in vitro. The goal of this study is to compare the gene expression profile of primary CLL cells in monoculture to that one following cell-cell contact with MSCs Overall design: Primary CLL cells isolated from 6 different patients were cultured for 4h in normal growing medium or for 48h in coculture with EL08-1d1 cells	Co-expression
SRP108709	“Stealth Dissemination” of Macrophage-Tumor Cell Fusions Cultured from Blood of Patients with Pancreatic Ductal Adenocarcinoma	Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploid. Immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and pancreatic stem cells, as well as markers of M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs also express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in control of metastasis (such as MALAT-1). When cultured MTFs were transplanted orthotopically into pancreas of mice, they grew as obvious well-differentiated islands of cells in the pancreas, but in addition they disseminated widely throughout multiple tissues in “stealth” fashion. They were found distributed throughout multiple different organs at 4, 8, or 12 weeks after transplantation (including liver, spleen, lung), occurring as single cells or small groups of cells, without formation of obvious tumors or any apparent progression over the 4-12 week period. We suggest that MTFs may play a critical role in metastatic progression of PDAC: They may disseminate widely from primary tumors early in development of PDACs, and prepare pre metastatic “niches” for subsequent development of metastatic foci, although they themselves do not appear to form tumors.	Co-expression
SRP108712	TGIRT-seq of RNA extracted from extracellular vesicles and exosomes.	Using thermostable group II intron reverse transcriptase sequencing (TGIRT-seq) to characterize the RNA extracted from HEK293T cell EVs isolated by buoyant density gradient ultracentrifugation and from exosomes further purified from the gradient fractions by immunoisolation.	Co-expression
SRP108720	RNA-Seq of polysome profiling fractions and whole cell lysates of UVB-irradiated N-TERT keratinocytes	In response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2a (eIF2a-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2a-P cytoprotection in response to UVB. Loss of eIF2a-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2a-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2a-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5'-leader of CDKN1A mRNA. We conclude that eIF2a-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. Overall design: Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.	Co-expression
SRP108761	B-cell activating factor (BAFF) stimulation of Burkitt Lymphoma cell line [RNA-Seq]	RNA-Seq profiling of Burkitt Lymphoma cell line (BL2) with B-cell activating factor (BAFF) for 24 hrs . The Burkitt Lymphoma cell line were either only cultured in cell culture medium supplemented with 10 mM HEPES at 1 × 106 cells/ml  or additionally incubated with B-cell activating factor (BAFF) for 24 hrs Overall design: Two conditions of  BL2 cells each in 3 replicates:  1. non-stimulated control (BL2),  2. Baff stimulated (BL2Baff)	Co-expression
SRP108762	RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells	G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the ß-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways Overall design: Human CASMCS cells were subject to various treatments: basal, thrombin, thrombin + SB, thrombin + AG and thrombin + SB + AG. Gene expression was studies after 30 minutes to assess genes that are differentially expressed by treat emnt with agonists and antagonists. The agonoists and antagonists are associated with transactivation of GPCRs and the gene expression results will help identify relevant genes.	Co-expression
SRP108772	Gene expressions of H9s in different culture systems	H9s were cultued in 2D, static 3D and dynamic 3D suspension and in the microspace cell culture system for 3 days. mRNAs were sequenced. Overall design: RNA deep sequencing	Co-expression
SRP108785	Persistence of stem cell metabolism in cancers as a failure of differentiation	Tumor glucose uptake was measured by FDG-PET in 859 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake values (SUV) distributions and tested for association between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we performed pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal with a low peak at SUV 2-4 and a high peak at SUV 8-11. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and of death. Carbohydrate metabolism and the pentose related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/ high SUV clusters. Overall design: Comparison of gene expression pattern in cancer with high and low SUV.	Co-expression
SRP108803	Activation of the p53 transcriptional program sensitizes cancer cells to Cdk7 inhibitors	Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7as inhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1 or the more selective YKL-1-116. The effects were allele-specific; a CDK7as mutation conferred both sensitivity to bulky adenine analogs and resistance to covalent inhibitors. Non-transformed colon epithelial cells were resistant to these combinations, as were cancer-derived cells with p53-inactivating mutations. Apoptosis was dependent on death receptor DR5, a p53 transcriptional target whose expression was refractory to Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to sensitize cancer cells to Cdk7 inhibition. Overall design: RNAseq in colorectal cancer cell line HCT116 in the presence or absence of CDK7 and p53 inhibitors	Co-expression
SRP108807	Single-cell RNA-seq reveals a subpopulation of prostate cancer cells with enhanced cell cycle-related transcription and attenuated androgen response	Increasing evidence indicates that minor subpopulations intrinsic to androgen-independence are present in prostate cancer cells, poised to become clonal dominance under prolonged androgen-deprivation selection. To stratify different subpopulations, we conduct transcriptome profiling of 144 single LNCaP prostate cancer cells treated and untreated with androgen after cell cycle synchronization. At least eight subpopulations of LNCaP cells are identified, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displays stem-like features, the advanced growth of which depends more on enhanced expression of 10 cell cycle-related genes and less on androgen-dependent signaling. Concordant upregulation of these genes appears to be linked to recurrent prostate cancers and can be used for early detection of tumors that subsequently develop androgen independence. Moreover, this single-cell approach provides a better understanding of how cancer cells respond heterogeneously to androgen-deprivation therapies and to reveal which subpopulations are resistant to this treatment. Overall design: For each of 3 treatment groups, forty eight LNCaP single cells and 1 representative bulk cell RNA sample (1ng) were collected for SMART-seq2 amplification and later single-cell RNA-seq (total 144 single cells and 3 bulk cell samples). All of the treatment groups were harvested from after synchronizing the cells at the G1/S phase with a double thymidine block and androgen depriving the cells for ~24 hours. Treatment groups 2 and 3 were cultured in the absence and presence of androgen (1 nM R1881) for 12 hours, respectively. Treatment group 1 was a baseline comparison treatment group and was collected right after cell synchronization and androgen deprivation (considered 0 hour).	Co-expression
SRP108810	Homo sapiens Transcriptome or Gene expression	Although the general prognosis of patients with papillary thyroid cancer (PTC) is favourable, some cases shows aggressive phenotype. Numerous studies showed that lymph node metastasis is associated with recurrence in thyroid cancer and increase the mortality rate particularly in elderly patients. This study aims to characterize differentially expressed genes in PTC with and without lymph node metastasis as compared to paired normal adjacent tissues.	Co-expression
SRP108836	Neural Precursor Cell-Derived Pleiotrophin Mediates Glioma Invasion of the Subventricular Zone	The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain.  Pleiotrophin, in complex with the binding partners and signaling through the receptor PTPRZ1, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion. Overall design: RNA-seq in patient-derived DIPG cell cultures in two replicates. Libraries were sequenced on Illumina NextSeq 500, 1x75.	Co-expression
SRP108852	Genome-scale Activation Screen Identifies a LncRNA Locus Regulating a Gene Neighborhood [RNA-Seq]	The mammalian genome contains thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to play critical roles in diverse cellular processes through a variety of mechanisms. While some lncRNA loci encode RNAs that act non-locally (in trans), emerging evidence indicates that many lncRNA loci act locally (in cis) to regulate expression of nearby genes—for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. To address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen targeting more than 10,000 lncRNA transcriptional start sites (TSSs) to identify noncoding loci that influence a phenotype of interest. We found 11 novel lncRNA loci that, upon recruitment of an activator, each mediate BRAF inhibitor resistance in melanoma. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation results in dosage-dependent activation of four neighboring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit to systematically discover functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function. Overall design: RNA-seq on A375 cells overexpressing candidate lncRNA or protein-coding gene.	Co-expression
SRP108853	Transcriptional profile of human iPSC and HIOs with APC mutations	Background and Aims: mutations in the gene Adenomatous Polyposis Coli or APC appear in most sporadic cases of colorectal cancer and it is the most frequent mutation causing hereditary Familial Adenomatous Polyposis. The detailed molecular mechanism by which APC mutations predispose to the development of colorectal cancer is not completely understood. This is in part due to the lack of accessibility to appropriate models that recapitulate the early events associated with APC mediated intestinal transformation. Methods: we have established a novel platform utilizing human induced Pluripotent Stem cells or iPSC from normal or FAP-specific APC mutant individuals and evaluated the effect of the mutation in the cells before and after differentiation into intestinal organoids. In order to minimize genetic background effects we also established an isogenic platform using TALEN-mediated gene editing. Results: comparison of normal and APC mutant iPSC revealed a significant defect in cell identity and polarity due to the presence of APC in heterozygosity as well as chromosomal aberrations including abnormal anaphases and centrosome numbers. Importantly, upon specification into intestinal progeny, APC heterozygosity was responsible for a major change in the transcriptional identity of the cells with dysregulation of key signaling pathways, including metabolic reprogramming, abnormal lipid metabolism and intestinal-specific cadherin expression. Conclusions: we have developed a novel iPSC/intestinal model of APC mutagenesis and provide strong evidence that APC in heterozygosity imparts a clear phenotypic and molecular defect, affecting basic cellular functions and integrity, providing novel insights in the earlier events of APC-mediated tumorigenesis. Overall design: Four independent biological replicates of each (APC+/+ vs APC+/-) were analyzed in triplicates, before and after differentiation into intestinal organoids, for a total of 48 samples	Co-expression
SRP108854	zUMIs: a fast and flexible pipeline for RNA sequencing data with UMIs	Background Single-cell RNA-sequencing (scRNA-seq) experiments typically analyze hundreds or thousands of cells after amplification of the cDNA. The high throughput is made possible by the early introduction of sample-specific bar codes (BCs), and the amplification bias is alleviated by unique molecular identifiers (UMIs). Thus, the ideal analysis pipeline for scRNA-seq data needs to efficiently tabulate reads according to both BC and UMI. Findings zUMIs is a pipeline that can handle both known and random BCs and also efficiently collapse UMIs, either just for exon mapping reads or for both exon and intron mapping reads. If BC annotation is missing, zUMIs can accurately detect intact cells from the distribution of sequencing reads. Another unique feature of zUMIs is the adaptive downsampling function that facilitates dealing with hugely varying library sizes but also allows the user to evaluate whether the library has been sequenced to saturation. To illustrate the utility of zUMIs, we analyzed a single-nucleus RNA-seq dataset and show that more than 35% of all reads map to introns. Also, we show that these intronic reads are informative about expression levels, significantly increasing the number of detected genes and improving the cluster resolution. Conclusions zUMIs flexibility makes if possible to accommodate data generated with any of the major scRNA-seq protocols that use BCs and UMIs and is the most feature-rich, fast, and user-friendly pipeline to process such scRNA-seq data. Overall design: HEK293T cells were sequenced using the mcSCRB-seq protocol (Bagnoli et al., 2017)	Co-expression
SRP108858	Molecular pathogenesis of human prostate basal cell hyperplasia reveals a keratinocyte metaplasia	The incidence of basal cell hyperplasia (BCH) has been reported at 8-10%, but a molecular and cellular characterization has not been performed on this phenotype. Using freshly digested tissue from surgical specimens, we performed transcriptomic analysis of flow cytometry-purified basal epithelia from patients with and without a majority BCH phenotype. Gene set enrichment analysis revealed an increased expression of members of the epidermal differentiation complex, resembling the progression of other metaplastic diseases. Overall design: In order to generate a clean molecular profile of BCH, free of contaminating signal from leukocytes, stroma and luminal epithelia, we performed RNA sequencing on bulk-isolated basal epithelia from 3 patients with basal hyperplasia and 4 patients without BCH	Co-expression
SRP108867	22Rv1 in vivo progression model	Genome-wide transcriptomic analysis of the tumor gene expression in 22Rv1 in vivo progression model	Co-expression
SRP108872	Inhibitors of the histone methyltransferases EZH2/1 induce a potent antiviral state and suppress infection by diverse viral pathogens [RNA-Seq]	Epigenetic regulation is based upon a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development.  Thus, epigenetic modulators represent novel therapeutic targets to treat a range of diseases including malignancies.  Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach to control infection, persistence, and the resulting recurrent disease.  The histone methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3 enriched chromatin domains.  However, while EZH2/1 are implicated in repression of herpesviral gene expression, inhibitors of these enzymes suppressed HSV primary infection in vitro and in vivo.  Furthermore, these compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia.  Suppression correlated with the induction of multiple inflammatory, stress, and anti-pathogen pathways as well as enhanced recruitment of immune cells to in vivo infection sites.  Importantly, EZH2/1 inhibitors induced a cellular antiviral state that also suppressed infection with DNA (hCMV, Adenovirus) and RNA (Zika virus) viruses.  Thus, EZH2/1 inhibitors have considerable potential as general antivirals through activation of cellular antiviral and immune responses. Overall design: The dataset includes gene expression profiling of human foreskin fibroblast (HFF) cells and mouse trigeminal ganglia. HFF cells were treated with GSK126 (30 µM) or vehicle for 1 hour, 2 hours, and 5 hours with biological triplicates.  Trigeminal ganglia from mock or HSV-1 latently infected BALB/c mice were explanted in media containing GSK126 (30 µM) or vehicle for 12 hours with biological triplicates (pooled 4-5 trigeminal ganglia per replicate).	Co-expression
SRP108875	Progressive  motor  neuron  pathology  and  the  role  of  astrocytes  in  a  human  stem  cell model of VCP-related ALS [terminally differentiated iPSC-derived astrocytes]	Motor   neurons (MNs)   and   astrocytes   (ACs) are   implicated   in   the   pathogenesis   of amyotrophic  lateral  sclerosis  (ALS),  but  their  interaction  and  the  sequence  of  molecular events leading to MN death remain unresolved. Herewe optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (>85%) functional populations of  spinal  cord  MNs  and  ACs.  We  identifysignificantlyincreased  cytoplasmic  TDP-43  and  ER stress as  primary  pathogenic  events in patient-specific  valosin-containing  protein  (VCP)-mutant MNs, with  secondary  mitochondrial  dysfunction  and  oxidative  stress.  Cumulatively these  cellular  stresses  result  in  synaptic  pathology  and  cell death  in  VCP-mutant  MNs. We additionallyidentify  a  cell-autonomous VCP-mutant  AC  survival  phenotype, which   is   not attributable  to  the  same  molecular  pathology  occurring in VCP-mutant MNs. Finally, through iterative  co-culture  experiments,  we  uncover  non-cell-autonomous  effects  of  VCP-mutant ACs  on  both  control  and  mutant  MNs.  This  work  elucidates  molecular  events  and  cellular interplay thatcould guide future therapeutic strategies in ALS. Overall design: Bulk RNA-seq at different timepoints throughout a 35-day differentiation protocol that converted iPSC cells to highly enriched motor neurons and a further dataset from terminally differentiated iPSC-derived astrocytes	Co-expression
SRP108894	Transcriptome of melanoma cell lines resistant to inhibition of the MAPK pathway.	ABSTRACT: Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implemented in cancer development and response to different therapeutics and are thus potential treatment targets; however, the majority of their functions and molecular interactions remain unexplored. In this study we identify a cytoplasmic intergenic lincRNA (MIRAT), differentially expressed in drug-resistant melanoma samples. MIRAT is upregulated in early drug tolerance to MAPK inhibition and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1. Collectively, our results present MIRAT's direct modulatory effect on the MAPK pathway and highlight the relevance of cytoplasmic lncRNA's as potential targets for drug resistant cancer. Overall design: RNA-seq data from parental cell lines and their cell clones that are resistant to the MEK inhibitor Trametinib or BRAF inhibitor PLX-4720 (suffix RM; Resistant to MAPK inhibitor)	Co-expression
SRP108951	Pseudouridines of human foreskin fibroblasts	RNA-Seq performed on cells +/- CMCT to identify pseudouridines. Cells were grown in normal conditions as well as stressed conditions (low nutrient, high pH) to identify pseudouridines induced in stress conditions.	Co-expression
SRP109018	Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development	Human embryonic stem cells (hESCs) were specified as ventral telencephalic neuroectoderm (day 4) and then into medial ganglionic emininence (MGE)-like progenitors (day 15) and were subsequently differentiated into cortical interneuron (cIN)-like cells (day 25-35), by modification of previously published protocols. RNA-seq analysis at days 0, 4, 15, 25, and 35 defined transcriptome signatures for MGE and cIN cell identity. Further integration of these gene expression signatures with ChIP-seq for the NKX2-1 transcription factor in MGE-like progenitors defined NKX2-1 putative direct targets, including genes involved in both MGE specification and in several aspects of later cIN differentiation (migration, synaptic function). Among the NKX2-1 direct targets with MGE and cIN enriched expression was CHD2, a chromatin remodeling protein. Since CHD2 haploinsufficiency can cause epilepsy and/or autism, which can involve altered cIN development or function, we evaluated CHD2 requirements in these processes. Transcriptome changes were evaluated in CHD2 knockdown MGE-like progenitors at day 15, revealing diminished expression of genes involved in MGE specification and cIN differentiation including channel and synaptic genes implicated in epilepsy, while later cIN electrophysiological properties were also altered. We defined some shared cis-regulatory elements bound by both NKX2-1 and CHD2 and characterized their ability to cooperatively regulate cIN gene transcription through these elements. We used these data to construct regulatory networks underlying MGE specification and cIN differentiation and to define requirements for CHD2 and its ability to cofunction with NKX2-1 in this process. Overall design: To comprehensively define changes in gene expression profiles that accompany cortical interneuron (cIN) specification and differentiation process, we have performed RNA sequencing analysis at days 0 (hESCs), 4, 15, 25, and 35. To understand the gene regulatory networks through which NKX2-1 may directly control these processes, we defined its direct targets by performing NKX2-1 ChIP-seq in day 15 MGE-like cells.  Chromatin enrichment for NKX2-1 binding was compared to input and IgG controls. To define the CHD2-dependent gene expression programs during cIN specification, we used CHD2 knockdown (KD) to conduct RNA-seq analysis in d15 CHD2 KD MGE-like cells.	Co-expression
SRP109080	Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans [RNA-seq]	High fat feeding is deleterious for skeletal muscle metabolism, while exercise has well documented beneficial effects for these same metabolic features. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression (by RNA-seq) and DNA methylation (by Reduced Representation Bisulfite Sequencing). HFD markedly induced expression of immune and inflammatory genes which was not attenuated by Ex. In contract, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed significant association between DNA methylation changes and gene expression were glycogen phosphorylase, muscle associated (PYGM), which was epigenetically regulated in both groups, and angiopoiten like 4 (ANGPTL4), which was regulated only following Ex. We conclude that Short-term Ex does not prevent HFD-induced inflammatory response, but provokes a genomic response that may preserve skeletal muscle from atrophy. Epigenetic adaptation provides important mechanistic insight into the gene specific regulation of inflammatory and metabolic processes in human skeletal muscle. Overall design: Sedentary or exercising human subjects undergo high-fat diet intervention.	Co-expression
SRP109107	Next Generation Sequencing Facilitates Quantitative Analysis of Normoxia and Hypoxia Macrophage Transcriptomes	To test in an unbiased manner for hypoxia effect, we performed a transcriptomic analysis using high throughput RNA sequencing. Overall design: Homo Sapiens Macrophage gene expression	Co-expression
SRP109111	Whole blood RNA-seq of pediatric cases of natural Chikungunya infection	The primary aim of this study was to characterize the transcriptomic changes between the acute and convalescent phase of natural Chikungunya infections in pediatric patients as observed in peripheral blood samples. Overall design: 43 pediatric cases of natural Chikungunya infection were sampled for whole blood at two timepoints (1-2 and 15-17d post symptom onset). Two technical replicates were sequenced per blood sample.	Co-expression
SRP109118	Increased dermal collagen bundle alignment in Systemic Sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs [ECMs]	Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2).  Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. Overall design: This experiment is to perform RNASeq on human fibroblasts cultured on engineered extracellular matrices (ECMs) with patterned surfaces. Dermal fibroblasts were cultured for 48 hours, on collagen-adsorbed aligned nanofibers vs. randomly oriented nanofibers coated with type I collagen. Total RNA was extracted, and analyzed by RNASeq.	Co-expression
SRP109126	Widespread translational remodeling during human neuronal differentiation	Faithful cellular differentiation requires precise coordination of changes in gene expression. However, the relative contributions of transcriptional and translational regulation during human cellular differentiation are unclear. Here, we induced forebrain neuronal differentiation of human embryonic stem cells (hESCs) and characterized genome-wide RNA and translation levels during neurogenesis. We find that thousands of genes change at the translation level across differentiation without a corresponding change in RNA level. Specifically, we identify mTOR complex 1 signaling as a key driver for elevated translation of translation-related genes in hESCs. In contrast, translational repression in active neurons is mediated by transcript 3' UTRs, through regulatory sequences. Together, our findings identify a functional role for the dramatic 3' UTR extensions that occur during brain development, and provide insights to interpret genetic variants in post-transcriptional control factors that influence neurodevelopmental disorders and diseases. Overall design: Forebrain neural cultures differentiated from human embryonic stem cells were isolated and cellular RNA, polysomal RNA, and ribosome protected footprints were deep sequenced.	Co-expression
SRP109153	Homo sapiens Transcriptome or Gene expression	human heart test	Co-expression
SRP109188	Hit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors [RNA-seq]	Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation in the absence of genetic mutations is not clear. To investigate this question, we use a CRISPR/dCas9 based epigenetic editing tool, where an inactive form of Cas9 is fused to DNMT3A and its regulator DNMT3L. Using this system, we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary myoepithelial cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct and results in sustained repression of CDKN2A and RASSF1 transcripts which prevents cells from entering senescence. The phenotype is associated with retuned expression of a subset of genes to levels in early passage cells; however, the outgrowing myoepithelial cells are not immortal but proliferate for 18-20 population doublings before cell cycle arrest. Finally, we show that the key driver of this phenotype is repression of CDKN2A transcript p16, but prolonged proliferation is enhanced by combined hypermethylation and repression of both CDKN2A transcripts p16 and p14. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, a potential first step in the disease process. Overall design: RNA-seq experiment with n=3 biological replicates of primary myoepithelial transfection with 26x gRNAs targeting DNA methylation as described.	Co-expression
SRP109272	RNA-seq reveals abundant circRNA, lncRNA and mRNA in blood exosomes of patients with colorectal carcinoma	Exosomes are small membrane vesicles of endocytic origin secreted by most cells, and contain a wealthy cargo of protein and RNA species that can modulate recipient cells' behaviors and may be used as biomarkers for diagnosis of human diseases. They have been found in blood and are valuable sources for biomarkers due to selective cargo loading and resemblance to their parental cells. The goal of this study is to identify circRNA, lncRNA and mRNA profiles in human blood by high-throughput RNA sequencing (RNA-seq). 1-4 ml plasma or serum were used to extract exosomal RNAs by exoRNeasy Serum/Plasma Maxi kit (Qiagen). The exosomal RNAs were further treated with DNAse I and subjected to ribosome minus low-input RNAseq library preparation. The libraries were sequenced by Illumina Hiseq platform. Overall design: Human blood exosomal RNAs were generated by deep sequencing using Illumina Hiseq.	Co-expression
SRP109278	Transcriptome sequencing analysis of BRAF-mutant melanoma metastases.	Melanoma patients carry a high risk of developing brain metastases, and improvements in survival are still measured in weeks or months. Durable disease control within the brain is impeded by poor drug penetration across the blood-brain barrier, as well as intrinsic and acquired drug resistance. In this study, we used high-throughput pharmacogenomic profiling to identify potentially repurposable compounds against BRAF-mutant melanoma brain metastases. One of the compounds identified was ß-sitosterol, a well-tolerated and brain-penetrable phytosterol. We found that ß-sitosterol attenuated melanoma cell growth in vitro and significantly inhibited brain metastasis in vivo. Large-scale phosphoproteomic and in silico analyses indicated that the therapeutic potential of ß-sitosterol was linked to mitochondrial interference. Mechanistically, ß-sitosterol effectively reduced mitochondrial respiration and respiratory capacity in melanoma cells, mediated by a selective inhibition of mitochondrial complex I. This led to increased oxidative stress and apoptosis. Notably, we observed completely abrogated BRAF inhibitor resistance when vemurafenib was combined with either ß-sitosterol or a functional knockdown of mitochondrial complex I. Based on its favorable tolerability, excellent brain bioavailability, and capacity to inhibit mitochondrial respiration, ß-sitosterol represents a promising candidate for drug repurposing in patients with, or at risk for, melanoma brain metastases. Overall design: A total of 12 samples were analyzed by transcriptome sequencing (RNA-seq) in this study. The study included metastaic xenograft tumors derived from intracardiac injection of H1_DL2 melanoma cells into 5 mice. Metastases to brain, brain, adrenals, ovaries, and femurs in each mouse were identified by bioluminescence imaging, and metastic tumor cells were collected and counted by cell sorting for GFP fluorescence. Replicate tumor cell samples (triplicates) with the highest number of cells from each organ metastasis were selected for RNA-seq analysis.	Co-expression
SRP109284	Developmentally-Faithful and Effective Human Erythropoiesis in Immunodeficient and Kit Mutant Mice	Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis of various developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. Overall design: (mRNA-seq) RNA-seq of human CD235a+ cells isolated 14-16 weeks post-implantation from mouse bone marrow were performed for three biological replicates each of mice xenograted with adult bone marrow-derived human CD34+ cells and cord blood-derived CD34+ cells.	Co-expression
SRP109286	Discovery of naturally occurring ESR1 mutations during acquisition of resistance to endocrine therapy in widely used estrogen receptor positive breast cancer cell lines [RNA-Seq]	We report the first discovery of naturally occurring ESR1Y537C and ESR1Y537S mutations in MCF7 and SUM44 ESR1-positive cell-lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Overall design: RNAseq examination of gene expression changes due to long term estrogen deprivation in two breast cancer cell lines with and without ESR1 mutations	Co-expression
SRP109287	Mining the stiffness-sensitive transcriptome in human vascular smooth muscle cells identifies long non-coding RNA stiffness regulators	Vascular extracellular matrix (ECM) stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic (Ao) and coronary (Co) vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long non-coding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive transcriptome of human Ao and Co VSMCs and identify potentially key lncRNA regulators of stiffness-dependent VSMC functions. Ao and Co VSMCs were cultured on hydrogel substrates mimicking physiologic and pathologic ECM stiffness. Total RNA-seq was performed to compare the stiffness-sensitive transcriptome profiles of Ao and Co VSMCs. Overall design: 4 unique sample types with 4 replicates (16 total samples). Donor-matched Aortic and Coronary VSMCs were serum starved for 48 hours, then cultured in serum containing media for 24 hours on both soft and stiff fibronectin coated hydrogel matrices.	Co-expression
SRP109301	The E3 ubiquitin ligase HectD1 suppresses EMT and metastasis by targeting the +TIP protein ACF7 for degradation	Cancer cells exploit the epithelial-to-mesenchymal transition (EMT) program toward metastasis. Cytoskeletal regulators are dually required in mesenchymal cells by promoting EMT-induced migration and sustaining the EMT program itself. In search for novel regulators of metastasis, we conducted an shRNA screen targeting a class of microtubule regulators, the plus-end tracking proteins (+TIPs). We show that the +TIP ACF7 is required for both the maintenance of EMT and to promote migration. We identified HectD1 as a potent E3 ubiquitin ligase mediating ACF7 degradation. Depletion of HectD1 robustly increases ACF7 protein levels and this is sufficient to enhance migration and EMT in cells, as well as facilitate metastasis in vivo. Ours results report the HectD1/ACF7 axis as a novel regulator of metastasis of breast cancer cells. Overall design: Differential gene expression profile following ACF7 overexpression or Hetd1 depletion by RNA sequencing (Illumina HiSEq 2500)	Co-expression
SRP109351	Homo sapiens strain:HUVEC Raw sequence reads	HUVECs overexpressing FOS or delta FOS and PLV controls to identify genes involved in regulating angiogenesis as seen in epithelioid hemangioma.	Co-expression
SRP109549	Cross-Site Comparison of Ribosomal Depletion Kits for Illumina RNAseq Library Construction	In a cross-site study we evaluated the performance of ribosomal RNA removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded RNA samples. We found that all of the kits were capable of performing significant ribosomal depletion, though there were differences in their ease of use. All kits were able to remove ribosomal RNA to below 20% with intact RNA and identify ~14,000 protein coding genes from the Universal Human Reference RNA sample at >1FPKM. Analysis of differentially detected genes among kits suggested that transcript length may be a key factor in library production efficiency. These results provide a roadmap for labs on the strengths of each of these methods and how best to utilize them. Overall design: The Universal Human Reference RNA (Agilent) was diluted to 500 ng/ul in 200ul of RNase-free water and 3.94ul of the Spike-in RNA Variant Control E2 Mix (Lexogen) were added. The sample was split into two aliquots, one of which was then heated at 94° C for 1 hour and 27 minutes. 1ul of ERCC RNA Spike-In Mix 1 was added to both the intact and degraded samples. The final intact and degraded RNA samples were then diluted to 25 ng/uL and were distributed to each of the ten genomics core facilities (members of ABRF) for ribo-depletion and library preparation following vendor protocol. Each site prepared between one and four library types. Indices were assigned by the group to prevent overlapping among libraries. Libraries were pooled at an equimolar concentration from each kit using site-specific quantification and pooling SOPs and return each pool along with individual un-pooled libraries to the designated sequencing site. The sequencing site quantified each pool, multiplexed and sequenced over three high output paired-end 75bp runs on the Illumina NextSeq 500. contributor: The Association of Biomolecular Resource Facilities (ABRF) DNA Sequencing Research Group (DSRG) members	Co-expression
SRP109666	RNA-seq reveals abundant circRNA, lncRNA and mRNA in blood exosomes of normal persons	Exosomes are small membrane vesicles of endocytic origin secreted by most cells, and contain a wealthy cargo of protein and RNA species that can modulate recipient cells’ behaviors and may be used as biomarkers for diagnosis of human diseases. They have been found in blood and are valuable sources for biomarkers due to selective cargo loading and resemblance to their parental cells. The goal of this study is to identify circRNA, lncRNA and mRNA profiles in human blood by high-throughput RNA sequencing (RNA-seq). 1-4 ml plasma or serum were used to extract exosomal RNAs by exoRNeasy Serum/Plasma Maxi kit (Qiagen). The exosomal RNAs were further treated with DNAse I and subjected to ribosome minus low-input RNAseq library preparation. The libraries were sequenced by Illumina Hiseq platform. Overall design: Human blood exosomal RNAs were generated by deep sequencing using Illumina Hiseq.	Co-expression
SRP109668	RNA-seq reveals abundant circRNA, lncRNA and mRNA in blood exosomes of patients with hepatocellular carcinoma	Exosomes are small membrane vesicles of endocytic origin secreted by most cells, and contain a wealthy cargo of protein and RNA species that can modulate recipient cells' behaviors and may be used as biomarkers for diagnosis of human diseases. They have been found in blood and are valuable sources for biomarkers due to selective cargo loading and resemblance to their parental cells. The goal of this study is to identify circRNA, lncRNA and mRNA profiles in human blood by high-throughput RNA sequencing (RNA-seq). 1-4 ml plasma or serum were used to extract exosomal RNAs by exoRNeasy Serum/Plasma Maxi kit (Qiagen). The exosomal RNAs were further treated with DNAse I and subjected to ribosome minus low-input RNAseq library preparation. The libraries were sequenced by Illumina Hiseq platform. Overall design: Human blood exosomal RNAs were generated by deep sequencing using Illumina Hiseq.	Co-expression
SRP109672	Increasing quality, throughput and speed of sample preparation for strand-specific messenger RNA sequencing	RNA-Sequencing (RNA-seq) is now commonly used to reveal quantitative spatiotemporal snapshots of the transcriptome, the structures of transcripts (splice variants and fusions) and landscapes of expressed mutations. However, standard approaches for library construction typically require relatively high amounts of input RNA, are labor intensive, and are time consuming. Here, we report the outcome of a systematic effort to optimize and streamline steps in strand-specific RNA-seq library construction, which resulted in the identification of an optimized messenger RNA isolation protocol, a potent reverse transcriptase for cDNA synthesis, an efficient chemistry, and a simplified formulation of library construction reagents. We also present an optimization of bead-based purification and size selection designed to maximize the recovery of cDNA fragments. These developments have allowed us to assemble a rapid high throughput pipeline that produces high quality data from amounts of total RNA as low as 25ng. While the focus of this study is on RNA-seq sample preparation, some of these developments are also relevant to other next-generation sequencing library types.	Co-expression
SRP109692	Functional co-operativity of long-noncoding RNAs at the neuroblastoma susceptibility locus 6p22.3 controls disease progression via USP36-CHD7-SOX9 gene regulatory axis.	We report 6p22 locus lncRNAs, which were identified as differentially expressed between high and non-high risk neuroblastoma  tumors using RNA sequencing. we identified CASC15-003 and CASC15-004 lncRNAs act as prognostic biomarker in neuroblastoma. Overall design: Functional characterization for CASC15-003 and CASC15-004 lncRNAs was done using knockdown strategies followed by RNA-seq	Co-expression
SRP109765	Assessing the developmental and malignant potential of human pluripotent stem cells by RNA-seq analysis of Teratomas	The International Stem Cell Initiative compared three common approaches for assessing pluripotent stem cells (PSC).  The formation of teratomas in vivo, or embryoid bodies (EB) in vitro, provide direct tests of differentiation, whereas PluriTest predicts pluripotency through bioinformatic analysis of transcriptomes of undifferentiated cells.  We studied the teratomas by histology and TeratoScore, which analyzes gene expression in each tumor.  For the EB assay, we assessed differentiation under neutral conditions and under conditions promoting differentiation to ectoderm, mesoderm, or endoderm lineages.  Comparison of each method showed that all assays predict pluripotency, but they have different endpoints that provide different insights.  For example, tumors from a subset of lines also contained undifferentiated cells and yolk sac elements that indicate possible malignant potential.  This characteristic was not detected by the other two methods.  Our results highlight the need for multiple assays to assess both pluripotency and potential malignancy in clinical applications of PSCs. Overall design: RNA-seq analysis of human pluripotent stem cell-derived teratomas obtained from 15 human pluripotent stem cells lines from 4 laboratories with 2-3 replicates each, 37 samples in total.	Co-expression
SRP109781	RNA-seq of chordoma of skull base and spine	Transcriptome analysis and comparison of human skull base and spine chordoma to find disease biomarkers, drivers and to improve the understanding of this disease.	Co-expression
SRP109805	A map of human circular RNAs in clinically-relevant tissues	Cellular circular RNAs (circRNAs) are generated by head-to-tail splicing and are present in all multicellular organisms studied so far. Recently, circRNAs have emerged as large class of RNA which can function as post-transcriptional regulators. It has also been shown that many circRNAs are tissue- and stage specifically expressed. Moreover, the unusual stability and expression specificity make circRNAs important candidates for clinical biomarker research. Here, we present a circRNA expression resource of twenty human tissues highly relevant to disease-related research: vascular smooth muscle cells (VSMCs), human umbilical vein (HUVECs), artery endothelial cells (HUAECs), atrium, vena cava, neutrophils, platelets, cerebral cortex, placenta, and samples from mesenchymal stem cell differentiation. In eight different samples from a single donor, we found highly tissue-specific circRNA expression. Circular-to-linear RNA ratios revealed that many circRNAs were higher expressed than their linear host transcripts. Among the 65 validated circRNAs, we noticed potential biomarkers. In adenosine deaminase-deficient, severe combined immunodeficiency (ADA-SCID) patients and in Wiskott-Aldrich-Syndrome (WAS) patients' samples, we found evidence for differential circRNA expression of genes that are involved in the molecular pathogenesis of both phenotypes. Our findings underscore the need to assess circRNAs in mechanisms of human disease. Overall design: To explore circRNA expression patterns in human tissues, we performed rRNA-depleted RNA sequencing and circRNA detection in twenty clinically relevant samples.	Co-expression
SRP109806	Transcriptome of locally advanced colorectal tumours	Here, we report the genomic-scale characterization of locally advanced colon cancer transcriptome. Paraffin embedded samples was used to asses differences between normal colon, primary colon tumor an lymph node metastasis. Overall design: Total RNA was isolated from three location from each recruited patient: normal colon, colon tumor and lymp node metastasis.	Co-expression
SRP109817	RNA-seq during MCF10A-ER-Src cell transformation and upon factor knockdowns	We performed RNA-seq to examine RNA expression profiles during MCF10A-ER-Src cell transformation and upon knockdowns of transcription factors Overall design: RNA-seq before and after MCF10A-ER-Src cell transformation, and RNA-seq upon factor knockdowns after inducing cell transformation	Co-expression
SRP109826	Transcriptional impact of MTHFD2 in Human Aortic Endothelial Cells	We performed transcriptome analysis of Human Aortic Endothelial Cells after siRNA mediated knockdown of MTHFD2. We identified MTHFD2 as a key driver for a gene cluster which integrates mitochondrial one-carbon metabolism, serine synthesizing enzymes as well as common amino acid and ER stress response genes. Overall design: Human Aortic Endothelial Cells were treated with three different siRNAs against MTHFD2 or scramble for 72 h	Co-expression
SRP109837	HPIP controls osteoarthritis cartilage degeneration  [RNA-seq]	To underly the potential downstream transcriptional regulation of HPIP that could account for cartilage and skeletal development. RNA-seq analysis were performed in HPIP knockout and control primary chondrocytes.Among the 1271 significantly differentially expressed genes, transcripts for 486 (7%) of them were upregulated while transcripts for 785 (11%) were downregulated in HPIP knockout  chondrocytes compared to the controls. We found HPIP was closely correlated with the cartilage development. Overall design: Total RNA was isolated with TRIzol from the HPIP knockout and the control primary chondrocytes. Complementary DNA library were prepared and then sequenced by Novel Bioinformatics Co, Ltd (https://en.novogene.com/). Clean reads was obtained from the raw reads by removing the adaptor sequence before read mapping. Reference genome and gene model annotation files were downloaded from genome website browser (NCBI/UCSC/Ensembl). HTSeq V0.6.1 was used to count the read numbers mapped of each gene. And then RPKM of each gene was calculated based on the genes reads count mapped to this gene. Differential expression analysis was performed using the DESeq R package (1.10.1).	Co-expression
SRP109992	Sox5/6/21 prevent oncogene driven transformation of brain stem cells	Using Sox5/6/21 knock out mice and overexpression in human glioblastoma cell lines, we show that these genes act as tumour suppressors.	Co-expression
SRP110003	FOXP2''s impact on the primate transcriptome	The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In spite of its relevance, the FOXP2-controlled network and its functional implications are only partially understood. Therefore, we analyzed the transcriptomes of human neuroblastoma cells (SH-SY5Y) stably overexpressing human, chimpanzee, macaque, and marmoset FOXP2 cDNAs. Clones carrying empty vector served as a standard of baseline expression. All conditions were represented by two biological replicates (A, B), each. By comparing expression levels (bases which map per kb of exon model per million mapped bases) across the different conditions we were able to identify genes with differential expression in clones overexpressing human FOXP2 relative to each other condition. Overall design: Examination of expression profiles in SH-SY5Y clones that were alternatively transfected with different primate FOXP2 cDNAs	Co-expression
SRP110035	Whole transcriptome sequencing of the human thyroid primary cells with knock-down of the NRG1 gene	The protein encoded by the NRG1 gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. Here we report gene expression profiles of human thyroid primary cells on Day 5 treated with NRG1 siRNA. The primary cells were generated from fresh nontumorous thyroid tissues obtained from thyroid cancer patients. A number of new dysregulated genes of NRG1 were discovered. This study reveals a novel role of NRG1 in downstream gene regulation and provides a new explanation of NRG1's function in thyroid cancer. Overall design: Profiling of 3 human thyroid primary cells (generated from 3 different patient samples) transfected with NRG1 siRNA (75pmol) was performed using RNA-seq. Cells were cultured for 24h after transfection and then lysed prior to RNA isolation, DNase treatment, purification and RNA-seq library construction. Profiling of 3 human thyroid primary cultures (3 nontarget siRNA treated) derived from the fresh thyroid tissues of 3 individuals was also performed using RNA-seq.	Co-expression
SRP110040	RNA-sequencing profiles of five different pancreas cancer cell lines that were engineered to express a form of the basic helix-loop-helix transcription factor, E47, that localizes to the nucleus in response to tamoxifen.	E47 had been shown previously to inhibit cell cycle progression in pancreas cancer cell lines. This study was designed to identify global changes in gene expression that occurred in response to E47 with the goal of identifying molecular mechanisms involved inE47-mediated inhibition of the cell cycle. Overall design: Total RNA was isolated from No Tamoxifen (NT) and With Tamoxifen (WT) treated samples 48-72 hrs after induction of nuclear E47, sequenced and analyzed to identify candidate regulators of cell cycle inhibition that were common to all five cell lines examined.	Co-expression
SRP110043	KMT2C medaites the estrogen dependence of breast cancer through regulation of ERa enhancer function	KMT2C is a key regulator of ERa activity whose loss allows for hormone independent proliferation in MCF7 cells Overall design: Examination of RNA seq and ChIP seq in cells with KMT2C knockdown as well as cells with KMT2C knockdown that have gorwn out in hormone-deprived media	Co-expression
SRP110148	Integrated Transcriptomic and Proteomic Dynamics of Everolimus Treatment in B Lymphoblastoid Cells	The investigation aims to profile the molecular dynamics of Everolimus treatment in cells.  Specifically, a B-lymphoblast cells line was treated with Everolimus and sampled every half-hour over a 12 hour period. Treated and untreated cells were processed to extract RNA and protein that were subsequently used in high-throughput analysis of the transcriptome (RNA-Sequencing) and proteome (mass spectrometry). Overall design: Examination of dynamics in a treated cell line and a parallel untreated controlline, both sampled over 12hrs every half hour. Validation using a new repeated experiment, with treated and untreated tracks, sampled over 6 selected time points.	Co-expression
SRP110187	Type I IFNs and TNF Cooperatively Reprogram Epigenomic Landscape of Human Macrophages to Promote Inflammatory Activation [RNA-seq]	Crossregulation of TLR responses by cytokines is essential for effective host defense, avoidance of toxicity, and homeostasis, but underlying mechanisms are not well understood. A comprehensive approach integrating RNA-seq, ChIP-seq and ATAC-seq digital footprinting showed that TNF and type I IFNs extensively remodel chromatin states in human macrophages to differentially regulate transcriptional induction of NF-?B, STAT, antiviral, and metabolic genes by LPS. IFN-a potentiated TNF inflammatory function by abrogating feedback silencing of inflammatory genes via priming of chromatin to enable robust transcriptional responses to weak upstream signals. Similar chromatin regulation occurred in human diseases. Our findings provide insights into epigenomic mechanisms by which cytokines reprogram inflammatory responses, and identify new functions and mechanisms of action of TNF and IFNs. Overall design: Analysis of transcriptional changes in human macrophages stimulated with or without TNF and LPS	Co-expression
SRP110248	Probing the Roles of SUMOylation in Cancer Cell Biology Using a Selective SAE inhibitor	Small ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking.  Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi	Co-expression
SRP110282	Dual RNAseq - Human hepatocytes infected with Plasmodium berghei	A dual RNA sequencing study of the Plasmodium exoerythrocytic stage of infection has identified a novel host biomarker of infection, Mucin13.	Co-expression
SRP110289	CUREfast: Accelerating research with families	RNA sequencing of tissue samples taken from pediatric cancer patients of varying disease type. Patients represented those with terminal disease with samples taken from resection or autopsy. Overall design: snap frozen tumor tissue were processed to isolate DNA and RNA from resected or autopsy tissues. Tissues were generally acquired following therapeutic regimens	Co-expression
SRP110339	Homo sapiens Raw sequence reads	Next generation sequencing of esophageal squamous cell carcinoma (ESCC) cell line KYSE-180 bulk transcriptomes for radio-resistance analysis	Co-expression
SRP110347	Elucidation of molecular pathogenesis of Spinocerebellar Ataxias Type -12 (SCA-12) through Induced pluripotent stem cell based models	RNA sequencing of iPSCs and differentiated neural cells	Co-expression
SRP110479	Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response	Elevated expression of RNA binding protein HNRNPC has been reported in cancer cells, while the essentialness and functions of HNRNPC in tumors were not clear. We showed that repression of HNRNPC in the breast cancer cells MCF7 and T47D inhibited cell proliferation and tumor growth. Our computational inference of the key pathways and extensive experimental investigations revealed that the cascade of interferon responses mediated by RIG-I was responsible for such tumor-inhibitory effect. Interestingly, repression of HNRNPC resulted in accumulation of endogenous double-stranded RNA (dsRNA), the binding ligand of RIG-I. These up-regulated dsRNA species were highly enriched by Alu sequences and mostly originated from pre-mRNA introns that harbor the known HNRNPC binding sites. Such source of dsRNA is different than the recently well-characterized endogenous retroviruses that encode dsRNA. In summary, essentialness of HNRNPC in the breast cancer cells was attributed to its function in controlling the endogenous dsRNA and the down-stream interferon response. This is a novel extension from the previous understandings about HNRNPC in binding with introns and regulating RNA splicing. Overall design: Cytoplasmic total RNAs were profiled upon HNRNPC knock-down in MCF7 (2 replicates) and T47D cells, NC and LAMN knock-down cells served as controls.	Co-expression
SRP110507	4sU-seq of HFF exposed to salt and heat stress	Primary human foreskin fibroblasts (HFF) were exposed to either salt stress (80mM KCl) or heat stress (44ºC). Newly transcribed RNA was labelled by adding 500µM 4-thiouridine (4sU) to the cell culture media for 1h. Total cellular RNA was isolated using Trizol. Newly transcribed RNA was purified following the protocol described in Raedle et al. JoVE 2013. Overall design: Newly transcribed RNA was labelled in one hour intervals during either salt or heat stress (prior to stress, 0-1h or 1-2h). All 4sU-RNA samples were sent for sequencing. Two independent biological replicates were analysed.	Co-expression
SRP110509	Next Generation Sequencing Study of Circadian Changes in Transcriptome of Human Pineal Gland	Purpose: We performed an NGS study on the circadian changes in human pineal gland transcriptome in order to elucidate novel and conserved elements in the circadian clock, as well as to conduct a comparative analysis of pineal transcriptomes of several animal species. Methods: Total RNA from human pineal glands of individuals that died at 2 timepoints (Mid-Day, Midnight)  was deep sequenced, using Illumina HiSeq2500. Reads were aligned using STAR aligner and differential expression was asssessed using DESeq2. Results: We discover a variety of genes that show circadian activivty in human pineal gland. Conclusions: Our study represents part of a comparative analysis of  pineal gland transcriptome of several species, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: Pineal glands were obtained from NDRI (National Disease Research Interchange), (Pennsylvania Medical Center, Philadelphia, PA). Two glands were from individuals that died at mid-day (11:00-13:00) and four from deaths occurring at mid-night (23:00-01:00). Samples were stored at -80 o C until use. RNA was extracted from individual glands with Trizol (Invitrogen, Carlsbad,CA) and subsequently cleaned up using an RNeasy Micro Kit with on-column DNase treatment(Qiagen, Valencia, CA). The amount and quality of RNA were determined using a NanoDropspectrophotometer (NanoDrop, Wilmington, DE) and an Agilent 2100 Bioanalyzer (AgilentTechnologies, Santa Clara, CA), respectively. RIN values ranged from 7.3-8.7. RNA-Seq library preparation and sequencing: Ribosomal-depleted RNA was used to construct stranded libraries from 1 µg aliquots of total RNA using a TruSeq Stranded Total RNA Sample Prep Kit (Illumina cat. no. RS-122- 2301) according to the manufacturer''s instructions. The library insert sizes were approximately 170 bp. Unique barcode adapters were appended to each library. Equal volumes of individual libraries were pooled and run on a MiSeq (Illumina, San Diego, CA). The libraries were then re-pooled based on the MiSeq demultiplexing results. The pooled libraries were sequenced on a HiSeq 2500 (Illumina, San Diego, CA) using version 4 chemistry. The  data was processed using RTA version 1.18.64 and CASAVA 1.8.2. This yielded an average of 81 million 126-bp read-pairs for each sample. Reads were aligned using STAR aligner and differential expression was asssessed using DESeq2. GRCh37/hg19 genome build with Gencode 19 annotation was used.	Co-expression
SRP110512	Oxidative stress triggers selective tRNA retrograde transport in human cells	In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol where they deliver aminoacids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, recent discoveries demonstrated an active shuttling of tRNAs between cytosol and nucleus, named tRNA retrograde transport. This pathway is conserved in eukaryotes, suggesting a fundamental function, however little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid and reversible. Next generation sequencing of tRNAs revealed that retrograde transport is selective for certain tRNA species, mostly with shorter 3' ends. mTOR and PERK regulate tRNA nuclear import, linking it to the endoplasmic reticulum unfolded protein response. Thus tRNA retrograde transport is a new component of the cellular response to oxidative stress.	Co-expression
SRP110516	RNA-seq of MDA-MB-231 cells with TET1 knockout	DNA hypermethylation is known to contribute to the formation of cancer.  However, DNA hypomethylation has received far less attention and the factors controlling the balance between hypo and hypermethylation and its impact on tumorigenesis remains unclear.  Triple negative breast cancer (TNBC), a subtype of breast cancer that does not overexpress the hormone receptors or HER2/NEU, is one of the most hypomethylated cancers observed.  Importantly, TNBCs are often a therapeutic challenge because of advanced presentation and lack of targeted therapies. TET1 is a DNA demethylase that regulates DNA methylation, hydroxymethylation and gene expression.  We found that TET1 is specifically overexpressed in TNBC, where it is associated with hypomethylation and a worse overall survival.  Further, we uncover an intricate network connecting TET1 expression to maintaining activation of cancer specific pathways, including PI3K, EGFR and PDGF.  In TET1 KO cells, we observed reduced phospho-4EBP1 and decreased expression of genes in the PI3K pathway, suggesting loss of PI3K-mTOR activity is concomitant with loss of TET1.  Additionally, TET1 KO cells have reduced cellular proliferation and migration.  Our work establishes TET1 as an oncogene that contributes to the aberrant hypomethylation observed in cancer and suggests TET1 could serve as a novel druggable target for therapeutic intervention. Overall design: Triplicates were performed for a total of 12 samples. Fold change of each gene was calculated by comparing changes in expression in KO compared to the empty vector control samples	Co-expression
SRP110517	mRNA profiles of JMJD3 overexpression- and JMJD3 knockout- HL-60 cells	Next Generation Sequencing Facilitates Quantitative Analysis of HL-60 cells transduced with control or JMJD3-expression vector, and HL-60 parental and JMJD3 knockout cells Overall design: mRNA profiles of HL-60 cells were generated by deep sequencing, in triplicate, using  Illumina HiSeq 4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using  SYBR Green assays.	Co-expression
SRP110537	The dynamics of cellular response to therapeutic perturbation using multiplexed quantification of the proteome and transcriptome at single-cell resolution	We developed a scalable assay permitting the simultaneous quantification of hundreds of proteins and the full transcriptome in thousands of individual cells from samples where cell number is limiting.  The RNA Expression and Protein Sequencing assay (REAP-seq) uses DNA-labeled antibodies to permit DNA sequencing of both mRNA and antibodies in a single workflow using droplet microfluidics. We describe the development and validation of REAP-seq in human PBMCs, and use the assay to assess the costimulatory effects of an anti-CD27 agonist antibody in naïve CD8+ lymphocytes. Protein quantification using REAP-seq was more sensitive than parallel mRNA measurements and differentiated cell states with fewer analytes. Unbiased profiling of single cells without prior selection enabled identification and characterization of an unexpected cell type that would have been missed with population-averaged profiling methodologies. Overall design: The RNA Expression and Protein Sequencing assay (REAP-seq) which uses DNA-labeled antibodies to permit DNA sequencing of both mRNA and antibodies in a single workflow using droplet microfluidics was developed and validated in human PBMCs and naïve CD8+ T cells that were costimulated with either 1) aCD3 and aCD28 or 2) aCD3, aCD28 and aCD27.	Co-expression
SRP110564	Identification of circular RNAs with host gene-independent expression in human model systems for cardiac differentiation and disease	Aims: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5’ splice site to an upstream 3’ splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts.[1,2] Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments.Methods and Results: Deep RNA sequencing of cardiomyocyte development and ß-adrenergic stimulation uncovered 4,518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intri-guingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes.Conclusion: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene inde-pendent expression dynamics in patient samples and may interact with the ribo-some and RISC complex. In summary, the hiPSC-CM model uncovered a new sig-nature of potentially disease relevant circRNAs which may serve as novel therapeu-tic targets.	Co-expression
SRP110582	Mutational landscape of splicing genes and functional consequences across 33 cancer types	Hotspot mutations in the spliceosome component genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of this pathway in cancer. However, a comprehensive survey of splicing factor mutations across tumor types has not yet been performed. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA) in order to discover recurrent mutations in spliceosome components, identifying 119 genes with significant non-silent mutation patterns, including mutation overrepresentation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). We used RNA sequencing data to identify altered splicing events associated with these spliceosome mutations. In addition, we were able to discover common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of the splicing pathway is common in solid tumors and may represent an underappreciated hallmark of tumorigenesis. Overall design: 6 U87MG cell line samples, including 3 treated with siRNA against FUBP1 and 3 with a non-specific siRNA	Co-expression
SRP110609	RNA-sequencing analysis of response to P.falciparum infection in Fulani and Mossi ethnic groups, Burkina Faso	The Fulani ethnic group is relatively protected from Plasmodium falciparum malaria, however a genetic basis for this is unknown. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani, compared to a sympatric ethnic group, the Mossi. When we compared uninfected and infected individuals in Fulani and Mossi, a strong transcriptional response was only detected in the monocyte fraction of Fulani, and this was not related to differences in DNA methylation. Overall design: RNA sequencing analysis of CD14+ (monocyte) and CD14- (predominantly lymphocyte), and DNA-methylation analysis of CD14+ (monocyte) fractions of PBMCs,  from of Fulani and Mossi individuals, uninfected or infected with P.falciparum. This Series represents the RNA-Seq dataset.	Co-expression
SRP110611	Microfluidics-based molecular profiling of circulating tumor cells in checkpoint inhibitor immunotherapy and BRAF/MEK-treated melanoma patients	Gene expression profiling of circulating tumor cells-enriched cells obtained from blood of three melanoma patients on immunotherapy. Overall design: mRNA profiles generated by deep sequencing using Illumina HiSeq 2500.	Co-expression
SRP110620	Global transcriptomic analyses of bronchial epithelial cells exposed to 5 ng/mL TGF-ß1 and 10 nM Estrogen individually and in combination	To begin to identify downstream consequences of TGF-ß1-induced reduction of estrogen receptor expression, we employed RNA-Seq.  Results of global transcriptomic analysis showed that TGF-ß1 and E2 inversely modulated the expression of several genes involved in both known pro-fibrotic cellular processes such as extracellular matrix turnover and newly identified events including airway smooth muscle cell contraction and calcium flux regulation. We also report, for the first time, that E2 specifically modulated the expression of genes involved in chromatin remodeling pathways and that this regulation was absent in the presence of TGF-ß1. Collectively, these results suggest that E2 influences pathways relevant to pulmonary fibrosis and highlights potential roles for E2 in the lung that may contribute to sex-specific differences in IPF. Overall design: Four treatment groups were analyzed; cells exposed to vehicle control (n = 5), 5 ng/mL TGF-ß1 (n = 5), 10 nM Estrogen (n = 3), or 5 ng/mL TGF-ß1 and 10 nM Estrogen in combination (n = 4)	Co-expression
SRP110623	Subcellular RNA fractions of HSV-1 infected primary human fibroblasts	Primary human foreskin fibroblasts (HFF) were infected with wild-type simplex virus 1 (HSV-1) strain 17 at a multiplicity of infection (MOI) of 10. Subcellular RNA fractions including total RNA, cytoplasmic RNA, nucleoplasmic RNA and chromatin-associated RNA were prepared and subjected to RNA-seq Overall design: HFF were infected with HSV-1 strain 17 for 8h (or mock). Subcellular RNA fractions were prepared combinig the following two protocols (PMID: 19656867, RNA 2009; and PMID: 23449254, Nature Protocols 2013). Two independent biological replicates were analysed.	Co-expression
SRP110659	Dynamics of Proteo-Transcriptomic Response to HIV-1 Infection	Throughout HIV-1 replication cycle, a complex interplay of host-pathogen interactions takes place in the infected cell, leading to production of new virions. The virus modulates the host cellular machinery in order to support its life cycle, while controlling intracellular defense. We have investigated the dynamic host response to HIV-1 infection by systematically measuring transcriptome, proteome and phosphoproteome expression changes in infected and uninfected SupT1 CD4+ T cells at 5 time-points throughout the HIV-1 replication cycle. Genome-wide transcript levels were assessed by RNA-Seq, while protein and phosphoprotein relative abundances were obtained using SILAC mass spectrometry. By the means of a Gaussian mixed-effects model, we stratified host genes based on their gene expression temporal patterns at the three levels, showing how HIV may affect regulation of certain host genes. The results of the implemented integrative analysis of time-series omics data offers a catalogue of dynamic host response to HIV infection allowing a more comprehensive understanding of host-virus interactions. Furthermore, it facilitates identifying novel host factors potentially promoting or restricting HIV replication. Overall design: Host-HIV interactions in CD4+T-cells. Time-series RNA-Seq was performed in mock-treated and HIV-infected CD4+ T-cells at 6h, 12h, 18h, 24h and 30h.	Co-expression
SRP110699	Single Cell RNA sequencing analysis of human haemopoietic lympho-myeloid progenitor populations (LMPP, MLP and GMP)	We performed single cell RNA sequencing of human haemopoietic lympho-myeloid progenitors with the aim to separate functionally and transcriptionally distinct progenitors within the heterogeneous GMP, LMPP and MLP populations. We performed RNA sequencing in a total of 415 single cells. From donors 1 (CB369) and 2 (CB431), 163/166 and 157/249 cells passed quality control.We further analysed the 320 single cells that passed quality control from two  different donors (157 and 163 from each donor; 91 LMPP, 110 MLP and 119 GMP). We performed clustering using Seurat package, which identified 3 clusters of cells.  We identified genes that were differentially expressed among cells of the different clusters. The majority of the cells in cluster 1 were MLP, the majority of cluster 3 were GMP while cluster comprised of LMPP and GMP cells. Cluster 1 showed high expression of lymphoid-affiliated genes. Conversely, cluster 3 showed increased expression of myeloid genes, while cluster 2 showed a mixed transcriptional signature. PCA analysis revealed a transcriptional continuum of LMPP, MLP and GMP populations. Overall design: Transcriptional heterogeneity of LMPP, MLP and GMP human lymphomyeloid progenitors at the single cell level.	Co-expression
SRP110704	Transcriptomic profiling of CD8+ T cells from steroid-sensitive and steroid-resistant asthmatics and healthy controls	The heterogeneity of asthma has prompted attempts at classifications based on clinical phenotypes and cluster designations. Although helpful, reliance on clinical parameters fails to address fundamental issues resulting in specific phenotypes, in particular, steroid-resistant (SR) asthma. Limited data are available defining the mechanisms or pathways (endotypes) causing the failure of inhaled corticosteroids (ICS) in SR asthmatics. Unlike CD4+ T cells, both human and mouse CD8+ T cells fail to undergo apoptosis in the presence of corticosteroids (CS) positioning them as unique effector cells. Whole transcriptome analyses of peripheral CD8+ T cells from steroid-sensitive or steroid-resistant asthmatics or healthy controls on days 0 and 8 were performed. Overall design: RNA-sequencing of activated (anti-CD3/CD2) CD8+ T cells purified from the peripheral blood from steroid-sensitive and steroid-resistant asthmatics and healthy controls on day 0 and cultured in the presence of IL-2 for 8 days.	Co-expression
SRP110765	Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi  (amastigotes and host cell)	Trypanosoma cruzi, the protozoan that causes Chagas disease, has a complex life cycle involving several morphologically and biochemically distinct stages that establish intricate interactions with various insect and mammalian hosts. It has also a heterogeneous population comprising strains that show distinct properties such as virulence, sensitivity to drugs, antigenic profile and tissue tropism. We present here a comparative transcriptome analysis of two cloned T. cruzi strains that display contrasting virulence phenotypes in animal models of infection: CL Brener is a virulent strain and CL-14 is a strain that is neither infective nor pathogenic in in vivo models of infection. Gene expression analysis of trypomastigotes and intracellular amastigotes harvested at 60 and 96 hours post-infection (hpi) of human fibroblasts revealed large differences that reflect the parasite's adaptation to distinct environments during the infection of mammalian cells, including changes in energy sources, oxidative stress responses, cell cycle control and cell surface components. While extensive transcriptome remodeling was observed when trypomastigotes of both strains were compared to 60 hpi amastigotes, differences in gene expression were much less pronounced when 96 hpi amastigotes and trypomastigotes of CL Brener were compared. In contrast, the differentiation of the avirulent CL-14 from 96 hpi amastigotes to extracellular trypomastigotes was associated with considerable changes in gene expression, particularly in gene families encoding surface proteins such as trans-sialidases, mucins and the mucin associated surface proteins (MASPs). Thus, our comparative transcriptome analysis indicates that the avirulent phenotype of CL-14 may be due, at least in part, to a reduced or delayed expression of genes encoding surface proteins that are associated with the transition of amastigotes to trypomastigotes, an essential step in the establishment of the infection in the mammalian host. Transcriptome data is provided for parasites and host cells (infected and uninfected).	Co-expression
SRP110769	Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders	Background: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs have emerged as important modulators of brain development and neuronal function and are implicated in several neurological diseases. Previous studies found miR-146a upregulation is the most common miRNA deregulation event in neurodevelopmental disorders such as autism spectrum disorders (ASD), epilepsy and intellectual disability (ID). Yet, how miR-146a upregulation affects the developing fetal brain remains unclear. Methods: We analyzed the expression of miR-146a in the temporal lobe of ASD children using Taqman assay. To assess the role of miR-146a in early brain development, we generated and characterized stably induced H9 human neural stem cell (H9 hNSC) overexpressing miR-146a using various cell and molecular biology techniques. Results: We first showed that miR-146a upregulation occurs early during childhood in the ASD brain. In H9 hNSC, miR-146a overexpression enhances neurite outgrowth and branching and favors differentiation into neuronal like cells. Expression analyses revealed that ten percent of the transcriptome was deregulated and organized into two modules critical for cell cycle control and neuronal differentiation. Twenty known or predicted targets of miR-146a were significantly deregulated in the modules, acting as potential drivers. The two modules also display distinct transcription profiles during human brain development, affecting regions relevant for ASD including the neocortex, amygdala and hippocampus. Cell type analyses indicate markers for pyramidal and interneurons are highly enriched in the deregulated gene list. Up to 40% of known markers of newly defined neuronal lineages were deregulated, suggesting that miR-146a could participate also in the acquisition of neuronal identities. Conclusion: Our results demonstrate the dynamic roles of miR-146a in early neuronal development and provide new insight into the molecular events that link miR146a overexpression to impaired neurodevelopment. This, in turn, may yield new therapeutic targets and strategies. Overall design: For each cell line, we used technical triplicates. The samples are matched based on passage number.	Co-expression
SRP110770	Immunophenotyping and Transcriptomic Outcomes in PDX-Derived TNBC Tissue	Cancer tissue functions as an ecosystem of a diverse set of cells that interact in a complex tumor microenvironment. Genomic tools applied to biopsies in bulk fail to account for this tumor heterogeneity, whereas single-cell imaging methods limit the number of cells which can be assessed or are very resource intensive. The current study presents methods based on flow cytometric analysis and cell sorting using known cell surface markers (CXCR4/CD184, CD24, THY1/CD90) to identify and interrogate distinct groups of cells in triple-negative breast cancer clinical biopsy specimens from patient-derived xenograft (PDX) models. The results demonstrate that flow cytometric analysis allows a relevant subgrouping of cancer tissue and that sorting of these subgroups provides insights into cancer cell populations with unique, reproducible, and functionally divergent gene expression profiles. The discovery of a drug resistance signature implies that uncovering the functional interaction between these populations will lead to deeper understanding of cancer progression and drug response. Overall design: Triple-negative breast cancer PDX-derived tumors were dissociated and sorted into subpopulations of CD24+/CD184 high and CD24+/CD184 low expressing cells using flow cytometry and the transcriptomes of these subpopulations were characterized using bulk RNAseq.	Co-expression
SRP110805	RNA-Seq of Kaposi's sarcoma reveal alterations in glucose and lipid metabolism	Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). In sub-Saharan Africa, the high prevalence of both HIV-1 and KSHV has made KS a leading cancer in the region, associated with poor prognosis and high mortality due to late medical presentation and advanced disease stages. A better understanding of the cellular and viral transcriptome profiles during neoplastic growth will aid in the definition of biomarkers and cellular functions associated with KS tumorigenesis and progression. Our approach is to examine the transcriptome profile in actual KS lesions versus non-cancer tissues from the same individual for a total of four male African epidemic KS patients. These patients have undetectable HIV-1 plasma viral load after successful anti-retroviral therapy. Our results capture the cellular complexity of in vivo lesion environment and provide a marked contrast to those derived from in vitro monoculture models.  The findings demonstrate that latency and immune modulation related functions dominate the viral gene expression pattern. Moreover, KSHV significantly affected the cellular transcriptome profile with genes involved in lipid and glucose metabolism disorder pathways being the most substantially dysregulated. Despite the implied infiltration of immune cells into the lesions as predicted by CIBERSORT, KS tumor continued to progress, suggesting immunological dysfunction in these KS patients despite control of HIV-1 viremia. Lastly, there is limited overlap of our in vivo dataset with in vitro studies, suggesting a limitation of in vitro KS models. Overall design: RNA-seq of Kaposi's sarcoma lesions and control tissues	Co-expression
SRP110816	RNA-Seq analysis of breast cancer cells after shikonin treatment	We performed RNA-seq analysis using differnt breast cancer cell lines (MCF-7, SK-BR-3 and MDA-MB-231) after shikonin treatment. We reported that shikonin enhances the expression of DUSP-1 and DUSP-2. Shikonin induces apoptosis and decreases the phosphorylation of JNK1/2 through activationg DUSP-1 and DUSP2. Overall design: We treated three breast cancer cell lines with 10 µ? shikonin for 6 hr. The gene expression profiling was performed using RNA-seq. Numbers of significantly differentially expressed (SDE) genes in different human breast cancer cell lines under shikonin treatment had been identified. We analyzed the functional annotation and performed the pathway analysis using 38 common SDE genes.	Co-expression
SRP110985	Gene Expression Profiling of SPOP Knocked Down Cell	SPOP is one of the most frequent mutated genes in prostate cancer. In the current study, we identified CCNE1 as its substrate. SPOP directly interacts with CCNE1, poly-ubiquitinates CCNE1 in vivo and in vitro, and represses cancer-related phenotypes induced by CCNE1 expression. Thus, we reveal a new mechanism for SPOP in repressing prostate cancer tumorigenesis. Overall design: SPOP was knocked down by siRNA in DU145 and 769-P, the gene expression profile was studied by RNA sequencing	Co-expression
SRP110991	RNA-seq analysis of YFV-17D specific and total naive CD8 T cells in humans	These 14 samples originate from peripheral blood mononuclear cells (PBMC) from donors at different times after they were vaccinated with the YF-17D vaccine. Overall design: 10,000 to 100,000 tetramer+ CD8 T cells specific for the NS4B-214 epitope in YFV-17D were purified by flow cytometry based sorting, from 8 vaccinees. Total Naive (CD45RA+ CD8+) CD8 t cells were also sorted from these donors.  Subsets were defined based on the time after vaccination. The subsets (cell types) include: Naive CD8 T cells (n=6); YFV-specific Effector CD8 T cells (day 14 after vaccination, n =3) and YFV-specific long term memory CD8 T cells (4 to 12 years after vaccination, n=5).	Co-expression
SRP110994	Repression of stress-induced LINE-1 expression protects cancer cell populations from lethal drug-exposures [RNA-Seq]	DTP heterochromatin in genomic repeat regions protects the population from drug-induced death. Overall design: Investigation of RNA expression changes in heterogenous parental populations as compared to drug treated and drugtolerant populations. Also included are TSA treated parental and drug-tolerant populations	Co-expression
SRP111005	Spindle-localized mRNA translation mediated by CPEB1 and CPEB4 controls mitotic progression	Sequencial functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase-specific activation to promote cell phase transitions and correct chromosome segregation Overall design: RNA-seq of total and spindle-associated mRNAs in Hela S3 cells	Co-expression
SRP111058	In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [HS1001 differentiation protocol]	Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology. Overall design: Human embryonic stem cells HS1001 were cultured in wells coated with LN-521 and LN-221 using RPMI1460 supplemented with B21 without insulin medium. Differentiation commenced when cells reached confluency. Small molecule inhibitor CHIR99021 (inhibitor of GSK3) was added at day 0 followed by IWP2 (inhibiot of Wnt production) at day 3. Cells continue to be cultured in RPMI1460 supplemented with B21 without insulin medium for 10 days with medium change every other day. After day 10, medium was changed to RPMI1460 supplemented with B21 CTS grade medium. RNA was extracted from triplicates wells at day 0, 1, 3, 11, 14, 20, 30 and 90 and from 5 wells at day 5, 7 and 9.	Co-expression
SRP111096	Human-specific features of special gene expression and regulation in eight brain regions	Despite the substantial efforts made to compile the molecular maps of the human brain, they do not fully inform us of the features unique to humans. Yet, identification of these features might help us to understand both the evolution and nature of the human cognitive traits. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, gibbon and macaques. Integrated analysis of these data revealed existence of 1,851  human-specific transcriptome differences affecting one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than a half of these differences represented elevated expression in human hippocampus, while the rest affected microglial functions in neocortex. Analysis of predicted regulatory interactions driving these differences revealed role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Overall design: Transcriptome across eight brain regions (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, anterior cingulate cortex, premotor cortex, primary visual cortex, striatum, hippocampus, cerebellum) of humans, chimpanzees, gorillas and gibbon were measured using RNA-seq.	Co-expression
SRP111102	Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [RNA-seq]	Transcriptomic profiling of human breast tumors using RNA sequencing Overall design: Evaluation of common fusion transcripts, genetic variants, and gene expression patterns in 8p11-p12 amplified breast carcinomas	Co-expression
SRP111135	Mechanisms of Cancer Resistance to Immunogenic Cytotoxicity	The majority of cancer patients do not respond to immunotherapy. In order to systematically discover pathways promoting cancer cell resistance to effector immune cells, we generated immunity-resistant Head and Neck Squamous Cell Carcinoma cell lines. We utilized RNA-Seq to determine what are the genes and pathways that are significantly altered when cancer cells become resistant to effectors. Overall design: RNA-Seq was performed on four cell lines, including two biologic replicates of wildtype and immune-resistant PCI-13 cells. The two immune-resistant PCI-13 cell lines were generated separately using the same protocol described in the manuscript.	Co-expression
SRP111145	Ebola virus (EBOV) infection of ARPE-19 cells	We inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site and network analyses. Human retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28% of 560 up-regulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Overall design: Transcriptomic profiles of ARPE-19 cells 24 hours following infection with EBOV or mock-infection	Co-expression
SRP111173	Transcriptional Consequences of XPA Disruption in Human Cell Lines	Purpose: Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. Methods: We analyzed the human transcriptome by RNA sequencing (RNA-Seq). Four genetically matched human cell line pairs deficient or proficient in XPA were analyzed Results: Of the ~14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2  protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. Conclusions: We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum. Overall design: Eight cell lines were used as follows. For HeLa-derived cells, HeLa S3 (XPA+, two cultures), HeLa KO38 (XPA-), and HeLa KO142 (XPA-), XPA2OS (XPA-). A fibroblast cell pair was XP2OS (XPA-) and an XPA complemented clone XPA/XPA2OS (XPA+). A second fibroblast cell pair was XP12RO (XPA-) and an XPA complemented clone XPA/XPA12RO (XPA+). Each culture was treated with a DMSO control or with retinoic acid in DMSO. Independent cultures and libraries were prepared and analyzed in triplicate, for a total of 48 samples.	Co-expression
SRP111183	mRNA-Seq profiling of human developing kidney	To characterize the molecular features of human kidney development, and to capture timing of emergence of important kidney compartments, we generated mRNA-Seq data from human kidneys at various developing stages. In order to capture tissue representing the entire kidney, we sampled kidneys with a wedge spanning from the cortex to medulla region. Overall design: Comparing gene expression profiles of human kidneys at different stages and find the features of early versus late kidneys in development	Co-expression
SRP111184	Monitoring Nivolumab binding as a method to clarify the residual therapeutic effects and to characterize the immune profile in antibody bound T cells in previously treated non-small cell lung cancer patients	The goal of this study is to evaluate immune profile in anti PD-1 antibody, Nivolumab, bound CD8 T cells vs Nivolumab unbound CD8 T cells. Overall design: We performed sorting for IgG4 positive and negative CD8 T cells from five individual patients at the time after one dose treatment and compared transcriptome profile between them.	Co-expression
SRP111199	Gene expression profile in breast cancer cell lines using RNA sequencing	In order to identify novel molecular targets associated with TNBC progression, we initially performed transcriptome analysis using RNA sequencing in breast cancer cell lines, classified as either the luminal subtype (MCF-7, T47D, ZR-75B) or basal-like subtype (MDA-MB-231, MDA-MB-435, Hs578T). Overall design: Total RNAs of each cell were isolated using the TRIzol reagent for RNA sequencing following manufacturer's instructions. The total RNAs were treated with DNase I, purified with miRNeasy Mini Kit and subsequently quality checked using an Agilent 2100 Bioanalyzer. An Illumina platform was used to analyze transcriptomes with 90 bp paired-end library. Samples were paired-end sequenced with the Illumina HiSeq 2000 using HiSeq Sequencing kits.	Co-expression
SRP111290	Anti-Tumor Activity of Entrectinib, a Pan-TRK, ROS1 and ALK Inhibitor, in ETV6-NTRK3-Positive Acute Myeloid Leukemia	Activation of TRK family tyrosine kinases by chromosomal rearrangement has been shown to drive a wide range of solid tumors and hematologic malignancies. TRK fusions are actionable targets as evidenced by recent clinical trial results in solid tumors. Entrectinib (RXDX-101) is an investigational, orally available, CNS-active, highly potent and selective kinase inhibitor with low nanomolar potency against TRKA/B/C, ROS1 and ALK kinase activities. Here, we demonstrate that TRK kinase inhibition by entrectinib selectively targets preclinical models of TRK fusion-driven hematologic malignancies. In acute myeloid leukemia (AML) cell lines with endogenous expression of the ETV6-NTRK3 fusion gene, entrectinib treatment blocked cell proliferation and induced apoptotic cell death in vitro with sub-nanomolar IC50 values. Phosphorylation of the ETV6-TRKC fusion protein, as well as phosphorylation of known TRKC downstream signaling effectors, was inhibited by entrectinib treatment in a dose-dependent manner. Sensitivity to entrectinib was dependent on expression of the ETV6-TRKC fusion protein. In xenograft models, entrectinib treatment at clinically relevant doses resulted in tumor regression, which was accompanied by elimination of residual cancer cells from the bone marrow. Our preclinical data demonstrate the potential of entrectinib as an effective treatment for patients with TRK fusion-driven AML and provide rationale for the clinical development of entrectinib in molecularly defined hematologic malignancies. Overall design: Analysis of exon-level rna expression and putative fusions in two cell lines	Co-expression
SRP111293	Identification of downstream genes regulated by YAP1 through knockdown and overexpression of YAP1 in U251 cell with a stably expression of mutant APP	Upstream regulator genes are central hub nodes in a network and their expression may response to  upstream trigger factors of a disease and influence expression of hundreds of downstream genes, and further facilitate disease development. Therefore, the identification of upstream regulator genes are vital for understanding the pathophysiology of the disease and seek for potential therapeutic targets for the treatment of the disease. YAP1 was identified as a candidate upstream regulator for Alzheimer''s disease (AD) in our study. To test whether expression alterations of YAP1 can lead to AD expression network disturbance and thus promoting AD progression, we knockdown and overexpressed YAP1 in U251 cell line with a stably expression of mutant APP (K670N/M671L) (U251-APP cells). RNA-seq (by IlluminaHiseq 4000) and following analyses were then performed to detect genes whose expression were influenced by YAP1 expression changes. The results indicated that expression alterations of YAP1 can significantly disturbe the whole AD expression network. Overall design: YAP1 inteference and overexpression were performed in U251 cell with a stably expression of mutant APP (K670N/M671L) (U251-APP cells) with three biological triplicates for each condition (siNC, si-YAP1, vector, and YAP1, one outlier for YAP1 overexpression was removed).  Differential expression genes were obtained by comparing gene expression levels in YAP1 knockdown (si-YAP1) or overexpression (YAP1) cells with control cells (siNC or vector).	Co-expression
SRP111343	RNAseq analysis of chemotherapy and radiation therapy-naïve breast tumors	Assessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq. Overall design: 103 total samples from 63 unique patients. Clinical details were provided only for the 50 samples in current publication. However, all 103 samples were analyzed together.	Co-expression
SRP111348	SCD – Stem Cell Differentiation on board the International Space Station [RNA-seq]	The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends from the continuous remodeling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblasts of mesenchymal origin. This disease is frequent in aged people, but develops much more rapidly in space. Our experiment, selected by ESA (European Space Agency), aimed to determine how human bone marrow mesenchymal stem cells (hBMSCs) react and differentiate in real microgravity, on board the International Space Station, in approx. 2 weeks time. Overall design: The SCD experiment consisted of 24 experimental hardware modules (EH) (12 flight modules and 12 ground modules), each of which had one experiment unit (EU) integrated into the KUBIC interface container single level (KIC-SL). Each EU consisting of a brick containing 5 cylinders (for the medium and chemicals), a cell culture chamber (CC), and connecting channels. Five small valves were placed to separate the different fluids and the CC. Each cylinder had a piston to inject a new fluid into the CC; the waste medium was collected in the previously emptied cylinder and suitably preserved. EH were trasferred on board the ISS by the Soyuz-TMA-16M (ISS 42S, launched on March 27, 2015); 27°C was the temperature recorded for the samples in the Soyouz vehicle before docking and installation in the KUBIK incubator on board the ISS The experimental proifile consisted of: 1) installation in KUBIK (T0); 2) Start with the first medium exchange (T0+7h); 3) Second medium exchange (T0+7d); 4)Third medium exchange with PBS (T0+14d); 5) Stop by means of two subsequent exchanges with RNAlater Here, the effect of microgravity on hBMSCs were investigated by means of mRNA sequencing using Ion Proton. Four spaceflight samples were considered; three samples were cultured in standard medium (SM) while one sample was cultured in osteogenic medium (OM).	Co-expression
SRP111361	Microsatellite expansion RNA visualization, elimination, and reversal of molecular pathology by RNA-targeting Cas9	In this Study, we used RNA-targeting Cas9 (RCas9) to reverse characteristic Myotonic Dystrophy (DM1) cellular phenotypes such as elimination of RNA foci, MBNL relocalization, and reversal of transcriptome-wide splicing. Overall design: We performed RNA-seq for control and myotonic dystrophy (DM1) myoblasts and myotubes with various treatments including lentivirus mediated expression of either non-targeting (NT) or CTG-targeting (CTG) single guide RNA (sgRNA) and PIN-dCas9.Lentivirus mediated GFP expression was used as control.	Co-expression
SRP111371	Whole transcriptome analysis reveals a pro-inflammatory profile of ductular reaction cells in AH.	Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.	Co-expression
SRP111402	Next Generation Sequencing of total RNA from 9 bladder cancer cell lines and 3 fractionated bladder cancer cell lines	We profile the cell line expression of 279 circRNAs, that are highly expressed across 457 bladder cancer patient samples. Additionally, we investigate their cellular location in fractionated cell lines Overall design: 9 bladder cancer cell lines and 3 fractionated bladder cancer cell lines	Co-expression
SRP111405	IFNa impairs autophagic degradation and promotes the autoreactivity of SLE monocytes through cell-autonomous mitochondrial DNA sensing	IFN-a impairs autophagic degradation and promotes the autoreactivity of SLE monocytes through cell-autonomous mitochondrial DNA sensing.	Co-expression
SRP111436	P68-associated lncRNA LOC284454 is differentially expressed in human cancers and modulates gene expression	DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 75 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions. The RNA is located in the same primary transcript harboring miR-23a~27a~24-2 cluster.  LOC284454 is a stable, nuclear restricted and chromatin associated lncRNA. The sequence is conserved only in primates and is expressed in multiple human tissues. Expression of LOC284454 is significantly reduced in breast, prostate, uterus and kidney cancer and also in breast cancer cell lines. Global gene expression studies upon loss and gain of function of LOC284454 revealed perturbation of genes related to cancer-related pathways. Focal adhesion and cell migration pathway genes are downregulated under overexpression condition, and these genes are significantly upregulated in breast cancer cell lines as well as breast cancer tissue samples suggesting a functional role of LOC284454 RNA in breast cancer pathobiology. Overall design: We investigated the global effect of LOC284454 lncRNA on gene expression by transcriptome analysis in HEK293Tcells after siRNA mediated silencing of LOC284454 lncRNA.	Co-expression
SRP111459	TFAP2C regulates transcription in human naive pluripotency by opening enhancers	Naive and primed pluripotent human embryonic stem cells bear transcriptional similarity to pre- and post-implantation epiblast and thus constitute a developmental model for understanding the pluripotent stages in human embryo development. To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATAC-seq and found enrichment of the activator protein-2 (AP2) transcription factor binding motif at naive-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naive reversion and becomes widespread at naive-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naive-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naive human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse. Overall design: This dataset includes 52 RNA-seq, 37 ATAC-seq and 20 ChIP-seq samples.	Co-expression
SRP111461	In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [LN-521 or LN-521+LN-221]	Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology. Overall design: Human embryonic stem cells were cultured in wells coated with LN-521 or LN-521+LN-221 using nutristem medium. RNA is extracted when cells reached confluence.	Co-expression
SRP111481	Transcriptomic and genomic profiling of early-stage ovarian carcinomas associated with histotype and overall survival [RNA-Seq]	Ovarian cancer is the most lethal gynecological malignancy in the western world. Despite recent efforts to characterize ovarian cancer using molecular profiling, few targeted treatment options are currently available. Here, we examined genetic variants, fusion transcripts, SNP genotyping, and gene expression patterns for early-stage (I, II) ovarian carcinomas (n=96) in relation to clinicopathological characteristics and clinical outcome, thereby identifying novel genetic features of ovarian carcinomas. Furthermore, mutation frequencies of specific genetic variants and/or their gene expression patterns were associated with histotype and overall survival, e.g. SLC28A2 (mucinous ovarian carcinoma histotype), ARCN1 (low expression in 0-2 year survival group), and tumor suppressor MTUS1 (mutation status and overall survival). The long non-coding RNA MALAT1 was identified as a highly promiscuous fusion transcript in ovarian carcinoma. Moreover, gene expression deregulation for 23 genes was associated with tumor aggressiveness. Taken together, the novel biomarkers identified here may improve ovarian carcinoma subclassification and patient stratification according to histotype and overall survival. Overall design: Whole-transcriptome RNA sequencing (RNA-seq) was performed for 96 early-stage primary invasive ovarian carcinomas.	Co-expression
SRP111511	In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [H1 differentiation protocol]	Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology. Overall design: Human embryonic stem cells were cultured in wells coated with LN-521 and LN-221 using RPMI1460 supplemented with B21 without insulin medium. Differentiation commenced when cells reached confluency. Small molecule inhibitor CHIR99021 (inhibitor of GSK3) was added at day 0 followed by IWP2 (inhibiot of Wnt production) at day 3. Cells continue to be cultured in RPMI1460 supplemented with B21 without insulin medium for 10 days with medium change every other day. After day 10, medium was changed to RPMI1460 supplemented with B21 CTS grade medium. RNA was extracted from triplicates wells at day 0, 1, 3, 11, 14, 20, 30 and 90 and from 5 wells at day 5, 7 and 9.	Co-expression
SRP111526	CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL1.RNAseq.lg]	We provide evidence that shRNAs and siRNAs derived from CD95 and CD95L preferentially target the 3'' UTRs of survival genes culminating in a very robust mode of cell death we call DISE (Death Induced by Survival gene Elimination) Overall design: 293T cells were infected with either pTIP-shScr or pTIP-shL1 and following puromycin selection RNA was analyzed by deep sequencing 100hrs after addition of doxycycline	Co-expression
SRP111532	CD95L derived si- and shRNAs and the CD95L mRNA kill cancer cells through an RNAi mechanism by targeting survival genes [siL3.RNAseq.lg]	We provide evidence that shRNAs and siRNAs derived from CD95 and CD95L preferentially target the 3'' UTRs of survival genes culminating in a very robust mode of cell death we call DISE (Death Induced by Survival gene Elimination) Overall design: RNA isolated from HeyA8 cells 48 hrs after transfection with either a nontargeting siRNA (siScr) or a CD95L derived siRNAs (siL3) were subjected to deep sequencing, using Illumina HiSeq4000.	Co-expression
SRP111535	SUMOylation Regulates miR-34b/c Targeted Gene Expression Program [RNA-seq]	The microRNAs known as miR-34 family suppress the expression of a suit of proteins involved in oncogenesis and pluripotency, including c-Myc.  Their expression is frequently down regulated in cancers; however the regulation of their expression is not well understood. Through genome-wide miRNA profiling and mechanistic analysis, we identified an important role of SUMOylation in miR-34b/c expression, regulating the expression of c-Myc and all other tested miR-34 targets. Overall design: We established HCT116 cell line that can be induced to express shRNA targeting the catalytic subunit of the SUMO E1 enzyme, SAE2 by adding doxocycline (DOX).  To rule out non-specific shRNA effects, we established two separate cell lines using two independent shRNAs Sh1 and Sh2.	Co-expression
SRP111557	High-throughput single cell transcriptome analysis and CRISPR screen identify key ß cell-specific disease genes	Pancreatic endocrine cells orchestrate the precise control of blood glucose levels, but the contribution of each cell type to diabetes or obesity remains elusive. Here we used a massively parallel single-cell RNA-seq technology (Drop-Seq) to analyze the transcriptome of 26,677 pancreatic islets cells from both healthy and type II diabetic (T2D) donors. We have analyzed cell type-specific gene signatures, and detected several rare a or ß cell subpopulations with high sensitivity. We also developed RePACT, a sensitive single cell analysis algorithm to identify genes associated with rare disease causing cells, or to capture the subtle disease-relevant cellular variation. We successfully identified both common and specific signature genes of obesity and T2D with only a small number of islet samples. We also performed an unbiased genome-wide CRISPR screen and mapped these Drop-Seq signature genes to the core insulin regulatory network in ß cells. Notably, our integrative analysis discovered a ß cell-specific function of the cohesin loading complex in regulating insulin gene transcription, and a previously unrecognized role of the NuA4/Tip60 histone acetyltransferase complex in regulating insulin release. These data demonstrated that single-cell trancriptomics is necessary to dissect the heterogeneity, disease state, and functionality of islet ß cells and other cell types. Overall design: Single cell sequencing (Drop-seq) for Human Pancreatic islet from 9 individuals respectively. Including 6 Healthy donor and 3 Type II diabetes patient donor. 4 Chipseq for further validation.	Co-expression
SRP111577	CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [FasLRNAseq.lg]	>80% of a large number of tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death that is characterized by the simultaneous activation of multiple death pathways and preferentially affects transformed and cancer stem cells. We now show that these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect.  We also provide evidence showing that the full length CD95L mRNA is also toxic and produces small Ago-associated RNAs. Overall design: Examination of differential gene mRNA expression in empty vector control cells versus cells over-expressing CD95L mRNA.	Co-expression
SRP111653	CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL3.shR6.RNAseq.lg]	The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. However, most siRNAs or shRNAs targeting either CD95 or CD95L induce DICE (Death Induced by CD95/CD95L Elimination), a form of cell death in which a combination of different cell death pathways are activated, that is selective for transformed cells, and that preferentially affects cancer stem cells. We now provide evidence that both CD95 and CD95L are part of a network of genes that contain sequences that when expressed as either siRNAs or shRNAs are toxic to cancer cells. They act through canonical RNAi by targeting the 3''UTRs of critical survival genes. We propose that these embedded toxic sequences are part of a conserved mechanism that regulates cell death, and we predict the existence of endogenous siRNAs, that when produced, induce cell death to regulate genome fidelity. Our data have implications for cancer therapy and the use of RNAi. Overall design: 293T (shL3 site deleted) cells were infected with either pTIP-shScr or pTIP-shL3 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of doxycycline/HeyA8 (shR6 site deleted) cells were infected with either pLKO-shScr or pLKO-shR6 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of selection.	Co-expression
SRP111737	RNA sequencing to compare gene expession in hepatic stellate cells on a soft (400 Pa) and stiff (25000 Pa) polyacrylamide hydrogels	Primary human hepatic stellate cells (HSCs) isolated from healthy patients were purchased from Sciencell.  They were seeded on either 400 Pa or 25000 Pa polyacrylamide hydrogels for 2 days and collected for RNA isolation.  The goal of this study is to determine genes transcriptionally regulated by a stiff matrix. 2 RNA samples of HSCs on 400 Pa and 3 RNA samples of HSCs on 25600 Pa were sent to the University of Minnesota Genomics Center for RNA sequencing. Overall design: 2 RNA samples isolated from HSC on 400 Pa stiffness and 3 from HSCs on 25600 Pa stiffness.  They were converted to Illumina sequencing libraries using Illumina’s Truseq Stranded mRNA Sample Preparation Kit.  Truseq libraries were then subjected to cluster using Illumina cBot instrument and sequencing using HiSeq2500	Co-expression
SRP111818	Next generation sequencing of human monocyte derived dendritic cells stimulated for two hours with LPS, C5a and/or MSK inhibitor SB-747561	In order to determine the full breath of C5aR and TLR crosstalk in human DC, RNA sequencing analysis on human moDC stimulated in the absence or presence of C5a and TLR4 ligand lipopolysaccharide (LPS) was performed. To minimize interference of induced positive and negative feedback loops, we analyzed gene expression after two hours of DC activation. The involvement of CREB signaling in C5aR and TLR crosstalk was investigated by including moDC stimulated in the presence of MSK inhibitor. Overall design: Human monocyte-derived dendritic cells of 4 independent donors were were sequenced on Illumina HiSeq 2000 platform	Co-expression
SRP111855	Luminal subtype-specific circRNAs in breast cancer cells by a novel tool for external data analysis.	Circular RNAs are molecules present in all eukaryotes that are generated from a large number of genes by a particular processing of transcripts. We have exploited poly(A-) RNA-Seq data generated in our lab in MCF-7 breast cancer cells to define a compilation of exonic circRNAs more comprehensive than previously existing lists. Development of novel computational algorithms allowed us to quantitatively evaluate expression of these circRNA also in publicly available data. We report here novel findings with important implications both for circRNA biogenesis and as specific markers for breast cancer. We observed and confirmed by ChIP analysis that exons involved in circularization events display significantly higher levels of the histone post-transcriptional modification H3K36me3 than non-circularizing exons. This suggests a clear link with a published alternative splicing mechanism in the circRNA biogenesis mechanism. We also found that circRNAs contain an unexpectedly elevated number of Ago binding sites, revamping the hypothesis of circRNAs acting as miRNA sponges in some cases. Finally, we report that a subset of MCF-7 circRNAs are specific to tumor versus normal tissue, while others can differentiate the Luminal tumor subtype, thus suggesting that circRNAs can be exploited as novel biomarkers and drug targets for breast cancer. Overall design: The RNA-seq datasets were obtained from libraries generated with the TruSeq stranded library preparation kit (Illumina) using as input material RNA depleted of both poly(A+) and ribosomal RNAs fractions. Pool of 12 libraries (pooled at equimolar concentration) was generated, quantified and run on the HiSeq2000 (Illumina) sequencer in 50 nts paired-end sequencing mode following manufacturer instruction. A total of 12 datasets, with an average depth from 30.7 to 116.1 million paired-end reads, were obtained, composed of triplicates of four MCF-7 culture conditions: i) hormone-deprived (HD) media ii) HD+ 17b-estradiol (6h) iii) medium added of FSC 5% iv) double-stranded RNA complementary to ESR1 mRNA (siRNA) (48h).	Co-expression
SRP111862	Tracking transcriptional changes in a species-specific manner during experimental hepatoblastoma progression in vivo	Hepatoblastoma is a primitive liver cancer occurring mainly in infants with defined molecular alterations driving its progression, which is difficult to model in vivo. Here we present a new animal model for hepatoblastoma on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of hepatoblastoma in patients. Expression of classic tumor-associated proteins such as ß-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of hepatoblastoma cells on the CAM, with significant deregulation of more than 6000 genes including more than half of all HOX genes. Bioinformatic analysis could clearly distinguish between tumor cell-expressed genes and chick host genes, thereby shedding new light on the complex interactions taking place during experimental hepatoblastoma progression. Importantly, human tumor suppressive ribosomal genes were downregulated after implantation, whereas mitochondrial genes encoding for anti-apoptotic peptides were strongly induced in vivo. Meprin-1a expression was increased during evolution of CAM tumors and confirmed by immunohistochemistry. Cisplatin, a commonly used chemotherapeutic agent for hepatoblastoma, showed significant anti-tumoral effects in this model. Our results broaden the understanding of the molecular adaptation process of human cancer cells to the microenvironment and might help to elaborate novel therapeutic concepts for the treatment of this pediatric liver tumor. Overall design: HuH6 cells and CAM mRNA profiles were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500 and HiSeq 2000, respectively	Co-expression
SRP111868	The phosphatidylinositol 3-kinase pathway as a potential therapeutic target in bladder cancer	Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated and RNA-sequencing was performed to explore drug resistance mechanisms. The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild type PIK3CA. Pictilisib exhibited stronger anti-tumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than a model with wild-type. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth and prolonged survival compared with single drug targeted treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as biomarker to predict response to pictilisib. The inhibitor activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by co-treatment with the RAF inhibitor sorafenib. RNA-sequencing of tumors resistant to treatment suggested that LSP1 down-regulation might play a role in inducing drug resistance. These preclinical results provide new insight into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Overall design: A total of 9 samples were analyzed by transcriptome sequencing (RNA-seq) in this study. The study included BL0269 bladder cancer patient-derived xenograft (PDX) tumors derived from subcutaneous injection of tumor pieces into 10 mice. Mice were randomized into 5 treatment groups: control (untreated), cisplatin, pictilisib (GDC-0941), combination (cisplatin+pictilisib), and sequential (cisplatin -> pictilisib) treatments. Each treatment group had biological duplicate tumors from two separate mice.	Co-expression
SRP111915	Homo sapiens Raw sequence reads	The human MDA MB 231 breast cancer and MDA MB 435 melanoma cell lines were selected for isolates able to pass through narrow 3 micron pores in Transwell tissue culture inserts. In addition, MDA MB 231 breast cancer cells were selected for a population of small sized cells in parallel by flow cytometric sorting. RNA sequencing of the three populations (parental, selected, flow sorted) of MDA MB 231 breast cancer cells, and two populations (parental, selected) of MDA MB 435 melanoma cells, was performed.	Co-expression
SRP111941	Next Generation Sequencing Facilitates Quantitative Analysis of Health donors and SLE patients'' PBMC Transcriptomes	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare SLE patients to Health donors PBMCs-derived transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to discovery the potential pathway which can be used as a therapeutic target. Overall design: Methods: Peripheral blood from Health donors and SLE patients with high or low peli1 expression was collected,PBMCs was processed to RNA-sequencing.	Co-expression
SRP112521	Genome-wide RNA deep sequencing of CAL-101 or AKTi primed human T cells in comparison to traditionally expanded T cells	Differential expression patterns of total mRNA in traditionally expanded T cells (vehicle) compared to T cells expanded under drugs (AKT inhibitor and CAL-101) Overall design: Comparison of transcriptional effects of two different drugs	Co-expression
SRP112533	Transcriptome analysis of V336Y mutant mitochondrial ribosomal protein in human HEK293 cell line	Analysis of HEK293 cells lines expressing V336Y mutant mitochondrial ribosomal protein. Overall design: mRNA profiles of wild-type and V336Y mutant HEK293 cell culture samples generated by deep sequencing.	Co-expression
SRP112551	Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide	Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorder Overall design: We examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group).	Co-expression
SRP112552	Large-scale low-cost NGS library preparation using a robust Tn5 purification and tagmentation protocol [i5i7]	In recent years, tagmentation-based library preparation using a hyperactive version of the Tn5 transposase gained more and more popularity. The limited hands-on time, robustness and high efficiency of the method are essential for the processing of next-generation sequencing libraries from little input material like single cells or the processing of hundreds of samples simultaneously. The hyperactive Tn5 is commercially available (Nextera XT DNA library preparation kit), however, high-throughput experiments with hundreds of samples are costly. Here, we present a highly reproducible Tn5 transposase purification strategy via an N-terminal His6-Sumo3 tag and the workflow for the tagmentation-based NGS library preparation. We demonstrate that NGS libraries processed with the in-house produced Tn5 are of the same quality like those processed with the Nextera XT DNA library preparation kit and that the purification of the transposase is reproducible across institutes. Producing the Tn5 transposase in-house allows for customized experimental design and reduces costs of large-scale experiments dramatically. We describe a novel single cell polyadenylation site mapping protocol that benefits from the fact that the in-house produced Tn5 can be loaded with any desired linker oligonucleotide for tagmentation. Overall design: For samples labeled i5i7, full-length cDNA was amplified from 15pg of HeLa RNA using the smart-seq2 protocol. 75-225pg of cDNA was tagmented using various conditions as outlined in the sample specification. Samples were sequenced using a dual-indexed single read strategy, unless specified differently. Technical tagmentation replicates were processed from the same cDNA input.	Co-expression
SRP112571	Overall expression of genes in CRYM overexpressed Prostate cancer cell line LNCaP	RNA sequencing was employed to profile the entire mRNA transcripts. Total RNA from LNCaP transfected with control vector or CRYM bearing vector was isolated. RNA and samples were subjected to the sequencing on illumina''s HiSeq 4000 platform. RNA-seq revealed the expression of 58,540 transcripts and of 34,878 (59.6 %) genes were expressed in LNCaP cells. 3226 (9.25 %) genes were altered by CRYM and 2.72 % were upregulated and 6.53 % were downregulated. Overall design: Cells were in transiently transfected cells with CRYM vector vs control in duplicate. GFP expression was monitored and total RNA was isolated at 48 hours upon transfection.	Co-expression
SRP112583	PolyA RNA-seq from HCT116 (WT and CDK8as/as) cells in normoxia or hypoxia and treated with DMSO or 3MB-PP1	To determine the impact of CDK8 kinase activity on steady-state mRNA levels, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116 (CDK8wt/wt and CDK8as/as) in the presence of absence of 3MB-PP1 to specifically inhibit analog senstitive (as) CDK8. Overall design: PolyA RNA for two independent biological replicates was purified  from HCT116 cells (CDK8wt/wt and CDK8as/as) incubated in normoxic (ambient oxygen) or hypoxic (1% oxygen) conditions for 24 hrs and treated with DMSO or the ATP-analog 3MB-PP1, and was sequenced on the Ion Torrent Proton platform. Reads were aligned (GSNAP) to the human genome (hg19) and gene-level counts (HTseq-count) were used for differential expression analysis (DESeq2).	Co-expression
SRP112584	RNA seq analysis of human Fetal and adult derived Enterospheres	enterospheres (FEnS) from six aborted fetal' small intestines, ranging in gestational age from 11 to 22.5 weeks ), and from adult duodenum AEnS  were generated based on previously developed protocols for human organoids cultures . We sought to compare the global gene expression profile of FEnS and AEnS by whole transcriptome shotgun sequencing (WTSS) analysis. We evaluated FEnS (N=6) and AEnS (N=3) samples at a low passage, ranging from P6 to P14. Overall design: Examination of 2 groups of enterospheres (organoids) from human intestine  from Fetal and adult developmental age	Co-expression
SRP112586	Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer	The Ras-family small GTPase RAB25 is involved in numerous aspects of endosomal protein trafficking and cell polarity. Recent evidence has established a role for RAB25, as well as related RAB-family and effector proteins, in oncogenic signaling, highlighting the need for chemical probes targeting this class of proteins. Here we report the development of all-hydrocarbon stabilized peptides targeting RAB25 derived from the RAB-binding FIP-family of proteins. Relative to unmodified FIP peptides, optimized stapled peptides show markedly increased structural stability, binding affinity, cell permeability and inhibition of RAB25:FIP complex formation. RAB25 expression has been shown to promote both pro- and anti-oncogenic phenotypes in specific cellular contexts. Stapled peptide RFP14 treatment of breast and ovarian cancer cell lines, in which RAB25 is pro-oncogenic, inhibited migration and proliferation in a RAB25-dependent manner. In contrast, treatment of a triple-negative breast cancer cell line in which RAB25 is tumor suppressive augmented proliferation and migration. Gene expression (RNA Seq) profiling identified significantly altered transcripts in response to RAB25 expression in ovarian cancer cells, and treatment with the optimized stapled peptide RFP14 reversed this expression profile. These data validate first-in-class chemical probes targeting RAB-family proteins and support the role of RAB25 in regulating context-specific oncogenic phenotypes. Overall design: Hey ovarian cancer cells with stable overexpression of RAB25 (10 cm plate, 70-80% confluent) were treated with stapled peptide RFP14 (10 µM) or the equivalent amount of DMSO in serum free media  (RPMI) overnight, followed by stimulation with 5% FBS for 8 hours. pcDNA3 mock vector expressing HEY ovarian cancer cells labelled as HeyCont were similarly treated with DMSO overnight and stimulated with 5% FBS for 8 hours in parallel. Individual biological replicates performed on different days were used for RNAseq studies. Therefore, combining the two replicate experiments (experiment 1 and experiment 2), RNA samples analyzed included Hey Cont DMSO, Hey RAB25 DMSO, and Hey RAB25 RFP14, totalling six samples.	Co-expression
SRP112623	Whole transcriptome sequencing data of GBSCC patients from India	Our study has elucidated the immunoregulatory gene expression landscape in primary tumors of Gingivo-Buccal Squamous Cell Carcinoma, as compared to their adjacent normal tissue and computationally estimated a relative composition of various immune cell classes in those tissues. A detailed portrayal of expression variation of immune evasion genes alongwith other potential therapeutic targets have been highlighted in the study. Overall design: 12 pairs of tumor and adjacent normal from same patient have been included in the study	Co-expression
SRP112723	RNA-seq of HBV-infected differentiated HepaRG under RG7834	Monitor expression of all viral mRNAs including polyA-deficient viral mRNAs Overall design: 36 HepaRG + HBV infection; treated with RG7834 100 nM or not treated; timepoints 6h, 9h, 12h, and 24h	Co-expression
SRP112726	Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 45d)	Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids Overall design: Comparison of transcriptomes from different brain tumor organoid groups	Co-expression
SRP112744	Aberrant expression profile of lncRNA and mRNA in dilated cardiomyopathy by RNA-sequence	We aimed to identify aberrantly expressed lncRNA and mRNA expression profiles of dilated cardiomyopathy (DCM) and explore their potential functions. 8 DCM blood samples and paired healthy control blood samples underwent RNA-sequence. Overall design: A prospective case-control study was designed to identify the changes in expression of lncRNA and mRNA. 8 DCM blood samples and paired healthy control blood samples underwent RNA-sequencing, using Illumina HiSeq 4000.	Co-expression
SRP112751	A Low-cost Multiplex Biomarker Assay Stratifies Colorectal Cancer Patient Samples into Clinically-relevant Subtypes: Singapore Cohort RNA-seq	Objective: In order to personalise standard therapies based on molecular profiles, we previously classified colorectal cancers (CRCs) into five distinct subtypes (CRCAssigner) and later into four consensus molecular subtypes (CMS) with different prognoses and treatment responses. For clinical application, here we developed a low-cost multiplex biomarker assay. Design: Three cohorts of primary (except one liver metastases) untreated and fresh frozen CRC samples (n=57) profiled by microarray and RNA-Seq were analyzed. A reduced 38-gene panel (CRCAssigner-38) was selected from the 786-gene CRCAssigner signature (CRCAssigner-786) using an in-house class prediction approach. A customised NanoString Technologies' nCounter platform-based assay (NanoCRCAssigner) was developed for comparison with different classifiers (CMS subtypes), platforms (microarrays and RNA-Seq), and gene sets (CRCAssigner-38 and CRCAssigner-786). Results: NanoCRCAssigner classified samples (n=48; except those showing a mixture of subtypes) into all five CRCAssigner subtypes with overall high concordance across platforms (>87%) and with CMS subtypes (81%) irrespective of variable tumour cellularity. The association of subtypes with their known molecular (microsatellite-instable and stemness), mutational (KRAS/BRAF), and clinical characteristics (including overall survival) further demonstrated assay validity. To reduce costs, we switched from standard protocol to a low-cost protocol with a high Pearson correlation co-efficient (0.9) between protocols. Technical replicates were highly correlated (0.98). Overall design: Gene expression of primary CRC samples from the Singapore cohort was profiled using Illumina HiSeq and TPM values calculated for subsequent subtyping.	Co-expression
SRP112852	Transcriptome of U251 cells overexpression complement component 7	We identified a rare coding variant (p.K420Q) in the complement component 7 (C7) gene affecting the risk of Alzheimer's disease. To investigate the cellular effects of the mutant, we performed RNA-seq in cell line overexpression wilt-type and mutant C7.   U251 glioma cells with stable expression of mutant APP (K670N/M671L) (U251-APP cells), which produce Aß42 under Dox inducing, were used as the model cell. Total RNA of U251-APP cells overexpressing wild type and mutant C7 proteins were subjected to transcriptome sequencing using Illumina Hiseq 4000 platform. Overall design: C7 overexpression was performed in U251 cell with a stably expression of mutant APP (U251-APP cells) with three biological triplicates for each condition (vector, wild-type, and mutant).	Co-expression
SRP112886	Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin B in HCT116 cells treated with or without TNF-alpha	We have investigated the effects of CDK8/19 inhibitor Senexin B on NF?B-mediated transcription, induced by a canonical NF?B activator, TNFa. Overall design: HCT116 cells were pre-treated with or without 1 µM Senexin B for 1 hour, followed by 2 hour treatment with 10 ng/ml TNFa. Each treatment condition was done in biological triplicate.	Co-expression
SRP112887	Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin B in HEK293 cells treated with or without TNF-alpha	We have investigated the effects of CDK8/19 inhibitor Senexin B on NF?B-mediated transcription, induced by a canonical NF?B activator, TNFa. Overall design: HEK293 cells were pre-treated with or without 1 µM Senexin B for 1 hour, followed by 2 hour treatment with 10 ng/ml TNFa. Each treatment condition was done in biological triplicate.	Co-expression
SRP112897	RNA-seq from human meningioma samples	We performed RNA-seq on 42 meningioma samples isolated from human patients to characterize the transcriptome of these tumors Overall design: Poly A selected RNA-seq from 42 meningioma samples	Co-expression
SRP112902	O-glcnAc reprograms cellular energetics	Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with ß-linked N-acetylglucosamine (O- glcnAcylation) via overexpression of the O-glcnAc–regulating enzymes O- glcnAc transferase (OGT) or O- glcnAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O- glcnAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-glcnAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-glcnAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq in SH-SY5Y cells indicated transcriptome reprogramming and down regulation of the NRF2-mediated antioxidant response. Sustained O-glcnAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-glcnAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-glcnAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases. Overall design: SY5Y cells were adapted to long term O-glcnAcase (OGA) inhibition using the specific OGA inhibitor Thiamet-G (tmg) or glucosamine treatment for 3 weeks. After adaptation to the growth conditions, cells were harvest and RNA isolated for Next Generation RNA sequencing. Briefly, cDNA library was prepared using Illumina TruSeq Stranded mRNA sample preparation kit (Illumina) as manufacturer's instruction. Total RNA was isolated using the same method as previously described and 800 ng of the total RNA per reaction was used to initiate the protocol. The quality of RNA sequencing results was first assessed using FastQC (0.11.2). RSEM (1.2.22) was utilized to align the reads to the human reference genome HG38 and to calculate gene expression values. EdgeR (3.14.0) was then used to normalize the expression values using the TMM-method (weighted trimmed mean of M-values), and for differential expression analyses. First, the negative binomial conditional common likelihood was maximized to estimate a common dispersion value across all genes (estimateCommonDisp). Next, tagwise dispersion values were estimated by an empirical Bayes method based on weighted conditional maximum likelihood (estimateTagwiseDisp). Finally, the differentially gene expression was calculated by computing genewise exact tests for differences in the means between two groups of negative-binomially distributed counts. Hierarchical clustering analysis was determined using Euclidean distance. The following R-packages were utilized for calculations and visualizations: plots and edgeR.	Co-expression
SRP113004	Homo sapiens Transcriptome or Gene expression	Background: The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities from the body to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia.Methods: RNA-Seq measurements of gene expression were performed on small subregions of 16 human trigeminal ganglia. The samples were also characterized for viral, and bacterial genomic transcripts. Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the luciferase immunoprecipitation assay.Results: Molecular heterogeneity across the samples was prominent and could be explained by sampling of anatomically distinct sub-regions of the excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann, cell enriched regions. The levels of HSV-1 transcripts detected in trigeminal ganglia correlated with levels of HSV-1 antibodies in blood. Multiple migraine susceptibility genes are strongly expressed in neurally-enriched trigeminal samples and in blood vessels.Conclusions: These data provide a comprehensive description of the trigeminal transcriptome and a framework for evaluation of the parameters impinging on post-mortem studies in inhomogeneous tissues by proposing an extensive quality control and refined downstream analyses for RNA-Seq methodologies. Expression profiling of migraine susceptibility genes from genetic association studies appears to emphasize the blood vessel component of the trigeminovascular system.Keywords: RNA-Seq, transcriptome, trigeminal ganglion, herpes simplex virus, post-mortem, migraine	Co-expression
SRP113012	Deep sequencing of transcript levels in pluripotent stem cells and their differentiated derivatives in all three germ layers	Human pluripotent stem cells (hESCs) are an excellent model to dissect the transcriptional changes that direct cell fate decisions and lineage specification during development. Utilizing directed differentiation protocols to derive definitive endoderm, splanchnic mesoderm, neural progenitor cells (NPCs), and pre-neural crest stem cells (NCSCs) from hESCs. Transcriptional profiling via RNA-seq on hESCs and cells differentiated to all three germ layers revealed lineage specific transcriptional networks that remodeled many cell processes, including epigenetic status, cell surface markers, cell cycle profiles, metabolic flux, and cellular signaling pathways. From this data we were able to verify that metabolic flux within NPCs and pre-NCSCs are regulated in a lineage specific manner that is distinct from endoderm and mesoderm formation. Overall design: Profiles of mRNA transcripts levels were generated for 5 cell types by deep sequencing, in duplicate, on a Illumina Hisec 2500 platform.  Cell types analyzed were WA09 human embryonic stem cells (hESCs), as the control sample, and 4 WA09 hESC-derived cell types: definitive endoderm (DE), splanchnic mesoderm (MESO), neural progenitor cells (NPCs) and pre-neural crest cells (NCSCs).	Co-expression
SRP113027	Expression profiles of the four human major ectodermal lineages	Here we report a chemically defined strategy to derive the entire human ectoderm from pluripotent stem cells.  Using reporter lines for various lineages of the ectoderm, the expression profiles generated were: PAX6+ neuroectoderm (NE), SOX10+ neural crest (NC), SIX1+ cranial placodes (CP).  The non-neural ectoderm (NNE) samples did not have a reporter associated, but was quality controlled for the expression of TFAP2A positive, SIX1 and SOX10 negative to proceed with the sequencing.  We observe a clear demarcation between the NE versus the non-neural ectoderm lineages (NC, CP and NNE) accompanied by specific expression patterns for the different lineages.  The cells with potential to become neurons can be further differentiated to become functional. Overall design: Ectodermal lineages (NE, NC, CP and NNE) were differentiated from hPSCs using various small molecules and growth factors and assayed for their expression profile on day 12 (12 days after pluripotency).	Co-expression
SRP113171	PRDM1 inhibits proliferation of human colon cancer organoids	We reports the transcript landscape of PR Domain Containing 1, with ZNF domain (PRDM1)  in RKO colon cancer cells. We show that PRDM1 alpha and PRDM1 beta transcript isoforms repress and activate a largely overlapping suite of genes, many of which belong to the embryonic stem cell core transcript program. Overall design: To evaluate the roles of PRDM1 in colon cancer cells,  we generated PRDM1 knock out derivatives in RKO colon cancer cells by employing CRISPR/Cas9 technology and PRDM1a and PRDM1ß overexpressing derivatives of RKO colon cancer cells. mRNA profile of these RKO derivatives were generated by deep sequencing, in replicate, using Illumina NextSeq 500	Co-expression
SRP113226	SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia [RNA-seq]	We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases. Overall design: RNA sequencing (Illumina HiSeq 2500) of 10 index patients compared to 5 healthy donors (controls).	Co-expression
SRP113256	Transcriptome profiling of human umbilical vein endothelial cells (HUVEC)	No description.	Co-expression
SRP113305	Functional and genomic characterization of a xenograft model system for the study of metastasis in triple-negative breast cancer.	To define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors. Overall design: Gene expression analysis from PAT-Seq of 4 increasingly metastatic breast cancer xenograft tumours	Co-expression
SRP113319	Exploring the gene expression profile upon FXR1 knockdown in H358 cells using RNA-seq	We performed the RNA-seq in control samples and FXR1 knockdown samples, and compared the gene expression profiles to explore the effect of FXR1 knockdown on gene expression. The study was performed in H358 cells. Doxycycline inducible shRNA3 (sh3) was used to knockdown FXR1. Control shRNA (ctrl) samples were used to get rid of the effect of Doxycycline treatment. Both the Doxycycline treament for 3 days (D3) and 5 days (D5) samples were collected. Each sample has three repeats (rep 1, rep 2, and rep 3). The mRNA profiles were generated by deep sequencing using Illumina.Sequenced reads were trimmed for adaptor sequence, then mapped to hg19 whole genome using STAR v2.5.3 with parameters --bamRemoveDuplicatesType UniqueIdentical --outSAMmultNmax 1. Raw reads and Reads Per Kilobase per Megabase of library size (RPKM) were calculated using HOMER (PMID: 20513432). Differential gene expression was analyzed using R package DESeq2 using the raw reads. Overall design: The mRNA profiles of control sample and FXR1 knockdown samples of H358 cells were generated by deep sequencing, in triplicate, using Illumina.	Co-expression
SRP113321	Intrinsic Plasma Cell Differentiation Defects in BENTA Patient B cells	From purified naïve B cells from a BENTA patient cohort, we performed differential expression analysis by RNA-seq to show that BENTA B cells exhibit intrinsic defects in B cell differentiation with poor induction of specific genes required for plasma cell commitment. Overall design: Transcriptome profiling of one cell type in technical duplicate for 4 individuals per group	Co-expression
SRP113324	Transcriptomic analysis of senescent cells upon PTBP1 knockdown.	IMR90 ER:RAS cells were stably transduced with either an empty vector or 2 deconvoluted shRNAs targeting PTBP1. Following selection with puromycin, the cells were treated with 4OHT to induce senescence. 6 days later the cells were collected for total mRNA analysis. PTBP1 is a regulator of alternative splicing. Our previous experiments had shown that PTBP1 depletion inhibits the expression of pro-inflammatory genes without affecting other senescence-associated phenotypes. By performing RNA-seq we confirmed those observations at a global level and analysed how PTBP1 knockdown alters alternative splicing as a potential mechanism of action. Overall design: 4 conditions were examined: proliferating cells (Vector), senescent cells (Vector + 4OHT), senescent cells expresssing an shRNA targeting PTBP1 (shPTBP1_53 + 4OHT) and senescent cells expressing a different shRNA targeting PTBP1 (shPTBP1_86 + 4OHT).	Co-expression
SRP113338	Whole transcriptome analysis of iPSC-derived hepatic organoids cultures	A heatmap, which focused upon 2458 genes that were involved in stem cell differentiation and liver development, was prepared to visualize the relative relationship between the transcriptomes of iPSCs, PHHs, human liver tissue and HO1. The dendrogram indicates that HO1 is more closely related to liver tissue than to PHHs; this is because cholangiocytes are present in HO1 and liver, but are absent (or rare) in PHHs. Examination of the genes within this heatmap indicated that there was a lack of expression of pluripotent genes in HO1; and that HO1 had an increased level of expression of cellular markers for liver lineages and liver development, which included mature hepatocytes, bile duct cells and NOTCH signaling components. A cluster analysis of 1510 genes indicates that there were major changes in the transcriptome after the cells that were dissociated from an HO1 were transferred from the growth medium into the differentiation medium. As with the HO1s, the gene expression profile of HO2s resembled that of PHHs and human liver. Of importance, the level of expression of mRNAs that are of importance for various human liver functions (ADH4, CYP3A4, TTR, GSRA1, TDO2, GSTA1 and FAH) were markedly increased in HO2s. Overall design: Whole transcriptome analysis was performed on iPSCs, primary human hepatocytes (PHH), HO1 (primary hepatic organoids) and human liver tissue. For this analysis, over 100 organoids that were generated from a single donor were analyzed. Next, whole transcriptome analysis was performed to characterize HO2s (secondary organoids) and their relationship to iPSCs, PHHs and human liver tissue. This analysis utilized 1,000 HO2s that were prepared from a single donor.	Co-expression
SRP113431	Homo sapiens Raw sequence reads	ER regulated transcriptome	Co-expression
SRP113436	Features of cancer stem cells in colorectal tumors revealed by complex single cell analysis	Tumor recurrence and metastasis remain unavoidable due to a distinct tumor subpopulation known as cancer stem cells (CSCs). To explore the unique cell types contribute to colorectal cancer (CRC) progression, we profiled 831 single cells by simultaneous analysis of RNA sequencing (scRNA-seq) and telomere length in the same cell. Specific markers CD44, CD133 and LGR5 were used to enrich. We find small subpopulations with special features including quiescent CSCs, and epithelial lineage cancer cells (EPCs). Those quiescent CSCs have distinct features including higher level of pluripotency and Wnt signature, and shorter telomeres. Lineage tracing analysis showed that quiescent CSCs could plasticized and generate to epithelial lineage cancer cells with high proliferation and telomeres elongation, and these cells could also transform to each other. New marker genes for CSCs were identified including PROX1, TNFRSF19 and SMOC2. Survival analysis revealed that higher signatures of CSCs and EPCs predicts poor clinical outcome in CRC patients and could be a prognostic biomarkers. These findings provide insight into molecular classification of colorectal cancers and telomere function in CSCs.	Co-expression
SRP113442	CBFb-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia [RNA-seq]	We recently reported the discovery of a small molecule inhibitor, AI-10-49 which can specially inhibit the protein-protein interaction between RUNX1 tumor suppressor and CBFß-SMMHC oncogene. We also demonstrated that AI-10-49 can re-establish the RUNX1 transcriptional program in inv(16) cells and can extend the survival of inv(16) leukemic mice. To identify the transcriptional changes associated with AI-10-49, we performed RNA-seq analysis in ME-1 cells [human inv(16) leukemia cell line] treated with AI-10-49. Overall design: ME-1 cells were treated with DMSO/ AI-10-49 (1uM) for six hours, followed by RNA isolation. RNA libraries were sequenced using 90bp paired end reads on an Illumina HiSeqTM 2000.Three independent experiments were conducted for DMSO as well as AI-10-49 treatments.	Co-expression
SRP113470	Age-of-Onset Dependent Immune maturation in Pediatric Crohn Disease	Purpose:  To clarify the biological processes underlying variation in disease location and antimicrobial sero-reactivity across age-of onset in pediatric Crohn disease. Methods:  We characterize the ileal global pattern of gene expression using single-end, 50bp RNA-sequencing using the Illumina HiSeq2000 in 304 treatment-naïve pediatric Crohn patients and non-IBD controls.  Reads were quantified using Kallisto with Gencodev23 annotations.  For all analyses, data were stratified by patient age-of-onset. Results:  Performing differential analysis of all reasonably-expressed transcripts (TPM>5 in =5 samples, with significance defined as FDR-corrected p-value<0.05 and fold change=1.5), we identify a robust gene signature with higher expresison of an immune gene set in older patients (=10 years at diagnosis) compared to younger patients (<10 years at diagnosis), and a decrease in expression of antimicrobial Paneth cell-derived a-defensins. Conclusion:  We provide evidence for maturation of mucosal Th1 immune response and loss of epithelial antimicrobial a-defensins with increasing age-of-onset. Overall design: Ileal gene expression profiles were generated for 304 treatment-naïve pediatric Crohn patients and non-IBD controls.	Co-expression
SRP113495	Intron retention induced by microsatellite expansions as a disease biomarker.	Microsatellite expansions often occur in non-coding regions of the genome. In this study, we test their effect on host transcript RNA processing. Overall design: RNA-seq on affected tissues and peripheral blood from control and affected patients.	Co-expression
SRP113531	Uncovering mechanisms of early human lineage specification by CRISPR/Cas9-mediated genome editing [RNA-seq]	Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR?Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocys  t development was established, but maintenance was compromised. We conclude that CRISPR?Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development. Overall design: Single-Cell RNA-seq	Co-expression
SRP113537	Effect of SETD1A knockdown on global gene expression in MCF-7 cells	SETD1A is a histone H3K4 methyltransferase and function as a coactivator for nuclear receptors (NRs) and other transcription factors. We performed genome-wide gene expression analysis in non-specific siRNA transfected or SETD1A knockdown MCF-7 cells to investigate global gene expression changes induced by SETD1A knockdown. Overall design: Differential expresssion profile of transcripts in shNS or shSETD1A expressing cells in presence or absence of beta-estradiol (E2).	Co-expression
SRP113548	A unified activation mechanism for mRNA 3' end processing and splicing mediated by SR superfamily proteins	Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3' processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3' processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PAS). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is modulated by phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like regions in regulatory and core factors may provide a common activation mechanism for mRNA 3' processing, splicing, and potentially other steps in RNA metabolism. Overall design: Total RNAs from control HEK293T cells, CFIm59 KO cell lines (2 different cell lines), and CFIm68 KO cell lines (2 different cell llines) were fragmented, and reverse transcribed with an oligo(dT) primer containing a linker sequence. cDNAs were circularized, re-linearized by restriction digestion, and PCR amplified to generate libraries. The libraries were sequenced on HiSeq 2000 (single end 150 nucleotides).	Co-expression
SRP113549	RNA Missplicing in Fuchs Endothelial Corneal Dystrophy	RNA-Seq splicing data from the corneal endothelia of FECD patients and controls reveal hundreds of differential alternative splicing events. These include events previously characterized in the context of myotonic dystrophy type 1 and epithelial-to-mesenchymal transition, as well as splicing changes in genes related to proposed mechanisms of FECD pathogenesis Overall design: RNA-Seq was used to compare corneal endothelial specimens from subjects with Fuchs endothelial corneal dystrophy and control subjects	Co-expression
SRP113550	Catalogue of differentially expressed long non-coding RNAs following activation of human and mouse innate immunity	Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs) are novel regulators of immunity, there has been no systematic attempt to identify and characterise the lncRNAs whose expression are changed following the induction of the innate immune response. To address this issue, we have employed next generation sequencing data to determine the changes in the lncRNA profile in LPS-stimulated human macrophages, IL1beta-stimulated human airway A549 epithelial cells and and LPS-stimulated mouse RAW 264.7 macrophages Overall design: RNAseq was performed in human macrophages (Ribozero isolated), human alveolar A549 epithelial cells (polyA+ isolated) and mouse RAW 264.7 macrophages (polyA+ isolated) at 4h following exposure to media (control) or LPS (human macrophages and mouse RAW 264.7 macrophages) or IL1beta (human epithelial A549 cells)	Co-expression
SRP113558	Transcriptional changes during naturally-acquired ZIKA Virus infection render dendritic cells highly conducive to viral replication	Although dendritic cells (DCs) are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with Zika Virus (ZIKV). Using highly-purified mDC isolated from individuals with naturally-acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to uninfected patients. Interestingly, we noted a remarkable downregulation of antiviral Interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress Interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV, SOCS3, a negative regulator of ISG expression, and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection. Overall design: Examination of transcriptional changes in myeloid dendritic cells between ZIKV-infected patients and healthy donors	Co-expression
SRP113586	RNA-sequencing of neonatal monocyte responses to E. coli and S. epidermidis	Newborns, particularly those born prematurely, are extremely vulnerable to sepsis and this has been attributed to 'immature' innate monocyte defences. Predominant pathogens include Escherichia. coli and Staphylococcus. epidermidis but no studies have assessed global transcriptional responses of neonatal monocytes to live sepsis-causing bacteria. Here, we aimed to identify and characterise the common and pathogen-specific, neonatal monocyte transcriptional responses to E. coli and S. epidermidis to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (<32 weeks gestational age, GA) and term infants (37-40 weeks GA) following standardised challenge with live S. epidermidis or E. coli. Overall design: 43 samples in total from 4 term infants, 5 preterm infants exposed to chorioamnionitis and 6 preterm infants without exposure to chorioamnionitis. Each individual has an unstimulated monocyte sample, and a E. coli- or S. epidermidis-stimulated monocyte sample (3 samples per individual) except for two individuals (preterm infants without exposure to chorioamnionitis) which only have an unstimulated monocyte sample and one of either E. coli- or S. epidermidis-stimulated mnocytes.	Co-expression
SRP113619	Species and Cell-Type Properties of Classically Defined Human and Rodent Neurons and Glia [Human RNA-Seq]	Determination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping, quantitative PCR, and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions. Overall design: RNA purified from nuclei or cytoplasm from mouse, rat, or human cerebellum. ATAC-seq was also performed using cerebellar nuclei from the three species.	Co-expression
SRP113629	Gene expression profile of multiple myeloma cell lines treated with CB-5083	The goal was to determine the gene expression differences between CB-5083 and Bortezomib treated multiple myeloma cell lines Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis. CB-5083 decreases viability in MM cell lines and patient derived MM cells, including those with background proteasome inhibitor (PI) resistance.  CB-5083 has a unique mechanism of action that combines well with PIs which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant MM models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with MM standard of care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several MM disease models and provide the rationale for clinical evaluation as monotherapy and in combination in MM. Overall design: Cells were treated with compound or DMSO for 8hrs and then processed for RNAseq	Co-expression
SRP113639	Ancestry as a potential modifier of gene expression in breast tumors from Colombian women	Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value. Overall design: RNA profile of 42 luminal breast cancer tumors (21 luminal A and 21 luminal B) from Colombian patients	Co-expression
SRP113661	Distinct gene expression profile of Huh7 cell lines stably overexpressing CRABP1 or 2	The metabolism of ROL to the biogenesis of ATRA occurs in the cytoplasms of hepatocytes, which in turn translocates into nucleus upon binding to Cellular Retinoic Acid Binding Proteins, CRABP1 or CRABP2. However, the differential effect of CRABP1 and CRABP2 on the intracellular environment is not well understood.  Here,  we report polyA RNA sequencing data of the CRABP1 or CRABP2 overexpressing Huh7 cells. Overall design: The RNA sample was collected from CRABP1 or CRABP2 overexpressing Huh7 cells. This study examined the gene expression profile in CRABP1 or CRABP2 overexpressing Huh7 cells.	Co-expression
SRP113705	Obstructed defecation – an enteric neuropathy? An exploratory study of patient samples	The aim of this experimental study is to elucidate alterations of the autonomous enteric nervous system at the molecular level in patients with obstructed defecation, who represent one of the most predominant groups of constipated patients. Overall design: Full-thickness rectal wall samples of patients with obstructed defecation (OD) were analyzed by RNA-Seq and compared with controls.	Co-expression
SRP113713	RNA-seq analysis of the role of HBO1 (KAT7/MYST2) in the ovarian cancer cell line UWB1.289.	Analysis of change in transcriptosome after stable lentiviral HBO1 knockdown in UWB1.289 ovarian cancer cell line. Overall design: Total RNA was obtained from UWB1.289 cells transduced with shCtrl and shHBO1. shHBO1 samples were compared to shCtrl samples.	Co-expression
SRP113754	Acid suspends the circadian clock in hypoxia through inhibition of mTOR	Recent reports indicate hypoxia influences the clock through the transcriptional activities of hypoxia inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify, recapitulating the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation. Acidification of several human and murine cell lines, as well as primary murine T cells, suppresses mechanistic target of rapamycin complex 1 (mTORc1) signaling, a key regulator of translation in response to metabolic status. We find acid drives peripheral redistribution of normally perinuclear lysosomes, inhibiting lysosome-bound mTOR. Restoring mTORc1 signaling and the translation it governs rescues clock oscillation, revealing a model in which lactic acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents. Overall design: RNA-sequencing was performed over a 52-hour timecourse using total RNA collected every 4 hours from U2OS human osteosarcoma cells in media of pH 7.4 or pH 6.3	Co-expression
SRP113755	Transcriptome characterization of radiation-induced sarcomas	No description.	Co-expression
SRP113766	SERPINA3- a novel keratinocyte differentiation promotor mediates epidermal barrier repair response in psoriatic lesion	To excavate the genes regulated by SERPINA3, We profiled SERPINA3 silenced differentiated KC versus control using a RNA-seq approach. The genes down regulated in SERPINA3 silenced cells represent targets that are positively regulated by SERPINA3. Overall design: mRNA profiles of differentiated keratinocytes which are SERPINA3-silenced by 3 different siRNA and Scramble siRNA transfected differentiated keratinocytes were generated by deep sequencing.	Co-expression
SRP113770	ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells	Loss of organelle homeostasis is a hallmark of aging. However, it remains elusive how this occurs at transcriptional levels. Here, we report that human mesenchymal stem cell (hMSC) aging is associated with dysfunction of double-membrane organelles and downregulation of transcription factor ATF6. CRISPR/Cas9-mediated inactivation of ATF6 in hMSCs, not in human embryonic stem cells (hESCs), resulted in premature cellular aging, characteristic of loss of endomembrane homeostasis. Comparative transcriptomic analyses in hMSCs identify 145 constitutive and 112 tunicamycin-induced ATF6-regulated genes implicated in different layers of cellular homeostasis regulation. Notably, FOS was identified as one of the constitutive ATF6 responsive genes, downregulation of which contributes to accelerated hMSC senescence. Our study identifies a novel transcriptional program related to homeostatic regulation of membrane organelles, and provides mechanistic insights into aging-associated attrition of human stem cells. Overall design: RNA Seq and ChIP-Seq	Co-expression
SRP113807	Shewanella oneidensis belwo-background gamma radiation Transcriptome	This is a scientific investigation on the effects of below-background gamma radiation to the fitness of micro-organism at gene expression level.	Co-expression
SRP113813	Transcriptome profiling at day 30 of microRNA-mediated neuronal reprogramming [RNA-seq d30]	Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons. Overall design: Human fibroblasts were reprogrammed by microRNAs miR-9/9* and miR-124 (miNs). To profile transcriptome of the reprogrammed cells, mRNA were isolated from miNs day 30 and starting fibroblasts.	Co-expression
SRP114321	Base-resolution mapping reveals distinct classes of N1-methyladenosine methylome in nuclear- and mitochondrial-encoded transcripts	Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location, regulation and function. Here, we develop a single-nucleotide resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in the 5'-untranslated region, particularly those located exactly at the first nucleotide of mRNA transcripts, associates with increased translation efficiency. A different subset of m1A sites exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome and are dependent on the methyltransferase complex TRMT6/61A. Additionally, we show for the first time that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation. Overall design: We developed a method named "m1A-MAP" to detect m1A in both the nuclear-encoded and mitochondrial encoded  transcriptome in a single-base resolution. We first tested several available RTases (including AMV, SuperScript II, SuperScript III and TGIRT) under different conditions for their performance on capturing m1A-induced reverse transcription signature (RT1-RT10). Then we applied our methods to detect m1A sites in the human transcriptome (m1A_input_TGIRT,m1A_IP_TGIRT, m1A_IP_demethylase_TGIRT, two replicates for each sample) . We also perform m1A seq for RNA fractions below 200nt in TRMT6/61 KD cells to evaluate the substrat specifity of m1A sites in tRNA (Mock and TRMT6_61A). Lastly, we investigated the correlation between m1A-mRNAs and their translation efficiency by performing ribosome profiling (HEK293T_RNA-seq and HEK293_Ribo-seq). Please note that these data were produced from the X-ten sequencing platform, and the output raw data were pair-end. However, due to the particularity of our library construction (a random barcode of 10 nt were included in our 3'' end cDNA adapter, which cannot be precisely located in Read 1), data of Read 1 were discarded and only the data of Read 2 were used in our analysis and, therefore, submitted as single-end files.	Co-expression
SRP114371	G-Protein-Coupled Receptor 68 Negatively Regulates IL-22 Production in Human Th17 Cells	Purpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods:  Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500.  A total of six donors were analyzed. Results:  AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22.  AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production.  On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191).  11 common genes were significantly regulated by all three treatments.  One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production.  Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions:  Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist.  RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases. Overall design: Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500.  Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media).  Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.	Co-expression
SRP114413	Unraveling cis-regulatory elements by mapping structural changes in mRNAs	mRNA molecules are generally thought to be messengers of genetic information in the cell. Stretches of RNA that are complementary in sequence have a propensity to pair, forming elements of secondary structure within RNA molecules. Although these structures will exist in every mRNA molecule, the role they play in gene regulation is not well understood. Currently two techniques are available to profile the cell RNA structure, in-vivo, in an unbiased manner. We applied one of those techniques, DMS-seq, for probing the human mRNA structure in primary foreskin fibroblasts (HFFs) along human cytomegalovirus (HCMV) infection. As a proof of concept, using DMS-seq, we managed to predict the already solved human 28S rRNA structure with high accuracy. Using our data, we are able to show for the first time in-vivo, that human coding sequences (CDSs) are less structured relative to UTRs. Additionally, we provide systematic in-vivo evidences for unwinding of the mRNA by the ribosomes during translation. Intriguingly, we also found structural changes in human CDSs around the start and stop codon, and also in 3'UTRs. The combination of accurate measurements of translation regulation and mapping changes in mRNA structure along a dynamic process can be used as a platform for deciphering cis-regulatory elements that control gene expression in various cell types, organisms and biological processes. Overall design: in-vivo DMS treatment, neutralization, RNA extration,linker ligation, reverse transcription , circulization, PCR and deep sequencing	Co-expression
SRP114429	Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq]	Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube.  Serous tubal intraepithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. RNA sequence and miRNA data did not identify any clear separation between cases with and without STIC lesions.  HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases. Overall design: In this study, 96 previously untreated high-grade serous carcinoma samples were selected to have half with STIC lesions and half without.  Molecular assays were performed that included RNAseq, microRNA expression, and copy number variation.	Co-expression
SRP114458	VHL/HIF2a axis alters transcriptomic profiles in ccRCC	VHL loss is the most common genetic alteration event in ccRCC. VHL loss stabilizes hypoxia-inducible factor-2 alpha (HIF2a). We compared the changes in transcriptomics profiles after VHL restoration or HIF2a siRNA knockdown in 786-O cells. Overall design: RNA-seq profiles of ccRCC cell line 786-O with and without wild-type VHL restoration, with non-targeting control or pooled siRNA against HIF2a	Co-expression
SRP114482	Transcriptomics profiles of patient-matched normal kidney and ccRCC pairs	VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. We describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors by comparing the epigenetic changes in terms of histone modifications (H3K27ac, H3K4me1, H3K4me3)  with the transcriptomics profiles in 10 pairs of normal kidney and ccRCC tissues. Overall design: RNA-seq profiles of 10 patient-matched normal kidney and ccRCC pairs	Co-expression
SRP114503	RNAseq analyze global transcriptome of changes between siIRF3 and siYAP in Gastric cancer cells	Purpose: To investigate the signal crosstalk between IRF3 and YAP, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by the knockdown of IRF3 or YAP in HGC-27 cells. Methods: Total RNA was extracted from HGC-27 cell after transfection with negative control siRNA (n.c.), IRF3 siRNA (siIRF3) or YAP siRNA (siYAP). Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina  HiSeq 2500 platform. Results: Approximately one thousand transcripts showed differential expression between the siIRF3/siYAP and n.c., with a Fold-change>=2 and q-value <= 0.05. Gene ontology (GO) and gene set enrichment analysis (GSEA) showed a significant negative enrichment of YAP target genes identified by three independent studies in IRF3-knockdown condition. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding the signal crosstalk between IRF3 and YAP. Overall design: RNA was extracted from HGC-27 cells transfected with siRNAs for 48 h. The quality assessed on the Agilent 2100 and sequencing on the Illumina Hiseq2500.	Co-expression
SRP114504	Acetylation of cytidine in messenger RNA	Generation of the "epitranscriptome through post-transcriptional ribonucleoside modification embeds a layer of regulatory complexity into RNA structure and function. Here we describe N4-acetylcytidine (ac4C) as an mRNA modification that is catalyzed by the acetyltransferase NAT10. Transcriptome-wide mapping of ac4C revealed discretely acetylated regions that were enriched within coding sequences. Ablation of NAT10 reduced ac4C detection at the mapped mRNA sites and was globally associated with target mRNA down-regulation. Analysis of mRNA half-lives revealed a NAT10-dependent increase in stability in the cohort of acetylated mRNAs. mRNA acetylation was further demonstrated to enhance substrate translation in vitro and in vivo. Codon content analysis within ac4C peaks uncovered a biased representation of cytidine within wobble sites that was empirically determined to influence mRNA decoding efficiency. These findings expand the repertoire of mRNA modifications to include an acetylated residue and establish a role for ac4C in the regulation of mRNA translation. Generation of the “epitranscriptome” through post-transcriptional ribonucleoside modification embeds a layer of regulatory complexity into RNA structure and function. Here we describe N4-acetylcytidine (ac4C) as a novel mRNA modification that is catalyzed by the acetyltransferase NAT10. Transcriptome-wide mapping of ac4C revealed discretely acetylated regions that were distributed across target mRNAs with the majority of peaks occurring within coding regions. Depletion of ac4C through NAT10 ablation revealed a relationship to gene expression wherein loss of ac4C was globally associated with transcript downregulation. The presence of ac4C within coding sequences was associated with elevated ribosome density and enhanced translation, as assessed in vivo and in vitro. In addition to expanding the repertoire of mRNA modifications to include an acetylated residue, these findings highlight a role for ac4C in the control of mRNA metabolism at the level of translation. Overall design: Detection of acetylated cytide in RNA with immunoprecipitation (RIP), along with RNA-Seq, Ribo-Seq, and BRIC-Seq to analyze effects on RNA processing and stability.	Co-expression
SRP114505	Differential expression of long non-coding RNA and mRNA in children with Henoch-Schönlein purpura nephritis	Long non-coding RNAs (lncRNAs) serve an essential role in regulating immunological functions. However, their impact on Henoch-Schönlein purpura nephritis (HSPN), has remained elusive. Overall design: The present study determined the expression of lncRNAs and mRNAs in the peripheral blood of 6 children with HSPN and recruited 4 healthy children for comparative study. High-throughput sequencing revealed outstanding differences in lncRNA and mRNA expression, which were verified through reverse transcription-quantitative polymerase chain reaction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the associated biological functions and possible mechanisms of lncRNAs and mRNAs in HSPN.	Co-expression
SRP114515	Novel Form of JARID2 is Required to Regulate Differentiation in Keratinocytes.	Polycomb repressive complex-2 (PRC2) is a group of proteins that play important role during development and in cell differentiation. PRC2 is a histone-modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co-factor of PRC2 and is important for targeting PRC2 to chromatin as well as modulating its activity. Here, we show that in many human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N-terminal PRC2-interacting domain (?N-JARID2). We show that ?N-JARID2 is a cleaved product of full-length JARID2 spanning the C-terminal conserved region consisting of jumonji domains. JARID2 knockout in keratinocytes results in up-regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID2-null keratinocytes can be relieved by expression of ?N-JARID2 suggesting that this form promotes activation of these genes and has opposing function to that of PRC2 in regulation of differentiation.  We propose that a switch from expression of full-length JARID2 to ?N-JARID2 is important for the up-regulation of genes during differentiation. Overall design: RNA-seq analysis of Wildtype and JARID2-null keratinocytes (HaCaTs) on day 0 and day 3 of calcium induced differentiation.	Co-expression
SRP114518	Genomic signatures of platinum re-sensitization in ovarian cancer [RNA-Seq]	Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer. A multi-institutional randomized clinical trial compared a regimen of a DNA methyl transferase (DNMT) inhibitor guadecitabine and carboplatin to physician's choice chemotherapy for patients with recurrent platinum resistant ovarian cancer. Tumor biopsies or malignant ascites were collected at day 1 of cycle 1 (pre-guadecitabine) and after two cycles of treatment (post-decitabine). The goal of the current study was to analyze guadecitabine-induced DNA methylation and gene expression changes and correlate pretreatment levels with clinical outcomes. Epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450) and RNA sequencing revealed extensive methylation and gene expression changes induced by guadecitabine in ovarian tumors. Ninety-four gene promoters were significantly hypomethylated after treatment with guadecitabine and 949 genes were differentially expressed in pre vs. post-treatment tumors. Pathways associated with immune reactivation and DNA repair were significantly altered by guadecitabine treatment.  Expression levels of 1155 genes involved in 25 networks on day 1 of cycle 1 correlated with progression free survival. Increased expression of selected genes (e.g. DOK2, miR193a) silenced through promoter methylation restored platinum sensitivity in ovarian cancer cells.  Together, these results support that guadecitabine altered DNA methylation and expression of genes and gene networks correlate with re-sensitization to carboplatin in ovarian cancer patients. Overall design: 93 samples are analyzed, including tumor samples collected from patients with platinum resistant ovarian cancer before treated by guadecitabine and after treated by guadecitabine.	Co-expression
SRP114529	RNA-seq of hiPSCs-derived NPCs from 3 pairs of dizygotic discordant twins for Congenital Zika syndrome	Congenital Zika syndrome (CZS), caused by Zika virus (ZIKV) infection, has been associated to impairment of early brain development, particularly related to neural progenitor cells (NPCs) survival and growth. In this work we report in a high-throughput manner (RNA-Seq) the differences in the transcriptomes of hiPSCs(human induced pluripotent stem cells)-derived NPCs from 3 pairs of discordant twins for Congenital Zika syndrome (CZS). We found significant differences in the expression levels of genes relevant to the regulation of neural development between the NPCs from CZS-affected and non-affected twins, suggesting that epigenetic differences may contribute to the different susceptibilities of NPCs to ZIKV infection. Overall design: hiPSCs were generated from CD71+-cells, which were isolated from peripheral blood samples from three pairs of dizygotic/discordant twins. Then,  NPCs were obtained after hiPSCs differentiation and cultivated for 4 days before the RNA was extracted and deep sequenced using Illumina HiSeq4000.	Co-expression
SRP114567	Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis	Myositis is characterised by muscle inflammation and weakness. Although generally thought to be driven by a systemic autoimmune response, increasing evidence suggests that intrinsic changes in the muscle might also contribute to the pathogenesis. Long non-coding RNAs (lncRNAs) are a family of novel genes that regulate gene transcription and translation. To determine the potential role of lncRNAs, we employed next generation sequencing to examine the transcriptome in muscle biopsies obtained from two histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated myositis (Jo-1). Overall design: PolyA+ RNA was sequenced in human muscle biopsies obtained from control individuals or patients with inclusion body myositis or Jo-1 myositis	Co-expression
SRP114660	lncRNA and mRNA-sequencing of WS1 cells after 5Gy of X-Ray irradiation	Purpose: The goal of this study was to compare the lncRNA and mRNA expression profile of human fibroblast WS1 cells between 0 Gy and 5 Gy X-ray irradiation. Methods: lncRNA and mRNA-sequencing of WS1 cells were generated  using  Illuminal Hiseq4000, RNA-seq reads were mapped to human genome hg19 by hisat2 software. Cuffdiff software was used to analysis the differentially expressed levels of LncRNA and mRNA FPKM. Results: We  identified different expressed levels of  88780 lnRNA and 20311 mRNA transcripts in WS1 cells between 0 Gy and  5 Gy X-ay irradiation. Conclusion: Our study first  revealed the detail of  lncRNA and mRNA expression profiles of WS1 cells after 5Gy of X-Ray irradiation Overall design: lncRNA and mRNA-sequencing of WS1 cells were generated  using  Illuminal Hiseq4000, RNA-seq reads were mapped to human genome hg19 by hisat2 software. Cuffdiff software was used to analysis the differentially expressed levels of LncRNA and mRNA FPKM.	Co-expression
SRP114664	colorectal cancer metastasis	No description.	Co-expression
SRP114672	Recapitulation of Human Neural Microenvironment Signatures in iPSC-Derived NPC 3D Differentiation	Brain microenvironment plays an important role in neurodevelopment and function, where extracellular matrix (ECM) components and soluble factors modulate cellular features, as migration, proliferation survival and neuronal function. Disruption of microenvironment's homeostasis is often related to pathological conditions. Here, we addressed the microenvironment remodeling occurring during in vitro differentiation of human neural stem cells (NSC) in a three-dimensional (3D) culture system.  Proteome and transcriptome dynamics revealed significant changes namely at cell membrane and ECM composition during 3D differentiation, diverging significantly from the profile of monolayer cultures (2D). Structural proteoglycans typically found in brain ECM were enriched during 3D differentiation, while 2D cultures presented increased levels of basement membrane constituents (e.g., laminins, collagens and fibrillins). Moreover, higher expression levels of synaptic machinery and ion transport machinery constituents observed for 3D cultures, both at mRNA and protein levels, suggested a higher degree of neuronal maturation and organization relative to 2D differentiation. This work demonstrated that neural cellular and extracellular features can be recapitulated in the presented 3D neural cell model,  highlighting  its value to address molecular defects in cell-ECM interactions associated with neurological disorders. Overall design: mRNA profiles of day 0, 12 ad 30 of hiPSC-NSC 3D differentiation were generated by RNA sequencing for two hiPSC-NSC lines in duplicates, using Illumina HiSeq 4000.	Co-expression
SRP114701	Effect of FGF13 depletion on the H460 cell line	The purpose of our study was to explore the relevance of the FGF13 protein in a NSCLC cell line Overall design: RNA seq was performed on H460 cells transiently transfected with siRNA against FGF13 (siFGF13) or control siRNA (siC)	Co-expression
SRP114702	Targeting the androgen receptor N-terminus via the cochaperone Bag-1L [RNA-seq C-terminal mutant]	Targeting the activation function-1 (AF-1) at the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the BAG domain of the cochaperone Bag-1L. Mutations in this domain or loss of Bag-1L abrogates AR signaling and reduces PCa growth. Correspondingly, Bag-1L protein levels increase with progression of primary prostate tumors to castration-resistant PCa, correlating inversely with patient response to abiraterone therapy. Intriguingly, BAG domain residues important for its interaction with the AR AF-1 overlap a potentially druggable pocket of this protein. Bag-1L is therefore a putative therapeutic target for the inhibition of AR AF-1 activity. Overall design: We performed transcriptome analysis (RNA-Seq) of 2 cell lines (LNCaP Bag-1L WT and LNCaP Bag-1L CMut) cultured under hormone-starvation conditions for 72 h and then treated with vehicle (ethanol, EtOH) or 10 nM Dihydrotestosterone (DHT) for 16 h. Biological duplicate samples were analyzed for each cell line and each treatment condition.	Co-expression
SRP114703	Developmental stage specific chromosome architecture in human erythroid cells (RNA-seq)	Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and find that globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detect distinct folding patterns at the developmentally controlled b-globin locus. Specifically, new fetal stage-specific contacts are uncovered between a region separating the fetal (g-) and adult (b-) globin genes (encompassing the HBBP1 and BGLT3 non-coding genes) and two distal chromosomal sites (HS5 and 3''HS1) that flank the locus. In contrast, in adult cells the HBBP1-BGLT3 region contacts the embryonic e-globin gene, physically separating the fetal globin genes from the enhancer (LCR). Removal of the HBBP1 gene strongly reactivates g-globin expression, accompanied by increased LCR-g-globin and decreased BGLT3-e-globin interactions, mimicking the effects of deleting the fetal globin repressor BCL11A. Our results uncover a new critical regulatory region as a potential target for therapeutic genome editing for hemoglobinopathies and highlight the power of chromosome conformation analysis in discovering new cis control elements. Overall design: We compared the expression profiles of fetal and adult human erythroblasts at two differentiation stages by RNA-seq.	Co-expression
SRP114710	Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment	Purpose: In an HIV cure setting, Vorinostat may provide the “shock” capable of flushing HIV out of the persistent reservoir, while antiretroviral therapy is used to prevent new infections.  However, this drug may modulate the expression of human endogenous retroviruses (HERVs).  This study demonstrates significant modulation of HERVs and suggests that they should be considered as off-target effects of this drug treatment. Methods: Peripheral blood mononuclear cells were collected from 4 healthy donors.  Naive CD4 T cells were isolated and utilized to assess HERV dysregulation after treatment with Vorinostat.  Cells were collected for study and exposed to a dose of Vorinostat (10uM dose over a 24 hour period).  After this, RNA was extracted from cells and their untreated paired counterparts for deep sequencing by Expression Analysis. Sequence reads that passed quality filters were mapped to the HERVd reference database using Bowtie and counted using HTSeq.  Any HERV which did not achieve at least 1 count per million mapped and counted reads in at least 4 samples was discarded.  Differential expression was performed upon the filtered dataset with edgeR and using TMM normalization. Results: Using an custom built data analysis pipeline, ~100 million reads per sample were mapped to the HERVd reference database and identified 10784 distinct dysregulated elements Bowtie/HTSeq workflow. Differential expression analysis was performed between vorinostat treated and untreated conditions which demonstrated 2102 dysregulated HERV elements with 1007 downregulated and 1095 upregulated (FDR < 0.05) with EdgeR.  Results were further subset with a log2FC ± 3 which resulted in 451 upregulated and 363 downregulated HERV elements from 81 and 82 distinct families respectively.  HERV elements from the LTR12 family were by far the most dramatically upregulated in family frequency and fold change magnitude.  Further confirmation with droplet digital PCR confirmed upregulation of LTR12 elements and demonstrated an exponential dose response curve with HERV expression found at even moderate doses (334nM) of vorinostat treatment. Conclusions: This study represents the first detailed analysis of HERV dysregulation following vorinostat treatment using the untargeted approach of total RNA-Seq.  These results demonstrate that vorinostat dysregulates multiple HERV families with a propensity to upregulate members of the LTR12 HERV family.  This study also provides a methodology to analyze HERV dysregulation in future treatments with vorinostat or other drugs by providing a mechanism to choose primer and probe sets which will properly represent HERV dysregulation as expression across an HERV is not uniform or continuous.  Finally, this work suggests that HERV dysregulation by vorinostat treatment should be considered an off-target effect of this drug and HERV elements, such as LTR12, should be monitored as biomarkers during shock and kill clinical trials with HDAC inhibitors and that trial subjects should be screened to explore further HIV:HERV interactions. Overall design: Profiles of 4 healthy donors in 2 conditions (8 paired total samples) were generated with deep sequencing by Expression Analysis.	Co-expression
SRP114773	Transcriptome-wide analysis of the role of HTLV-1 Tax PBM in T-Cells from infected humanized-mice (hu-Mice)	Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization. Overall design: mRNA profiles of T-cells obtained from hu-Mice infected with wild-type or Tax-PBM HTLV-1 were generated by deep-sequencing in triplicates using Illumina's Hiseq3000 platform.	Co-expression
SRP114780	mRNA-Seq profiling SIX2+ and Foxd1+ cells in mouse embryonic and SIX2+ and SIX2-/MEIS1+ cells human fetal kidney	To characterize the molecular features of human and mouse nephron progenitors and stromal cells we performed intracellular labeling for SIX2 and/or MEIS1 antibodies, FACS, and RNA-seq. Mouse interstitial progenitors were isolated by Foxd1-Tdt transgenic line, FACS, and RNA-seq Overall design: Comparing gene expression profiles of human and mouse nephron progenitors and stromal cells	Co-expression
SRP114792	mTOR kinase inhibition effectively decreases progression of a subset of neuroendocrine tumors that progress on rapalog therapy and delays cardiac impairment	Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNETs) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi) such as CC-223 could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors which progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared to placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long term cardioprotective benefit in those NET patients prone to carcinoid syndrome. Overall design: We performed RNA sequencing analyses as an unbiased means to assess changes in gene expression. Our major goal was to identify the differences in tumor mRNAs between the CC-223- and non-CC-223 responders compared to the rapamycin alone treatment arm (Fig 5A in Orr-Asman et al manuscript). The analysis was conducted using 1 tumor each from 13 and 14 mice treated with rapamycin or switched to CC-223 respectively.	Co-expression
SRP114824	De novo mutations of MSL3 cause a novel X-linked syndrome due to impaired histone H4 lysine 16 acetylation	Epigenetic regulation by histone acetylation plays a key role in cellular homeostasis and its misregulation is associated with human disease. The Male Specific Lethal (MSL) complex associated MOF/KAT8 histone acetyl-transferase is responsible for bulk Histone 4 Lysine 16 acetylation (H4K16ac) in flies and mammals. H4K16ac is a peculiar case amongst the many histone tail modifications in directly affecting higher order chromatin compaction. Yet, its importance during human development and a potential involvement in human pathologies remains largely unknown. Here, we uncover that pathogenic variants in MSL3, a component of the MSL complex, are causative for a new recognizable X-linked syndrome affecting both male and female individuals. Common clinical features of the syndrome include a global delay in developmental milestones and speech, a progressive gait disturbance and recognizable dysmorphism. Using skin biopsies and patient-derived primary fibroblasts, we demonstrate that de novo variants or deletions of MSL3 affect the assembly and enzymatic activity of the MSL complex, hence globally impacting H4K16ac levels in vivo. Transcriptome analysis from patient cells showed misregulation of cellular pathways involved in morphogenesis, cellular shape and cell migration. Using RNAi and MSL3 reintroduction experiments, we phenocopy acute responses occurring on H4K16ac-sensitive MSL target genes, supporting that this syndrome is caused by the loss of MSL3. Finally, we use HDAC inhibitors to rebalance acetylation levels and are able to alleviate both molecular and cellular phenotypes of MSL3 patients cells. Taken together, we characterize a novel syndrome, which is caused by mutations of an epigenetic regulator, allowing us for the first time to unravel the crucial role of H4K16ac during human development. Overall design: RNA sequencing of human primary fibroblasts from control and patients with various truncations of MSL3 with and without panobinostat treatment	Co-expression
SRP114901	Homo sapiens lung adenocarcinoma transcriptome	This study was undertaken to identify genes responsible for mechanisms of mediastinal lymph node metastasis(MLNM)in lung adenocarcinoma with EGFR 19Del mutation or L858R mutation.	Co-expression
SRP114983	Granzyme A in Human Platelets Regulates Pro-Inflammatory Gene Synthesis by Monocytes in Aging	Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.	Co-expression
SRP115014	Sequential expression profile  of cortical neuron differentiation from human induced pluripotent stem cells (iPSCs) by RNA-Seq	We aim to profile the dynamic changes of gene expression dynamics during cortical neuron differentiation from human iPSCs. We used RNA-seq to map open chromatins in iPSCs, neural stem cells (NSCs) at day 33 and day 41. Overall design: We assembled gene expression profiles in iPSCs derived from fibroblasts (GM01835), and iPSC-differentiated cortical neural stem cells (NSCs) at day 33 and day 41 of neural induction (designated as iN-d33 for simplicity), and neurons at day 41 (iN-d41). At each stage (iPSC, iN-d33 or iN-d41), we included two cell culture replicates. We mapped the raw FASTA file against human g1000 transcriptome and counted the RPKM value of each gene using R-based scripts.	Co-expression
SRP115023	hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles	Alternative cleavage and polyadenylation (APA) can occur at more than half of all human genes, greatly enhancing the cellular repertoire of mRNA isoforms. As these isoforms can have altered stability, localisation and coding potential, deregulation of APA can disrupt gene expression and this has been linked to many diseases including cancer progression. How APA generates cancer-specific isoform profiles and what their physiological consequences are, however, is largely unclear. Here we use a subcellular fractionation approach to determine the nuclear and cytoplasmic APA profiles of successive stages of colon cancer using a cell line-based model. Using this approach, we show that during cancer progression specific APA profiles are established. We identify that overexpression of hnRNPC has a critical role in the establishment of APA profiles characteristic for metastatic colon cancer cells, by regulating poly(A) site selection in a subset of genes that have been implicated in cancer progression including MTHFD1L. Overall design: RNA was extracted from nuclear and cytoplasmic subcellular fractions from two biological replicates of the following cell lines: the non-malignant adult-derived human male colonic epithelial 1CT cell line and the SW480 and SW620 cell lines, which both derive from the same patient. The SW480 cell line was established from a Dukes' type B primary adenocarcinoma of the colon and the SW620 cell line was derived from a lymph node after cancer recurred with widespread metastasis. The 3' ends of extracted RNA were generated into libraries using the QuantSeq 3'mRNA-Seq library kit (Lexogen). Libraries were processed on the Ion Chef platform and subsequently sequenced on the Ion Proton system. Sequences were aligned using the Ion Torrent Server TMAP aligner to genome build hg19. RNA was also extracted from nuclear and cytoplasmic subcellular fractions from two biological replicates in SW620 cells following siRNA knockdown of HNRNPC, ELAVL1, or a control knockdown using scrambled siRNA. The 3' ends of extracted RNA were processed and sequenced as before.	Co-expression
SRP115033	RNA Sequencing of Novel HIV RNA TAR-gag and Host Genome of EVs from HIV-1 Infected Cells	We performed a 3' RACE of a novel HIV RNA TAR-gag in order to determine the sequence of the RNA at the 3' end.  Our data had shown that TAR-gag was potentially a noncoding RNA and our hypothesis was that TAR-gag ended somewhere prior to the end of the gag region of the HIV genome.  The 3' RACE experiment showed that TAR-gag actually consists of four different RNA clusters, the longest of which ends at 615 bases from the transcription start site; this is in the middle of the p17 region of the gag gene. In addition, we sequenced all host RNAs in the EVs. Overall design: RNA from J1.1 and U1 exosomes was isolated and converted to cDNA.  Sequencing libraries of the cDNA were made and a 3' RACE was perforemed to determine how long TAR-gag RNA is. Please note that the clustering analysis (published in PMID 28536264) was done only on the unfragmented samples (i.e. *-U samples).	Co-expression
SRP115040	Functional Genomics Analysis of Islets from Recent and Longstanding T1D Reveals the Need for Distinct Approaches to Therapy	Our current understanding of the pathogenesis of T1D arose in large part from studies using the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Of concern, therapeutic interventions shown to significantly dampen or even reverse disease in mouse models have not successfully translated into interventions in human T1D. The present study addresses this disconnect in research translation by directly analyzing human donor islets from individuals with T1D, aiming to provide insight into disease mechanisms and identify potential target pathways for therapeutic intervention. We obtained human islets from a young individual with short-duration T1D, an older individual with long-duration T1D and three non-diabetic donors, and performed unbiased functional genomic analysis by high depth RNA sequencing on these unique cases. This analysis identified several inflammatory pathways upregulated in short-duration disease, which surprisingly included many components of innate immunity. Subsequent manipulation of one of these pathways/factors in NOD mice resulted in a significant reduction in diabetes progression when inhibition occurred early in disease progression. Taken together our data demonstrates that the direct analysis of human islets is essential for identifying relevant and promising novel targets for translation into effective therapeutic interventions for human T1D. Overall design: 5 human islets of Langerrhans preparations. 3 in normo-glycemic individual, one individual with a long duration type 1 diabetes and one individual with short duration type 1 diabetes	Co-expression
SRP115049	Metastasis in triple negative breast cancer is dependent on ?Np63/CXCL2/CCL22-mediated recruitment of myeloid-derived suppressor cells	Gene expression analysis of the knockdown of ?NP63 in two different human breast cancer cell lines using RNA-Seq Overall design: RNA was collected and analyzed for biological replicates of each condition (sh?NP63 vs Vector) from two different human breast cancer cell lines (HCC1806 and SUM1315)	Co-expression
SRP115192	Temporal alterations in the HSAEC transcriptome following infection by virulent and attenuated strains of Rift Valley Fever Virus	Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export.  Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication.  Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored. Overall design: The study included triplicate samples of HSAEC cells infected with Mock, MP12, or ZH548 strains of RVFV, and collected at 3, 9, and 18 hourse post-infection. There are a total of 27 samples.	Co-expression
SRP115201	RNA sequencing of macrophages derived from monocytes differentiated in presence of M-CSF, GM-CSF and heat killed mycobacteria M. obuense	Earlier work has shown that macrophages derived from differentiation of monocytes by heat killed (HK) mycobacteria (e.g. M. obuense) exhibit unique immunophenotypic and molecular properties. Yet, our knowledge of these properties is still limited. The goal of the study is to understand global gene expression programs that are differentially modulated in macrophages derived from monocytes that were differentiated through three different routes: in presence of M-CSF, GM-CSF and the heat killed mycobacterium M. obuense. We performed RNA sequencing (RNA-Seq) of monocyte-derived macrophages (MDM) that were acquired from four separate healthy donors and differentiated by incubation with M-CSF (M-MDM), GM-CSF (GM-MDM) and HK M. obuense (Mob-MDM) (n = 12 samples). We report that Mob-MDM exhibit unique gene expression programs that may explain its unique immunophenotypic properties and thus immunomodulatory capacity. Overall design: We performed RNA-Seq of monocyte-derived macrophages (MDM) that were acquired from four phenotypically  healthy donors. Monocytes were differentiated by incubation with M-CSF (M-MDM), GM-CSF (GM-MDM) and HK M. obuense (Mob-MDM) (n = 12 samples).	Co-expression
SRP115218	Extracellular matrix (ECM) stiffness and collagen-1 (col-1) responsive genes in 3D cultured mammary epithelial cells	We report the expression profiles of MCF10A cells encapsulated in hydrogels of varying stiffness and composition. Cells were encapsulated for 7 days in either 1.) soft alginate and reconstituted basement membrane (rBM), 2.) stiff alginate and rBM, 3,) soft col-1 and rBM, or 4.) stiff col-1. We find global gene expression changes in response to enhanced ECM stiffness, independent of expression changes in response to col-1 exposure. These results provide a comprehensive study of the gene expression changes associated with increased ECM stiffness in addition to the gene expression changes associated with increased col-1 concentration in combination with, and independent of, ECM stiffness. Overall design: Expression profiling of MCF10A cells in four hydrogel conditions were sequenced in duplicate via Illumina HiSeq.	Co-expression
SRP115222	High-Throughput Drug Screening identifies Pazopanib and Clofilium tosylate as effective treatments for malignant rhabdoid tumors	mRNA expression in two different cell lines (DEV and G401) and two conditions (CLOFILIUM and DMSO) were assessed using the Illumina HiSeq2500 plateform in order to detect genes that are differentially expressed in CLOFILIUM condition compared to control (DMSO) Overall design: DEV and G401 cell lines were treated with CLOFILIUM and DMSO. mRNA were extracted 48 hours after treatment. 3 biological replicates were extracted for analysis.	Co-expression
SRP115226	Transcriptome sequencing of 15 normal lung parenchyma (NL), 17 atypical adenomatous hyperplasia (AAH) and 16 lung adenocarcinoma (LUAD) samples from 17 patients	We sought to characterize expression profiles signifying the development of atypical adenomatous hyperplasia (AAH) from normal lung parenchyma (NL), and its progression to lung adenocarcinomas (LUAD). Overall design: We performed transcriptome sequencing of 48 samples, comprising NLs, AAHs and LUADs, from 17 patients. Sequencing was performed using the Ion Torrent platform afterwhich gene profiles differentially expressed among the three groups were determined.	Co-expression
SRP115241	Analysis pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq	This study has been approved by the Medical Ethics Committee of the Southern Medical University. Written informed consent was provided by each patient and volunteer before sampling. Nine patients with SSNHL were included in this study, and 3 healthy volunteers were recruited as normal controls.	Co-expression
SRP115256	Characterisation of distinct states of human naive pluripotency	Human pluripotent stem cells (hPSCs) have been traditionally maintained in a primed state. In the context of the current study, we used a number of published or commercially available media to generated naïve-like hiPS cells from fibroblasts by different reprogramming strategies as well as convert primed hPSCs into a naïve-like state.	Co-expression
SRP115272	Inhibition of SF3B1 by molecules targeting the spliceosome in Rh18 cells	In order to examine the effects of sudemycin D1 on the whole transcriptome, we exposed Rh18 cells to 1µM of drug for 8hr and after extraction, subjected RNA to RNAseq analysis. Control samples were treated with the vehicle (DMSO) alone and all analyses were conducted in triplicate. Overall design: Compare differentially expressed genes in sudemycin treated verses control group.	Co-expression
SRP115408	Metformin alters human host responses to Mycobacterium tuberculosis in-vitro and in healthy human subjects [Ex vivo Blood RNA-Seq]	Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-a (-58%), IFN-gamma (-47%) and IL-1ß (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial  down-regulation of genes related to inflammation and the type 1 interferon response.   Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Ex vivo blood RNA samples analyzed from 11 healthy donors, prior to administration of metformin (control) and after 5 days of metformin (test). Total 22 samples, with 11 clinical replicates.	Co-expression
SRP115415	RNA seq_A375 gSMARCB1 +  A549 etoposide, Aurora kinases inhibitors treated	To study the senescence gene signatures in the cells, which were  genetic SMARCB1 depleted or treated with aurora kinase inhibitors or etoposide, we performed next generation RNA sequencing on these cell, and ''FRIDMAN_SENESCENCE_UP'' geneset was used to determine the enrichment of senescence-related genes. The RNA sequencing results include (1) A375 cells and SMARCB1 depleted counterparts. (2) A549 cells and aurora kinase inhibitor (Alisertib, barasertib or tozasertib) or etoposide treated counterparts. Overall design: RNA seq data of A375_gSMARCB1 +  A549_etoposide, Aurora kinases inhibitors treated, to check senescence gene expression signature one replicate of A375 cells parental V.S SMARCB1 KO (by CRISPR) + duplicates of A549 parental V.S etoposide, or 3 indepdent aurora kinase inhibitors (MLN8237/Alisertib, VX680/Tozasertib, AZD1132/Barasertib)	Co-expression
SRP115427	Transcription Factor Activating Protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma	Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole genome shRNA library screen and the computational inference of master regulator proteins, we identify Transcription Factor Activating Protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target. We demonstrate that TFAP4 is a direct target of MYCN in neuroblastoma cells, and that its expression and activity strongly negatively correlate with neuroblastoma patient survival. Silencing TFAP4 selectively inhibits MYCN-amplified neuroblastoma cell growth both in vitro and in vivo, in xenograft mouse models. Mechanistically, silencing TFAP4 induces neuroblastoma differentiation, as evidenced by increased neurite outgrowth and up-regulation of neuronal markers. Taken together, our results demonstrate that TFAP4 is a master regulator of MYCN-amplified neuroblastoma and may represent a valuable novel therapeutic target. Overall design: Control and TFAP4 KD RNA-seq in two neuroblastoma cell lines **Please note that raw data for the following 7 samples have been lost and thus are not included in the current records; GSM2742417 - SKNDZ Control RNASeq [SD013] GSM2742419 - SKNDZ TFAP4 KD RNASeq [SD008] GSM2742420 - SKNDZ TFAP4 KD RNASeq [SD0014] GSM2742422 - NGP Control RNASeq [SD011] GSM2742423 - NGP Control RNASeq [SD017] GSM2742425 - NGP TFAP4 KD RNASeq [SD012] GSM2742426 - NGP TFAP4 KD RNASeq [SD018]	Co-expression
SRP115428	Genome wide expression change by SMURF1 knocking down in MCF-7 cells	We aim to the investigate the role of SMURF1 in breast cancer progression. MCF-7 cells were used as the model and SMURF1 was silenced by siRNA. Overall design: The MCF-7 cells were treated with 50nM stramble siRNA and siSMURF1. After 48 hours, cells were harvested and the total RNA was extacted by Qiagen kit. The RNA sample was sent to BGI for RNA expression anaylsis.	Co-expression
SRP115446	Differential gene expression analysis of epithelial ovarian carcinoma and benign fallopian tube tissue	No description.	Co-expression
SRP115455	Global loss of epigenetic and transcriptional fidility defines a subclass of cancer with immunotherapy resistance [RCC]	We report that some cancers have extensive loss of epigenetic and transcriptional fidelity, characterized widespread spurious transcription and mRNA processing defects (Loss of transcriptional fidelity: LTF+). LTF impairs transcriptional elongation and imposes a highly specific molecular phenotype where pathways regulated by long genes, such as those involved in inflammatory response are consistently impaired in LTF+ tumors. Accordingly LTF blunts inflammatory response and confers resistance to immune mediated anti-tumor attack, and correlates with poor response to immunotherapeutic drugs in renal cell carcinoma and melanoma patients. We show that genetic or chemical perturbation of gene body histone methylation or of transcriptional elongation can recapitulate LTF-like phenotype, imposing resistance to immune-mediated anti-tumor mechanisms in-vitro and in-vivo. Overall design: Paired end  poly A selected RNAseq was performed on RNA extracted from 1-10 micro meter thickness OCT embedded renal clear cell carcinoma (RCC) tumors obtained from University of Cincinnati Tumor Bank. Expression profiling of these samples was used to identify LTF+ samples in an independent cohort.	Co-expression
SRP115462	Homo sapiens 3'' end sequencing with A-seq	The processing of 3' untranslated regions of messenger RNAs changes widely in relation to the cellular state, yet the key regulators remain largely unknown. To uncover sequence elements that drive the choice of polyadenylation (poly(A)) sites in specific conditions, we have developed KAPAC, a method to infer activities of oligomeric sequence motifs on polyadenylation site choice. We demonstrate that KAPAC readily uncovers the sequence elements, targets and binding site position-dependent activity of the mammalian cleavage factor I which regulates the length of 3' untranslated regions.	Co-expression
SRP115472	Effect of mTORC1 and 2 inhibition on myofibroblast global gene expression	Background: Mechanistic target of rapamycin (mTOR) is a nodal serine/threonine protein kinase critical for the control of fundamental cellular processes. Dysregulated mTOR signalling has been shown in cancer, COPD and idiopathic pulmonary fibrosis (IPF). mTOR forms the catalytic subunit of 2 protein complexes: mTORC1 and mTORC2 which differ in upstream inputs, downstream effects and sensitivity to the allosteric inhibitor rapamycin. Aim: To compare the effects of the mTORC1 inhibitor rapamycin with an ATP-competitive inhibitor of mTORC1/2, AZD8055, on TGFß1 induced transcriptional responses during myofibroblast differentiation by RNA-Seq analysis. Methods: Primary human lung fibroblasts were treated with TGFß1 for 24h to induce myofibroblast differentiation and extra cellular matrix (ECM) production in the presence of rapamycin or AZD8055. Fibroblasts were also treated with rapamycin or AZD8055 without TGFß1. Total mRNA was analysed by RNA-Seq. Results: On a global transcriptomic level, TGFß1 significantly affected the expression of ~4,200 genes by more than 1.5 fold, of which ~1,100 changes were reversed by pan-mTORC1/2 inhibition, while being insensitive to rapamycin. Only 15 gene changes were reversed exclusively by rapamycin. Analysis of the rapamycin-insensitive, mTOR sensitive myofibroblast transcriptome revealed ECM-receptor interaction, metabolism and actin cytoskeleton regulation as major affected pathways. Conclusions: Our data support the conclusion that therapeutic approaches aimed at interfering with TGFb1 induced myofibroblast differentiation and ECM production require dual mTOR1/2 inhibition and may, in part, explain the lack of clinical efficacy of everolimus in the context of IPF. Overall design: Primary human lung fibroblasts were treated with TGFß1 for 24h in the presence of rapamycin or AZD8055. Each treatment was done in quadruplicates, for a total of 16 samples. Untreated cells were used as control. Paired-end RNA sequencing was performed with the NextSeq sequencing platform (Illumina, San Diego, CA, USA). Each sample was run on 4 different lanes.	Co-expression
SRP115480	Metformin alters human host responses to Mycobacterium tuberculosis in-vitro and in healthy human subjects [PBMC RNA-Seq]	Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Peripheral Mononuclear Cells taken from 11 healthy donors, prior to administration of metformin and after 5 days of metformin. Samples were stimulated with Mycobacterium tuberculosis lysate or cultured unstimulated for 4 hours. Total 88 samples, with 11 clinical replicates.	Co-expression
SRP115520	First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor	The polycomb repressive complex 2 (PRC2) histone methyl-transferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with sub-nanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESC) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development. Overall design: 1 biological sample were isolated from naïve hESC cell line Elf1 and Elf1 expressing EED binder 22.2. RNA-seq and ChIP-seq (H3K27me3) was performed for each sample.	Co-expression
SRP115558	RNA sequencing (RNA-SEQ) of Human endothelial cells (HUVEC) in LFS, sFRP2OE, and WT conditioned media	Purpose: To understand molecular and cellular effects of secreted sFRP2 to endothelial cells Methods: We performed RNA sequencing of 9 samples from HUVEC cultured in WT, sFRP2OE, LFS conditioned media for 16 hours Conclusion: apoptosis and angiogenetic molecular factors are activated in HUVEC by secreted sFRP2 Overall design: cDNA library preparation and sequencing were performed at Novogen (http://www.novogen.com/home). Briefly, RNA quality was determined with an Agilent Bioanalyzer (RNA integrity number [RIN] > 7.0 for all samples). mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, and double stranded cDNA synthesized using random hexamers, M-MuLV Reverse Transcriptase (RNase H), and DNA Polymerase I. NEBNext Adaptor with hairpin loop structure were ligated to the cDNA in preparation for hybridization. In order to select cDNA fragments of preferentially 150~200 bp in length, the library fragments are purified with AMPure XP system (Beckman Coulter, Beverly, USA). Library of 150-200 bp fragments at an effective concentration of > 2nM were loaded onto an Illumina HiSeq 4000 for sequencing	Co-expression
SRP115559	RNA sequencing (RNA-SEQ) of WT and LFS patient specific iPSC derived pre-osteoblasts	Purpose: To understand molecular and cellular effects of sFRP2 overexpression in LFS patients Methods: We performed RNA sequencing of 32 samples from WT, sFRP2OE, LFS, and sFRP2 knockdown MSCs or preosteoblasts in four differentiation time points and performed RNAsequencing. Conclusion: molecular and cellular effects of sFRP2 overexpression in LFS patients Overall design: cDNA library preparation and sequencing were performed at Novogen (http://www.novogen.com/home). Briefly, RNA quality was determined with an Agilent Bioanalyzer (RNA integrity number [RIN] > 7.0 for all samples). mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, and double stranded cDNA synthesized using random hexamers, M-MuLV Reverse Transcriptase (RNase H), and DNA Polymerase I. NEBNext Adaptor with hairpin loop structure were ligated to the cDNA in preparation for hybridization. In order to select cDNA fragments of preferentially 150~200 bp in length, the library fragments are purified with AMPure XP system (Beckman Coulter, Beverly, USA). Library of 150-200 bp fragments at an effective concentration of > 2nM were loaded onto an Illumina HiSeq 4000 for sequencing	Co-expression
SRP115569	C/EBPa overexpression overrides epigenetic reprogramming by RUNX1-ETO and RUNX1-EVI1 [RNA-seq]	Acute myeloid leukemia (AML) is a heterogeneous disease caused by recurrent mutations in the transcription regulatory machinery. As a result, malignant myeloid cells display abnormal growth and are blocked in differentiation. One type of recurrent mutations affects RUNX1 which is subject to mutations and translocations, the latter giving rise to fusion proteins with aberrant transcriptional activities. We recently compared the mechanism by which the products of the t(8;21) and the t(3;21) translocation RUNX1-ETO and RUNX1-EVI1 globally reprogram the epigenome. We demonstrated that a main component of the block in differentiation in both types of AML is direct repression of the gene encoding for the crucial myeloid regulator C/EBPa by both fusion proteins. We also showed that CEBPA upregulation is required for the release of the differentiation block after oncogene knock-down. In the study presented here we examined at the global level the response of t(8;21) and t(3;21) cells to C/EBPa overexpression. We show that C/EBPa overexpression does not change oncoprotein expression or globally displace these proteins from their binding sites, but up-regulates a core set of common target genes important for myeloid differentiation and interferes with leukemic growth, highlighting CEBPA regulated pathways as targets for therapeutic intervention. Overall design: RNA-seq experiments with inducible version of CEBPA (C/EBPa-ER) have been used to study the effect of CEBPA overexpression on the gene expression of t(8;21) and t(3;21) AML	Co-expression
SRP115571	RiboZero Gold paired-end RNA-seq data from postmortem tissue of the dorsolateral prefrontal cortex of autism spectrum disorder samples and healthy control samples	Purpose: The goals of this study was to compare the expression of histamine related genes in ASD patients and controls. Methods: RNA-Seq was performed using strand-specific Ribosomal RNA depletion (RiboZero) library preparation and the TruSeq RNA Sample Preparation v2 kit from Illumina. One hundred base pair paired-end sequencing was run on the HiSeq 2000. TopHat (v2.0.4) was used to enforce strand specificity and to align the sequencing reads to known transcripts of the Ensembl Build GRCh37.67. FeatureCounts (v1.4.4) was used to count the total number of reads overlapping each gene using the default settings, with paired-end and reverse-stranded counting specified using the Ensembl Build GRCh37.67 gtf file. These counts were merged from both reads of the paired-end sequencing and normalized by library size and coding gene length to form Reads Per Kilobase of Gene per Million mapped reads (RPKM) values. The influence of diagnosis on expression was analyzed with linear regression transcriptome-wide and further evaluated using a gene set analysis. Results: There was no significant diagnosis effect on any of the individual genes but expression of the gene set of HNMT, HRH1, HRH2, and HRH3 was significantly altered. Conclusions: Our study represents the first specific analysis of the expression of histamine related genes in ASD and suggests that these genes may collectively be dysregulated. Overall design: Comparison of gene expression of 13 ASD cases and 39 matched controls.	Co-expression
SRP115576	Gene  expression profiles of ibrutinib-responsive and ibrutinib non-responsive cells in ERBB4 expressing cancer cell lines	By  using a unique functional protein microarray platform, we found that the FDA approved drug ibrutinib can inhibits ERBB4 activity in the same nM range as its canonical target, BTK. Cell-based assays revealed that ibrutinib treatment inhibited cell growth in some ERBB4 expressing cancer cells whereas no response was observed in other cells. Therefore, to identify global gene expression differences between ibrutinib responsive and non-responsive cancer cells, we performed RNA-Seq, and identified a signature featuring the WNT pathway that predicts growth responsiveness to ibrutinib in ERBB4 expressing cancers. Overall design: Examination of gene expression profiles of 4 ibrutinib responsive and 4 ibrutinib non-responsive ERBB4 expressing cancer cell lines	Co-expression
SRP115598	Studying the role of nuclear AGO1 in Chromatin Organisation	In this study we explore the non-canonical role of Ago1 protein in regulating chromatin architecture and gene expression in human HepG2 cells	Co-expression
SRP115672	Transcriptional profiling unravels enhanced xenobiotic metabolism in the skin of patients with atopic dermatitis but not with ichthyosis vulgaris	Previous transcriptome analyses confirmed the major role of immunological and skin barrier abnormalities in atopic dermatitis (AD). We here aimed at identifying novel pathogenic pathways involved in AD by comparing AD patients stratified for filaggrin (FLG) mutations not only to healthy donors but also to patients with ichthyosis vulgaris (IV). We applied single-molecule direct RNA-sequencing to analyze the whole transcriptome of nonlesional skin. Six hundred and one genes (478 up-regulated and 123 down-regulated by greater than 2-fold) were differentially expressed when all AD patients were compared to healthy donors. Expression of genes involved in RNA/protein synthesis, RNA splicing, and ATP synthesis was enhanced. Interestingly, genes involved in cell death, response to oxidative stress, DNA damage/repair and xenobiotic metabolism were largely enriched. Two hundred and thirty-seven genes (216 up-regulated and 21 down-regulated by greater than 2-fold) were altered in the skin of IV patients when compared to healthy donors. Remarkably, enhancement of xenobiotic metabolism was only detected in AD skin. Moreover, increased expression of genes encoding for keratinocyte cross-linking (SPRR2) and S100 proteins characterizes the skin of patients with AD flare when compared to patients without. We did not find significant differences in gene profiling between AD patients with and without FLG mutations.This work reveals new putative pathogenic pathways related to xenobiotic metabolisms involved in AD. Overall design: 29 samples, skin biopsies	Co-expression
SRP115815	RNA-seq of FSHD and control immortalised myoblasts I	FSHD and control immortalised myoblasts show repression of Pax7 target genes Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.	Co-expression
SRP115818	Sequencing facilitates quantitative analysis of transcriptomes in wild type and Lrp6-knockdown cells	Purpose: The goals of this study are to determine the LRP6-mediated splicing regulation, and cellular transcriptomes from rat and human are analysised by deep sequencing. Methods: The mRNA profiles of WT and LRP6 KD were generated by deep sequencing, using Illumina HiSeq 4000. And the transcript isoform difference betwwen the two group were analysied by bioinformation, Semiquantitative PCR was performed to identify the analysis result. Results and conclusions: We detected a substantial number of Lrp6 loss-induced AS events, and up to nearly 50 of them were exon-skipped. A gene ontology analysis of the conserved LRP6-driven network showed enrichment for ninety-four genes encoding proteins mainly involved in cellular and metabolic processes . Among them, a decade of genes with LRP6-dependent isoform expression showed identical splicing patterns on the exon level across species. The RNA sequencing results were further verified by Semiquantitative PCR. We conclude that LRP6 could regulate mRNA splicing. Overall design: Examination of  different transcriptome in 3 cell types	Co-expression
SRP115847	Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity	We queried the expression of CNTNAP2 in Ngn2-induced neurons from each member of this family trio, hypothesizing that heterozygous intragenic deletions may affect the expression of CNTNAP2. Overall design: RNA was harvested after 21 days of Ngn2-induction. The New York Genome Center prepared RNAseq libraries using the KAPA Total 350bp kit, followed by 2x125bp Illumina RNA sequencing to a read depth of 40M reads per sample on the HiSeq 2500.	Co-expression
SRP115894	The deregulated microRNAome contributes to the cellular response to aneuploidy [mRNA]	Aneuploidy severely alters cell physiology and is widespread in cancers and other pathologies. In model cell lines, aneuploidy impairs proliferation, leads to proteotoxic as well as replication stress and triggers conserved transcriptome and proteome changes. In this study we analysed for the first time miRNAs and demonstrate that their expression is altered in response to chromosome gain. Overall design: HiSeq Illumina sequencing of total RNA for four whole-chromosome aneuploid cell lines and their corresponding parental cell line.	Co-expression
SRP115904	RNA-seq analysis of iPSC-derived heptocytes with mutations in NR1H4	We discovered a rare missense mutation in NR1H4 (R436H), which encodes the farnesoid X receptor (FXR), associating with lower levels of total cholesterol in the Icelandic population. To explore the effects of R436H we used CRISPR-Cas9 to generate homozygous NR1H4 R436H and NR1H4 knockout human iPSC lines which we differentiated to hepatocytes. Hepatocytes were treated with an FXR agonist for 24 hours and transcript abundance measured by RNA-seq. The global response to FXR activation in NR1H4 R436H cells was very similar to that of wild-type cells showing that it is not a loss-of-function mutation. However, we did observe subtle gene expression differences compatible with an effect on lipids when we compared R436H agonist treated hepatocytes to wild-type agonist treated hepatocytes. Overall design: RNA-seq was performed on wild-type, NR1H4 knockout and NR1H4 R436H iPSC-derived hepatocytes treated with FXR agonist GW4064.	Co-expression
SRP115907	Genome-wide transcriptome analysis of NIPBL iPSC and commited cardiomyoctes	The purpose of this study was to compare the transcriptome of NIPBL patient derived iPSCs and patient-derived cardiomyocytes to healthy unaffected individuals Methods: iPSC transcriptome profiles of three CdLS patient iPSCs harboring mutations in the NIPBL gene  and cardiomyocytes derived from patient-iPSCS were generated by deep sequencing, in triplicate, using Illumina XXXXXX. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Results: Using an optimized data analysis workflow, we mapped about 15 million sequence reads per sample to the  human genome and identified XXXX transcripts in CdLS-iPSCs and XXXXXX transcripts in control-iPSCs with XXXX workflow. Conclusion: Our data is the represents the first human developmental model for studying CdLS through pluripotent stem cells and lineage commited subtypes (cardiomyocytes). This data highlights NIPBLs role in regulating transcriptional regulation and has significant consequences on DNA nucleosome involvement as it relates to global gene expression.  This work provides preliminary evidence that NIPBL  is required for normal epigenetic and DNA landscape establishment during embryonic cardiomyocyte generation. Overall design: Examine transcriptome of Control and NIPBL iPSC and Cardiomyoyctes	Co-expression
SRP115911	Transcriptomic analysis of healthy donor and Sickle Cell Disease (SCD) hematopoietic stem/progenitor cells	Human hematopoietic stem/progenitor cells (HSPCs) were either collected from bone marrow or mobilized from healthy donors and SCD patients. We performed RNA-seq analysis on RNA extracted from purified CD34+ HSPCs coming from the different sources to compare their gene expression profiles. Overall design: RNA-sequencing of CD34+ cells collected from bone marrow or mobilized from healthy donors and SCD patients.	Co-expression
SRP115921	Neuronal EphB1 induces STAT3 activation in astrocytes, which is impaired in ALS models [Hs]	Astrocyte  responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Overall design: Examination of transcriptome-wide gene expression profiles of terminally differentiated and enriched iPSC-derived astrocytes harboring the SOD1 D90A mutation	Co-expression
SRP115924	RNAseq data from SCCOHT1 and OVCAR8 ovarian cancer cells treated with BET inhibitors	The antitumor activity of bromodomain inhibitors (BETi) has been demonstrated across numerous types of cancer. As such, these inhibitors are currently undergoing widespread clinical evaluation. However, predictive biomarkers allowing the stratification of tumors into responders and non-responders to BETi are lacking. Here, we show significant anti-proliferative effects of BETi in vitro and in vivo against aggressive SCCOHT1 ovarian cancer models lacking the SWI/SNF-related, SMARCA4 protein . Transcriptomic analysis revealed that exposure to BETi potently down-regulated the oncogenic receptor tyrosine kinase HER3 in SCCOHT1 but not in resistant OVCAR8 cells. Repression of this pathway is found to be an important determinant of response to BETi in cells harboring a loss of SMARCA4. Overall, we propose that BETi represent a rational therapeutic strategy in poor prognosis, SMARCA4 deficient cancers. Overall design: Analysis of mRNA profile of 2 cell lines exposed to DMSO, OTX015 for 4 and 24 hours in duplicate	Co-expression
SRP115925	The hepatitis C viral protein NS5A stabilizes growth-regulatory human transcripts	Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization.  In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization.  An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells.  Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma. Overall design: Calculate mRNA decay rate by examining RNA-seq expression levels of 2 samples (Huh and Huh-HCV) at 3 time points (0h, 3h, and 6h) after transcription arrest. RNA-IP followed by RNA-seq on 2 samples (Huh and Huh-HCV).	Co-expression
SRP115931	Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles	We have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study has revealed that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of coloncarcinoma cells. The changes in gene expression correlated positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with tumour differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and does not require communication by direct contact with the bacteria. Overall design: Examination of mRNA profiles of three samples: untreated HCT8 cells (control), treated with membrane vesicles from V. cholerae, treated with membrane vesicle from E. coli (in triplicates), generated by RNAsequencing	Co-expression
SRP115953	Transcriptomal changes during differentiation of human iPS cells to PGC-like cells	Pluripotent stem cell-derived human primordial germ cell (PGC)-like cells (hPGCLCs) may provide important opportunities to study human PGCs. We produced CD38+ hPGCLCs with a high efficiency [~43% of FACS-sorted embryoid body (EB) cells] from primed-pluripotency induced pluripotent stem cells (iPSCs) via 72-hour reprogramming towards ERK-independent naïve pluripotency. RNA-seq confirmed transcriptomal consistency of our hPGCLCs with hPGCLCs previously produced using various other methods. Immunohistochemical studies identified hPGCLCs exclusively at the outermost surface layer of EBs mostly as scattered cells, and live cell imaging revealed actively migrating hPGCLCs forming cellular protrusions. Both CD38+ hPGCLCs and CD38- EB cells significantly expressed PRDM1 and TFAP2C, but PRDM1 mRNA of CD38- cells lacked the 3'-untranslated region with let-7 and other miRNA binding sites known to regulate PRDM1 mRNA stability. Genes expressed specifically in hPGCLCs included early-PGC markers KIT, NANOS3, and SOX17, and cell migration genes, and their promoter sequences were enriched with TFAP2C binding motif. Whereas all hPGCLCs strongly expressed the CXCR4 chemotaxis receptor, its ligand CXCL12/SDF1 was not significantly expressed in the whole EBs. Exposure of hPGCLCs to CXCL12/SDF1 induced cell migration and anti-apoptosis genes; in contrast, genes involved in nuclear division were suppressed. Our study demonstrates a transcriptomal consistency of hPGCLCs produced using varying methods as well as distinct roles and/or regulation of PRDM1 and TFAP2C expression in development of human and mouse PGCs. Relevance of hPGCLCs to early-stage human embryonic PGCs randomly migrating in the midline region of human embryos before initiating directional chemotaxis under CXCR4-CXCL12/SDF1 signaling has also been suggested. Overall design: Human iPS cells with primed pluripotency were converted to naïve pluripotency for 72 hours and then subjected to embryoid body formation, from which CD38-positive PGC-like cells and CD38-negative cells were isolated by FACS. Total RNA was extracted from FACS-enriched cells and subjected to RNA-seq.	Co-expression
SRP115954	SETDB2 links E2A-PBX1 to cell cycle dysregulation in acute leukemia through CDKN2C repression [sequencing]	Acute lymphoblastic leukemia (ALL) is associated with significant morbidity and mortality necessitating further improvements in diagnosis and therapy.  Targeted therapies directed against epigenetic regulators, which are frequently mutated or misregulated in acute leukemia, are emerging as candidate approaches in preclinical studies and early trials.  However, the epigenetic factors involved in most ALLs are not well defined or functionally characterized.  In this study, we demonstrate an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis.  It is over-expressed in a wide spectrum of leukemias, required for their maintenance in vitro and in vivo, and its elevated expression correlates with a poor prognosis in clinical cohorts.  In a subset of ALL with the preBCR+ phenotype, SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1.  In this subset, SETDB2 epigenetically suppresses expression of the cell cycle inhibitor CDKN2C through histone H3K9 tri-methylation thus establishing a novel oncogenic pathway subordinate to E2A-PBX1 that silences a major tumor suppressor in ALL.  In contrast, SETDB2 was relatively dispensable for normal hematopoietic stem and progenitor cell proliferation.  In addition to targeting SETDB2 alone, its knockdown significantly enhanced sensitivity to kinase and epigenetic inhibitors suggesting a potential approach to future combination treatments.  Our studies define an epigenetic role for SETDB2 in leukemia pathogenesis, and provide a mechanistic rationale for targeting SETDB2 therapeutically in a subset of leukemia. Overall design: For RNAseq experiment, E2A-PBX1 was specifically knocked down by two shRNAs in two human E2A-PBX1+ cell lines (RCH-ACV, 697). Finally, two cell lines with two shRNAs plus corresponding control in triplicates are submitted to RNAseq sequencing. For ChIP-seq, RCH-ACV cells depleted of SETDB2 by shRNA were immuoprecipitated with anti-H3K9me3 antibody, and together with input control were constructed for ChIP-seq libraries and submitted to single-end ChIP-sequencing (detailed protocol referred to, Wong et al., 2015, Cancer Cell).	Co-expression
SRP115956	Sex-specific Transcriptional Signatures in Human Depression	Rational: Major depressive disorder (MDD) is a leading cause of disease burden worldwide. While the incidence, symptoms and treatment of MDD all point toward major sex differences, the molecular mechanisms underlying this sexual dimorphism remain largely unknown. Methods: Here, combining differential expression and gene coexpression network analyses, we provide a comprehensive characterization of male and female transcriptional profiles associated with MDD across 6 brain regions. We overlap our human profiles with those from a mouse model of chronic variable stress and capitalize on converging pathways to define molecular and physiological mechanisms underlying the expression of stress susceptibility in males and females. Results: Our results show a major rearrangement of transcriptional patterns in MDD, with limited overlap between males and females, an effect seen in depressed humans and in stressed mice. We identify key regulators of sex-specific gene networks underlying MDD and confirm their sex-specific impact as mediators of stress susceptibility. For example, downregulation of the female-specific hub gene DUSP6 in prefrontal cortex mimics stress susceptibility in females only by increasing ERK signaling and pyramidal neuron excitability. Such DUSP6 downregulation also recapitulates the transcriptional remodeling that occurs in PFC of depressed females. Conclusions: Together, our findings reveal dramatic sexual dimorphism at the transcriptional level in MDD and highlight the importance of studying sex-specific treatments for this disorder. Overall design: RNA sequencing data from (1) 6 human postmortem brain regions in males and females with and without major depression and (2) 2 epuivalent brain regions in males and female mice with and without 21 days of chronic varibale stress (CVS). Note: The raw data for Samples GSM2740709-GSM2740726, GSM2740805, and GSM2740808 were updated in January 2018. The processed data have not changed.	Co-expression
SRP115959	APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer''s Disease Phenotypes in Human iPSC-Derived Brain Cell Types	The apolipoprotein E4 (APOE4) variant is the single greatest genetic risk factor for sporadic Alzheimer''s disease (sAD). However, the cell-type-specific functions of APOE4 in relation to AD pathology remain understudied. Here, we utilize CRISPR/Cas9 and induced pluripotent stem cells (iPSCs) to examine APOE4 effects on human brain cell types. Transcriptional profiling identified hundreds of differentially expressed genes in each cell type, with the most affected involving synaptic function (neurons), lipid metabolism (astrocytes), and immune response (microglia-like cells). APOE4 neurons exhibited increased synapse number and elevated Ab42 secretion relative to isogenic APOE3 cells while APOE4 astrocytes displayed impaired Ab uptake and cholesterol accumulation. Notably, APOE4 microglia-like cells exhibited altered morphologies, which correlated with reduced Ab phagocytosis. Consistently, converting APOE4 to APOE3 in brain cell types from sAD iPSCs was sufficient to attenuate multiple AD-related pathologies. Our study establishes a reference for human cell-type-specific changes associated with the APOE4 variant. Overall design: We used CRISPR/Cas9 to create isogenic APOE3 and APOE4 human iPSC lines that enable us to carry out comprehensive analysis of biochemical, cellular, and transcriptional changes by APOE variants in multiple iPSC-derived brain cell types	Co-expression
SRP116023	Stranded RNASeq of human mammary primary tumors ER+ and paired adjacent healthy tissues	Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing to highlight the potential role of NATs in gene regulations occurring in breast cancer. Overall design: 22 primary invasive breast cancer carcinoma expressing estrogen receptors and their paired adjacent mammary healthy tissues were analyzed by strand-specific RNA sequencing on a Illumina HiSeq.	Co-expression
SRP116042	SBF2-AS1 promotes tumorigenesis as a miRNA sponge in lung cancer	Long noncoding RNA (lncRNA) play important roles in the pathogenesis of cancer. LncRNA SBF2-AS1is unregulated in lung cancer tissues, while its biological function and molecular mechanism are largely unknown. RNA sequencing results suggest cell cycle-related genes are altered after SBF2-AS1 knockdown. In vivo and in vitro experiments confirm SBF2-AS1 could promote tumorigenesis of lung cancer. Further experiments prove SBF2-AS1 could bind with miR-338-3p and miR-362-3p to regulate various cell cycle-related genes, including E2F1. These results indicate the existence of ceRNA network driven by SBF2-AS1 through sponging miRNAs. Overall design: A549 cells are plated into 6-well plate and then transfected small interfering RNA (siRNA) specifically targeting SBF2-AS1 or negative control (NC) siRNA. 24 hours after transfection, cells are harvested and extract total RNA with TRIZol reagent.	Co-expression
SRP116052	Role of ß-estradiol in breast cancer.	This study aimed to investigate the role of ß-estradiol in MCF-7 breast cancer (BC) mechanism.	Co-expression
SRP116072	Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor	We report RNAseq gene expression data following ARS-1620 treatment and shKRAS expressing cells (NCI-H358).  We also compare gene expression changes following treatment with ARS-1620 or trametinib in NCI-H358, LU65 (KRAS-G12C+), and A549 (KRAS-G12S+) cells.  Additionally we report a time course (4, 24, 48hr) of ARS-1620 and trametinib treated NCI-H358 cells. Overall design: Examination of whole transcriptome RNAseq data from 3 separate experimental designs: 1. H358 cells, treated with ARS-1620 & DMSO (24hr) and transduced with shRNA control & KRAS (24hr post infection), 2. H358, LU65, and A549 cells treated with DMSO, ARS-1620, or trametinib (for 24hr), and 3. H358 cells treated as time course of ARS-1620 (1uM) or trametinib (50nM)	Co-expression
SRP116078	TAp73 is a marker of glutamine addiction in medulloblastoma	Metabolically-targeted therapies hold the promise of offering an effective and less toxic treatment for tumours including medulloblastoma, the most common malignant brain tumour of childhood. Current treatment relies on the sensitivity of these tumours to DNA damage that was discovered more than 50 years ago. Finding new tumour-specific susceptibilities to complement sensitivity to DNA damage is key to developing new more effective adjuvant therapies. The specific metabolic program of tumours is an attractive vulnerability, as restriction diet are low cost and easy to implement. Here, we present compelling pre-clinical evidence that glutamine restriction diet can be used as an adjuvant treatment for p73-expressing medulloblastoma. Overall design: siRNA constructs targeting p73 (ID: 2671-AMBION) and a non-targeting control siRNA (scramble) were transfected with 10?pM siRNA with lipofectamine 3000 according to the supplier's protocol for 48 hours	Co-expression
SRP116104	Folate modulation induces chromosomal instability and higher proliferation of immortalized human keratinocytes	Gene expression variation upon folate deficiency and repletion in human foreskin keratinocytes immortalized by HPV16E6E7 Overall design: Effects of folate modulation on several cellular events such as DNA stability	Co-expression
SRP116136	RNA-seq analysis of melanoma and carcinoma cells expressing FOXQ1	We report the genome wide RNA sequencing for high-throughput profiling of FOXQ1 target genes in melanoma and carcinoma cells. We generated melanoma (SK-Mel-147) and ovarian carcinoma cells (SCOV3) ectopically expressing FOXQ1. We find that FOXQ1 differentially regulates the expression of several genes in melanoma cells as compared to carcinoma cells. Specifically, FOXQ1 induces the expression of several genes in ovarian carcinoma cells SCOV3 and suppresses the expression of the same genes in melanom cells.  We show that this differentialy regulation of the same target gene depends upon the nuclear levels of beta-catenin. High levels of active nuclear beta-catenin promote FOXQ1 mediated transcriptional activation of genes whereas low levels contribute to TLE/Groucho- mediated repression. This study provides a framework for understanding the lineage specific pattern of transcriptional regulation by FOXQ1 and its contextual determinants. Overall design: Examination of FOXQ1 target genes in 2 cell lineages	Co-expression
SRP116140	Synergistic activity of BET inhibitor BI 894999 with PLK inhibitor volasertib in AML in vitro and in vivo	Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment. In vitro combination of both compounds leads to a decrease in S-Phase and to increased apoptosis. In vitro scheduling experiments guided in vivo experiments in disseminated AML mouse models. Co-administration of BI 894999 and volasertib dramatically reduces tumor burden accompanied by long-term survival of tumor-bearing mice and eradication of AML cells in mouse bone marrow. Together, these preclinical findings provide evidence for the strong synergistic effect of BI 894999 and volasertib, warranting future clinical studies in patients with AML to investigate this paradigm. Overall design: MV-4-11B cells were treated with either BI 894999 (1 nM or 35 nM) or volasertib (20 nM) or the combination of both for 4h or 24h. Subsequently cells were harvested for total RNA isolation using TriZol (Ambion) and further purified using miRNAeasy columns (Qiagen). Approximately 500ng of total RNA were subjected to library preparation using the TruSeq RNA Library Prep Kit v2 with polyA selection as recommended by the manufacturer (Illumina) without generating stranded information. Library were multiplexed and sequenced on a HiSeq1500 using paired-end sequencing with 50 cycles each.	Co-expression
SRP116159	Zhang_ RNA-seq of Bel-7402 and SMMC-7721 cells with CBX8 overexpression	This study aims to determine the clinical significance of CBX8 inhepatocellular carcinoma (HCC), to examine the role of CBX8 in tumor growthand metastasis, and to disclose the underlying mechanism of CBX8-mediatedphenotypes in HCC.	Co-expression
SRP116165	Homo sapiens RNAseq data on systemic perturbation of keratinocyte homeostasis by genetic loss of the extracellular matrix protein collagen VII	The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and plays a critical role in organismal homeostasis. Its genetic loss is linked to skin fragility and progressive injury- and inflammation-driven fibrosis that ultimately results in aggressive skin cancer. Because epithelial dysfunction is a principle initiator of fibrosis in other diseases, we performed comprehensive transcriptome and proteome profiling of human epidermal keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII.	Co-expression
SRP116190	ZIKV infection of monocytes activates inflammasome pathways	The objective of this assay was to determine the effect of ZIKV on host cellular pathways Overall design: Purified human CD14+ monocytes were infected with two strains of ZIKV (PR and NIG) and RNA was subjected for differential gene expression by next generation sequence analysis.	Co-expression
SRP116196	Human Adult Sorted Live Cell Erythroblasts transduced with Sigma shRNA Clone TRCN0000005418 targeting RIOK3 with puromycin selection RNAseq	Erythroblasts cultured from mobilized CD34+ cells from healthy adult human donors were used to generate an erythroblast transcriptome transduced with Sigma shRNA Clone TRCN0000005418 targeting RIOK3 gene. Cellular maturation was maintained including enucleation.  On culture day 14 total RNA was isolated (see PMID: 23798711 for details). These RNA-Seq profiles were generated after flow cytometric sorting (live cell gating of culture Day 14 erythroblasts according to forward and side scatter). Preliminary screening data demonstrated a robust increase in fetal hemoglobin that may be due to off-target effects from this shRNA clone. A non-targeting shRNA dataset was used for control. These samples were originally published in GSE94147 and are included in this series as well. Overall design: Human CD34+ cells from health donor transduced with lentivirus expressing Sigma shRNA Clone TRCN0000005418 to knockdown RIOK3 gene expression in serum free culture.  RNA extracted from sorted live cell gate on Day 14 using Qiagen miRNeasy Mini Kit.  1ug of RNA was used for library construction and Ribo depletion with globin subtraction. We would like to thank Gerard Bouffard and the National Human Genome Research Institute for their expertise and assistance with RNA-seq.	Co-expression
SRP116223	The TIA1 RNA-binding-protein family regulates EIF2AK2-mediated stress response and cell cycle progression	TIA1 and TIAL1 encode a family of U-rich-sequence-specific mRNA-binding proteins (mRBPs) ubiquitously expressed and conserved in metazoans. By PAR-CLIP, we determined that both proteins bind target sites with identical specificity in 3' UTRs as well as within introns proximal to 5' and 3' splice sites. Double knockout (DKO) of TIA1 and TIAL1 increased target mRNA abundance proportional to the number of binding sites and impacted the accumulation of aberrantly spliced mRNAs including the dsRNA-binding protein PRKRA, whose expression was completely blocked and subsequently triggered the activation of the dsRNA-activated protein kinase EIF2AK2/PKR and stress granule formation. Ectopic expression of PRKRA cDNA or knockout of EIF2AK2 in DKO cells rescued this phenotype. Perturbation of maturation and/or stability of additional targets also compromised cell cycle progression. Our study reveals the essential role of a single mRBP family contributing to fidelity of mRNA maturation, translation and RNA stress sensing pathways in human cells.	Co-expression
SRP116233	Resistance to BET inhibitor leads to new therapeutic vulnerabilities in castration resistant prostate cancer	BRD4 plays a major role in the transcription networks orchestrated by androgen receptor (AR) in castration resistant prostate cancer (CRPC) cells. Bromodomain and extraterminal protein (BET) inhibitors displace BRD4 protein from chromatin, resulting in the inhibition of oncogenic transcriptional programs. Several BET inhibitors (BETi) are currently being evaluated in clinical trials for a variety of malignancies, including CRPC. Here we describe a general mechanism of acquired resistance to BETi due to modulation of cellular pathways that are amenable to targeted therapies in CRPC cells. BETi resistant CRPC cells displayed cross resistance to a variety of BETi in the absence of gatekeeper mutations or persistent drug pump activation. Resistant cells exhibited reduced chromatin bound BRD4, and were less sensitive to Proteolysis Targeting Chimeric (PROTAC) -mediated degradation or genetic knockdown, suggesting a BRD4-independent transcription program. Transcriptomic analysis revealed reactivation of AR-signaling due to CDK9-mediated serine-81 phosphorylation of AR, with a consequent increase in sensitivity to CDK9 inhibitors and enzalutamide in BETi resistant cells. Additionally, increased DNA damage associated with PRC2-mediated transcriptional silencing of DNA damage response (DDR) genes was observed due to the loss of BRD4 from their proximal promoter regions in the resistant cells, leading to PARP inhibitor sensitivity. Collectively, our results identify the therapeutic limitation of BETi as a monotherapy in CRPC. However, data showing the reactivation of AR-signaling and increased DNA damage in the BETi resistant cells provide unique opportunities for combination therapies in managing CRPC. Overall design: Gene epxression by RNAseq in the parental vs BETi resistant 22RV1 and LNCaP cells	Co-expression
SRP116261	Gene expression patterns define the hepatocyte-like cells derived by different strategies [RNA-seq]	We performed genome-wide gene profiling in hiPSC-Hep and hiHep and compared gene expression patterns in these two types of hepatocyte-like cells.Genes involving in fat digestion and absorption and metabolism enzymes were induced in both hiHeps and hiPSC-Heps. There were also hepatic genes not expressed in either hiPSC-Heps or hiHeps, including cytochrome P450-based metabolism genes and coagulation complements. Interestingly, when genes were clustered based on their hepatic functions, we found that for each hepatic function there were always a few genes not fully induced in either hiPSC-Heps or hiHeps. Overall design: mRNA profiles of 4 cell types (UCF,hiHep,hiPSC-Hep,PHH) were generated by deep sequencing, UCF have 2 replications,hiHep and hiPSC-Hep have 4 replications,PHH have 3 replications, using Illumina Hiseq 2000.	Co-expression
SRP116272	Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease	To define mechanisms that underlie progression of Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB), we followed M.tb-infected adolescents longitudinally. Those who ultimately developed TB disease (“progressors”) were compared with matched controls, who remained healthy. Whole blood transcriptomic and plasma proteome analyses showed sequential modulation of immunological processes: type I/II interferon signalling and complement cascade were elevated 18 months before TB diagnosis, while changes in myeloid inflammation and lymphoid cell, monocyte and neutrophil gene modules occurred more proximally to TB disease. Analysis of gene expression in purified T cells revealed early suppression of Th17 responses in progressors. This was confirmed in an adult BCG re-vaccination cohort, where expression of interferon response genes in blood was associated with suppression of IL-17 expression by BCG-specific CD4 cells. We concluded that sequential inflammatory dynamics and immune alteration precede TB disease manifestation, with important implications for developing diagnostics, vaccines and host-directed therapies for TB. Overall design: 6,363 healthy adolescents, aged 12-18 years and enrolled into the Adolescent Cohort Study (ACS) (Zak et al. 2016), were followed for 24 months or more. Blood was collected at 6-monthly intervals. Among those with evidence of M.tbinfection (QuantiFERON and/or tuberculin skin test positive), 41 ultimately developed microbiologically confirmed TB disease >6 months after study enrolment; they were designated “progressors”. Among progressors, the time from blood collection to diagnosis of active TB (“time to diagnosis”) ranged from 1 to 894 days. Realigning blood collection to “time to diagnosis” allowed serial assessment of transition from infection to TB disease. Controls (N=104), who remained asymptomatic, were matched to progressors by age, gender, ethnicity, school and prior history of TB .	Co-expression
SRP116273	Plasma cell-free RNA sequencing for pregnant women	Simultaneously monitoring immune response and microbial infections during pregnancy through plasma cfRNA sequencing	Co-expression
SRP116284	Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms	Circulating epithelial cells (CECs) were purified using a microfluidic device from healthy donors, patients bearing intraductal papillary mucinous neoplasms, or pancreatic ductal adenocarcinoma and their transcriptomes were sequenced. Overall design: examination of mRNA expression of mucin genes in the above samples	Co-expression
SRP116312	Neutrophils in systemic onset Juvenile Idiopathic Arthritis display sepsis-like features which can be reverted by IL-1 blockade	This study investigated neutrophils in systemic onset Juvenile Idiopathic Arthritis (sJIA), one of the most common multifactorial autoinflammatory diseases, characterized by arthritis and severe systemic inflammatory manifestations like fever, rash, hepatosplenomegaly and serositis. Neutrophil counts were markedly increased at disease onset, correlated to levels of inflammatory mediators and normalized within days after initiation of therapy with recombinant IL-1 receptor antagonist (rIL-1RA). Neutrophils isolated from 3 sJIA patients with active disease, before initiation of therapy (2 disease onset, 1 systemic flare) and 3 healthy controls were compared. A clear separation between the transcriptome of sJIA patients and HCs was observed. In total, 1068 genes were significantly upregulated and 625 genes were downregulated in sJIA; GO-analyses indicated upregulation of inflammatory processes in sJIA neutrophils compared to HCs. GSEA analyses revealed a significant enrichment with the transcriptome of neutrophils in sepsis patients. Correspondingly, neutrophils from sJIA patients during active disease displayed a primed phenotype characterized by an increased respiratory burst, CD62L shedding and degranulation of secretory vesicles. This phenotype was completely reversed in sJIA patients in remission on rIL-1RA. Our data show an important role for neutrophils in the early inflammatory phase of sJIA and a strong susceptibility of neutrophil numbers and inflammatory activity to IL-1 signaling blockade. Overall design: Transcriptomes from peripheral blood neutrophils of 3 systemic JIA patients and 3 healthy controls	Co-expression
SRP116319	The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells	The WNT/ß-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior-posterior axis specification, organ and tissue development and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wildtype and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT signaling is most robust in cells with developmental potential, such as stem cells. These findings indicate a mechanism by which the developmental WNT signaling pathway reins in expression of transcriptional programs. Overall design: Time series analysis of Wnt3a-treated human embryonic stem cells, including knock-out of SP5 target transcription factor.	Co-expression
SRP116338	Identification of genes regulated by Long noncoding RNA H19 in hepatic cells	We used high throughput sequencing to compare the differential gene expression of HepG2 cells with and without H19 knockdown. We found critical genes involved in glucose production changed significantly after H19 konckdown compared to control. Overall design: HepG2 cells were transfected with either control siRNA or siH19. 48h after transfection, total RNA was extracted for library preparation and RNA-seq analysis to compare trancript profiles between siCon and siH19 cells.	Co-expression
SRP116341	Endometrial epithelial cell transcriptome response to co-culture with adipose stromal cells	The role of obesity in endometrial cancer development is tested by co-culturing adipose stromal cells (ASCs) with endometrial epithelial cells and endometrial cancer cell Ishikawa for 21 days. Control cells (not exposed to ASCs) were incubated for the same duration.  RNA-seq identified differential expression due to ASC exposure Overall design: Transcriptoms effects in enomdetrial epithelial cells is exmined by RNA-seq after adipose stromal cell co-culture	Co-expression
SRP116382	Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma	Despite extensive molecular characterization, we lack a comprehensive picture of lineage identity, differentiation, and microenvironmental composition in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq. While HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, implying a molecular interaction between glioma and immune cells. Finally, we found that myeloid cells can resemble microglia, macrophages, or a hybrid state, and enrichment of these cells is predictive of poor survival. Overall design: Performed single cell RNA-seq on tens of thousands of dissociated high-grade glioma tissue cells from 8 human patients.	Co-expression
SRP116604	Homo sapiens Raw sequence reads (circRNA in primary hBMEC upon meningitic E. coli infection)	circRNA in primary hBMEC upon meningitic E. coli infection	Co-expression
SRP116787	Knock down and complementation assay of U2AF35 wild-type and mutations in HEK cells	Recent work has identified cancer-associated U2AF35 missense mutations in two zinc-finger (ZnF) domains, but little is known about Q157R/P substitutions within the second ZnF. Surprisingly, we find that the c.470A>G mutation not only leads to the Q157R substitution, but also creates an alternative 5' splice site (ss) resulting in the deletion of four amino acids (Q157Rdel). Q157P, Q157R and Q157Rdel control alternative splicing of distinct groups of exons in cell culture and in human patients, suggesting that missplicing of different targets may contribute to cellular aberrations. Our data emphasize the importance to explore missense mutations beyond altered protein sequence.Here we sequenced a knock-down and complementation assay using wild-type, Q157P, Q157R and Q157Rdel U2AF35 in HEK293T cells.	Co-expression
SRP116894	Expression profiles in wild-type and IDH1 R132H/WT human astroglial cells [RNA-seq]	Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are critical to oncogenesis. The exact mechanism by which mutant IDH1 drives cell transformation is still not fully understood,  partially due to the difficulty of maintaining cells with endogenously mutated IDH1. We employed a “single base editing” technique and efficiently introduced the monoallelic point  mutation of IDH1 R132H (IDH1R132H/WT) into non-neoplastic human astroglial cells. Characterization of our cellular models revealed that IDH1R132H/WT inhibited cell proliferation  and promoted cell migration via mechanisms mediated by its oncometabolite 2-HG. Global gene expression and epigenetic analysis identified novel molecular targets of IDH1R132H/WT, namely  the Hippo pathway effector, Yes-associated protein (YAP), and its downstream signaling pathway Notch. In summary, the “single base editing” strategy introduces a new paradigm that  recapitulates the biological function of IDH1 R132H/WT and its oncometabolite 2-HG, which can be easily applied to other cell models. Our study provides a valuable model for novel discoveries of  molecular mechanisms during IDH1 R132H/WT-driven pre-cancerous events. Overall design: We measured gene expression profiles of a wild-type and two IDH1R132H/WT clones from human astroglial cells	Co-expression
SRP116895	The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing [RNA-seq]	While transcription as regulated by histones and their post-translational modifications have been well described, the connection between histone variants and changes to transcription remains poorly characterized. Potentially important insight into this process is provided by the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence on cellular growth behavior, gene expression, and chromatin compaction. The primary cells with G34W show increased colony formation, infiltration and proliferation, hallmarks in aggressive tumor development. Isogenic cell lines with G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and biopsies suggest that most genes are downregulated, which is also reflected in increased chromatin compaction. We identified components of the spliceosome complex specifically interacting with G34W in established isogenic cell lines with a GFP-tagged H3.3. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role in RNA processing and chromatin modulation that is blocked by G34W, potentially driving the tumorigenic process in GCTB. Overall design: We performed RNAseq on 7 samples, of which 3 were of the GCTB-H3.3_WT primary cell lines (GCTB08, 09, 11) and 3 were of the GCTB-H3.3_G34W primary cell lines (GCTB07,10,12). Control cell lines were the mesenchymal stem cell line KM1234. Collectively,	Co-expression
SRP116899	Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development	A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here, we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype. hPSC-podocytes in vitro progressively establish junction-rich basal membranes (nephrin+ podocin+ ZO-1+) and microvillus-rich apical membranes (podocalyxin+), similar to CLS podocytes in vivo. Ultrastructural, biophysical, and transcriptomic analysis of podocalyxin-knockout hPSCs and derived podocytes, generated using CRISPR/Cas9, reveals defects in the assembly of microvilli and lateral spaces between developing podocytes, resulting in failed junctional migration. These defects are phenocopied in CLS glomeruli of podocalyxin-deficient mice, which cannot produce urine, thereby demonstrating that podocalyxin has a conserved and essential role in mammalian podocyte maturation. Defining the maturity of hPSC-podocytes and their capacity to reveal and recapitulate pathophysiological mechanisms establishes a powerful framework for studying human kidney disease and regeneration. Overall design: 6 biological sample were isolated from wild type and PODXL mutant human pluripotent stem cells (12 samples in total). RNA-seq was performed on each sample.	Co-expression
SRP116901	Analysis by Whole Transcriptome Sequencing of the Effects of  LLC1 conditioned medium, LLC1 conditioned plus Calcitriol,  non-conditioned medium,  and non-conditioned medium plus Calcitriol on mRNA Expression in Primary Human Skeletal Muscle Cells	Primary human skeletal muscle cells (Lonza) were treated with  LLC1 conditioned medium, LLC1 conditioned medium plus Calcitriol, LLC1 non-conditioned medium or LLC1 non-conditioned medium plus Calcitriol for a period of 24 hours prior to isolation of RNA. Overall design: To assess the effects of  molecules produced by LLC1 cells on primary human skeletal muscle cells, LLC1 cells were grown and conditioned medium from LLC1 cells with or without added calcitriol was added to primary human skeletal muscle cells for 24 hours prior to the isolation of RNA.	Co-expression
SRP116908	Comprehensive comparative analysis of 5' end RNA sequencing methods	RNA-Seq is an effective method to study the transcriptome, but specialized methods are required to identify 5' ends of transcripts. Several published strategies exist for this specific purpose, but their relative merits have not been systematically analyzed. Here, we directly compare the performance of six such methods – testing five with cellular RNA as well as a novel spike-in RNA assay that helps address interpretation challenges that arise from uncertainties in annotation or RNA processing. Using a single human RNA sample, we constructed and sequenced 18 libraries with these methods and one standard, control RNA-Seq library. We find that the CAGE method performed best for mRNA and that most of its unannotated peaks are supported by evidence from other genomic methods. We then applied CAGE to eight brain-related samples and revealed sample-specific transcription start site (TSS) usage as well as a transcriptome-wide shift in TSS usage between fetal and adult brain. Overall design: Examination of 19 different RNA-Seq libraries starting from total RNA from 5 distinct 5'' end methods; also 1 control RNA-Seq library	Co-expression
SRP116920	Transcriptomic analysis of normal and IPF lung fibroblast SSEA4+ and SSEA4- cells	Recently, SSEA4+ mesenchymal progenitor cells have been described in stromal cultures, where IPF (but not normal) progenitor cells show pathological properties both in vitro and in vivo. The purpose of this study is to determine differences between mesenchymal progenitor cells sorted from stromal cultures derived from the lung biopsies of IPF patients showing a slow progressive versus rapid progressive decline of lung function as previously defined (Trujillo, G et al Science trans med 2010). Further, both groups were also compared to their normal lung counterparts as well as SSEA4- mesenchymal progeny. Overall design: SSEA4+ and SSEA4- cells were FACS sorted, RNA was extracted and sequenced.	Co-expression
SRP116922	T cell activation in skin explants from patients with psoriasis and controls	We have worked on skin explants and activated T cells locally with a CD3 antibody, whole biopsies were activated, then epidermal and dermal RNA was sequenced. Sequencing was performed by BGI (Hong Kong) as well as the group analysis. Overall design: Examination of skin tissue responses to local T cell activation (acd3) compared to isotype at the RNA level. Samples include biopsies from healthy controls and patients with psoriasis treated with Ustekinumab or untreated lesional psoriasis. All biopsy samples were treated either with acd3 or with isotype as indicated.	Co-expression
SRP116930	UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition	In this project we analyze the transcriptome of the human multiple myeloma isogenic cell lines ARP-1 (UTX wild-type) and ARD (UTX null). The transcriptome is studied at baseline, upon restoration of UTX levels in ARD cells for 3 and 6 days, and upon treatment of the cell lines with the EZH2 inhibitor GSK343. Moreover, we analyzed the transcriptome of a ARD resistant cell line that we generated. Overall design: Examination of transcriptome of two cell lines upon restoration of UTX and treatment with EZH2 inhibitors	Co-expression
SRP116934	RNA seq with AML (NB4) cells upon FTO inhibition	To determine the potential targets of FTO and identify treatment significance of FTO inhibition in AML, we conducted transcriptome wide RNA seq with NB4 cells upon DMSO and FTO inhibitors (FB23 and FB23-2) treatment. Overall design: NB4 cells were treated with FB23, FB23-2 and DMSO for 48 hours. Total RNA were isolated from the harvested cells and poly(A)+ RNA were enriched with NEBNext Poly(A) mRNA Magnetic Isolution Module. RNA-seq was performed on Illumina Hiseq system.	Co-expression
SRP116937	A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis [RNA-Seq]	Despite great scientific and technological advances, immune alterations predisposing to sporadic human inflammatory diseases remain mostly unknown. To fill this gap, we developed a strategy to evaluate blood leukocyte responses to innate stimuli, simultaneously at the transcriptional, cellular and secreted protein levels. The data were integrated using weighted gene co-expression network analysis. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During the remission phase of disease and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8 and TLR7 stimulation in blood. Isolated sJIA monocytes accumulated higher levels of intracellular IL-1ß after stimulation, and underexpressed the IL-1 inhibitor AHR at baseline. In line with the recent demonstration that AHR downregulation in monocytes is linked to macrophage differentiation, we show that the differentiation of sJIA monocytes in vitro was skewed towards macrophages, away from dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. The integrated analysis of these high-dimensional data can thus help unravel underlying immune alterations predisposing to complex inflammatory diseases. Overall design: 32 total samples, 4 control healthy in vitro, 6 control systemic JIA in vitro, 4 LPS healthy in vitro, 6 LPS systemic JIA in vitro, 5 healthy ex vivo, 7 systemic JIA ex vivo	Co-expression
SRP116952	Distinct cancer-promoting stromal gene expression depending on lung function	Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, but the underlying molecular mechanisms are unknown. We hypothesized that lung stromal cells activate pathological gene expression programs supporting oncogenesis. To identify molecular mechanisms operating in the lung stroma that support development of lung cancer. Study subjects included patients with- or without- lung cancer across a spectrum of lung function. We conducted multi-omics analysis of non-malignant lung tissue to quantify the transcriptome, translatome and proteome. Cancer-associated gene expression changes predominantly manifested as alterations in the efficiency of mRNA translation modulating protein levels in the absence of corresponding changes in mRNA levels. The molecular mechanisms driving these cancer-associated translation programs differed based on lung function. In subjects with normal to mildly impaired lung-function, the mammalian target of rapamycin (mTOR) pathway served as an upstream driver; whereas in severe airflow obstruction, pathways downstream of pathological extracellular matrix (ECM) emerged. Consistent with a role during cancer initiation, both the mTOR and ECM gene expression programs paralleled activation of previously identified pro-cancer secretomes. Furthermore, in situ examination of lung tissue documented that stromal fibroblasts express cancer-associated proteins from the two pro-cancer secretomes including IL6 in mild or no airflow obstruction and BMP1 in severe airflow obstruction. Two distinct stromal gene expression programs promoting cancer initiation are activated in lung cancer patients depending on lung function. Our work has implications both for screening strategies and personalized approaches to cancer treatment. Overall design: Polysome-profiling of non-cancerous lung stroma tissue samples from patients with or without lung cancer across a range of forced expiratory volume in one second (FEV1)	Co-expression
SRP116954	RNAseq to determine whether bidirectional transcription occurs over transposable elements following depletion of SETDB1 in THP-1 AML Cells	SETDB1 disruption leads to an increase in the expression of transposable elements as determined by our standard RNAseq, where bidirectional transcription has been reported. We repeated RNA seq on our samples with a stranded prep to determine whether bidirectional transcription occurs of transposable elements following depletion of SETDB1 in THP-1 AML Cells Methods: THP-1 cells were treated with two different SETDB1 sgRNAs (6, and 9) or Non-targeting control sgRNA (NTC) for 4 and 7 days. RNA was isolated and prepared for RNAseq with Qiagen RNeasy kits. Results: Consensus sequences for elements for upregulated TEs were downloaded from the Dfam database (Hubley et al., 2016). Stranded RNA-seq data was then aligned to consensus sequences using BWA-MEM and quantified using HTseq-count(Anders et al., 2015; Li, 2013). Reads were visualized using the IGV genome browser, using a custom pseudogenome that was generated from the Dfam consensus sequences (Robinson et al., 2011; Thorvaldsdottir et al., 2013). Conclusions: Our data determined that following the disruption of SETDB1, there is increased bidirectional transcription over a subset of transposable elements. Overall design: THP-1 RNA samples treated with 2 different SETDB1 sgRNAs (6, and 9) or NTC sgRNAs and collected at days 4 and 7 in triplicate for a total of 12 samples.	Co-expression
SRP116955	RNAseq to determine gene expression changes following depletion of SETDB1 in THP-1 AML Cells	Purpose: To determine how loss of SETDB1 effects gene expression in THP-1 AML cells. Methods: THP-1 cells were treated with two different SETDB1 sgRNAs (6, and 9) or Non-targeting control sgRNA (NTC) for 4 and 7 days. RNA was isolated and prepared for RNAseq with Qiagen RNeasy kits. Results: Using an optimized data analysis workflow, we mapped 23 million or more sequence reads per sample to the human genome (GRCh38) with GSNAP for obtaining standard gene expression measurements. Since SETDB1 is also know to regulate repetitive elements we also mapped sequences to a pseudogenome containing tranposable elements from hg19 repeatmasker annotations using RepEnrich and following the pipeline published on GitHub (https://github.com/nskvir/RepEnrich). Conclusions: Our data determined that immediately following the disruption of SETDB1, a strong type I Interferon response can be observed at day 4. In addition, many repetitive elements are also significanly induced, including L1 LINEs, Endogenous Retroviruses, and Satellite repeats. Overall design: THP-1 RNA samples treated with 2 different SETDB1 sgRNAs (6, and 9) or NTC sgRNAs and collected at days 4 and 7 in triplicate for a total of 18 samples.	Co-expression
SRP116963	Transcription factor NKX3-1 is required for reprogramming to pluripotency and can replace OCT4 in mouse and human iPSC induction [RNA-seq]	Resolution of early molecular events preceding endogenous OCT4 activation is critical to understanding the mechanism of reprogramming somatic cells to induced pluripotent stem cells (iPSCs), yet capturing transient regulators at the onset of reprogramming is difficult in heterogeneous populations of asynchronously reprogramming fibroblasts following four-factor transduction. To address this need, we used a heterokaryon system to identify an early and transiently expressed homeobox transcription factor, NKX3-1. Upon knockdown of NKX3-1, iPSC reprogramming is abrogated. Further, we identify that NKX3-1 functions downstream of the IL6-STAT3 regulatory network to activate endogenous OCT4. Importantly, we show that NKX3-1 can substitute for exogenous OCT4 to reprogram both mouse and human fibroblasts at comparable efficiencies generate fully pluripotent stem cells. Our findings establish an essential role for NKX3-1, previously known as a prostate-specific tumor suppressor, in iPSC reprogramming. Overall design: RNA-seq timecourse of heterokaryon reprogramming	Co-expression
SRP116965	Pharmacologic inhibition of STAT5 in AML	The transcription factors STAT5A and STAT5B are essential downstream mediators of many tyrosine kinases, particularly in hematopoietic cancers. As such, STAT5 is activated by FLT3-ITD, which is a constitutively active tyrosine kinase driving the pathogenesis of acute myeloid leukemia (AML). Since STAT5 is a critical mediator of diverse malignant properties of AML cells, direct targeting of STAT5 function is of significant clinical value. Here, we describe the novel small molecular weight inhibitor AC-4-130 that directly binds to the phosphotyrosine (pY)-binding pocket of the STAT5 SH2 domain, thereby disrupting STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent induction of gene transcription. AC-4-130 substantially impaired the proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+ AML patient cells in vitro and in vivo. Importantly, AC-4-130 synergistically increased the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol. In summary, we report the development and preclinical evaluation of a novel, potent STAT5 SH2 domain inhibitor that can efficiently block pathological levels of STAT5 activity in AML. The synergistic effects of AC-4-130 tyrosine kinase inhibitors as well as emerging treatment strategies provide new opportunities for combinatorial treatment of leukemia and potentially other cancers. Overall design: MV4-11 and MOLM-13 cells were treated in triplicates with 5 µM AC-4-130 or DMSO (Ctrl)	Co-expression
SRP117020	Identification of relationships between Molecular and Imaging Phenotypes in Non-small cell lung cancer using radiogenomics Map	Purpose:  To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Methods: A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results: RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. Conclusions: Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways Overall design: We studied 130 cases of NSCLC with CT, PET/CT and RNASeq data under IRB approval from Stanford University and the Veterans Administration Palo Alto Health Care System. The collection of tissue samples consisted of a distribution of poorly- to well-differentiated adenocarcinomas and squamous cell cancers. The surgeon had removed necrotic debris during excision and sampled cavitary lesions to include as much solid component as practical. Then, from the excised tumor, he cut a 3 to 5 mm thick slice along its longest axis, and froze it within 30 minutes of excision. We retrieved the frozen tissue and extracted the RNA that was then processed by centrillion genomic services using Illumina Hiseq 2500	Co-expression
SRP117034	Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor	Purpose: We designed this study to evaluate the feasibility of using only one factor to respecify human induced pluripotent stem cells (iPSCs)-derived blood cells into long-term engraftable hematopoietic stem and progenitor cells (HSPCs). We also parallelly compared iPSC-derived HSPCs (iHSPCs) with primary HSPCs under the same induction and transplantation condition in order to examine the functional equivalency between iHSPCs and bona fide HSPCs. Methods: In vitro derived human iPSC-HSPCs are induced with or without (w/o) doxycycline for the expression of MLL-AF4. In vivo derived bone marrow cells are harvested and FACS-sorted for human populations from primary transplants over nine to sixteen weeks after transplantation. Either iPSC-HSPCs or primary HSPCs, both of which are induced by MLL-AF4, is used for the transplantation experiments. iPSCs are either derived from peripheral blood mobilized CD34+ HSPCs (CD34-iPSC) or mononuclear cells (MN-iPSCs). Normal human CD34+ HSPCs and mononuclear cells are set as control groups. Results: MLL-AF4 can impart HSC and lymphoid potential to iPSC-derived blood cells in vitro, and induction of MLL-AF4 leads to the cellular identity transition from common myeloid progenitors to hematopoietic stem and progenitor cells. MLL-AF4 alone is sufficient to realize the potent engraftment of induced HSPCs (iHSPCs) from iPSCs, and multilineage and long-term hematopoiesis could be observed. Primary HSPCs with the induction of MLL-AF4 could gain significantly enhanced engraftability. During the long-term engraftment period, leukemic mutations with a bias to B-cell leukemia could be found in the iHSPCs and their derivatives. By contrast, MLL-AF4 induced primary HSPCs maintain the normal hematopoiesis without leukemic transformation. Conclusions: Our study has demonstrated for the first time, to our knowledge, that the pluripotency-dependent conversion of somatic cells to long-term engraftable HSPCs can be achieved by using a single factor in a non-integrative way. This study also suggests that iPSC-derived HSPCs are more prone to leukemic mutations during the long-term engraftment period, which provides a necessary caveat of using them in the actual therapies. Overall design: Human mRNA profiles of either in vitro derived iPSC-HSPCs or engrafted NSG mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 4000.	Co-expression
SRP117046	CARM1/PRMT4 is essential for myeloid leukemogenesis but dispensable for normal hematopoiesis	We investigated the role of PRMT4 in normal and malignant hematopoiesis. We found that knockdown of PRMT4 impairs cell cycle progression, induces apoptosis, and downgretulateds E2F target genes in leukemia cell lines, identifying several mechanisms for the leukemia-specific dependence on PRMT4. Overall design: Three AML cell lines (SKNO1, MV411, and MOLM-13) were subjected to high-throughput RNA sequencing three days after shRNA inhibition of PRMT4 or scramble control.   All cell lines sequencing experiments were repeated in triplicate. Differential expression of each cell line was performed independently comparing to controls.   Additionally, differential analysis was performed by combining all cell line PRMT4 inhibited cells and comparing to all controls.	Co-expression
SRP117048	SILAC identifies LAD1 as an oncogenic filamin binder regulating actin dynamics in response to EGF and marking aggressive breast tumors	Mutations mimicking growth factor-induced proliferation and motility characterize some aggressive subtypes of mammary tumors. To unravel novel players, we applied phosphoproteomics on untransformed mammary cells, which were pre-stimulated with the epidermal growth factor (EGF). This analysis identified ladinin-1 (LAD1), a hitherto poorly characterized protein, as a phosphor-effector of the EGF-to-ERK pathway. We report that LAD1 is essential for mammary cell proliferation and migration. LAD1 is transcriptionally induced, undergoes phosphorylation by EGF and co-localizes with actin stress fibers. Yeast 2-hybrids and co-immunoprecipitation screens revealed that LAD1 binds with filamins, actin cross-linking proteins. Co-sedimentation analyses attribute to LAD1 a role in actin treadmilling, probably in conjuction with SFN/14-3-3sigma. Depletion of LAD1 led to a decrease in viability related transcripts, and inhibited growth of mammary xenografts in an animal model. Furthermore, LAD1 is highly expressed in two aggressive subtypes of breast cancer, as well as predicts poor patient prognosis. These studies identify a new cytoskeletal component essential for signal transduction and for the acquisition of oncogenic attributes by human mammary tumors. Overall design: RNA-Seq – EGF treatemnt for 0, 40 and 240 minutes of HCC70 cell-line stably expressing LAD1 targeting shRNA (or scrambled control)	Co-expression
SRP117055	Influenza virus infection causes global RNAPII termination defects	Viral infection perturbs host cells and can be used to uncover host regulatory mechanisms controlling both cell response and homeostasis. Here, using cell biological, biochemical and genetic tools, we reveal that influenza virus infection induces global transcriptional defects at the 3'-end of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. This effect induces the biogenesis of aberrant RNAs (3'-extensions and host gene fusions) which ultimately causes global transcriptional downregulation of physiological transcripts, an effect that impacts antiviral response and virulence. We show that this phenomenon occurs with multiple strains of influenza virus and it is dependent on influenza NS1 protein expression. Mechanistically, pervasive RNAPII run-through can be modulated by SUMOylation of an intrinsically disordered region (IDR) of the NS1 expressed by the 1918 pandemic influenza virus. SUMOylation increases NS1 partitioning in nuclear granules and interference with the host transcriptional apparatus which result in augmentation of termination defects and a concomitant increase in global host gene shut off. Our data identify a general strategy used by influenza virus to suppress host gene expression and indicate that polymorphisms in IDRs of viral proteins, along with human genetic variation in enzymes that metabolize post-translational modifications, can determine the outcome of an infection. We thus propose that analysis of strain-specific determinant of pathogenesis can shed light on the molecular basis of virulence. Overall design: We performed directional RNA-Seq profiling (Illumina TruSeq protocol) of uninfected A549 cells, and at 6 and 12 hours after infection with wild-type H1N1 Influenza A/Puerto Rico/8/1934 (PR8-NS1) or PR8-NS1-SUMO Influenza A virus. In the NS1-SUMO virus we fused a SUMO domain to the C-terminus of the NS1 protein. We also performed RNA-Seq of A549 cells transfected with empty vector, or a vector expressing GFP or SUMO. Additionally, cells transfected with empty vector or a vector expressing SUMO were infected with PR8?NS1 virus and RNA-Seq was performed at 4 hours post-infection. Finally, we performed RNA-Seq of uninfected A549 cells depleted for Ubiquitin Conjugating Enzyme E2 (siUBE2I) and control (siCtrl). All experiments were performed in duplicate.	Co-expression
SRP117082	Single-cell RNA-seq analysis of human CD14+ monocytes	We performed single-cell RNA-seq on CD14+ monocytes isolated from the blood of healthy donors. Using the 10x chromium technology, we analyzed 425 and 431 cells from 2 individual donors. Overall design: Peripheral Blood Mononuclear Cells (PBMC) were prepared by centrifugation on a Ficoll gradient. Blood CD14+ monocytes were isolated from healthy donors' PBMC by positive selection using magnetic beads. Monocytes were 93-95% CD14+CD16- as assessed by flow cytometry. Cellular suspensions (1700 cells) were loaded on a 10X Chromium instrument (10X Genomics) according to manufacturer's protocol.	Co-expression
SRP117093	Transcriptome analysis of fetal Klinefelter testis tissue samples compared to controls	In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs. Overall design: Includes a total of 9 samples. 4 fetal Klinefelter and 5 age-matched controls testis samples	Co-expression
SRP117164	Transcriptome profiles of POM121-knockout prostate cancer cell lines	Nucleoporins are major constituents of nuclear pore complexes, molecular conglomerates embedded within the nuclear envelope that participate in bidirectional trafficking between nucleus and cytoplasm, chromatin silencing and organization, and transcriptional regulation . This functional vantage point is of utmost importance for fundamental cell processes such as intracellular signaling, cell migration, DNA repair and cell division, all of which can be impaired when the molecular identity of the NE and nuclear pore complex is compromised, as seen in cancer. Here we identify a nucleoporin POM121 as a key regulator of proliferation, tumourigenesis, and survival in chemoresistant prostate cancer. Mechanistically, POM121 regulates nuclear transport of specific survival-conferring transcription factors (MYC and E2F1) and androgen receptor that have been previously linked with advanced stages of prostate cancer. POM121-mediated deregulation of nucleocytoplasmic transport occurs through its interaction with Importin ß, which serves as a pharmacological target that decreases tumour growth, sensitizes the tumor cells to standard chemotherapy, and improves survival of patient-derived xenograft mice. These results indicate that nuclear pore complex represents a novel mechanism of chemoresistance, which can be therapeutically targetable in aggressive prostate cancer. Overall design: POM121 gene was knockout by siRNA in 2 prostate cancer cell lines, and transcriptome profiling was performed using RNA-Seq.	Co-expression
SRP117243	A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells	While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis.	Co-expression
SRP117245	Expression changes in melanoma cell lines under BRAFi treatment timepoints [RNA-Seq.CellLine.batch3]	Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively). Tumor cell-intrinsic reprogramming attenuated MAPK-dependency, while enhancing mesenchymal, angiogenic and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations. Overall design: Paired melanoma cell lines before treatment and during BRAFi treatment were sent for transcriptomic analysis by paired end 2x150bp RNAseq analysis	Co-expression
SRP117267	A map of gene expression in neutrophil-like cell lines	We report gene expression data for the human cell lines HL-60 and PLB-985, which serve as models for human neutrophils. We measured gene expression using RNA-Seq for these cell lines both prior and after differentiation into a neutrophil-like state using two differentiation protocols (treatment with DMSO or treatment with DMSO and replacement of serum with Nutridoma). Overall design: HL-60 and PLB-985 cells grown in culture were processed for RNA-Seq both before and after differentiation for six days in media supplemented with 1.3% dimethyl sulfoxide (DMSO). The cell lines were also analyzed after differentiation for six days in media with 1.3% DMSO, reduced serum (0.5% FBS), and Nutridoma-CS (2%). PLB-985 cells were also analyzed at intermediate time points of 2 days and 4 days with the Nutridoma protocol.	Co-expression
SRP117268	Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells	Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA-Seq analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0), differentiation initiation (days 2, 4, and 6), neural commitment (days 8–10), neural progenitor cell proliferation (days 12, 14, and 16), and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-Seq data with several other transcriptome profiling datasets from mice and humans indicated that module 3 associated with the day 8–10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR-Cas9–mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia–related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. Overall design: RNA-sequencing of twelve samples prepared every other day between hESC neuronal differentiation day 0 to day 22 .	Co-expression
SRP117282	Transcriptome-wide profiling of poly(A)-tail length, translation efficiency and mRNA stability using TED-seq, mRNA-seq, Ribo-seq and PRO-seq in ER stress conditions	We report systematical profiling of translation efficiency and mRNA stability dependent on the dynamics of poly(A)-tail length in stress conditions of human cells. In this study, we developed a new feasible method measuring poly(A)-tail length called TED-seq and applied it to investigate the change of mRNA''s poly(A)-tail lengths in ER stress pharmacologically induced by thapsigargin (THAP). Combined with other global RNA analyses such as RNA-seq, Ribo-seq and PRO-seq, we observed that ER stress induced lenthening poly(A)-tail length, in particular of ER-stress-regulators, upon ER stress. More specifically, these mRNAs are translationally de-repressed and more stabilized based on increase in poly(A)-tail length. We also identified that insoluble fractions which include stress-induced RNA-granules have overall shorter length of poly(A) tail. Taken together, our data suggest that poly(A)-tail lengths are dynamically regulated and influence both translation efficiency and mRNA stability in ER stress. Overall design: 1) TED-seq (5 replicates) in cytoplasm and RNA granule fractions (3 replicates) of DMSO- or THAP-treated HEK293 cells 2) RNA-seq (4 replicates), Ribo-seq (4 replicates) and PRO-seq (2 replicates) in whole cells with DMSO- or THAP-treated HEK293 cells	Co-expression
SRP117339	Long-term in vitro expansion of epithelial stem cells enabled by pharmacological inhibition of PAK1-ROCK-Myosin II and TGF-ß signaling (RNA-seq)	Despite substantial self-renewal capability in vivo, epithelial stem and progenitor cells located in various tissues expand for a few passages in vitro in feeder-free condition before they succumb to growth arrest. Here we describe the EpiX™ method that utilizes small molecules that inhibit PAK1-ROCK-Myosin II and TGF-ß signaling to achieve over one trillion-fold expansion of human epithelial stem and progenitor cells from skin, airway, mammary and prostate glands in the absence of feeder cells. Transcriptomic and epigenomic studies show that this condition helps epithelial cells to overcome stresses for continuous proliferation. EpiX-expanded basal epithelial cells differentiate into mature epithelial cells consistent with their tissue origins. Whole genome sequencing reveals that the cells retain remarkable genome integrity after extensive in vitro expansion without acquiring tumorigenicity. EpiX technology provides a solution to exploit the potential of tissue-resident epithelial stem and progenitor cells for regenerative medicine. Overall design: mRNA profiles of human foreskin keratinocytes in different culture conditions were generated by deep sequencing, in duplicate, using Illumina NextSeq.	Co-expression
SRP117344	Genome-wide analysis of herpes simplex virus type 1 (HSV-1) infected cells	The goal of this study was to compare the whole transcriptional profile (RNA-seq) of herpes simplex virus type 1 (HSV-1) infected and mock infected human fibroblast KMB17 strain at 48 hours post infection.There is increasing evidence that circular RNAs (circRNAs) are involved in diverse pathogenesis processes; however, their roles in virus infection remain unclear. Here, we profiled global changes of circRNAs, genes and microRNA (miRNAs) under herpes simplex virus type 1 (HSV-1) infection by RNA-seq. Numerous dysregulated transcripts comprised of 536 circRNAs, 3,885 genes and 207 miRNAs were found during viral infection. The dysregulated genes were enriched to NOD-like receptor signaling pathway, Jak-STAT signaling pathway and pathways of apoptosis, cell cycle progression and cell death, all of which may be implicated in viral pathogenesis and cellular immunity. Further integration analysis of circRNAs, genes and miRNAs reveals putative involvement of circRNAs in viral pathogenesis and antiviral immunity by circRNA-miRNA-gene regulatory axis. This work provides a comprehensive view for dysregulated circRNAs induced by HSV-1 and their interplay with miRNAs and genes, thus offering new insights into the mechanisms of interactions between HSV-1 and its host. Overall design: Whole transcriptome profiles of  herpes simplex virus type 1 (HSV-1) infected and mock infected human fibroblast KMB17 strain at 48 hours post infection were generated by deep sequencing, in triplicate, using Illumina Hiseq 4000 platform.	Co-expression
SRP117568	Analysis of transcriptional regulation by Myt1 and Myt1l	We report the changes in gene expression in U87 glioblastoma cells with re-introduced Myt1 or Myt1l. Overall design: U87 cells were stably infected with lentiviral vectors endoding Myt1, Myt1l, or with a control empty vector. We analyzed three replicate cultures for each condition by RNA-seq.	Co-expression
SRP117613	Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina Cultures Derived From Human Reporter Pluripotent Stem Cell Lines	We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration. Overall design: CRX+ flow sorted cells from human retina derived organoids were collected at 6 time points during differentiation (day (D) 37, 48, 67, 90, 134, 220).	Co-expression
SRP117619	Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2/M cell cycle arrest and enhanced vincristine sensitivity in Ewing sarcoma	A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), created from a chromosomal translocation, is implicated in driving the majority of Ewing sarcomas (ES) by modulation of transcription and alternative splicing. The small molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis. We tested 69 anti-cancer drugs in combination with YK-4-279 and found that vinca alkaloids exhibited synergy with YK-4-279 in five ES cell lines. The combination of YK-4-279 and vincristine reduced tumor burden and increased survival in mice bearing ES xenografts. We determined that independent drug-induced events converged to cause this synergistic therapeutic effect. YK-4-279 rapidly induced G2/M arrest, increased the abundance of cyclin B1, and decreased EWS-FLI1–mediated expression of microtubule-associated proteins, which rendered cells more susceptible to microtubule depolymerization by vincristine. YK-4-279 reduced the expression of the EWS-FLI1 target gene encoding ubiquitin ligase UBE2C, and this in part contributed to the increase in cyclin B1. Biochemical assays revealed that YK-4-279 also increased the abundance of proapoptotic isoforms of MCL1 and BCL2, presumably through inhibition of alternative splicing by EWS-FLI1, thus promoting cell death in response to vincristine. Thus a combination of vincristine and YK-4-279 might be therapeutically effective in ES patients. Overall design: Examination of mRNA profiles of TC32 on knockdown of EWS-FLI1 or treatment with YK-4-279: 3 samples Total: 1 TC32 WT Control, 1 TC32 shEF, 1 TC32 YK	Co-expression
SRP117620	Expression profile of lncRNAs in HCV patient	Serum samples of healthy controls and infected patients	Co-expression
SRP117628	Genome-wide profiling of siRNA targeting EWS-FLI1 in TC32 Ewing sarcoma cell line	Identification of genes and pathways that were influenced by knock-down EWS-FLI1 in TC32 Ewing sarcoma cell line. Overall design: TC32 Ewing sarcoma cell line were transfected with control siNeg or siRNA corresponding EWSR1 or FLI1 gene. Two samples in each group were analyzed.	Co-expression
SRP117629	ROR?t and RORa Signature Genes in Human Th17 Cells	In an effort to study gene expression modulated by ROR?t and RORa in human Th17 cells, global gene expression of human CD4 T cells activated under Th17 skewing conditions was profiled by RNA sequencing. ROR?t and RORa signature genes were identified in these Th17 cells treated with specific siRNAs to knock down ROR?t or RORa expression. In addition, selective small molecule ROR?t modulators were also utilized as pharmacological tools in ROR?t signature gene identification.	Co-expression
SRP117665	RNA expression in hepatocytes after GPR31 knockout under 12-HETE treatment	RNA-seq was used to verify whether GPR31 is a high affinity receptor of 12-HETE. Normal human liver L02 cells, GPR31 knockout L02 cells and rescue of GPR31 knockout L02 cells under 12-HETE treatment simultaneously was used for RNA-seq.	Co-expression
SRP117670	RNAseq to understand the host transcriptome during nontuberculous mycobacterial lung infection	We sought to elucidate the differentially expressed host factors in bronchoalveolar lavage cells (BALc) from nontuberculous mycobacteria (NTM)-infected subjects by studying the host transcriptome in during infection. A heatmap was created from the normalized expression of selected genes that showed statistically significant differential expression between NTM-infected and uninfected subjects. Genes with similar expression patterns were grouped and the most highly expressed genes are shown. One of the most differentially expressed gene in the NTM-infected group was the CFD (complement factor D) gene. Of note, a statistically significant three-fold increase in expression of the CAMP gene, encoding the LL-37 peptide was observed in the NTM-infected subject group (padj=0.05). Overall design: Bronchoalveolar lavage cell samples from 3 bronchiectatic patients with Mycobacterium intracellulare lung infection and 3 bronchiectatic patients without Mycobacterium intracellulare lung infection	Co-expression
SRP117686	Identification of global XBP1s target gene expression in human prostate cancer cells	To gain insight into the global XBP1s target gene profile in prostate cancer cells, we performed RNA-seq analysis in LNCaP cells upon either XBP1 siRNA-mediated knockdown (siXBP1) or MKC8866-mediated IRE1a inhibition. Overall design: Transcriptomics analysis upon two independent modalities to inhibit XBP1s expression in human LNCaP cells	Co-expression
SRP117691	Single cell analysis reveals cancer cell heterogeneities in hepatocellular carcinoma [SMART-seq]	Combined transcriptomic and functional analyses of HCC cells at single-cell level were performed to assess CSC heterogeneity. Overall design: Single-cell transcriptome analyses of two HCC cell lines (HuH-1 and HuH-7) and one patient-derived circulating tumor cells by using SMART-Seq protocol ***Due to patient privacy concerns, the submitter declares that patient data will be submitted to dbGaP.***	Co-expression
SRP117733	Transcriptome analysis of adult Klinefelter testis tissue samples compared to controls	In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced. Overall design: Includes a total of 22 testis samples. 3 adult Klinefelter, 3 Klinefelter-like, 4 Sertoli Cell-Only, 4 with full spermatogenesi, 4 pre-pubertal Klinefelter and 4 pre-pubertal controls	Co-expression
SRP117755	Single cell transcriptomic profiling of pluripotent stem cell-derived SCGB3A2+ airway epithelium reveals fate plasticity* - Fluidigm C1: bronchospheres day 27*	Many lung diseases involve alterations in the cellular identity of the lung epithelium. Improved insight into airway development and the changes to cellular identity that result from abnormal signaling may therefore improve understanding of the etiology of these complex diseases. We have previously described a protocol to generate epithelial airway spheres from human pluripotent stem cells (hPSCs), but still poorly understand the identity, development, and heterogeneity of these early airway cells. Here we use novel murine and human PSC lines to study developing secretory cells derived in vitro from hPSCs. Using an SCGB3A2CherryPicker (SC) reporter system together with population-based or single-cell global transcriptomic profiling we track, purify, and analyze hPSC-derived putative secretory airway progenitors and find that SC+ cells are enriched for expression of airway epithelial markers, including secretory cell markers, SCGB3A2 and SCGB1A1. Unexpectedly, some SC+ human cells also co-express distal type 2 cell genes, including SFTPC, ABCA3, NAPSA, CTSH and functional lamellar bodies, suggesting a significant level of plasticity within the hPSC-derived secretory population relative to concurrently generated proximal airway TP63+ cells or distal alveolar SFTPC+ cells. We establish that this plasticity is minimized by inhibiting low levels of endogenous canonical Wnt signaling post-lung specification, thus depleting the co-expressed type 2 cell program. Taken together, these findings suggest that, similar to in vivo mouse genetic models and diseased human lungs, hPSC-derived airway cells exhibit cellular plasticity in response to signaling cues, providing a human model system in which to study cellular identity in a disease-relevant context. Overall design: Single cell transcriptomic profiling of pluripotent stem cell-derived SCGB3A2+ airway epithelium reveals fate plasticity	Co-expression
SRP117763	Association of distinct gut microbiome patterns with consensus molecular subtypes of colorectal cancer	For the study, colorectal cancer tumour samples were collected from 34 patients and transcriptome sequencing of the samples was done to classify them into consensus molecular subtypes of colorectal cancer. To quantify relative abundances of bacterial strains in the samples, 16S rRNA amplicon metabarcoding was done and the non-human part of the transcriptome data was also analysed. Analysis of the association between the subtypes and microbiome was carried on and the targeted quantitative PCR was done to confirm the findings.	Co-expression
SRP117781	Genomic basis for clinical response to histone deacetylase inhibition in advanced urothelial carcinoma	Abstract  Background: Histone deacetylase (HDAC) inhibition has shown some efficacy in urothelial carcinoma (UC); the genomic basis for clinical response is not known.  Methods: In two separate phase I clinical trials testing HDAC inhibitors in advanced solid tumors, we identified one patient with advanced UC who had a complete response (CR) to belinostat and one with advanced UC who had a partial response (PR) to panobinostat. The archived tumor of the responders was genomically characterized and studied in comparison to others with UC, in the context of their response to HDAC inhibition on trial. UC cell lines treated with panobinostat were studied to elucidate the mechanisms of benefit.  Results: The two patients who responded to HDAC inhibition had ARID1A and FANCD2 mutations. The patient who had a CR to HDAC inhibition had the highest tumor mutational burden of all tumors. Corroborating the basis of sensitivity, transcriptional profiling of platinum resistant ARID1A mutated HT1197 cells treated with panobinostat revealed downregulation of cyto-proliferative and DNA repair gene sets and upregulation of inflammatory gene sets.  Conclusions: Clinical efficacy of HDAC inhibition in UC may be dependent on overlapping SWI/SNF pathway mutations and DNA repair defects. Tumor mutational burden may predict the depth and duration of benefit. Overall design: RNASeq analysis of urothelial carcinoma cell lines treated with HDAC inhibitor panobinostat	Co-expression
SRP117785	RNA sequencing analysis of triple cytokine-captured human CD4 T cells	GM-CSF positve CD4 cells are found at sites of inflammation. The purpose of this study was to understand their transcriptional profile relative to known Th1 and Th17 subsets. Overall design: Human CD4 T cells were isolated by magnetic negative selection and activated with PMA and ionomycin. A cytokine capture assay was used to isolate CD45RA-positive, cytokine negative, IFN-gamma-single-positive, IL-17A-single-positive, GM-CSF-single positive and IL-17A-GM-CSF-double positive cells.	Co-expression
SRP117885	Integration of metabolomics and transcriptomic expression profiling discloses pivotal role of arachidonic acid metabolism pathway in response to acute hypoxia exposure	Background: Arachidonic acid (AA) metabolism pathway is dominant in metabolic programming after hypoxia exposure, but its biological function is disputed and require in-depth studies. In this research, we aimed at integrating plasma metabolomics and transcriptomics approaches to systematically explore its roles in response to acute hypoxia based on model of acute high-altitude exposure. Methods: Blood samples were taken from 53 enrolled subjects before and after their exposure to high altitude. Ultra-performance liquid chromatography- quadrupole time-of-flight mass spectrometry and RNA sequencing were performed to acquire corresponding metabolomic and transcriptomic profiling along with hypoxia exposure, separately. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA) after integrating metabolic information with phenotypic and transcriptomic datasets, respectively. Results: Enrolled individuals showed significant alterations in heart rate, SpO2, hemoglobin and Lake Louise Score (LLS) in response to hypoxia. Metabolomics profiling demonstrated that AA metabolism pathway was remarkable in these metabolic alterations. Integrated analysis of metabolomic and transcriptomic data revealed that increasing AA metabolism pathway might count for gas transport incapacitation and disorders in hemoglobin metabolism under hypoxia stimuli. Moreover, identified in further analysis and another cohort, excessively elevated AA metabolism pathway was involved in poor response to hypoxia. Conclusion: Our study, for the first time, constructed the maps of AA metabolism pathway in response to hypoxia; and revealed the crosstalk between phenotypic variation to hypoxia and AA metabolism pathway. These findings will not only advanced pathophysiological mechanisms for acute hypoxic diseases, but provided new insights into critical roles of AA metabolism pathway in development and prevention of these diseases. Overall design: Transcriptome from blood samples of  individuals were measured and analyzed before their departure and upon their arrival at high altitude (5300m).	Co-expression
SRP117905	Differentiation of functional endothelial cells from human iPS cells	Endothelial cell (EC) therapy may promote vascular growth or reendothelization in a variety of disease conditions. However, the production of a cell therapy preparation containing differentiated, dividing cells presenting typical EC phenotype, functional properties and chemokine profile is challenging. We focused on comparative analysis of seven small molecule-mediated differentiation protocols of ECs from human induced pluripotent stem cells. Differentiated cells showed a typical surface antigen pattern of ECs as characterized with flow cytometry analysis, functional properties, such as tube formation and ability to uptake acetylated LDL. Gene expression analysis by RNA sequencing revealed an efficient silencing of pluripotency genes and upregulation of genes related to cellular adhesion during differentiation. In addition, distinct patterns of transcription factor expression were identified during cellular reprogramming providing targets for more effective differentiation protocols in the future. Altogether, our results suggest that the most optimal EC differentiation protocol includes early inhibition of Rho-associated coiled-coil kinase and activation of cyclic adenosine monophosphate signaling, and inhibition of transforming growth factor beta signaling after mesodermal stage. These findings provide the first systematic characterization of the most potent signalling factors and small molecules used to generate ECs from human induced pluripotent stem cells. Consequently, this work improves the existing EC differentiation protocols and opens up new avenues for controlling cell fate for regenerative EC therapy. Overall design: Comparison of the effects of signalling factors and small molecules on endothelial cell differentiation from induced pluripotent stem cells using RNA-Seq. Following small molecules and growth factors were used in different combinations and time courses: 10 uM TGFß-inhibitor SB431542, 10 uM ROCK-inhibitor Y-27632, 20 ng/ml recombinant human BMP-4 and 0,25 mM 8-Br-cAMP. In all groups without TGFß-inhibitor at day 1 in the differentiation, it was added at day 4. In those groups with BMP-4 at day 1, it was removed at day 4. Differentiating ECs were passaged every 4-6 days using Accutase.	Co-expression
SRP118056	Homo sapiens Transcriptome or Gene expression	mv4-11 Transcriptome analysis upon drug treatment	Co-expression
SRP118087	Impeding transcription of expanded microsatellite repeats by deactivated Cas9	Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs' endothelial corneal dystrophy, and C9orf72-ALS/FTD. Eliminating or reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that a deactivated form of the Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction in the abundance of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, and C9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention. Overall design: RNA-Seq was perfomed on DM1 and non-DM1 myoblasts treated dCas9 plus control gRNA or (CAG)6 gRNA.	Co-expression
SRP118175	RNA sequencing of nasopharyngeal carcinoma	comparing RNA expression levels between EBV positive and negative nasopharyngeal carcinoma	Co-expression
SRP118314	NUPR1 depletion activates premature senescence and overcomes tamoxifen resistance in breast cancer cells	Background Selective estrogen receptor modulators such as tamoxifen (Tam) and its derivatives are anti-breast cancer drugs known to cause resistance during chemotherapy. To support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells may gain a series of adaptive intracellular processes including autophagy for survival. Methods We utilized patient breast tumor tissue microarrays, human breast cancer cell lines, xenograft mouse model to investigate autophagic flux changes by NUPR1-mediated transcriptional control. In vitro and in vivo biological assays were performed to elucidate the molecular mechanisms of NUPR1 on chemoresistance. Results Here, we identify that nuclear protein 1 (NUPR1), a Tam-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through a physical interaction with estrogen receptor alpha (ESR1) in breast cancer. Mechanistically, NUPR1 binds to the promoter region of several genes, such as BECN1, GREB1 (growth regulation by estrogen in breast cancer 1), RAB31, GPR (progesterone receptor), CYP1B1 (cytochrome P450 family 1 subfamily B member 1), involved in the autophagy process and drug resistance and regulates the transcription of these genes. In Tam-resistant ESR1-positive breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam-resistant cells, which facilitates the transition from autophagic survival to premature senescence. Conclusions Collectively, these findings suggest a critical role for NUPR1 as a transcriptional regulator that enables the drug persistence of breast cancers, thus providing a susceptible target to diagnose and treat drug resistance. Overall design: RNA-seq of MCF-7 cells, tamoxifen resistant MCF-7 cells, tamoxifen resistant NUPR1-depleted MCF-7 cells	Co-expression
SRP118364	Human gut metagenome Targeted loci environmental	Multi omic study of mucosal microbiome	Co-expression
SRP118373	human and mouse pancreatic cancer-associated stellate cells Transcriptome	Here, we show that primary cancer-associated PSCs (caPSCs) isolated from PDAC surgical specimens express a wild-type p53 protein that can be activated by the Mdm2 antagonist Nutlin-3a. Our work reveals that p53 acts as a major regulator of PSC activation and a modulator of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound transcriptional changes and converts mouse and human activated PSCs to quiescence. In vivo, treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces stromal p53 activation, reverses caPSCs activation and decreases fibrosis.	Co-expression
SRP118468	The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin	The neurobiological functions of a number of kinases expressed in the brain are unknown.  Here, we report new findings on DCLK3 (Doublecortin-like kinase 3) which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington''s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington''s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington''s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture.  Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodeling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including TADA3, a core component of SAGA complex. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodeling in these brain cells, and show that reduced expression of the kinase in Huntington's disease could render the striatum highly vulnerable to neurodegeneration. Examination of DCLK3 as neuroprotector against mutant huntingtin in vivo and in vitro models. Overall design: Examination of DCLK3 as neuroprotector against mutant huntingtin in vitro experiments.	Co-expression
SRP118481	SOX9 has distinct regulatory roles in alternative splicing and transcription	SOX9 is known as a crucial transcription factor for various developmental processes and for tissue homeostasis. We examined here its potential role in alternative splicing by analyzing global splicing changes, using RNA-seq of colon tumor cells. We show that SOX9 knockdown alters the splicing of hundreds of genes without affecting their expression levels, revealing that SOX9 controls distinct splicing and transcriptional programs. SOX9 does not affect splicing patterns through the control of splicing factors expression. We identify mutants that uncouple SOX9 splicing function from its transcriptional activity. We demonstrate that SOX9 binds to RNA and associates with several RNA-binding proteins, including the core Exon Junction Complex component Y14. Half of SOX9 splicing targets are also modulated by Y14 and are no longer regulated by SOX9 upon Y14 depletion. Altogether, our work reveals that SOX9 is a moonlighting protein which modulates either transcription or splicing of distinct sets of targets. Overall design: DLD-1 colon tumor cells RNA-seq analysis of transcriptomic and splicing profiles	Co-expression
SRP118536	Expression analysis of BMP7 responsive P2RY1/ALK3 expressing progenitor like cells within the human exocrine pancreas	Purpose: Here we demonstrate ALK3Bright/PDX1+ cells residing within the human pancreatic ducts have progenitor like characteristics. Using flow cytometery, live-cell sorting of ALK3bright/PDX1+ cells is possible using a surrogate surface marker for PDX1 (P2RY1). Treating ALK3bright/P2RY1+ cells with BMP7 results in their expansion. Later removal of BMP7 results in the differentiation of these cells to ß-like cells. Here we compare the mRNA expression profiles of these three different cell types (in triplicate). Methods: mRNA profiles of ALK3Bright/P2RY1+ cells isolated from human non-endocrine pancreatic tissue, ALK3Bright/P2RY1+ cells treated with BMP7 and ALK3Bright/P2RY1+ cells differentiated to ß-like cells after BMP7 removal were generated by deep sequencing, in triplicate, using Illumina HiSeq PE Cluster Kit v4 and Illumina HiSeq Flow Cell v4 with 50 nt paired end reads plus dual index reads using the Illumina HiSeq SBS kit v4. Sequence reads that passed quality filters were analyzed at the transcript isoform level following alignment using TopHat v2.1.0 followed by exon and gene level counting using Bioconductor easyRNASeq v 2.4.7. Conclusions: Our study represents the first detailed analysis of ALK3Bright/P2RY1+ sorted cells with biological replicates. We demonstrate ALK3Bright/P2RY1+ cells were shown to form progenitor-like epithelial colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies responded to BMP-7 by generating new ß-like cells as well as cells from other pancreatic lineages. The transcriptional profile of these cells and their BMP7 treated counterparts suggest a mitotic and progenitor like state. Our studies confirm the progenitor-like nature of ALK3Bright/PDX1+ cells within the human pancreas and suggest a specific anatomical location within the ductal network. Overall design: Comparison of transcriptional expression in Alk3Bright/P2RY1+ cells, Alk3Bright/P2RY1+ cells treated with BMP7 and Alk3Bright/P2RY1+ cells allowed to differentiate after BMP7 removal. Human islets, isolated from the same donors were included as a control.	Co-expression
SRP118614	RNA sequencing of prostate cancer and normal tissue from African Americans and European Americans	Background:African American men (AAM) are at higher risk of being diagnosed with prostate cancer (PCa) and are at higher risk of dying from the disease compared to European American men (EAM). We sought to better understand PCa molecular diversity that may be underlying these disparities. We ran RNA-sequencing data analysis on high-grade PCa to identify genes showing differential tumor versus normal adjacent tissue expression patterns unique to AAM or EAM. Overall design: Matched high-grade (GS=7(4+3)) prostate tumor and adjacent normal specimens from 16 patients (8 AAM and 8 EAM) were subjected to two replicate runs of RNA-sequencing.	Co-expression
SRP118694	Epigenomes and transcriptomes of human monocytes before and after in vivo exposure to Bacillus Calmette-Guérin vaccine	Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components. In this study, we apply epigenomic and transcriptomic analysis to a clinical trial of BCG vaccination in healthy adults. Overall design: Healthy volunteers were injected with the BCG vaccine, and monocytes were collected before vaccination, and 1 month after vaccination.	Co-expression
SRP118733	Transcriptomic analysis of Multiple Myeloma bone marrow microenvironment	We report the RNA sequencing of the non-tumoral CD138- fractions of 74 MM patient BM aspirates taken at the time of diagnosis. Overall design: The sequencing of total RNA  from the non-tumoral CD138- fractions of 74 MM patient BM aspirates was performed using TruSeq Stranded mRNA Sample Preparation kit on a NextSeq 500 Illumina sequencing platform (Illumina) by 5 successive runs using NextSeq 500 High Output kit v2 (Illumina) generating in average 20 million pairs of reads per sample.	Co-expression
SRP118741	Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk	Integration of differential expression (DE) and expression QTL (eQTL) analysis in monocyte-derived macrophages (MDMs) from systemic sclerosis (SSc) patients and healthy controls reveals (i) changes in macrophage transcriptome as an important contributor in SSc and (ii) cis-regulation in GSDMA as a disease risk in macrophages, but not skin. Overall design: We carried out RNA-sequencing and genome-wide genotyping in MDMs from 57 SSc patients and 15 controls. Our differential expression and expression QTL (eQTL) analysis in SSc was further integrated with epigenetic, expression and eQTL data from skin, monocytes, neutrophils and lymphocytes.	Co-expression
SRP118760	The medium-chain free fatty acid receptor GPR84 is expressed in pro-inflammatory macrophages and mediates inflammatory sequelae in endometriosis	RNA sequencing was used to investigate the transcriptomic response of primary human macrophages to stimulation of GPR84 and the effect of inhibition of this receptor with a range of antagonists. Overall design: RNA-seq of polyA-selected RNA from five healthy human donor macrophages exposed to a combination of agonists and antagonists for GPR84.	Co-expression
SRP118775	RNA-Sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer	Long non-coding RNA (lncRNA) have been implicated in human pathology, however, their roles in colorectal carcinogenesis has not been fully elucidated. In the current study, whole-transcriptome was analyzed in 3 pairs of colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequencing (RNA-seq). Followed by confirmation using the Cancer Genome Atlas (TCGA) dataset, we identified 27 up-regulated and 22 down-regulated lncRNAs in CRC. Up-regulation of four lncRNAs, hereby named colorectal cancer associated lncRNA (CRCAL)-1 [AC021218.2], CRCAL-2 [LINC00858], CRCAL-3 [RP11-138J23.1] and CRCAL-4 [RP11-435O5.2], was further validated by real-time RT-PCR in 139 colorectal neoplasms and matched NM tissues. Knockdown of CRCAL-3 and CRCAL-4 in colon cancer cells reduced cell viability and colony formation ability, and induced cell cycle arrest. TCGA dataset supported the associations of CRCAL-3 and CRCAL-4 with cell cycle and revealed a co-expression network comprising dysregulated lncRNAs associated with protein-coding genes. In conclusion, RNA-seq identified numbers of novel lncRNAs dysregulated in CRC. In vitro experiments and GO term enrichment analysis indicated the functional relevance of CRCAL-3 and CRCAL-4 in association with cell cycle. Our data highlight the capability of RNA-seq to discover novel lncRNAs involved in human carcinogenesis, which may serve as alternative biomarkers and/or molecular treatment targets. Overall design: 6 total samples consisting of 3 matched pairs of colorectal cancer (CRC) and matched normal mucosa (NM)	Co-expression
SRP118776	Global modulation of signaling pathways by SARM RAD140 in AR/ER+ breast cancer xenografts	These data demonstrates the regulation of AR and ER pathways by the SARM RAD140 and suggested a unique mechanism of action of RAD140 via the AR-mediated transcription repression. Overall design: HBCx-22 PDX were treated with RAD140 or vehicle and snap frozen tumor samples were subjected to RNA-seq analysis at the end of the study	Co-expression
SRP118788	Hypoxia-mediated translational activation of ITGB3 in breast cancer cells enhances TGF-ß signalling and malignant features in vitro and in vivo	We performed a polysomal RNA-Seq screen in non-malignant breast epithelial (MCF10A) and TNBC (MDA-MB-231) cells exposed to normoxic or hypoxic conditions and/or treated with an mTOR pathway inhibitor. Analysis of both the transcriptome and the translatome identified mRNA transcripts translationally activated or repressed by hypoxia in an mTOR-dependent or -independent manner. The mRNA populations of each sample were converted to cDNA libraries using the TruSeq protocol and then sequenced using a HiSeq 2000 machine. Paired-end reads were mapped against the reference human genome (GRCh38) with STAR v2.5.1b (ENCODE parameters for long RNA) and GENCODE v24 annotation. Gene quantification was performed using RSEM v1.2.28 with default parameters. Only protein-coding genes were included in the analysis. Normalization of the count matrix was performed with the TMM method of the edgeR R package. Polysomal RNA (P) and RNA total (T) fold changes across conditions were calculated with edgeR. Significant genes (FDR < 5% for MCF10A cells and FDR < 10% for MDA-MB-231 cells) in polysomes were selected for translational efficiency calculation (log2FC RNA polysomes/log2FC RNA total). Genes with a z-score > 1.5 were considered to have an increased translational efficiency and genes with a z-score < –1.5 were considered to have a decreased translational efficiency. GO enrichment analysis of significant genes was performed with the DAVID database. Overall design: RNA-Seq profiles in polysomes vs total in Normoxia, Hypoxia, Hypoxia + PP242, Normoxia + PP242 in MCF10A and MDA-MB-231 cell lines	Co-expression
SRP118804	Whole blood stabilization for the microfluidic isolation and molecular characterization of circulating tumor cells	We report RNA sequencing data from enriched prostate circulating tumor cells (CTCs) from clinical blood specimens. The goal is to examine the stability of RNA signatures as a function of whole blood preservation. Each blood sample was split into two equal portions; one portion was processed immediately (i.e., 0 hour) for CTC isolation; the other was preserved in 4 deg C, using methods described in this publication, for 24, 48, or 72 hours prior to CTC isolation. CTCs were isolated using the CTC-iChip and processed for RNA sequencing. Overall design: Blood specimens from a total of four patients were included in this study; for one of the patients, blood was obtained from three different dates and the sample was preserved for different durations. Each patient has a paired 0 hour sample and a preserved sample (indicated as 24, 48, or 72 hours). A total of 12 samples were processed and sequenced.	Co-expression
SRP118836	NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells	The development of the central nervous system (CNS) depends on the orchestrated generation of neurons and glia from neural stem cells (NSCs). Although NSCs generate both cell types, they are produced sequentially as neurons are born first and glia later. In humans, this timing is extremely protracted and the underlying mechanisms remain unknown. Deriving glial cells such as astrocytes from human pluripotent stem cells requires 3-6 months of differentiation, greatly impeding their use in human disease modeling and regenerative medicine. Here, we report that expression of the transcription factor nuclear factor IA (NFIA) is sufficient to trigger glial competency in highly neurogenic NSCs and enables the derivation of human astrocytes within 10-12 days.  NFIA-induced astrocytes are functional and shown to promote synaptogenesis, protect neurons and generate calcium transients. The mechanism of NFIA-induced glial competency involves rapid but reversible chromatin remodeling, demethylation of the GFAP promoter and a striking effect on the cell cycle. NFIA titration and pharmacological studies indicate that acquisition of a glial-compatible G1 length is critical for achieving glial competency. Our results offer mechanistic insights into human glial competency and enable the routine use of astrocytes for studying human development and disease. Overall design: The timecourse consists of 4 timpoints.  Day 0 (d0) represents neurogenic LTNSCs, day 3 (d3) represents overexpression of NFIA with doxycycline and cells were harvested in bulk, day 6 (d6) represents cells sorted for CD44 while NFIA is overexpressed, day 9 (d9) represents CD44+ sorted cells replated in culture without the addition of doxycyline to downregulate NFIA and day 12 (d12) represents the same cultures in d9, but with 3 additional days of no doxycycline treatment.  Each timepoint has a minimum of 3 biological replicates.  Rosette cells (H9 d0) and neurons (Dapt) were profiled as controls where rosettes were one sample and neurons were performed in duplicate.	Co-expression
SRP118840	RNAseq of Granular Cell Tumours	Looking for novel cancer genes in rare breast cancer types.	Co-expression
SRP118904	Single-cell RNA-Seq reveals a developmental atlas of human prefrontal cortex	Mammalian prefrontal cortex contains billions of cells, some of which are known as neurons to play critical roles in memory, cognitive ability, decision making, social behavior etc. through participating into complex neural circuits. Although neural circuits build up in the late stage of human embryo development and even after birth, the diverse and functional cells start to generate and migrate to the appropriate location play essential roles as basis for developing future circuits. However, it remains challenging to identify cell types of developing human PFC and distinguish their developmental features. Here, to address these challenges, single cells from human embryos PFC were carried out for RNA-seq.  Detailed analysis of neural progenitor cells (NPCs) illustrated a developmental feature of intermediate progenitor (IP) cells and revealed new marker genes of IP cells. We also mapped the neurogenesis timeline of PFC excitatory neurons and intrinsic singles regulating neuron maturation and circuit formation. Our screening and characterization approach provides a blueprint of human PFC development in early and mid embryonic stages, with which to systematically discover the cellular basis and molecular regulation of PFC function in humans. Overall design: Here we performed single cell RNA-seq analysis for prefrontal cortex (PFC), covering the developmental stages of gestational weeks 8-26.	Co-expression
SRP118916	RNA-sequencing	RNA-sequencing for 4 samples Overall design: Examing 4 conditions	Co-expression
SRP118922	Comprehensive Analysis of Gene Expression Patterns in Friedreich's Ataxia Fibroblasts by RNA Sequencing Reveals Altered Levels of Protein Synthesis Factors and Solute Carriers	Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene.  FRDA patients have low FXN mRNA and frataxin protein levels when compared with heterozygous carriers or healthy controls.  Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking.  Peripheral tissues, including blood cells, buccal cells, and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis.  However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided.  Transcriptome profiling of FRDA skin fibroblasts revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins.  Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in the FRDA cells.  Finally, comparison of genes differentially expressed in FRDA fibroblasts to 3 previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes.  Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. Overall design: We used RNA sequencing to profile the transcriptomes of primary fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals.	Co-expression
SRP118934	Analysis of gene expression in SKOV3 ovarian cancer cells after knockdown of the long non-coding RNA DNM3OS	RNA-sequencing was performed to gain insight into the mechanism responsible for the mesenchymal-to-epithelial transition (MET) induced by loss of long non-coding RNA (lncRNA) DNM3OS in SKOV3 ovarian cancer cells. Following siRNA-mediated knockdown of DNM3OS or non-targeting control,  RNA-sequencing was performed. This high-throughput data revealed knockdown of DNM3OS down-regulated the expression of genes and pathways known to induce EMT in ovarian cancer. Overall design: DNM3OS was knockdown in SKOV3 ovarian cancer cells and gene expression profiles were compared with controls using RNA-sequencing.	Co-expression
SRP118972	Gene Expression Profile of human hepatocellular carcinoma by RNA sequencing	The aim of the present study was to investigate biomarkers in the malignant process of HCC by high throughput sequencing. Overall design: Tumors and paired non-tumor tissues were collected from HCC patients during surgeries at Sun Yat-sen University Cancer Center. Samples were profiled separately using the Illumina HiSeqâ„¢ 2500 by MyGene Diagnostics Co., Ltd (Guangzhou, China).	Co-expression
SRP118983	RNA characterization of the Physical Sciences - Oncology Network Bioresource Core Facility (PBCF) cell lines grown on various substrates	The NCI’s Division of Cancer Biology (DCB), Physical Sciences-Oncology Network (PS-ON) program has established a PS-ON Bioresource Core Facility (PBCF) which includes a panel of 49 model cell lines. At the Janmey Laboratory of the University of Pennsylvania, nine of these cell lines were grown on seven different substrates of varying stiffness, i.e., hydrogels with different viscoelastic properties and integrin ligands (collagen or fibronectin), for a total of 63 samples. The cell lines were pelleted and stored at -80oC, and RNA was extracted using Qiagen All Prep DNA/RNA kit by Stanford Functional Genomics Facility. The extracted mRNA and miRNA were then sequenced by Frederick National Laboratory for Cancer Research (FNLCR).	Co-expression
SRP119007	Molecular Genetics lab project	pancreatic cancer cells treated with or without pomegranate and caffeine	Co-expression
SRP119053	Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia	Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: We profiled the human HSCe (Lineage-, CD34+, CD38-) transcriptome with aging at the single cell level. Single-cell RNAseq was performed on FACS isolated human bone marrow derived HSCe from 5 young (24-37 yo) and 4 aged donor (64-71 yo). Donors had no known hematological malignancy.	Co-expression
SRP119065	SLEAR predisposes to systemic lupus erythematosus by regulating apoptosis [RNA-Seq]	Systemic lupus erythematosus (SLE) is an autoimmune disease, and affects all parts of the human body. Genome-wide association studies have been employed to identify susceptibility genes of SLE. However, most of the SLE associated variants are located in the noncoding regions of the human genome. We characterized SLE risk variants in Chinese populations. One of the most significant validated SNP was located in a gene which we named SLEAR. We found SLEAR was enriched in the nucleus and could regulate apoptosis. Apoptosis is a highly regulated process. And misregulation of the process could lead to autoimmune diseases, especially SLE. Our results suggest that SLEAR plays a key role in apoptosis regulation and is associated with SLE predisposition. Overall design: RNA-seq in Jurkat with MAPS strategy (Control shRNA VS SLEAR shRNA)	Co-expression
SRP119102	RNA-seq for gastric adenocarcinoma	Five pairs of gastric adenocarcinoma tissues and normal tumor-adjacent tissues were used in this study	Co-expression
SRP119165	Metformin induces chromosome reorganization and changes in gene expression in normal human fibroblasts	We report the effects of metformin treatment on the transcriptome of normal human dermal fibroblasts isolated from foreskin (designated 2DD). We sequenced mRNA from 2 replicates of proliferative (PRO) and 2DD cells treated with two concentrations of metformin (0.5mM and 1.0 mM;5 days exposure). Comparative analyses with PRO transcripts a baseline indicate that fibroblsts exposed to different concentration of metformin result in differnetial transcript profiles. Overall design: Examination of mRNAs from proliferative and metformin treated (0.5mM and 1.0 mM for 5 days) 2DD normal human dermal/foreskin fibroblasts.	Co-expression
SRP119170	Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-Seq of HSCe)	Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: We profiled the human HSCe (Lineage-, CD34+, CD38-) transcriptome with aging. RNAseq was performed on FACS isolated human bone marrow derived HSCe young (18-30yo) and aged (65-75) donors. Donors had no known hematological malignancy. For each age group, 10 biological replicates were used.	Co-expression
SRP119173	Genome-wide analysis of ferroptosis related genes in liver cancer cells.	To seek ferroptosis related genes in liver cancer cells, we treated HepG2 cells using ferroptosis inducer Erastin and inhibitor Ferrostatin, respectively. We found that a subset of genes were up-regulated in Erastin treatment groups and down-regulated in Ferrostatin treatment groups, suggesting that these genes might be correlated with ferroptosis. Overall design: Examination of ferroptosis related genes in HepG2 cells.	Co-expression
SRP119207	Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of human U2OS cells under mild replication stress by low dose aphidicolin (APH)	To detect transcripts before and after APH treatment, we subjected total RNA isolated from U2OS cells expressing human FANCD2-3xFLAG to next generation sequencing. Overall design: U2OS cells expressing human FANCD2-3xFLAG  were treated with 0.4 micro M APH, or left antreated for 24 hrs.	Co-expression
SRP119248	Clonally expanded CD4+ T cells with a unique gene signature contribute to persistence of the HIV-1 latent reservoir	Surface expression of the viral Envelope protein (Env) was used to enrich reactivated latent T cells producing HIV-RNA, and single cell RNASeq was performed to study gene expression differences between latent cells and controls. Overall design: Latent CD4+ T cells from virologically suppressed patients were reactivated in vitro and isolated using antibodies against HIV-1 Env. Single cell RNASeq was performed comparing reactivated latent cells with control, unpurified cells from the same donor and with cells actively infected in vitro using HIV-1(YU2).	Co-expression
SRP119274	Discovery of pan-Histone Acetyltransferase Inhibitors with Potent Antitumor Activity in vivo	we use MV4-11 as cellular models to analyze differential gene expression. Overall design: 4 samples including 20uM G47 treatment and DMSO control, repeat for 2 times	Co-expression
SRP119279	Reversible LSD1 Inhibition with HCI-2509 induces the p53 gene expression signature in high-risk neuroblastoma cells	Lysine-Specific Demethylase 1 (LSD1) over-expression correlates with poorly differentiated neuroblastoma and predicts poor outcome despite multimodal therapy. We have studied the efficacy of reversible and specific LSD1 inhibition with HCI-2509 in neuroblastoma cell lines and particularly the effect of HCI-2509 on the transcriptomic profile in MYCN amplified NGP cells.  Cell survival assays show that HCI-2509 is cytotoxic to poorly differentiated neuroblastoma cell lines in low micromole or lower doses. Transcriptional profiling of NGP cells treated with HCI-2509 shows a significant effect on p53, cell cycle, MYCN and hypoxia pathway gene sets. HCI-2509 results in increased histone methyl marks and p53 levels along with cell cycle arrest in the G2/M phase and inhibition of colony formation of NGP cells. Our findings indicate that LSD1 inhibition with HCI-2509 has a multi-target effect in MYCN amplified high-risk neuroblastoma cells. Overall design: One million NGP cells per well were plated in 6 well plates and treated with vehicle (DMSO) or 3 µM HCI-2509 for 4 and 24 hours in quadruplicate.	Co-expression
SRP119281	Transcriptomic profiles in dental pulp cells from one CCD patient with allelic RUNX2 deletion and one sex-age matched unaffected individual.	The goal is to investigate the downstream targets of RUNX2 signaling which are potentially involved in the disease process of Cleidocranial Dysplasia (CCD). RNA-seq was performned to compare the mRNA profiles in human dental pulp cells from one CCD patient with allelic RUNX2 deletion (CCD-011) and sex-age matched unaffected individual(Control).   Of 25,643 genes analyzed, 11,039 genes had no detectable signal in both CCD and control samples tested leaving 14,604 genes that were evaluated for differential gene expression.  In the detectable genes, 60 transcripts (4.1%) were found to be statistically significantly dysregulated with 63% upregulated and 27% downregulated (fold change = 2; q-value < 0.05).   Overall design: mRNA profiles of CCD-011 dental pulp cells and sex-age matched control cells were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP119315	SUV420H2 knockdown in PANC-1	PANC-1 cells were treated with siRNA against SUV420H2 to monitor the progressive transition between epithelial/mesenchymal states. Controls were untreated. Genentech internal expressionplot project id is PRJ0007677 Overall design: SUV420H2 knockdown in PANC-1	Co-expression
SRP119324	Triplet nucleotide repeat-based siRNAs are highly toxic to cancer cells	Triplet repeat siRNAs as found amplified in diseases such as Huntingtons disease can be used to kill cancer cells Overall design: RNA isolated from HeyA8 cells 48 hrs after transfection with either a nontargeting siRNA (siScr), siCAG/CUG or siCGA/UCG were subjected to deep sequencing, using Illumina HiSeq4000.	Co-expression
SRP119331	HNRNPH1 is required for rhabdomyosarcoma cell growth and survival	Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-year survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-year survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in 3 cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was dramatically reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a striking reduction in tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data show that HNRNPH1 may be an important molecular target for the development of future RMS therapy. Overall design: Two individual siRNAs targeting HNRNPH1 were used to knockdown HNRNPH1 in RD, RH30, and RH41 cells. Both siRNAs were done in triplicate in all cell lines. Briefly, 20nM siRNA was transfected with RNAiMax in 6-well dishes (2?×?105 RD and RH30 or 2.4?×?105 RH41) for 12 hours, after which media was changed and cells collected 48 hours post transfection.	Co-expression
SRP119392	'Naïve' ESRRB+ iPSCs with the capacity for rapid neural differentiation	Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naïve state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naïve-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naïve state through the transgenic expression of several reprogramming factors. The resulting cells express the components of the core transcriptional network of mESCs, including ESRRB, at high levels, which suggests the existence of naïve-state hiPSCs that are similar to mESCs. We also demonstrate that these cells differentiate more readily into neural cells than do conventional hiPSCs. These features may be beneficial for their use in disease modeling and regenerative medicine. Overall design: RNA-seq of primed and naïve-like hiPSCs in 3 biological replicates respectively.	Co-expression
SRP119404	Therapy-induced hypoxia contributes to AML drug-resistance through BMX Kinase upregulation	Oncogenic addiction to FLT3 kinase signaling is a hallmark of FLT3-ITD+ acute myeloid leukemia (AML). While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, utilizing RNA-Seq based analysis of patient leukemic cells, we found significant up-regulation of the Tec-family kinase BMX during sorafenib resistance. BMX upregulation was recapitulated in an in vivo FLT3-ITD+ model of sorafenib resistance. Mechanistically, we found that the anti-angiogenic effects of sorafenib led to increased bone-marrow hypoxia, which contributed to HIF-dependent BMX upregulation. In in vitro experiments, hypoxia-dependent BMX up-regulation was observed in both AML and non-AML cell lines. Functional studies in FLT3-ITD+ cell lines showed that BMX is part of a compensatory signaling mechanism that promotes AML cell survival during FLT3 inhibition. Our results demonstrate that hypoxia-dependent up-regulation of BMX contributes to therapeutic resistance through a compensatory pro-survival signaling mechanism. These results also reveal the role of 'off-target' drug effects on tumor microenvironment and development of acquired drug resistance. We propose that the bone marrow niche can be altered by anti-cancer therapeutics, resulting in drug resistance through cell non-autonomous microenvironment-dependent effects. Overall design: eight AML samples from 4 patients, 7 are relapses and 1 is a diagnosis sample	Co-expression
SRP119425	Early Changes In B Cell Subsets Predict Risk Of Autoimmunity Following Combination Immune Checkpoint Blockade	We report changes in B cells in patients treated with combination immune checkpoint blockade (CCB; anti-CTLA4 and anti-PD1) Overall design: We examine CD19+ sorted B cells before and after CCB therapy	Co-expression
SRP119431	Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes	Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets.	Co-expression
SRP119437	Truncated O-glycan connection to Cancer: Depletion of O-glycosyltransferase C1GALT1 leads to early PDAC onset and metastasis	Aberrant expression of truncated O-glycan structures, such as Tn and STn, is frequently observed in pancreatic ductal adenocarcinoma (PDAC). The focus of our study is to investigate the functional role of truncated O-glycans in PDAC progression and metastasis. Our study revealed that kmockout of C1GALT1 leads to increased expression of truncated glycans and accelerates PDAC progression and metastasis. Overall design: We performed the CRISPR/Cas9 knockout of C1GALT1 in human T3M4 PDAC cells followed by whole transcriptome analysis using RNA sequencing.	Co-expression
SRP119465	Homo sapiens Raw sequence reads	Single-cell Transcriptome Sequencing Analysis for Human Esophageal Squamous Carcinoma and Human Esophageal Adenocarcinoma	Co-expression
SRP119486	Characterization of transcriptomics landscape in HUVEC cells exposed to oxidative stress (Small RNA)	The aim of the project was to characterize the transcriptional landscape of human HUVEC cells exposed to oxidative stress (oxstress). In order to do so cell cultures have been exposed to 200uM H2O2 for either 16 hours or 36 hours to induce oxstress. Total ribodepleted RNA obtained from both time points have been sequenced and small RNA for the 16 hours time point have been sequenced as well. Datasets have been characterized and overlapped. This entry contains the dataset of small RNA. Overall design: Two conditions are available: control untreated HUVEC cells and HUVEC cells exposed to 200uM H2O2 for 16 hours. Each condition is available in triplicate. All samples underwent two unpooled rounds of sequencing, for a total of 24 samples.	Co-expression
SRP119487	Characterization of transcriptomics landscape in HUVEC cells exposed to oxidative stress (Total RNA)	The aim of the project was to characterize the transcriptional landscape of human HUVEC cells exposed to oxidative stress (oxstress). In order to do so cell cultures have been exposed to 200uM H2O2 for either 16 hours or 36 hours to induce oxstress. Total ribodepleted RNA obtained from both time points have been sequenced and small RNA for the 16 hours time point have been sequenced as well. Datasets have been characterized and overlapped. This entry contains the dataset of total ribodepleted RNA. Overall design: Three conditions are available: control untreated HUVEC cells, HUVEC cells exposed to 200uM H2O2 for 16 hours, HUVEC cells exposed to 200uM H2O2 for 36h. Each condition is available in triplicate, for a total of 9 samples.	Co-expression
SRP119503	Effect of human pulmonary MSCs isolated from normal and tumor tissues on the expression profile of primary lung cancer cells	Metastasis is a multi-step process that involves a direct cross-talk between cancer cells and their microenvironment. Here we assess the effect of paired mesenchymal stem cells (MSCs) isolated from the tumor tissue (T-) and normal lung adjacent tissue (N-) on the expression profile of primary lung cancer cells. We observed that MSCs induce the expression of tumor genes associated with a more aggressive phenotype and promote early tumor cell dissemination. Our observations provide new insight into mechanisms whereby MSCs promote lung cancer metastasis.	Co-expression
SRP119557	Clustering gene expression time series data using an infinite Gaussian process mixture model	In order to identify and characterize novel human gene expression responses to glucocorticoids, we exposed the human lung adenocarcinoma cell line, A549, to the synthetic glucocorticoid dexamethasone for 1, 3, 5, 7, 9, and 11 hrs in duration as well as to a paired vehicle control, ethanol. We assayed gene expression with RNA-seq and clustered gene expression profiles using an infinite Gaussian process mixture model. Overall design: Time series treatment of human A549 cells with dexamethasone or paired vehicle control.	Co-expression
SRP119585	OBESITY IS ASSOCIATED WITH IMPAIRED EXPRESSION OF THE GLYCOSYLTRANSFERASE EOGT IN DECIDUALIZING ENDOMETRIUM	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the feto-maternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential post-translational modification that links glucose sensing to downstream stress resistance. Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-GlcNAc modified proteins, reflecting down-regulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase, OGT) but not the enzyme that removes the modification (O-GlcNAcase, OGA). Notably, EOGT, an endoplasmic reticulum-specific O-GlcNAc transferase that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs. Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions. The most responsive gene downregulated upon EOGT knockdown in decidualizing cells was ENHO, which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index. Taken together, our findings reveal that obesity impairs the EOGT-adropin axis in decidual cells, which in turn provides a new mechanism that links between metabolic disorders to adverse pregnancy outcome. Overall design: Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-EOGT, either undifferentiated or decidualized with 8-br-cAMP and MPA for 4 days were generated by deep sequencing, in triplicate using Illumina	Co-expression
SRP119606	RNA-Seq analysis of prostate cancer cell line C4-2 treated with siRNA control (siCont), siEAF2, sip53 or concurrent siEAF2 and sip53	The tumor suppressor genes EAF2 and p53 are frequently dysregulated in prostate cancers. Recently, we reported that concurrent p53 nuclear staining and EAF2 downregulation were associated with high Gleason score. Combined loss of EAF2 and p53 in a murine model induced prostate tumors, and concurrent knockdown of EAF2 and p53 in prostate cancer cells enhanced proliferation and migration, further suggesting that EAF2 and p53 could functionally interact in the suppression of prostate tumorigenesis. Here, RNA-seq analyses identified differentially regulated genes in response to concurrent knockdown of p53 and EAF2. Several of these genes were associated with the STAT3 signaling pathway, and this was verified by significantly increased p-STAT3 immunostaining in the Eaf2-/-p53-/- mouse prostate. STAT3 knockdown abrogated the stimulation of C4-2 cell proliferation by concurrent knockdown of EAF2 and p53. Furthermore, immunostaining of p-STAT3 was increased in human prostate cancer specimens with EAF2 downregulation and/or p53 nuclear staining. Our findings suggest that simultaneous inactivation of EAF2 and p53 can act to activate STAT3 and drive prostate tumorigenesis. Overall design: C4-2 prostate cancer cells treated with siEAF2 and/or sip53 mRNA profiles were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP119607	Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer	Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but resistance to hormonal treatment is common. We use transcriptomics to reveal gender-selective and genomic location-specific hormone receptor actions, which associated with survival in MBC patients. Overall design: Gene expression analysis of male breast tumors (RNA-seq on 46 samples).	Co-expression
SRP119610	Non-synchronized cell cycle transcriptomics in U2OS and HeLa cancer cells	Sorting U2OS and HeLa cells genetically modified with the Fucci System allowed us to separate cells according to cell cycle progression followed by RNA Sequencing to characterize the oscillating transcriptome in cells without the need for chemical synchronization. Overall design: HeLa cells were sorted at three timepoints, while U2OS cells were sorted at two timepoints. Each time into three groups, categorized as "G1", "S", and "G2".	Co-expression
SRP119636	Integration of genome-wide analysis to characterize long noncoding RNAs in diverse immune cell types of the stage IV melanoma patients	We investigated the expression profiles in the CD4+, CD8, and CD14+ peripheral blood cells (PBLs) of the stage IV melanoma patients and the healthy donors. Overall design: Examination of long noncoding RNA in the CD4+, CD8, and CD14+ peripheral blood cells (PBLs) of the stage IV melanoma patients and the healthy donors.	Co-expression
SRP119657	Differential gene expression tools exhibit substandard performance for long non-coding RNA-sequencing data	Paired End PolyA-+ RNA-sequencing of NGP cells with and without NGP treatment in 10 replicates. Overall design: NGP cells treated with and without Nutlin	Co-expression
SRP119676	New insights into diagnosis and therapeutic options for proliferative hepatoblastoma	Surgery and cisplatin-based treatment of hepatoblastoma (HB) currently guarantee the survival of 70-80% of patients. However, some important challenges remain in diagnosing high risk tumors and identifying relevant targetable pathways offering new therapeutic avenues. Previously, two molecular subclasses of hepatoblastoma tumors have been described, namely C1 and C2; C2 being the subgroup with the poorest prognosis, a more advanced tumor stage and the worst overall survival rate. An associated 16-gene signature to discriminate the two tumoral subgroups was proposed but it has not been transferred into clinical routine. To address these issues we performed RNA sequencing of 25 tumors and matched normal liver samples from patients. The transcript profiling separated HB into three distinct subgroups named C1, C2A and C2B, identifiable by a concise four-gene signature: HSD17B6, ITGA6, TOP2A and VIM, with TOP2A being characteristic for the proliferative C2A tumors. Differential expression of these genes was confirmed by RT-qPCR on an expanded cohort and by immunohistochemistry. We also revealed significant overexpression of genes involved in Fanconi Anemia (FA) pathway in the  C2A subgroup. We then investigated the ability of several described FA inhibitors to block growth of HB cells in vitro and in vivo. We demonstrated that bortezomib, an FDA-approved proteasome inhibitor, strongly impairs the proliferation and survival of HB cell lines in vitro, blocks FA pathway associated double-strand DNA repair and significantly impedes HB growth in vivo.  In conclusion, the highly proliferating C2A subtype is characterized by TOP2A gene up-regulation and FA pathway activation and HB therapeutic arsenal could include Bortezomib for the treatment of patients with the most aggressive tumors. Overall design: mRNA profiles from hepatoblastoma cell lines and hepatoblastoma tissues together with corresponding normal livers were generated by deep sequencing using Illumina HiSeq 2500	Co-expression
SRP119679	In vitro infection of A549 cells with Aspergillus fumigatus	Human A549 airway epithelial cells were subject to in vitro infection withAspergillus fumigatus (strains Af293 or CEA10) for 6 or 16 hours and then subject to RNA-seq analysis of both the host and fungal transriptomes.	Co-expression
SRP119687	Single-cell RNA-seq analysis reveals the progression of human osteoarthritis	Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index analysis and correspondence analysis. We identified seven molecularly defined populations of chondrocytes in human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles and transcriptional networks among chondrocytes at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA. Overall design: 34 Samples	Co-expression
SRP119766	Molecular anatomy of the developing human retina	Clinical and genetic heterogeneity associated with retinal diseases makes stem cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 150. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared to peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, though morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as resource for molecular staging of human stem cell-derived retinal organoids. Overall design: Whole human fetal retina samples [spanning 12 time points: D52/54, D53, D57, D67, D80, D94 (2 samples), D105, D107, D115, D125, D132 and D136] or dissected retinal regions [at four time points: D59 (periphery and central, 2 samples each), D73 (periphery and fovea/macula), D96 (periphery, fovea/macula, and nasal central) and D132 (periphery, fovea/macula, and nasal central)] were used to generate RNA-seq libraries.	Co-expression
SRP119775	Differentially expressed LncRNAs and mRNA identified by SEQ analysis in colorectal cancer patients	LncRNA plays an important role in gene regulation, but its impact on the pathogenesis of colorectal cancer and the biological function of cancer cells is unclear. In this study, we will use the next generation sequencing technique to study the differences of the expression profiles of lncRNA and mRNA in colorectal cancer tissues, analyzing the differentially expressed genes by GO/KEGG enrichment, and predicting the new lncRNAs' function. Our results revealed that Comparing with the nontumor colorectal tissues, 1019 lncRNAs (512 upregulated, 507 downregulated) and  3221 mRNAs (1606 upregulated, 1615 downregulated) were differentially expressed in tumor colorectal tissues (fold change>2 and P<0.05). Overall design: lncRNA and mRNA profiles of 10 paired tissues (nontumor and colon cancer tissues)  were generated by deep sequencing, in triplicate, using Illumina.	Co-expression
SRP119776	RNA-seq of YB5 cells treated with HH1	RNA-seq was performed after YB5 cells were treated with DAC,  HH1 or the combination of the two. RNA-seq was also perfomed after viral transduction using a TET-off dnCDK9 construct Overall design: Biological triplicates were performed for a total of 48 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples	Co-expression
SRP119788	Gene-expression profiling of single cells from archival tissue	RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed, paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here we present a new method, Smart-3SEQ, that accurately quantifies transcript abundance even with small amounts of total RNA and effectively characterizes small samples extracted by laser-capture microdissection (LCM) from FFPE tissue. Here we obtain distinct biological profiles from FFPE single cells, which have been impossible to study with previous RNA-seq protocols, and detect both gene-expression differences and copy-number alterations in single macrophages vs. ductal carcinoma in situ from a breast-cancer case. We propose Smart-3SEQ as a highly scalable method to enable large gene-expression profiling experiments unconstrained by sample size and tissue availability. In particular, Smart-3SEQ''s compatibility with FFPE tissue unlocks an enormous number of archived clinical samples, and combined with LCM it allows unprecedented studies of small cell populations and single cells isolated by their in situ context.	Co-expression
SRP119800	Gene expressions in nucleus and cytoplasm at the single cell resolution	Single-cell RNA-seq with SINC-seq(single-cell integrated nuclear and cytoplasmic RNA-seq) that resolves the RNA expression in the subcellular compartments by the physical fractionation of nuclear and cytoplasmic RNAs of single cells.	Co-expression
SRP119818	Suspension of breast cancer cells MDA-MB-231 Transcriptome	To research the effect of suspension state on metastasis of breast cancer.	Co-expression
SRP119822	MicroRNA-125a-5p overexpression in human macrophages	Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy with features of autoinflammation. Monocytes and macrophages in SJIA have a complex phenotype with both pro- and anti-inflammatory properties that combine features of several well characterized in vitro conditions used to activate macrophages.  An important anti-inflammatory phenotype is expression of CD163, a scavenger receptor that sequesters toxic pro-inflammatory complexes that is highly expressed in both active SJIA and macrophage activation syndrome (MAS).  CD163 is most strongly upregulated by IL-10 (M(IL-10)), and not by other conditions that reflect features seen in SJIA monocytes such as M(LPS+IC).  MicroRNA play key roles balancing and integrating cellular signals such as those in macrophage polarization, and as such we hypothesize microRNA regulate macrophage functional responses in SJIA including CD163 expression in vitro.  We find that two microRNA previously found to be elevated in active SJIA, miR-125a-5p and miR-181c, significantly reduced macrophage CD163 expression through two distinct mechanisms.  Neither microRNA was elevated in M(IL-10) with robust CD163 expression, but were instead induced in M(LPS+IC) where they restricted CD163 mRNA expression.  Mir-181 species directly targeted CD163 mRNA for degradation.  In contrast, transcriptome analysis of miR-125a-5p overexpression identified “cytokine-cytokine receptor interactions” as the most significantly repressed gene pathway, including decreased IL10RA, which is required for IL-10-mediated CD163 expression. Finally, overexpression of miR-181c inhibited CD163 anti-inflammatory responses to hemoglobin or high mobility group box 1 complexes. Together, these data show that microRNA utilize multiple mechanisms to integrate well characterized polarization phenotypes and regulate macrophage functional properties seen in SJIA. Overall design: THP-1 human monocytic cells were transfected in triplicate with negative control microRNA mimic or miR-125a-5p mimic. RNA extracted 24hours after transfection	Co-expression
SRP119824	Ribosome-free RNA sequencing of long noncoding RNAs and circular RNAs in lung adenocarcinoma	Noncoding RNAs play important roles in various biological processes and diseases, including cancer. Expression profile of circular RNAs (circRNA) is largely unknown in lung adenocarcinoma. This study is designed to explore mRNA, long noncoding RNA (lncRNA), and circRNA in lung adenocarcinoma. Overall design: 9 pairs of lung adenocarcinoma tissues and paired nontumor tissues were collected. Every 3 tumor and every 3 nontumor tissues were pooled together for RNA sequencing, and 6 samples were sequenced. Primary lung adenocarcinoma tissues and paired nontumor tissues were snap frozen with liquid nitrogen immediately after resection and stored in liquid nitrogen till RNA extraction.	Co-expression
SRP119826	SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA	The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. NORAD is a recently characterized, abundant, and highly conserved cytoplasmic lncRNA that is required for proper mitotic divisions in human cells. NORAD antagonizes repressors from the Pumilio family that bind at least 17 sites spread through 12 repetitive units  in NORAD sequence. Here we study conserved sequences in NORAD repeats, identify additional interacting partners, and characterize the interaction between NORAD and the RNA binding protein SAM68 (KHDRBS1), which is required for NORAD function in antagonizing Pumilio. The interactions between NORAD, Pumilio and SAM68 provide a paradigm for how specific repeated and structured elements with a lncRNA can facilitate its function. Overall design: RNA-seq following perturbations of SAM68 in U2OS cells and NORAD lncRNA in HCT116 WT and SAM68 KO cells	Co-expression
SRP119838	AhR activity directs BRAF inhibitors resistance in metastastic melanoma	BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.	Co-expression
SRP119842	RNA Seq of Alagille liver biopsies	Needle biopsies were performed to obtain liver samples from patients for clinical purposes from patients with Alagille syndrome. A small portion was snap frozen and later used for RNA sequencing analysis. Needle biospies from 5 patients with other liver disorders were included as controls. Overall design: Examination of RNA expression in Alagille patients'' liver samples, compared to other control liver samples (with other chronic liver diseases).	Co-expression
SRP119844	RNA Seq of C2C12 cells stimulated with Control, Jag1-expressing or Jag1Ndr-expressing cells	RNA sequencing of control or Notch1-expressing mouse cells co-cultured with control, Jag1WT, or Jag1Ndr-expressing human cells. Deep sequencing and bioinformatical separation of mouse and human reads reveals transcripts specifically regulated in mouse receptor-expressing cells. Overall design: Mouse C2C12 control and C2C12-FLNotch1, and human HEK-293-Flp-In cells (Hansson et al., 2010): HEK293-Flp control (Flp Ctrl), HEK293-Flp-Jag1WT (Flp Jag1+), HEK293-Flp-Jag1Ndr (Flp Jag1Ndr) were used in this experiment. In one 12-well plate, we seeded 3 wells of mouse C2C12 control cells and 3 wells of C2C12-FLN1 cells, with 3.6x105 cells in 1 mL antibiotic-free medium per well. Cells were allowed to settle for 8 hours. C2C12 control and C2C12-FLN1 cells were transfected with pcDNA5 (1.6 ug/well). All transfections were done using Lipofectamine® 2000 (InvitrogenTM, cat. no. 11668-019) with Opti-MEM® I Reduced Serum Medium (Gibco®, cat. no. 31985-062), according to manufacturer's instructions. The following day (18 hours post transfection), 3.6x105 cells in 0.5 mL antibiotic-free medium of Flp Ctrl, Flp Jag1+, or Flp Jag1Ndr cells were added. Cells were co-cultured for 6 hours, then lysed in 350 uL per well Buffer RLT (QIAGEN, cat. no. 79216) with 1% 2-Mercaptoethanol (Sigma-Aldrich®, cat. no. M3148) and stored at -80°C until RNA extraction.	Co-expression
SRP119863	A novel non-canonical signaling pathway mediates TGF-ß1-induced glucocorticoid insensitivity in epithelial cells	Limited therapeutic responses to glucocorticoids in chronic inflammatory disease are partly attributable to interleukins and transforming growth factor-ß1 (TGF-ß1). Global inhibition of TGF-ß1 carries known risks, including autoimmune disease.  Here we elucidate the signaling pathway subserving modulation of glucocorticoid activity by TGF-ß1. The proteomic response of airway epithelial cells to TGF-ß1 revealed 24 candidate proteins of which 3 were prioritized by exclusion of changes induced by: TGF-ß2, which lacks the modulatory activity of TGF-ß1 and TGF-ß3; and those of TGF-ß1 that were prevented by small molecule inhibitors of non-canonical TGF-ß1 signaling, that did not prevent glucocorticoid modulation. Pharmacological and genetic approaches establish that TGF-ß1-induced glucocorticoid insensitivity is mediated by a novel signaling cascade involving LIM domain kinase 2 mediated phosphorylation of phospho-cofilin1 that activates phospholipase D to generate the effector(s) (lyso)phophatidic acid. This study identifies several promising drug targets that potentially enable safe modulation of TGF-ß1 in chronic inflammatory diseases. Overall design: Biological triplicates of BEAS-2B cell lines treated with Dexamethasone, TGFbeta1 and a combination of Dexamethasone +TGFbeta1 were compared among themselves and with an untreated control	Co-expression
SRP119864	Differentially Expressed Genes upon Knockdown of ZRANB1 or EZH2 in LM2 Cells	EZH2, the catalytic component of the Polycomb repressive complex 2 (PRC2), silences gene transcription by methylating histone H3 at lysine 27. Recently we identified ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. To determine whether ZRANB1 is a functional regulator of EZH2, we performed RNA-Seq analysis to compare the effect of ZRANB1 knockdown or EZH2 knockdown on global gene expression. Overall design: mRNA profiles of control, ZRANB1 knockown, or EZH2 knockdown LM2 cells were generated from triplicate samples using RNA-Seq	Co-expression
SRP119895	RNA-seq of exosomes identifies lncRNA profiles that distinguish early-stage esophageal squamous cell carcinoma (ESCC) from non-malignant esophagitis	We report the application of RNA sequencing technology for high-throughput profiling of transcriptomes in plasma exosomes from early-stage ESCC and  esophagitis.  By analyzing over 95G of clean reads (depleted rRNA), we found that expression features of exosomal lncRNAs were distinct from that of exosomal mRNAs. We identified differentially expressed exosomal lncRNAs and mRNAs for ESCC, and esophagitis. We further analyzed the biological functions of differentially expressed lncRNAs using GO, KEGG, as well as knockdown assay with siRNAs. This study provides information for identifying cancer and non-malignant disease relevant exosomal lncRNAs through integrative analyses of RNA sequencing data. Overall design: Examination and comparison of lncRNAs and mRNAs in exosomes from ESCC, esophagitis, and healthy control, respectively.	Co-expression
SRP119917	Homo sapiens Transcriptome or Gene expression	Gene expression in prostate tumor and normal tissue of patients	Co-expression
SRP119952	Comparison of RNA-seq and Microarray Platforms for Splice Event Detection using a Cross-Platform Algorithm [RNA-Seq]	In this study, we compare the performance of RNA-seq (Illumina HiSeq) and junction arrays (Affymetrix Human Transcriptome array) for the analysis of splicing events. Three different cell lines were treated with CX-4945, a drug that severely affects splicing. To make a fair comparison, we developed EventPointer, an algorithm that detects and labels alternative splicing events in both junction arrays and RNA-seq. Common results and discrepancies between both technologies were validated or resolved by more than 200 PCRs. Overall design: Three different triple negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, SUM 149) treated with CX4945 and DMSO with 5 replicates. A total of 30 samples	Co-expression
SRP119967	WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription	Transcription termination and mRNA export from the nucleus are closely regulated and coordinated processes. Nuclear export factors are recruited to actively transcribed genes through their interactions with protein complexes associated with transcription and co-transcriptional pre-mRNA processing. We determine a new role for the kinase WNK1 in the cross-talk of transcription termination and mRNA export.  WNK1 was previously attributed a cytoplasmic role as a regulator of ion transport. However, we now show a nuclear function for this kinase where it is required for efficient mRNA export along with the transcription termination factor PCF11. Finally, we identify the phosphorylation of the CID domain of PCF11 as an important step for the release of the mRNA from the transcription locus, thus allowing efficient mRNA export to the cytoplasm. Overall design: RNA from cytoplasmic and nuclear extracts of HeLa cells was obtained, upon depletion of WNK1 kinase or from control cells. Upon pA selection, libraries were generated and sequenced. A duplicate experiment was performed for each sample.	Co-expression
SRP120012	Transcriptomic analysis of neuroblastoma cells in response to stable over-expression of FOXD3 antisense RNA 1 (FOXD3-AS1)	Neuroblastoma (NB), a malignant embryonic tumor arising from primitive neural crest cells, accounts for more than 7% of malignancies and around 15% of cancer-related mortality in childhood. Better elucidating the mechanisms of tumorigenesis and aggressiveness is important for improving the therapeutic efficiencies of NB. Through mining of publically available microarray datasets, we discovered a novel 963-bp lncRNA, named FOXD3 antisense RNA 1 (FOXD3-AS1), as an independent prognostic marker for favorable clinical outcome of NB patients. To investigate the mechanisms underlying the oncogenic functions of FOXD3-AS1, we employed the Illumina HiSeq PE125/PE150 as a discovery platform to analyze the transcriptome profiling changes of human BE(2)-C cells in response to stable over-expression of FOXD3-AS1. The results showed that stable over-expression of FOXD3-AS1 led to altered expression of 3191 human mRNAs, including 1542 up-regulated genes and 1650 down-regulated genes. Then we found the possible roles of these differentially regulated mRNAs in selected pathways including cell cycle/proliferation, apoptosis, and cytokine/chemokine responses by Bioinformatic analysis. Furthermore, we validated the RNA-seq results by real-time RT-PCR with high identity. Overall, our results provided fundamental information about the transcriptomic changes in response to FOXD3-AS1 over-expression in human NB cells, and these findings will help us understand the pathogenesis of NB. Overall design: Total RNA of cells stably transfected with empty vector or FOXD3-AS1 was extracted using the TRIzol® reagent according to the manufacturer's instructions.RNA concentration was measured using a Qubit® RNA Assay Kit with a Qubit® 2.0 Fluorometer (Life Technologies, Inc.), and integrity was assessed using the RNA Nano 6000 Assay Kit with a Bioanalyzer 2100 system (Agilent Technologies, CA). Library preparation and transcriptome sequencing on an Illumina HiSeq 2000 platform were performed by Novogene Bioinformatics Technology Co., Ltd. (Beijing, China), and 100 bp paired-end reads were generated. HTSeq v0.6.0 was used to count the reads numbers mapped to each gene.	Co-expression
SRP120018	Gene expression analysis of human liver progenitor-like cells in culture	To compare the global expression profiles among primary human hepatocytes and liver progenitor-like cells with or without in vitro differentiation. Overall design: Human liver progenitor-like cells were derived from 3 donor and cultured in the transition and expansion medium for 4 days, 10 days, passage 5 and passage 10 or in the differentiation medium for 8 days. Primary hepatocytes were isolated using a two-step collagenase perfusion technique.	Co-expression
SRP120040	hESC-based human glial chimeric mice reveal glial differentiation defects in Huntington disease	Huntington's disease (HD) is characterized by hypomyelination as well as by neuronal loss. To assess the basis for white matter involution in HD, we generated bipotential glial progenitor cells (GPCs) from human embryonic stem cells (hESCs), derived from either huntingtin (mHTT)-mutant embryos or normal controls, and performed RNA sequence analysis to assess mHTT-dependent changes in gene expression. In hGPCs derived from 3 distinct mHTT-expressing hESC lines, a set of transcription factors associated with glial differentiation and myelin synthesis was sharply down-regulated, relative to normal hESC GPCs. In particular, NKX2.2, OLIG2, SOX10 and MYRF were all suppressed, with the consequent diminution of myelinogenesis-associated transcription. Accordingly, when mHTT-expressing hGPCs were transplanted into hypomyelinated shiverer mice, the resultant mHTT glial chimeras were hypomyelinated. The mHTT hGPCs also manifested impaired astrocytic differentiation, and developed abnormal fiber domain architecture. These data suggest that white matter involution in HD is a product of a cell-autonomous mHTT-dependent suppression of both astrocytic and oligodendrocytic differentiation by affected GPCs. Overall design: Embryonic stem cells (hESCs) derived from 3 Huntington's disease embryos (designated to HD lines 17, 18, and 20) and 2 healthy control embryos (designated to CTR lines 02 and 19) were obtained from Genea Biocells, Sydney, Australia (http://geneabiocells.com/services/shelf-products/human-embryonic-stem-cells/). The hESC lines were differentiated into glia by previously described methods (Wang et al., 2013) and further purified by FACS targeting CD140a for enriched populations of Glial Progenitor Cells (GPCs) and CD44 for enriched populations of Astrocyte Progenitor Cells (APCs). The purified glial cell populations where then used in mRNA isolation by PolyA selection and mRNA sequencing analysis. Please note that the FASTQ files in the submission were edited by Trimmomatic. The software is used to trim adapter sequences and low-quality bases (see processing steps). The overall file structure and format remained unchanged. The count matrix in the submission is as obtained directly from featureCounts tool, that is, no manipulation was performed to the count data. The data normalization was performed internally in the analysis but the raw count data were used in differential expression analysis. Please refer to the Materials and Methods section in supplementary files. Additionally, the complete workflow, including R scripts and count matrix, was deposited to https://github.com/cbtncph/HD-Glial-Differentiation-Block-Goldman-Lab-2017.	Co-expression
SRP120050	Homo sapiens strain:BCBL1 Exome	Exome sequencing to determine the causative mutations behind Rapamycin resistant clones of BCBL1-1TREX-RTA-Luc	Co-expression
SRP120056	CCDC50S deficiency effect on hepatocellular carcinoma	To assess the impact of CCDC50S on cellular signaling and functions in HCC, particularly cell proliferation and migration, we explored transcriptome pro?ling by RNA-seq in Bel-7404 cells transfected with siNC, siCCDC50S and siSRSF3.	Co-expression
SRP120122	Transcriptomic insights into human decidual and peripheral blood CD8 T cells	We performed the analysis of transcriptional and alternative splicing landscapes for paired decidual and peripheral blood CD8 T cells at the first trimester of human healthy pregnancy by high-throughput mRNA sequencing. Overall design: Healthy women at the first trimester of pregnancy were recruited, and FACS was performed to isolate and purify the CD8+ T cells from the decidua and maternal peripheral blood. We sequenced the mRNA samples on an Illumina Hiseq 2500 platform.	Co-expression
SRP120158	Targeting multiple effector pathways in pancreatic ductal adenocarcinoma with a G-quadruplex-binding small molecule	Human pancreatic ductal adenocarcinoma (PDAC) involves the dysregulation of multiple signalling pathways. A novel approach to the treatment of PDAC is described, involving the targeting of cancer genes in PDAC pathways having over-representation of G-quadruplexes, using the quadruplex-binding compound CM03. This has been designed by computer modelling, is a potent inhibitor of cell growth in PDAC cell lines and has anti-cancer activity in PDAC models, with a superior profile compared to gemcitabine, a commonly used therapy.   Whole-transcriptome RNA-seq methodology has been used to analyse for the first time the effects of a quadruplex-binding small molecule on gene expression. This has revealed the down-regulation of a large number of genes, rich in putative quadruplex elements and involved in essential pathways of PDAC survival, metastasis and drug resistance.   The changes produced by CM03 represent a global response to the complexity of human PDAC, and may be applicable to other currently hard-to-treat cancers. Overall design: 12 libraries for MIA PACA-2 cell line (6 and 24 hrs treatment with CM03 drug plus untreated control); 12 libraries for PANC-1 cell line (6 and 24 hrs treatment with CM03 drug plus untreated control); 28 libraries for MIA PACA-2 cell line (6 and 24 hrs treatment at 3 different concentrations with gemcitabine drug plus untreated control); 52 libraries for PANC-1 cell line (6 and 24 hrs treatment at 5 different concentrations with gemcitabine drug plus untreated control). Each condition has 3 or 4 biological replicates. See details below for concentration, treatment and replicates.	Co-expression
SRP120383	Identification of the networks that regulate human monocytic myeloid-derived suppressor cell differentiation into inflammatory macrophages	Background: Monocytic myeloid-derived suppressor cells (mMDSC) support immune evasion of tumors by blocking tumoricidal T and NK cell response. Efforts to reverse mMDSC-mediated immunosuppression identified that the TLR7/8 agonist R848 induces their maturation into tumoricidal macrophages Purpose: The factors that determine whether human mMDSC differentiate into MACinflam or MACsuppress are unclear. To investigate this issue, the role of cytokines and genes activated following R848 treatment was examined. Methods: After 4 hour stimulation, cells from stimulated mMDSC were stored in RNA protect (Qiagen, Frederick, MD).  Total RNA was isolated using the RNeasy micro kit (Qiagen) and RNA quality was assessed using an Agilent 2200 TapeStation. mRNA libraries were generated using the Smart-Seq ultra-low input kit (Clontech) and sequenced using a HiSeq2500 sequencer using IlluminaTruSeq v4 chemistry with 125bp paired-end reads. Sequences were aligned to the human (hg19) reference genome. Genes that were differentially expressed compared to untreated samples were identified using CLC genomics workbench (version 10). Results: TNFa combined with IL-6 effectively supports the differentiation of mMDSC into tumoricidal macrophage by activating expression of conserved set of genes. Mechanistically, transcription factors NF-KB and STAT4 emerge as important regulators and potential targets to modify mMDSC behavior. Overall design: Blood was received from human donors, FACS sorted for MDSC cells and then cultured with IFNg,  R848 or Il6-TNFa for 4 hours.  Rna was collected and mRNA libraries were generated using the Smart-Seq ultra-low input kit (Clontech) and sequenced using a HiSeq2500 sequencer using IlluminaTruSeq v4 chemistry with 125bp paired-end reads. Sequences were aligned to the human (hg19) reference genome. Genes that were differentially expressed compared to untreated samples were identified using CLC genomics workbench (version 10)	Co-expression
SRP120476	Bone marrow-derived and dental pulp-derived human mesenchymal stem cell RNA-Seq	Lineage commitment and tumorigenesis specify adult stem cells from different tissues or organs. To gain insight into the mechanism of this programming, phenotypic, functional and transcriptome analyses were performed in mesenchymal stem cells derived from human dental pulp (DPSCs) and bone marrow (BMSCs). DPSCs and BMSCs had similar morphologies and flow cytometric profiles, and were capable of tri-lineage differentiation into osteoblast, adipocyte and chondocyte. However, compared with BMSCs, DPSCs increased in osteogenic potential, decreased in adipogenic potential, and formed dentin-pulp-like complexes in vivo. Genome-wide RNA-seq and differential expression analysis revealed that signalings such as, phosphatase and tensin homolog (PTEN)/PI3K/AKT pathway, and cancer-related pathway were different in both cells. Differential PTEN expression, higher in DPSCs than BMSCs, was responsible for the lineage commitment and tumorigenesis differences in both cells. Besides, BMSCs decreased in PTEN DNA methylation compared to DPSCs, which was mediated by increased DNA (cytosine-5) methyltransferase 3B (DNMT3B) expression. Furthermore, histone methyltransferase G9a mediated repressive epigenetic mark H3K9Me2 was selectively enriched in BMSCs. Moreover, DPSCs were more resistant to oncogenic transformation than BMSCs. To link lineage commitment with tumorigenesis, we demonstrated that DPSCs were more resistant to oncogenic transformation than BMSCs and PTEN deficiency increased the sensitivity of DPSCs for tumorigenic transformation. The results help understanding the roles of the epigenetic factors in lineage commitment and tumorigenesis and also for therapeutic uses of adult stem cells. Overall design: RNA-Seq of bone marrow-derived and dental pulp-derived mesenchymal stem cells with 3 biological replicates	Co-expression
SRP120487	Trnascriptome analysis of HeLa cells infected with rTHOV-wt, -dML, -SW mutant or mock-treated	The goal of the study was to compare transcriptome changes in HeLa cells after infection with recombinant Thogoto virus (wild-type, ML deletioin mutant or ML SW mutant not able to interact wiith TFIIB. While wild-type virus is able to inhibit inflammatory genes, ML deletion mutant and TFIIB-non-interacting mutant lose this effect on gene transcription. Overall design: Examination of transcriptome changes in HeLa cells under steady state or after THOV infection using Illumina HiSeq.	Co-expression
SRP120496	Glutaminolysis is a metabolic dependency in FLT3 ITD Acute Myeloid Leukemia unmasked by FLT3 Tyrosine Kinase Inhibition	FLT3ITD are common mutations in Acute Myeloid Leukemia (AML) and carry a particularly bad prognosis. Although new generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3-mutated AML patients remains poor and demands the identification of novel, specific and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide CRISPR/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3 TKI treatment. Using complementary metabolomic and gene-expression analysis, we demonstrate that glutamine metabolism, through its ability to support both mitochondrial function and cellular redox metabolism, becomes a metabolic dependency of FLT3ITD AML, specifically unmasked by FLT3-TKI treatment. We extend these findings to AML subtypes driven by other tyrosine kinase activating mutations, and validate the role of GLS as a clinically actionable therapeutic target in both primary AML and in vivo models. Our work highlights the role of metabolic adaptations as a resistance mechanism to several TKI inhibitors, and suggests glutaminolysis as a therapeutically targetable vulnerability when combined with specific TKI in FLT3ITD and other TK activating mutation driven leukemias. Overall design: Gene expression analysis by RNA-Seq of FLT3ITD mutant cell lines MV411 and MOLM13 treated with AC220 1nM vs vehicle control and of BCR-ABL mutated K562 cells treated with Imatinib 2uM vs vehicle control.	Co-expression
SRP120552	Aligning single-cell developmental and reprogramming trajectories identifies molecular determinants of reprogramming outcome	Cellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy, as well as for expanding our understanding of the general principles of gene regulation. MYOD-mediated myogenic reprogramming, which converts many cell types into contractile myotubes, remains one of the best characterized model system for direct conversion by defined factors. However, why MYOD can efficiently convert some cell types into myotubes but not others remains poorly understood. Here, we analyze MYOD-mediated reprogramming of human fibroblasts at pseudotemporal resolution using single-cell RNA-Seq. Successfully reprogrammed cells navigate a trajectory with two branches that correspond to two barriers to reprogramming, with cells that select incorrect branches terminating at aberrant or incomplete reprogramming outcomes. Differential analysis of the major branch points alongside alignment of the successful reprogramming path to a primary myoblast trajectory revealed Insulin and BMP signaling as crucial molecular determinants of an individual cell's reprogramming outcome, that when appropriately modulated, increased efficiency more than five-fold. Our single-cell analysis reveals that MYOD is sufficient to reprogram cells only when the extracellular milieu is favorable, supporting MYOD with upstream signaling pathways that drive normal myogenesis in development. Overall design: scRNA-seq experiment for MYOD-mediated human fibroblasts reprogramming. HSMM derivation, expansion and differentiation was as previously described (Trapnell et al., 2014). Foreskin Human Fibroblasts obtained from commercial vendor (Stemgent) were expanded in alpha-mem supplemented with glutamax, 10% FBS and 16ng/ul of FGF-b (ThermoFisher Scientific). The fibroblasts were then infected with a mixture of lentiviruses encoding hTERT (and Puromycin resistance gene), Tetracycline Repressor (and Geneticin resistance gene) and TR-controlled hMYOD (and Blasticidin resistance gene) (ThermoFisher Scientific). All the resistance genes are constitutively expressed and therefore triple selection was performed and maintained using 1ug/ml of Puromycin, 500ug/ml of Geneticin and 2ug/ml of Blasticidin to generate the hFib-MYOD line.   To perform reprogramming and differentiation experiments HSMM and hFib-MYOD cells were plated in 24-well formats at a density of 50.000 cells per well. Gelatin was sometime used as a coating agent with no significant difference with respect to uncoated dishes. Differentiation and reprogramming was induced using a differentiation media containing alpha-mem supplemented with glutamax and 2% HS (ThermoFisher Scientific), supplemented with 2ug/ml of doxycycline to enact MYOD expression. When indicated, Insulin was used at 8ug/ml (ThermoFisher Scientific), BMP inhibitor LDN-193189 was used at 0.1uM (Stemgent), LSD1 inhibitor RN-1 was used at 1uM (EMD Millipore). At the indicated time points, cells were harvested by gentle dissociation using TrypLE (ThermoFisher Scientific) and processed for full-length transcriptome sequencing using the Fluidigm C1 Single Cell or bulk mRNA sequencing as previously described (Trapnell et al., 2014). Cells were loaded onto the microfluidic chip at a concentration of ~250 cells/µl to maximize the number of single cells captured and minimize the occurrence of doublets. In some instances, cells were reloaded if the majority of capture sites were not occupied on the first attempt. As in Trapnell et al, 2014, captured cells were scored by manual on-chip microscopic inspection to determine if they were singletons and free of other debris.	Co-expression
SRP120559	Expression analysis of THP1 cells following shRNA knock-down of RUVBL2	We used an inducible shRNA system and RNA-Seq to examine gene expression changes in acute myeloid leukemia THP1 cells following silencing of RUVBL2. RUVBL2 is a AAA+ ATPase that functions in a number of cellular processes, including chromatin remodeling and trnascriptional control, and is critical for survival of acute myeloid leukemia cells and in vivo disease progression. Overall design: Total cellular RNA was extracted using the RNeasy Plus Mini Kit from THP1 cells transduced with RUVBL2-specific inducible shRNA, following 4 days exposure to doxycycline or medium controls. In total, 5 pairs of control and doxycycline-treated samples were analysed.	Co-expression
SRP120600	Uridilation by TUT4/7 restricts retrotransposition of human Line-1s	Purpose: the goal of this study was to test whether the amounts of genome-encoded Line-1s are influenced by TUTases and Mov10 Methods: RNA-Seq data were obtained for PA-1 or Hek293 Flp-IN T-Rex cells in which wild-type or mutant TUTases or Mov10 were overexpressed or the proteins were depleted by RNA interference Results: Minor changes (less than 0.4-fold) were observed in the amounts of mRNAs of Homo sapiens-specific Line-1 families in Hek293 Flp-IN T-Rex and PA-1 either overexpressing or depleted of TUTases and Mov10 Overall design: LINE-1 repetitive elements profiles of Hek293 Flp-IN T-Rex and PA-1 generated by deep sequencing, in triplicate, using Illumina NextSeq 500 and Illumina HiSeq 2500.	Co-expression
SRP120604	ICE1 promotes the link between splicing and nonsense-mediated mRNA decay	Identification of RNAs differentially expressed during depletion of ICE1, UPF1 or a non-targeting control (NS) in HEK-293TO cells. Overall design: Paired-end high throughput RNA sequencing on 293 cells treated with siRNA against ICE1, UPF1 or a non-targeting control (NS).	Co-expression
SRP120630	APT1 regulates the asymmetric partitioning of Notch and Wnt signaling during cell division	Asymmetric cell division results in two distinctly fated daughter cells to generate cellular diversity. A major molecular hallmark of an asymmetric division is the unequal partitioning of cell-fate determinant proteins.  We have previously established that growth factor signaling promotes protein depalmitoylation to foster polarized protein localization, which in turns drives migration and metastasis. Here, we report protein palmitoylation as a key mechanism for the asymmetric partitioning of the cell-fate determinants Numb (Notch antagonist) and ß-catenin (canonical Wnt regulator) through the activity of a depalmitoylating enzyme, APT1. Using point mutants, we show specific palmitoylated residues on proteins, such as Numb, are required for asymmetric localization. Furthermore, by live-cell imaging, we show that reciprocal interactions between APT1 and CDC42 regulate the asymmetric localization of Numb and ß-catenin to the plasma membrane. This in turn restricts Notch and Wnt transcriptional activity to one daughter cell.  Moreover, we show altering APT1 expression changes the transcriptional signatures to those resembling that of Notch and ß-catenin in MDA-MB-231 cells.  We also show loss of APT1 depletes the population of CD44+/CD24lo/ALDH+ tumorigenic cells in colony formation assays. Together, the findings of this study demonstrate that palmitoylation, via APT1, is a major mechanism of asymmetric cell division regulating Notch and Wnt-associated protein dynamics, gene expression, and cellular functions. Overall design: Gene expression by RNAseq of MDA-MB-231 triple receptor negative breast cancer cells expressing scramble control vector, shAPT1 knockdown, and APT1wt performed in triplicate. Total of 9 samples were analyzed.	Co-expression
SRP120966	Transcriptional change of HTR8/Svneo cells over expressed with PLAC8-EGFP	The goal of this this project was to study the transcriptional change when PLAC8-EGFP was over expressed in the trophoblast cell line, HTR8/Svneo. Overall design: HTR8/Svneo cells which were stably over expressed with PLAC8-EGFP and EGFP were established.Then trancriptional sequencing experiment was performed to explore the effect of PLAC8 on trophoblast cells.	Co-expression
SRP120979	T47D RNA-seq and ChrRNA-seq data	We performed genome-wide RNA-seq and ChrRNA-seq experiments in T47D cell lines  after PADI2 knock down . Both the mRNA and  chromatin RNA seq  peformed in sicontrol  and siPADI2  as in biological replicates . Also we performed  mRNA seq in T47D cells expressing HA Tagged amanitin resistant wild type in comparison to R1810A mutant form of RNAP2. Overall design: We designed experiment to perform   mRNA  sequencing in T47D after PADI2 knock down as in biological replicate experiemnt .  Given the fact we found significant number of genes differentailly expressed after PADI2 knockdown in T47D cells, we designed to perform Chromatin RNA seq in  T47D cells after PADI2 knock down as in biological replicates.  We find that PADI2 deiminates R1810 at CTD (C-terminal domian)  of RNAP2 , So in order to analyse the mRNA  gene expression level in T47D cells expressing amanitin resistant  HA - tagged wild type and mutant form of RNAP2 , we performed mRNA seq as in biological replicate in T47D cells expressing   amanitin resistant  HA - tagged wild type and mutant form of RNAP2.	Co-expression
SRP121007	Oncogenic Role of THOR, a Conserved Cancer/Testis Long Noncoding RNA	Large scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer/testis lncRNAs whose structure and function have undergone positive evolutionary selection.	Co-expression
SRP121075	Homo sapiens Transcriptome or Gene expression	Individual CD27+ CD38+ individual human B cells were analyze with a new RNAseq protocol that captures the 5'' end of transcripts	Co-expression
SRP121331	Stromal Mir-20a modulates paracrine CXCL8 secretion in colitis and colon cancer	We report the results of RNA-Seq on fibroblasts cultivated from cancerous, colitic and normal primary patient colon tissues Overall design: Transcriptome analysis of fibroblasts isolated from cancerous/colitic and normal primary tissues.	Co-expression
SRP121350	Single-Cell Transcriptome Analysis Maps the Developmental Track of the Human Heart	The heart is the central organ of the circulatory system, and its proper development is vital for maintaining human life. Here we used single-cell RNA-sequencing to profile the gene expression landscapes of ~4,000 cardiac cells from human embryos and identified four major types of cells: cardiomyocytes (CMs), cardiac fibroblasts, endothelial cells (EC) and valvar interstitial cells (VICs). During heart development, atrial and ventricular CMs acquired distinct features early in development. Furthermore, both CMs and fibroblasts show stepwise changes in gene expression. As development proceeds, VICs might be involved in the remodeling phase, and ECs display location-specific characteristics. Finally, we compared gene expression profiles between human and mouse and identified a serial of unique features of human heart development. Our study lays the groundwork for elucidating the mechanisms of in vivo human cardiac development and provides potential clues to understand cardiac regeneration. Overall design: single cell RNA seq data set 1: 77 samples single cell RNA seq data set 2: 21 samples	Co-expression
SRP121445	a Cell Function and Gene Expression Are Compromised in Type 1 Diabetes	Many patients with type 1 diabetes (T1D) have residual beta cells producing small amounts of C-peptide long after disease onset, but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual beta cells and alpha cells persisting in the islet endocrine compartment are largely unknown due to difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced and these cells had alterations in transcription factors constituting and alpha and beta cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of alpha-to-beta cell conversion. These results suggest a new explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia. Overall design: Total of 8 samples were analyzed, 5 were non-diabetic control donors and 3 were T1D donors. a cells were FACS-sorted and RNA was extracted from each of these samples. RNAseq was performed on all 8 samples	Co-expression
SRP121466	Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and TWIST1 knock out U87 xenograft mice transcriptomes	Purpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.	Co-expression
SRP121474	Polyol pathway links glucose metabolism to the aggressiveness of cancer cells	Cancer cells alter their metabolism to support their malignant properties. By transcriptomic analysis we identified the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) as strongly correlated with epithelial-to-mesenchymal transition (EMT). This association was confirmed staining samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing profiling confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGF-Beta signature genes. Mechanistically, excess glucose was found to promote EMT through autocrine TGF-Beta stimulation, while PP-deficient cells were refractory to glucose-induced EMT. PP represents a molecular link between glucose metabolism and cancer differentiation and aggressiveness, and a novel potential therapeutic target. Overall design: 3x3 biological replicated samples; 2 groups of samples with shRNA-mediated specific gene inhibition and scrambled control cells	Co-expression
SRP121475	RNA-seq analysis of umbilical cord blood cells upon knockdown of NAP1L3	The nucleosome assembly proteins (NAPs) are histone chaperones with an important role epigenetic regulation of gene expression. We find that high gene expression levels of murine Nap1l3 is restricted to hematopoietic stem cells. Loss of function of murine and human NAP1L3 impair maintenance of  hematopoietic stem cells and differentiation both in vitro and in vivo. NAP1L3 inhibition in human hematopoietic cells causes a growth arrest in the G0 phase of cycle progression, and induces gene expression signatures that highly significantly correlate with downregulation of genes involved in cell cycle regulation, including E2F and MYC target genes. In addition, we also show that the HOXA3, HOXA5, HOXA6 and HOXA9 are markedly upregulated when NAP1L3 is suppressed in Human hematopoietic cells. Taken together, our findings establish an important role for NAP1L3 in HSC homeostasis and hematopoietic differentiation. Overall design: Umbilical cord blood cells were transduced with shRNA targeting NAP1L3 or negative control vectors and RNA was isolated for RNA-seq analysis 72hour post transduction.	Co-expression
SRP121624	Transcriptomic data of MDA-MB-231 cells adapted to culture in media containing different sugars (glucose or fructose) and cultured as mammospheres	We report the single-cell RNA sequencing data obtained from MDA-MB-231 breast cancer cells cultured in standard DMEM with 25 mM glucose, or adapted to culture in DMEM with 10 mM fructose to reduce glycolysis, and then cultured as mammospheres Overall design: Examination of transcriptomic changes in MDA-MB-231 breast cancer cells mammospheres in response to restriction of glycolysis	Co-expression
SRP121666	Peripheral whole blood mRNAs and lncRNAs expression analysis in eosinophilic asthmatics	Long non-coding RNA (lncRNA) plays roles in many diseases including asthma. Several lncRNAs function in the early differentiation of T-helper cells. lncRNA controls gene transcription, protein expression and epigenetic regulation; As one of the four asthma phenotypes, eosinophilic asthma(EA) occupies the largest proportion in asthma patients; However, lncRNA associated with eosinophilic asthma have not to be identified so far.   We designed the study to identify the circulating lncRNA signature in EA samples. We tested whether any significant changes in lncRNA expression was observed in EA and healthy people (Control) sample' blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed through lncRNA-mRNA co-expression network. lncRNA expression was measured by means of microarray, quantitative real-time PCR.   A total of 41 dysregulated lncRNAs and 271 dysregulated mRNAs (difference =2-fold) were found in EA compared to Control samples. GO terms and KEGG pathway annotation data revealed that several lncRNA were significantly associated with EA. By qRT-PCR, lncRNA is confirmed significantly expression between EA and control samples.   The results presented here show several lncRNA may take part in the immune process of EA. Whether these lncRNA can be used as biomarkers need to be further study in future trials Overall design: The eosinophilic asthmatics (EA n=9) are included according the accepted standard (induced sputum eosinophil counts >3% and neutrophil<63%)1. Exclusion criteria included recent (past month) respiratory tract infection, recent asthma exacerbation, recent unstable asthma or change in maintenance therapy and current smoking (or past smoking within 6 months of cessation).All of the patients were selected from People's Liberation Army General Hospital. EA samples were subdivided into high expression IgE group (EAH n=6) and low expression IgE group (EAL n=3). Healthy people were selected as Control samples (n=3). The clinical data are provided for individual samples in Table 1. This study was approved by the Ethics Committee of the People's Liberation Army General Hospital. Informed consent was obtained from each donor. The results presented here show several lncRNA may take part in the immune process of EA. Whether these lncRNA can be used as biomarkers need to be further study in future trials.	Co-expression
SRP121791	Human embryonic stem cell, chimpanzee induced pluripotent stem cell, orangutan induced pluripotent stem cell, rhesus embryonic stem cell, and their derived cortical organoid RNA-seq	We compared a 5 week time course of cortical organoid differentiation across human, chimpanzee, orangutan, and rhesus using bulk RNAseq. In addition, single cell RNAseq was performed on a subset of time points from human cells in weeks 0, 1, 2, and 5. Overall design: Bulk RNAseq of hESCs, ch-iPSCs, or-iPSCs, rhESCs, and each of 6 time points corresponding to weeks 0, 1, 2, 3, 4, and 5 during cortical organoid differentiation. Single cell RNAseq of human ESCs, week 1, week 2, and week 5 organoids.	Co-expression
SRP121799	Stable oxidative cytosine modifications accumulate in cardiac mesenchymal cells from Type2 diabetes patients: rescue by alpha-ketoglutarate and TET-TDG functional reactivation [human cells RNA-seq]	Background: Here, the role of a-ketoglutarate (aKG) in the epi-metabolic control of DNA demethylation has been investigated in therapeutically relevant cardiac mesenchymal cells (CMSCs) isolated from controls and type 2 diabetes donors. Methods & results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs). Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high fat diet (HFD), injected with streptozotocin (STZ) or both in combination (STZ-HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of aKG synthesis in D-CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised thymine DNA glycosylase (TDG) and ten eleven translocation protein 1 (TET1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that aKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatched or 5fC. Accordingly, an exogenous source of aKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5fC accumulation thus partially mimicking the diabetic epigenetic landscape in cells of non- diabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of aKG-dehydrogenase, increased the aKG level in D- CMSCs and in the heart of HFD mice eliciting DNA demethylation, glucose uptake and insulin response. Conclusions: In this report we established that diabetes may epigenetically modify and compromise function of therapeutically relevant cardiac mesenchymal cells. Restoring the epi-metabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes. Overall design: Human primary cardiac mesenchymal cells (CMSC) from 7 diabetic (D) and 7 non-diabetic (ND) donors were analyzed after few rounds of ex vivo expansion. RNA was isolated and sequenced.	Co-expression
SRP122496	Transcriptome profiling of A2M treated A549 Cell Line Samples	The goal of the study was to identify changes in transcriptome expressions upon treatment of A549 cell line samples with activated A2M. Overall design: Sixteen A549 cell cultures divided into eight pairs were prepared. Each pair consisting of one A2M* treated and one untreated culture. Five samples could not be adequately quantified and subsequently needed to be excluded from downstream sequencing.	Co-expression
SRP122507	Leucegene: AML sequencing (part 6)	RNA-sequencing of human acute promyelocytic leukemias Overall design: The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer.	Co-expression
SRP122516	Whole transcriptomic sequencing of CD133+CD44+ cancer stem cells from laryngeal squamous carcinoma cell line	To understand the gene expression profiling of cancer stem cells of laryngeal squamous carcinoma, the total RNA of CD133+CD44+ laryngeal cancer stem cells (isolated from LSCC cell line TU-177, named TDP), CD133-CD44- cells (TDN) and parental TU-177 (unsorted TU-177 cells, named TPT) was extracted, followed by RNA sequencing. Differentially expression of lncRNA, mRNA, and circRNA was identified. Overall design: The CD133+CD44+ cells (TDP) and CD133-CD44- cells (TDN) were isolated from TU-177 cells and cultured. Total RNA was extracted using TRizol reagent (Invitrogen, Carlsbad, CA) following the manufacturer's instruction, followed by DNase I treatment to remove DNA contamination. Equal quantities of RNA from 3 samples in one group were mixed. The lncRNA library (including lncRNA, mRNA, and circRNA) was prepared. The library products were finally sequenced on Illumina HiSeq 2000 platform.	Co-expression
SRP122528	Obesity Weight Loss Study	RNA Sequencing of human adipose tissue before and after diet-induced weight loss Overall design: Prospective cohort study https://academic.oup.com/jes/article/1/6/625/3754346/Effects-of-Rapid-Weight-Loss-on-Systemic-and?searchresult=1	Co-expression
SRP122534	Induced MIST1 and PTF1a Expression in Pancreatic Ductal Adenocarcinoma Cells	Purpose: The goal of the study was to determine the effects of forced expression of the acinar transcription factors MIST1 and PTF1a in PDAC cells. Methods: Doxycycline inducible MIST1myc and PTF1amyc Panc-1 cells were generated using Clontech's Tetone System and subjected to RNA-Sequencing following doxycycline treatment. Results: 50 million sequence reads were mapped to the human genome. Data suggests acinar associated molecules were induced upon doxycyline treatment. Conclusions: MIST1 and PTF1a retain functional activity and can promote acinar gene expression in the context of pancreatic cancer cells. Overall design: Panc-1 tet-inducible MIST1 and PTF1a cells were treated in the absence or presence  of 1 µg/ml doxycycyline for 72 hours.	Co-expression
SRP122540	Effects on gene expression of doxorubicin in human stem cells-derived cardiomyocytes	To gain into the molecular mechanisms and pathways involved in doxorubicin induced cardiotoxicity, we performed whole genome transcriptome profiling via RNA-seq in hESCs-derived CMs treated with doxorubicin or vehicle only control. Cells were treated with 0, 1 or 2.5 µM of doxorubicin for 16 hours and RNA was isolated for high throughput sequencing Overall design: To identify genes that are significantly regulated by doxorubicin treatment, we analyzed read count data from RNA-seq using edgeR software. We also performed KEGG pathway analysis and GO analysis	Co-expression
SRP122876	Extrachromosomal circular DNA and RNA sequencing of 16 healthy men	We purified and sequenced eccDNA from muscle and blood of 16 healthy men, detecting 170,000 eccDNAs from 16 million nuclei, covering 13% of the human genome. Furthermore, in order to assess if eccDNA correlates with gene expression we extracted and sequenced total RNA from muscle tissue of the 16 healthy men.	Co-expression
SRP122898	Human Sandhoff Disease Cerebral Organoids Exhibit Enlarged Size, Increased Cellular Proliferation, and Impaired Differentiation	Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of b-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells with CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids but not the HEXB-corrected organoids accumulated GM2 ganglioside, and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses Overall design: Sandhoff disease and corrected cerebral organoids grown for 8 and 10 weeks were analyzed: four samples at each time point, each consisting of 4–6 pooled organoids, for both Sandhoff and corrected. Whole transcriptome from Sandhoff disease and corrected organoids for both time points were generated by deep sequencing on an Illumina HiSeq 2500.	Co-expression
SRP122939	Gene expression profiling study by RNA-seq in PDX model based diffuse type gastric cancers.	We established PDX lines from diffuse type gastric cancers (DGCs). Using these cells, we carried out RNA-seq based transcriptome profiling using 15 stomach samples including three PDX lines (HGC-3, HGC-8, and HGC-20) and normal-looking surrounding tissues. Via comparative analysis between cells and tissues, we identified significant gene set associated with each cell and observed that genes involved in AKT signalling pathway were commonly associated with all PDX lines. Overall design: RNA-seq data of 15 gastric samples were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x75 bp) using Hiseq-2500 (Illumina).	Co-expression
SRP122941	Transcriptional changes in pancreatic cancer cells associated with gemcitabine resistance	The goal of this study was to determine the transcriptional changes in pancreatic cancer cells after treatment with gemcitabine. Overall design: HPAFII cells were treated with PBS or Gemcitabine for 72 hours. RNA was harvested from 3 independent, experimental replicates per treatment group.	Co-expression
SRP123057	Mitochondrial levels globally modulate gene expression	Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Cell-to-cell differences in mitochondrial content, probably originated by asymmetric segregation at cell division, contribute to heterogeneity in gene products.	Co-expression
SRP123065	Cooperation of GRSF1 and the mitochondrial degradosome (hSuv3-PNPase complex) in degradation of mitochondrial RNA	Vertebrate mitochondrial genomes show extraordinary GC skew which results in the synthesis of RNAs prone to form G-quadruplexes (G4). Such RNAs, although mostly non-coding, are transcribed at high rate and swiftly degraded by an unknown mechanism. Comprehensive proteomic and transcriptomic approaches revealed that quasi-RRM protein GRSF1 together with the mitochondrial degradosome composed of RNA helicase hSuv3 and PNPase control the levels of G4 containing RNAs in mitochondria. When this machinery is inactivated non-coding mtRNAs are upregulated and novel, previously undescribed transcript, which we named tRNA-like, strongly accumulates. In vitro reconstitution experiments showed that GRSF is responsible for G4 RNA melting essential for degradosome-mediated decay. Overall design: There are 2 sets of data which correspond to two RNAseq studies (degradosome set and GRSF1 set). Each set includes experiments which were performed in triplicates. The aim of the first studies was to analyze the effect of inactivation of the mitochondrial degradosome components (hSuv3, PNPase) on mitochondrial RNA (mtRNA). In the second studies we examined influence of GRSF1 silencing of mtRNA. In both cases we analyzed long transcripts and small RNAs. Strand-specific library preparation procedures were applied. Ligation-based approach was used to analyze short RNAs (from ~20 to ~200 nucleotides) whereas longer RNAs (> ~100 nucleotides) were analyzed after their random fragmentation followed by reverse transcription primed with random oligomers (dUTP-based protocol). RNA was isolated from unfractionated cells using TRI-Reagent. Before preparation of long transcripts libraries total RNA was subjected to rRNA depletion. This step was omitted in preparation of libraries dedicated for analysis of short RNAs. Total RNA was used for preparation of small RNA libraries. Libraries from different studies (degradosome and GRSF1) were sequenced with the help of different Illumina sequencing platforms. Dysfunction of hSuv3 was achieved by inducible expression of its dominant-negative mutant form (hSuv3-G207V), which we shown to be equivalent to hSuv3 silencing (PMID: 19864255), whereas PNPase or GRSF1 were depleted by siRNA transient transfections. In the case of GRSF1 studies as controls we analyzed untreated cells and cells transfected with non-targeting siRNA. In the case of degradosome studies as controls we analyzed untreated cells and cells expressing siRNA-insensitive version of PNPase (rescue experiment).	Co-expression
SRP123293	Mutational landscape of aggressive natural killer-cell leukemia and drug profiling highlight JAK-STAT signaling as a therapeutic target in NK-cell malignancies	Cell lines derived from NK cell neoplasms were characterized using RNA sequencing and high-throughput drug sensitivity profiling to identify therapeutically actionable drivers in malignant NK cells. Overall design: RNA sequencing data was obtained from natural killer and T cell lines for gene expression profiling and mutation detection in parallel with drug sensitivity profiling. The ''NK_cell_line_GEO_drug_sensitivity.txt'' contains drug sensitivity scores of cell lines screened using 459 compounds. Breifly, compounds were preprinted on 384-well plates (Corning) in five different concentrations covering a 10,000-fold concentration range with an acoustic liquid handling device (Echo 550, Labcyte Inc.) and dissolved in 5   l culture medium on a shaker for 10 min. 20   l of single-cell suspension of cell lines (3,000 cells per well) were dispensed using Multi-Drop Combi peristaltic dispenser (Thermo Scientific). Plates were incubated at 37   C and 5% CO2 for 72 h after which cell viability was measured using CellTiter-Glo 2.0 reagent (Promega) according to the manufacturer   s instructions with a Pherastar FS plate reader (BMG Labtech). Cell viability luminescence data were normalized to DMSO-only wells (negative control) and 100 mM benzethonium chloride-containing wells (positive control). The data were quantified using the drug sensitivity score (DSS) (Yadav et al., Scientific Reports 2014).	Co-expression
SRP123294	RNA-seq analysis of THP-1 cell line upon knockdown of CHD4	Epigenetic alterations contribute to leukemogenesis in childhood acute myeloid leukemia (AML). We used RNAi screens of AML cells together with non-transformed bone marrow cells and identified CHD4 as being required for AML maintenance. RNAi and CRISPR-Cas9 approaches, showed that CHD4 is essential for cell growth of leukemic cells in vitro, and disease progression in vivo, including primary childhood AML cells. Loss of function of CHD4 arrests AML cells in the G0 phase of the cell cycle, which is associated with downregulation of MYC and its target genes. Conversely, CHD4 suppression is not essential for normal blood cells. Taken together, our results identify CHD4 as a potential therapeutic target in childhood AML. Overall design: THP-1 cell line were trasnduced with shRNA targeting CHD4 or negative control vectors and RNA was isolated for RNA-seq analysis 72hour post transduction.	Co-expression
SRP123295	Determining mRNA half-lives on a transcriptome-wide scale	Translation and mRNA decay are intimately connected processes, and translational inhibition often precedes and stimulates transcript degradation. Here, we have focused on methods that allow determination of mRNA stability on a transcriptome-wide scale. We describe experimental and computational methods for the two most commonly used approaches (transcriptional inhibition and metabolic labeling), and we discuss associated caveats. Overall design: Metabolic labeling time courses (1, 2, 4, 8, 12, 24 hr) using 4SU were performed in HEK293.	Co-expression
SRP123359	Human lymph nodes maintain a unique subset of resident memory T cells with high functional potential important for protective immunity and immunotherapies	Tissue resident memory T cells (TRM) predominate in barrier sites and mediate protective immunity, while their role in lymphoid tissues is undefined. Here we analyzed memory CD8+ T cells in different lymphoid compartments including bone marrow, spleen, and lymph nodes (LN) relative to lung within diverse individuals. We identify an organ-specific subset in human LN (TLN) not found in blood or other tissues, expressing high levels of TCF-1 and transcriptionally enriched for markers of quiescence, self-renewal and follicular-helper cells. High dimensional CyTOF analysis reveals TLN as intermediate in differentiation between naive and TRM cells, with circulating memory T cells the most differentiated. TLN exhibit higher TCR diversity, lower in vivo turnover, yet higher proliferative responses compared to memory cells in other lymphoid or mucosal sites. These findings establish human LN as reservoirs for diverse memory T cells poised for high expansion and TLN as important targets for in vivo immunotherapies. Overall design: Here we did RNA-sequencing of T cell subsets isolated from human tissues. We isolated memory T cells (CD3+CD4-CD8+CD45RO+) that were either CD69+ or CD69- from either bone marrow or lymph nodes from the same individual and isolated RNA for RNA-seq. We did this from three different individuals, totaling 12 samples (2 from bone marrow (CD69 pos and neg) and 2 from lymph nodes(CD69 pos and neg) of three individuals). All RNA-seq samples were sequenced in the same batch.	Co-expression
SRP123587	Odorant Receptors in Human RPE Cells	The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments suggest a potential role of OR51E2 in controlling Ca2+ homeostasis in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, extracellular-signal-regulated kinases 1/2 and protein kinase B. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand ß-ionone. These findings suggest that the involvement of OR51E2 in RPE development and the regulation of cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.	Co-expression
SRP123588	RNA-seq of MCF10A cells stably expressing empty vector, GFP, miR-105, or MYC	To identify gene expression changes associated with overexpression of miR-105 or MYC in MCF10A non-cancerous human mammary epithelial cells, we analyzed RNA isolated from engineered MCF10A cell lines that stably express empty vector, GFP, miR-105, or MYC by RNA-seq.  Gene expression in cells overexpressing miR-105 or MYC was compared to cells expressing the empty vector or GFP, both of which served as controls in this experiment. Overall design: RNA was extracted from MCF10A cells stably expressing pBabe vector, pBabe-GFP, pBabe-miR-105, or pBabe-MYC; RNA was then subjected to library construction and RNA sequencing.	Co-expression
SRP123589	RNA-seq of cancer-associated fibroblasts (CAF) treated with PBS or extracellular vesicles (EV) from MCF10A or MDA-MB-231 cells	To identify gene expression changes associated with treatment of EV that carry high levels of miR-105 (from MDA-MB-231 and MCF10A/miR-105 cells) in human breast tumor derived CAF, we analyzed RNA isolated from PBS- or EV-treated CAF.  Gene expression in CAF treated with EV from MDA-MB-231 or MCF10A/miR-105 cells was compared to cells treated with PBS or EV from MCF10A cells, both of which served as controls in this experiment. Overall design: RNA was extracted from PBS- and EV-treated CAF, and subjected to library construction and RNA sequencing.	Co-expression
SRP123594	Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis	Spermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscape and underlying molecular signals during human spermatogenesis remain unknown. Here, we examined human spermatogenesis using transcriptome-wide single-cell RNA sequencing of 2,854 individual testicular cells from donors with normal spermatogenesis (donors with normal fertility or OA) and 174 testicular cells from one donor diagnosed as having nonobstructive azoospermia (NOA). Systematic bioinformatics analyses enabled us to delineate the full developmental trajectories of human spermatogenesis. A hierarchical model was established, which was characterized by the sequential and step-wise development of three spermatogonia subtypes, seven spermatocyte subtypes, and four spermatid subtypes. Furthermore, we recapitulated key hallmarks of human spermatogenesis at the single-cell level, including spermatogonial development, mitosis-to-meiosis transition, meiotic recombination, meiotic sex chromosome inactivation, and histone-to-protamine exchange. Remarkably, BMPR1B and FGFR3 were identified as novel markers of human spermatogonial stem cells, indicating the potentially critical role of BMP and FGF signaling pathways for SSC maintenance. Further analysis identified several novel marker genes of specific cell type such as HMGA1, PIWIL4, TEX29, SCML1, and CCDC112, the expression patterns of which were confirmed via RNA FISH or immunostaining. We also demonstrated that scRNA-seq provided a platform to find differentially expressed genes correlated with one type of nonobstructive azoospermia (NOA) at the genome-wide transcriptional profiling level, which might pave way for further diagnosis and dissecting the underlying mechanisms of male infertility. Our work allows for the reconstruction of transcriptional programs inherent to sequential cell fate transition during human spermatogenesis and has implications for deciphering male-related reproductive disorders. Overall design: Here we performed scRNA sequencing for 2,854 individual human testicular cells including spermatogonia, spermatocytes, spermatids, and testicular somatic cells (soma) from donors with normal fertility and obstructive azoospermia.Besides, another 174 human testicular cells from one NOA male were included as an example of infertilty. Some samples were sorted by FACS based on preliminary ploidy. These samples include "1N", "2N", or "4N" in the sample title. This information is also available in the sample characteristics.	Co-expression
SRP123604	Immune Profiling of Premalignant Lesions in Patients with Lynch Syndrome	mRNA expression from adenomas of patients with Lynch Syndrome and Familial Adenomatous Polyposis Overall design: 24 adenoma samples analyzed	Co-expression
SRP123611	RNA-seq in neutrophils from patients with intracranial aneurysms	In this study, we explored transcriptional differences in human neutrophils from patients with intracranial aneurysms and a demographic and comorbidity paired population of controls Overall design: We compared differentially expressed genes among neutrophils from 11 blood samples from patients with intracranial aneurysms and 11 blood samples from paired controls. We used an independent, unpaired, corroboration cohort of 5 intracranial aneurysm patients and 5 control patients to confirm our findings.	Co-expression
SRP123633	Human telomerase RNA-RNA interactome	Identifying the RNA interaction partners of human telomerase RNA in cancer cells by RNA affinity purification followed by RNA sequencing.	Co-expression
SRP123728	Long noncoding RNA LNMAT1 promotes lymphatic metastasis in bladder cancer	Long non-coding RNAs (lncRNAs) are a large class of non-protein-coding transcripts that are over 200nt in length. LncRNAs have emerged as key regulator of biological process involved in the development and progression of bladder cancer. Bladder cancer is one of the most common genitourinary malignancies worldwide, with approximately 429,800 new cases and 165,100 deaths annually in the world. To identify critical lncRNAs that contributes to the progression of bladder cancer, Next generation sequencing (NSG) was performed in five paired high-grade muscle invasive bladder cancer (MIBC) and normal adjacent tissues (NAT), and in five lymph node (LN)-positive and LN-negative bladder cancer tissues. Our results indicate that the differential expressed lncRNAs in both MIBC tissues and LN-positive tissues associated in a variety of biological functions, such as metastasis. Overall design: To identify critical lncRNAs that contributes to the progression of bladder cancer, NSG was performed in five paired high-grade muscle invasive bladder cancer and normal adjacent tissues and in five lymph node-positive and lymph node-negative bladder cancer tissues. The RNA of tissue was extracted and hybridized on illumina Hiseq 2500.	Co-expression
SRP124072	RNA Sequencing Facilitates Quantitative Analysis of differentially expressed genes after UCA1 knockdown in human erythroid cells	Purpose: The goals of this study are to determine possible  downstream targets of UCA1 on day8 of  erythroid differentiation with or without UCA1 knockdown. Methods:gene expression profiling with or without UCA1 knockdown in differentiated erythroblasts at day8  were generated by deep sequencing, induplicate, using Illumina GAIIx.The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: heme metabolism genes were down-regulated after UCA1 knockdown during erythroid differentiation Overall design: mRNA profiles of day8 erythroid cells with or without UCA1 knockdown were generated by deep sequencing, in duplicate, using Illumina GAIIx.	Co-expression
SRP124156	Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and AXL-/- astrocytes Transcriptomes	Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare Wild Type astrocytes transcriptome profiling (RNA-seq) to AXL-/- astrocytes transcriptome profiling and to explore the mechanism by which AXL interferes with type I IFN signaling in WT astrocytes. We performed an RNA-Seq analysis of WT and AXL-/- U-251MG cells in the absence of ZIKV. Surprisingly, the intrinsic level of type I IFN signaling was lower in AXL-/- cells than in WT cells. This result was further confirmed by RT-qPCR Overall design: U251 mRNA profiles of wild type (WT) and AXL-/- cells were generated by deep sequencing, in triplicate, usingIllumina Hiseq, PE150.	Co-expression
SRP124161	Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis [10X genomics]	CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective role in several viral infections. However, little is known in humans about the biology of CD4-CTL generation, their functional properties, heterogeneity and clonal diversity, especially in relation to other well-described CD4+ memory T cell subsets. We performed single-cell RNA-seq in over 9000 cells to unravel CD4-CTL heterogeneity, transcriptional profile and clonality in humans. The single-cell differential gene expression analysis, revealed a spectrum of known transcripts, including several linked to cytotoxic and co-stimulatory function, and transcripts of unknown cytotoxicity-related function that are expressed at higher levels in the TEMRA subset, which is highly enriched for CD4-CTLs, compared to cells in the central and effector memory subsets (TCM, TEM). Simultaneous T cells antigen receptor (TCR) analysis in single-cells and bulk subsets revealed that CD4-TEMRA cells show marked clonal expansion compared to TCM and TEM cells and that the majority of CD4-TEMRA were dengue virus (DENV)-specific in subjects with previous DENV infection. The profile of CD4-TEMRA was highly heterogeneous across subjects, with four distinct clusters identified by the single-cell analysis. Most importantly, we identified distinct clusters of CD4-CTL effector and precursor cells in the TEMRA subset; the precursor cells shared TCR clonotypes with CD4-CTL effectors and were distinguished by high expression of the interleukin-7 receptor. Our identification of a CD4-CTL precursor population may allow further investigation of how CD4-CTLs arise in humans and thus could provide insights into the mechanisms that may be utilized to generate durable and effective CD4-CTL immunity. Overall design: Single cell RNA-seq analysis of  purified populations of human CD4 memory cell subsets by both bulk TCR-sequencing.	Co-expression
SRP124220	Homo sapiens Transcriptome or Gene expression	Human U937 histiocytic lymphoma cells, optionally also differentiated to macrophages, were treated with lysozyme (LZ) and LZ extracted from LZ-containing microspheres (MSLZ) at different concentrations. Here we investigate the differential gene expression induced by rteatment with LZ and MSLZ-extracted-LZ to get insights on the farmacological effects of these changes. The cells were exposed to LZ for 1h or 24h to analyse, by RNA-seq, the differential expression at different time points after the end of the treatment.	Co-expression
SRP124243	Super-enhancer-driven CCAT1 is co-activated by SOX2 and TP63 and promotes squamous cancer from esophagus, head and neck and lung [RNA-seq]	Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that the transcription factors TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. Our recent study have identified TP63 and SOX2 as super-enhancer-associated genes. However, functional consequences of their frequent co-localization at super-enhancers region remains unexplored. Here, ChIP-seq result indicated TP63 and SOX2 co-occupied peaks are significantly located the super enhancer region compare with unique of TP63 and SOX2 signaling, and combined RNA-seq analyses of different types of SCCs reveal that TP63 and SOX2 cooperatively regulate expression of the super-enhancer-associated the long non-coding RNA (lncRNA) gene, CCAT1. CCAT1 is highly expressed in SCCs compared to either other tumor types or normal tissues. CCAT1 expression strongly correlates with expression levels of TP63 and SOX2. Silencing of CCAT1 significantly reduces cellular growth both in vitro and in vivo, phenotyping the effect of silencing either TP63 or SOX2. Furthermore, ChIP-Seq and luciferase reporter assays demonstrate TP63 and SOX2 co-occupy the promoter and super-enhancer regions of CCAT1. Interaction of CCAT1 with TP63 and SOX2 are validated by RNA immunoprecipitation. In addition, ChIRP analysis suggests that CCAT1 regulates EGFR expression by binding to the super-enhancer of EGFR. Further investigations shows that CCAT1 activates both the MEK/ERK1/2 and PI3K/AKT signaling pathways through up-regulation of EGFR. In conclusion, CCAT1 is driven by master transcription factors TP63 and SOX2 and is recruited to the super-enhancer of EGFR, promoting SCC tumorigenesis through activation of the MEK/ERK1/2 and PI3K/AKT signaling pathways. These studies help to explain the pathogenesis of SCC and aids in providing novel therapeutic strategy. Overall design: Gene Expression profile was measured following shRNA mediated knock down of TP63, SOX2, and CCAT1 in Esophageal Squamous Carcinoma Cell lines	Co-expression
SRP124244	RNA Sequencing Facilitates Quantitative Analysis of differentially expressed genes after PTBP1 knockdown in human erythroid cells	Purpose: The goals of this study are to determine possible  downstream targets of PTBP1 on day8 of  erythroid differentiation with or without PTBP1 knockdown. Methods:gene expression profiling with or without PTBP1 knockdown in differentiated erythroblasts at day8  were generated by deep sequencing, induplicate, using Illumina GAIIx.The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: heme metabolism genes were down-regulated after PTBP1 knockdown during erythroid differentiation Overall design: mRNA profiles of day8 erythroid cells with or without PTBP1knockdown were generated by deep sequencing, in duplicate, using Illumina GAIIx.	Co-expression
SRP124299	Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with signatures from post mortem adult brains	Whereas highly penetrant variants have proven well-suited to human induced pluripotent stem cell (hiPSC)-based models, the power of hiPSC-based studies to resolve the much smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. In developing a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons, we identified and accounted for a variety of technical and biological sources of variation. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal in hiPSC-based models and increased the concordance with post mortem datasets. Because this concordance was strongest in hiPSC-neurons, it suggests that this cell type may better model genetic risk for SZ. We predict a growing convergence between hiPSC and post mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones. Overall design: RNA-seq from hiPSC-derived neural progenitor cells and neurons	Co-expression
SRP124307	Transcriptome profiling of colorectal adenocarcinoma HT-29 cells after 5-FU treatment	We performed RNA-Seq analysis of transcriptomic alterations in HT-29 colon cancer cells treated with 20 µM 5-FU for 72 h, the time period roughly equivalent to three consecutive cell doublings. We expected that the high dose of the drug, which corresponds to 10 x IC50 and kills nearly 80% of cells, would selectively favor the survival of cells that acquire a transient resistance to 5-FU.We identified lincRNAs LINC00973, LINC00941, CCAT1, and CASC19 as the most upregulated in 5-FU treated HT-29 cells. These results were further validated by RT-qPCR in HT-29 cells harvested after 72 h and 144 h of treatment with 2 µM 5-FU or 2 µM OXP (corresponding to the IC50 dose) or 5 µM IRI (one third of its IC50).We also added lincRNA BCAR4 to the analysis, which is undetectable by RNA-Seq, but according to our RT-qPCR data is upregulated in 57% of colorectal tumors. Obtained results demonstrated that all five lincRNAs are upregulated by the treatment with all three drugs, indicating that monitoring by RT-qPCR of just two of the lincRNAs (LINC00973 and BCAR4) provides a robust instrument for distinguishing of untreated and treated cells.	Co-expression
SRP124308	Silencing SPIB in attached and floating state of H1703 lung cancer cells	To gain mechanistic insight into the role of SPIB in anoikis resistance, we assessed the transcriptional profile of the genes involved using RNA sequencing Overall design: mRNA profiles of attached H1703 control,attached H1703 SPIB-KD,ECM detached H1703 control,ECM detached H1703 SPIB-KD. There are two biological repeats in each group.	Co-expression
SRP124449	tRNA modification landscape selectively controls mitochondrial translation efficiency in MERRF	We identified a novel N1-methyladenosine (m1A) modification in tRNALys with distinct effects on the synthesis and stabilities of the 13 mitochondrial proteins. Moreover, we observed regulated RNA modifications of mitochondrial tRNAs for the control of mitochondrial gene expression. Collectively, our data provide unprecedented insight into the regulation of mitochondrial tRNAs and reveal greater complexity to the molecular pathogenesis of MERRF. Overall design: Comprehensive biochemical and sequencing analysis of wild-type and MERRF samples treated or not with AlkB demethylase (DM)	Co-expression
SRP124458	strand-specific RNAseq of hepatoblastoma	To gain insight into the mechanism of hepatoblastoma, we performed strand-specific RNA sequencing analysis on 24 hepatoblastoma paired samples. We focus on the differential expressed genes and lncRNAs and expected to find some biomarkers in the treatment of HB.	Co-expression
SRP124462	Covalent inhibitor of the Rho family inhibits the migration of breast cancer cells	Small GTPase proteins usually serve as molecular switches in various biological process, such as the proliferation, survival, and migration of cells. Mutations or aberrant activations of small GTPase proteins, such as Ras, are frequently observed in various kinds of cancers. Drug discovery efforts that target the Ras family proteins are making breakthroughs, while the discovery of efficient inhibitors that target the Rho family proteins is still stagnant. Protein members from the Rho family, such as RhoA and Cdc42, are key regulators of the migration and invasion of cancer cells. Thus inhibitors of the Rho family proteins are promising to become drug candidates that target cancer metastasis, which is a principal cause of cancer recurrence and chemotherapy failure. Here we show the discovery and characterization of a novel covalent inhibitor named DC-RC-063 that targets the Rho family proteins, using a combined approach of computations and experiments. Revealed by solved crystal structures, compound DC-RC-063 inhibited the activation of RhoA, by disrupting protein-protein interactions, in an allosteric manner. As compound DC-RC-063 inhibited the migration and invasion of breast cancer MDA-MB-231 cells, our findings proved that the Rho family proteins are targetable for covalent inhibitors via an allosteric mechanism. The novel binding site revealed by this inhibitor can be exploited for further development of anti-cancer drugs that target cancer metastasis. Overall design: RNA-Seq in breast cancer MDA-MB-231 cells in the presence or absence of Rho family covalent inhibitor	Co-expression
SRP124477	Genome wide expression change by RNF168 knocking down in MCF-7 cells	We aim to the investigate the role of RNF168 in breast cancer progression. MCF-7 cells were used as the model and RNF168 was silenced by siRNA. Overall design: The MCF-7 cells were treated with 50nM stramble siRNA and siSMURF1. After 48 hours, cells were harvested and the total RNA was extacted by Qiagen kit. The RNA sample was sent to BGI for RNA expression anaylsis.	Co-expression
SRP124496	ETS1 acts as a tumor suppressor in breast cancer by inhibiting growth-related factors	To characterize the effect of Core regulatory element (CRE) deletion in breast cancer cell line (MDA-MB-231 cells), we performed gene expression RNA-seq analysis for WT and KO (Core Regulatory Element deleted) MDA-MB-231 cells after 0h, 6h and 24h of P/I treatment. Overall design: Total RNA was extracted from WT and KO (CRE deleted) MDA-MB-231 cells of mock and PMA/Ionomycin treated group.	Co-expression
SRP124500	Next Generation Sequencing  Quantitative Analysis of altered expression of genes in lncRNA LNMAT1 knockdown bladder cancer cells	Bladder cancer is one of the most common genitourinary malignancies worldwide, with approximately 429,800 new cases and 165,100 deaths annually in the world. LNMAT1 is reported to play diverse roles in the development and progression of human cancer. However, its function and underlying mechanism in bladder cancer remains unclear. The goal of this study is to identify the target genes of LNMAT1 in bladder cancer. Our results indicate that the genes regulated by LNMAT1 associated in a variety of biological functions, such as proliferation and metastasis. Overall design: To investigate the functional roles of LNMAT1 in bladder cancer, the UM-UC-3 and 5637 bladder cancer cell lines were established to stably downregulate LNMAT1 expression. The RNA of the transfected cells was extracted and hybridized on illumina Hiseq 2000. We indentified the putative target genes of LNMAT1 in both LNMAT1 shRNAs by comparing the different expressed genes among NC, sh-LNMAT1-1 and sh-LNMAT1-2. We further validated the data of next generation sequencing in UM-UC-3 and 5637 bladder cancer cells by qRT-PCR and western bloting.	Co-expression
SRP124601	Repression of Human and Mouse Brain Inflammaging Transcriptome by Broad Gene Body Histone Hyperacetylation (RNA-seq)	RNA-seq data of human prefrontal cortex and mouse brain during aging and/or SAHA treatment were generated. Overall design: For RNA extraction, human brain samples with similar age were pooled together, mouse brain samples were extract individually. After RNA extraction by TRIzol, library construction and high-throughput sequencing was done.	Co-expression
SRP124620	GRHL2 is a key lineage determining factor which collaborates with FOXA1 to establish a targetable collateral pathway in the setting of endocrine therapy-resistant breast cancer (RNA-Seq data set 1)	The estrogen receptor (ER) is expressed in the majority of luminal breast cancers and inhibition of its transcriptional activity with selective estrogen receptor modulators, selective estrogen receptor degraders and/or aromatase inhibitors is a standard approach used in the management of this disease. Despite the positive clinical impact of these interventions, de novo and acquired resistance limits the therapeutic lifespan of these classes of drugs. Considering what is known about the complex mechanisms that contribute to the development of resistance it is likely that further development of ER-modulators will yield only incremental improvements. Thus, with the view that resistance is inevitable, we undertook the development of a new approach to treat ER-positive breast cancer by identifying and exploiting targetable vulnerabilities that emerge in endocrine therapy resistant disease. Genomic discovery platforms, including DNASeq, ChIPSeq and RNASeq were used to assess the epigenome, targeting global transcription factor binding profile, and transcriptome in cellular models of endocrine therapy sensitive and resistant disease. DNASeq was first used to identify the chromatin state, with a focus on differences, between these two models. Motif enrichment analysis indicated FOXA1 was a candidate transcription factor influencing the chromatin architecture, which was consistent with previously published studies. This led to the examination of the FOXA1 chromatin binding profile in these models. FOXA1 has previously been described to bind at enhancers. Furthermore, the relative transcription activity of specific enhancers has been shown to be indicated by the epigenomic marks on histones flanking transcription factor binding sites. For this reason, we assessed the specific pattern of histone 3 lysine 4 methylation to confirm enhancer status and histone 3 lysine 27 acetylation as an indicator of transcriptional activity.  The specific patterns and distribution of FOXA1 binding was then integrated with this epigenomic information to reveal a subset of enhancers that became activated and another subset that gained enhanced activation in the tamoxifen resistant setting relative to the tamoxifen sensitive model from which it was derived. These results were integrated with the differential transcriptome, or genes shown to be differential expressed based on RNASeq, in the TAMR model as compared to its parental cell line, MCF7-WS8, and confirmed that the active enhancers were in fact associated with genes that were expressed more highly, on average, in the TAMR model.   Motif enrichment at these two subgroups of enhancers indicated that another transcription factor, GRHL2, likely interacts with FOXA1 at these active sites. These results were again integrated with the “differential transcriptome” based on RNASeq and confirmed that the active enhancers, and indicated an even stronger enrichment of genes that were expressed more highly, on average, in the TAMR model relative to the MCF7-WS8 model. The GRHL2 transcriptome was then further defined by both GRHL2 ChIPSeq as well as RNASeq by comparing TAMR samples in which downregulation of GRHL2 expression had been achieved via siRNA as compared to control siRNA sequences.  The collection of these data defined a subset of genes, the GRHL2 dependent transcriptome, that demonstrated increased expression in TAMR. The results of these cell lines studies were corroborated by assessing the transcriptome of xenograft mouse models of endocrine therapy sensitive and resistant disease. Integrative analysis of these data identified a collateral ER-independent signaling pathway in endocrine therapy resistant tumors that converges upon and modulates the FOXA1 and GRHL2 cistrome/transcriptome.   Overall design: In total, 12 samples were analyzed for transcript expression profiles. This study has 3 cell lines(MCF7, WS8, and TAMR) with two replicates each. Samples were grown in hormone-free media for 24 hours and then treated with either Vehicle or 4-hydroxytamoxifen for 24 hours.	Co-expression
SRP124631	Dynamic reorganization of nuclear architecture during human cardiogenesis [RNA-seq]	While chromosomal architecture varies among cell types, little is known about how this organization is established or its role in development. We integrated Hi-C, RNA-seq and ATAC-seq during cardiac differentiation from human pluripotent stem cells to generate a comprehensive profile of chromosomal architecture. We identified active and repressive domains that are dynamic during cardiogenesis and recapitulate in vivo cardiomyocytes. During differentiation, heterochromatic regions condense in cis. In contrast, many cardiac-specific genes, such as TTN (titin), transition to an active compartment coincident with upregulation. Moreover, we identify a network of genes, including TTN, that share the heart-specific splicing factor, RBM20, and become associated in trans during differentiation, suggesting the existence of a 3D nuclear splicing factory. Our results demonstrate both the dynamic nature in nuclear architecture and provide insights into how developmental genes are coordinately regulated. Overall design: Hi-C, RNA-seq and ATAC-seq analysis of four stages of human pluripotent stem cell differentiation to cardiomyocytes, including stem cell, mesoderm, cardiac progenitor, and cardiomyocyte, with two biological replicates of each condition. Hi-C and RNA-seq analysis of two biological replicates fetal heart samples.	Co-expression
SRP124640	GRHL2 is a key lineage determining factor which collaborates with FOXA1 to establish a targetable collateral pathway in the setting of endocrine therapy-resistant breast cancer (RNA-Seq data set 2)	The estrogen receptor (ER) is expressed in the majority of luminal breast cancers and inhibition of its transcriptional activity with selective estrogen receptor modulators, selective estrogen receptor degraders and/or aromatase inhibitors is a standard approach used in the management of this disease. Despite the positive clinical impact of these interventions, de novo and acquired resistance limits the therapeutic lifespan of these classes of drugs. Considering what is known about the complex mechanisms that contribute to the development of resistance it is likely that further development of ER-modulators will yield only incremental improvements. Thus, with the view that resistance is inevitable, we undertook the development of a new approach to treat ER-positive breast cancer by identifying and exploiting targetable vulnerabilities that emerge in endocrine therapy resistant disease. Genomic discovery platforms, including DNASeq, ChIPSeq and RNASeq were used to assess the epigenome, targeting global transcription factor binding profile, and transcriptome in cellular models of endocrine therapy sensitive and resistant disease. DNASeq was first used to identify the chromatin state, with a focus on differences, between these two models. Motif enrichment analysis indicated FOXA1 was a candidate transcription factor influencing the chromatin architecture, which was consistent with previously published studies. This led to the examination of the FOXA1 chromatin binding profile in these models. FOXA1 has previously been described to bind at enhancers. Furthermore, the relative transcription activity of specific enhancers has been shown to be indicated by the epigenomic marks on histones flanking transcription factor binding sites. For this reason, we assessed the specific pattern of histone 3 lysine 4 methylation to confirm enhancer status and histone 3 lysine 27 acetylation as an indicator of transcriptional activity.  The specific patterns and distribution of FOXA1 binding was then integrated with this epigenomic information to reveal a subset of enhancers that became activated and another subset that gained enhanced activation in the tamoxifen resistant setting relative to the tamoxifen sensitive model from which it was derived. These results were integrated with the differential transcriptome, or genes shown to be differential expressed based on RNASeq, in the TAMR model as compared to its parental cell line, MCF7-WS8, and confirmed that the active enhancers were in fact associated with genes that were expressed more highly, on average, in the TAMR model.   Motif enrichment at these two subgroups of enhancers indicated that another transcription factor, GRHL2, likely interacts with FOXA1 at these active sites. These results were again integrated with the “differential transcriptome” based on RNASeq and confirmed that the active enhancers, and indicated an even stronger enrichment of genes that were expressed more highly, on average, in the TAMR model relative to the MCF7-WS8 model. The GRHL2 transcriptome was then further defined by both GRHL2 ChIPSeq as well as RNASeq by comparing TAMR samples in which downregulation of GRHL2 expression had been achieved via siRNA as compared to control siRNA sequences.  The collection of these data defined a subset of genes, the GRHL2 dependent transcriptome, that demonstrated increased expression in TAMR. The results of these cell lines studies were corroborated by assessing the transcriptome of xenograft mouse models of endocrine therapy sensitive and resistant disease. Integrative analysis of these data identified a collateral ER-independent signaling pathway in endocrine therapy resistant tumors that converges upon and modulates the FOXA1 and GRHL2 cistrome/transcriptome.   Overall design: In total, 18 samples were analyzed for transcript expression profiles. This study compares depletion of GRHL2 by siRNA vs siCtrl. Independent biological triplicates and two technical replicates were used for each siRNA (siCtrl, SiGRHL2-A, siGRHL2-C).	Co-expression
SRP124641	RNA-seq analysis of gene expression in scramble and GPR126 knockdown colon cancer cells (HT-29)	Purpose: Identify genes regulated by GPR126 in colon cancer cells by RNA-seq analysis Methods: Use shRNAs to knock down GPR126 in HT-29 cells, total RNAs from scramble group (NC) and GPR126 knockdown group (Sh1) were subjected to RNA-sequencing. Results: Around 700 transcriptomes were up-regulated in GPR126 knockdown HT-29 cells, and 14000 transcriptomes were down-regulated in GPR126 knockdown HT-29 cells.GPR126 mainly regualtes genes from DNA synthesis and cell cycle-related pathways. Conclusions: Our study firstly showed the function of GPR126 regulating colon cancer cell proliferation by targeting genes invovled in DNA synthesis and cell cycle-related pathways. Overall design: RNA interference in colon cancer cell line HT-29, knock down GPR126 expression, and conduct gene expression profiling by RNA-seq. Two groups, one sample from each group.	Co-expression
SRP124661	Expression profile of GIST48 cells with siETV1 or siFOXF1 knockdown	To study FOXF1 transcriptome and compare that with ETV1 transcriptome, we knocked down ETV1 or FOXF1 with siRNA in GIST48 cells and studied the transcriptome changes Overall design: 6 samples including 2 controls are included	Co-expression
SRP124705	Decreased TGFBR3/Betaglycan expression enhances the metastatic abilities of renal cell carcinoma cells through TGF-b-dependent and independent mechanisms	It is unclear how the loss of TGF-b signaling components affects metastatic abilities in clear cell renal cell carcinoma (ccRCC). In this study, we identified that low TGFBR3 expression in ccRCC cells enhanced primary tumor formation and lung metastasis. In the presence of TGFBR3, TGF-b2 decreased the aldehyde dehydrogenase (ALDH)-positive ccRCC cell population, in which renal cancer-initiating cells are enriched. Loss of TGFBR3 also enhanced cell migration in cell culture and induced expression of several mesenchymal markers in a TGF-b-independent manner. Increased lamellipodium formation by FAK-PI3K signaling was observed with TGFBR3 downregulation, and this contributed to TGF-b-independent cell migration in ccRCC cells. Taken together, our findings reveal that loss of TGFBR3 endows ccRCC cells with multiple metastatic abilities through TGF-b-dependent and independent pathways. Overall design: Target genes for TGF-b2 and TGFBR3 in ccRCC cells were identified.	Co-expression
SRP124786	Risk SNPs mediated promoter-enhancer switching promotes prostate cancer progression through lncRNA PCAT19 (RNA-seq data sets)	To determine the functional mechanisms of PCAT19-long isoform and HNRNPAB, we conducted siRNA knockdown RNA-sequencing in prostate cancer cell line V16A. Overall design: Profiling transcriptomic changes after knockdown of PCAT19-long isoform and HNRNPAB in V16A cells.	Co-expression
SRP124834	Engineered Nanointerfaces for Microfluidic Isolation and Molecular Profiling of Tumor-specific Extracellular Vesicles	Tumor-EVs were captured on a nanostructured interface through immunoaffinity immobilization in a microfluidic channel containing herringbone (HB) structure for efficient mixing (EVHB-Chip).  Processing serum and plasma samples from glioblastoma multiforme (GBM) patients, isolated tumor EVs were analyzed using next-generation RNA sequencing analysis, and identified genes specific to glioblastoma as well as transcripts that are hallmarks for the four genetic subtypes of disease (e.g., classical, mesenchymal, neural, and pro-neural). Overall design: Plasma or serum isolated from 13 GBM patients than run through the EVHB-Chip coated with antibodies.(EGFR, EGFRvIII, PDGFR) Isolated Evs analysed using next-generation RNA sequencing analysis.	Co-expression
SRP124848	MARS Seq data from human cortical organoids	We analyze gene expression data of human organoid developmet Overall design: Three developmental time points and two genotypes were examined	Co-expression
SRP124875	A facile method for generating tumorigenic cancer stem cell spheroids from diverse cancer cell lines	Although cancer stem cells (CSCs) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of patient-derived diverse CSCs. Here, we developed a functional polymer thin film (PTF) platform that promotes conversion of human cancer cell lines to highly tumorigenic spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular spheroids within 24 hours, with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed an enormous increase in the expression of CSC-associated genes and acquired dramatically increased drug resistance compared with monolayer-cultured controls. These spheroids also showed greatly enhanced xenograft tumor-forming ability and metastasis capacity in nude mice. By enabling the generation of tumorigenic spheroids as a patient-derived CSC substitute, the surface platform described here will likely contribute to CSC-related basic research and drug development. Overall design: mRNA profiles of 8 day-SKOV3-ssiCSC spheroids and 2D-cultured SKOV3 control were generated by deep sequencing, in duplicate, using Hiseq-2500.	Co-expression
SRP124954	Nicotinamide Nucleotide Transhydrogenase as a novel treatment target in adrenocortical carcinoma	RNA-seq samples used to support a study in to the understanding of antioxidant targeting in adrenocortical carcinoma Overall design: Pairwise comparison of knockdown samples against controls (scrambled si/sh-RNA)	Co-expression
SRP124955	Combinatory RNA sequencing analyses reveal RNA editing-dependent and -independent gene regulation by ADAR1 in gastric cancer	To investigate the role of ADAR1 in gastric carcinogenesis, RNA sequencing and small RNA sequencing were performed in AGS and MKN-45 cells with stable ADAR1 knock-down. Changed frequencies of editing and messenger RNA (mRNA) and microRNA (miRNA) expression were then identified by bioinformatic analyses. Overall design: mRNA and miRNA sequencing were performed before and after stable knockdown of ADAR1 in AGS and MKN-45 cell line	Co-expression
SRP124967	Comparative Single Cell Transcriptomics Reveals Distinct Cell Fate Transition Statuses during Human Cardiac Reprogramming	Direct lineage conversion among various somatic cell types revolutionized the field of stem cell and regenerative medicine. In addition, the platform of cellular reprogramming offered a powerful system to gain new knowledge about cell plasticity and cell fate determination and ultimately challenged previous notions of cell identity. Previously, we successfully utilized single cell transcriptomics to reconstruct the molecular routes of how a murine fibroblast adopts cardiomyocyte fate following a continuum of states. In this study, we employed a comparative single cell transcriptomics approach to study human cardiac reprogramming. In comparison with murine fibroblasts and other human cell types, we identified unexpected heterogeneity in human cardiac fibroblasts that was mainly due to variance in cell cycle status. Trajectories inferred by SLICER suggest molecular routes and pathways taken by human fibroblasts when transiting into CM fate. Importantly, by assigning a “cell fate index” to each single cell on the iCM trajectories resolved from both mouse and human fibroblasts, we discovered species differences in fibroblast plasticity and intermediate cell fate statuses when reprogrammed towards a CM fate. Collectively, our comparative single cell transcriptomics study of human cardiac reprogramming revealed previously unrecognized molecular features of human cardiac fibroblasts and regulatory mechanisms in human cardiomyocyte cell fate control. Overall design: Primary human cardiac fibroblasts were isolated and reprogrammed with polycistronic human MEF2C, GATA4, TBX5 and miR-133. Single cells were captured using the Fluidigm C1 system with the capacity of up to 96 single cells per experiment. A total of eight individual single-cell experiments were performed. One plate (D0hCF) contained uninfected d0 human primary fibroblasts. Two plates (D3M1 and D3M2) contained d3 MGT+miR-133-transduced cells. The fourth plate (D3UN) contained d3 DsRed-transduced cells (DsRed+ by FACS) mixed with d3 uninfected cells at 3:1 ratio. The rest four plates contained MGT+miR-133-transduced cells mixed with Tdtomato-transduced cells (Tdtomato+ by FACS) at 3:1 ratio, which were collected on d3 (D3M3), d5 (D5M1), d7 (D7M1), and d9 (D9M1), respectively. Control RNA spike-ins were added to the plate before cell lysis and processed in parallel to cellular RNA. Lysate from 704 wells containing single cells were selected for mRNA sequencing (raw data files) and a total of 652 high-quality single-cell transcriptomes were analyzed after QC (processed data).	Co-expression
SRP124973	RNA sequencing of  human periodontal ligament stem cells (PDLSCs) with Illumina HiSeq2000	To study the molecular mechanisms underlying PDLSC osteogenic differentiation, we developed RNA sequencing with Illumina HiSeq2000 to comprehensively identify RNA expression profiles in normal PDLSCs, osteogenic inductive PDLSCs and mechanical force-induced PDLSCs. Plenty of RNAs were found to be differentially expressed by RNA sequencing. Furthermore, the potential functions of these RNAs were investigated using bioinformatic analysis. Overall design: The experiment included three samples: PDLSCs cultured with  normal media; PDLSCs cultured with osteogenic induction for seven days and PDLSCs stretched for 12h in a Flexcell® FX-5000™ Tension system.PDLSCs cultured with  normal media were considered as control group.	Co-expression
SRP125001	Multi-Omic Molecular Profiling of Lung Cancer Risk in Chronic Obstructive Pulmonary Disease	Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer suggesting that the COPD stroma contains factors supporting tumorigenesis. Since cancer initiation is complex we used a multi-omic approach to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumor and adjacent non-malignant tissue) and those with COPD without lung cancer for proteomic and mRNA (cytoplasmic and polyribosomal) profiling.  We used the joint and individual variation explained (JIVE) method to integrate and analysis across the three datasets.  JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples. Predictive variables that associated with the tumor, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas, predictive variables associated with adjacent tissue compared to controls was represented at the translatomic level. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed extracellular matrix (ECM) and PI3K-Akt signaling pathways as important signals in the pre-malignant stroma. COPD stroma adjacent to lung cancer is unique and differs from non-malignant COPD tissue and is distinguished by the extracellular matrix and PI3K-Akt signaling pathways. Overall design: Polysome-profiling of lung tumor, adjacent non-cancerous lung stroma tissue samples from the same patient compared to patients without lung cancer across a range of forced expiratory volume in one second (FEV1)	Co-expression
SRP125008	Lung resident mesenchymal stromal cells reveal transcriptional dynamics of lung	We report the correlation between lung-derived neonatal MSCs and 2 clinical variables among preterm newborns: corrected gestational age (CGA) at collection and the severity of bronchopulmonary dysplasia (BPD) Overall design: To test the correlation between the transcriptional profiles of tracheal aspirate-derived mesenchymal stromal cells with late stage lung development and with bronchopulmonary dysplasia.	Co-expression
SRP125023	The impact of lncRNA LAST knockdown on gene expression profile in HCT116 cells	High-throughput sequencing was employed to analyze the genes whose expression are altered when lncRNA LAST is downregulated by shRNA in HCT116 cells. The Gencode Gene ID of lncRNA LAST is ENSG00000254682.1. Overall design: In order to identify the genes whose expression levels were changed under the condition of LAST knockdown,  we performed High-throughput sequencing and mRNA expression profile data analyzing.	Co-expression
SRP125101	Investigate A2M treatment on human prostate cancer xenograft in mice	Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumor development. Here we found that A2M modulates tumor cell adhesion, migration and growth by inhibition of tumor promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumor xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumor cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumor promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent. Overall design: 11 samples: 5 treated with PBS, 6 treated with A2M	Co-expression
SRP125103	RNA-seq analysis of human expandable arterial endothelial precursors (eAEPs), expandable mesenchymal precursors (eMPs), and controls	The following is an excerpt from the abstract of Miller et al. In this study, we find that two transcription factors, MYCN and SOX17, enable the indefinite propagation of human endothelial arterial precursors in vitro (“expandable arterial endothelial precursors,” eAEPs). Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders. Some lines spontaneously become mesenchymal over time in culture, an effect exacerbated by inhibition of the fibroblast growth factor (FGF) receptor, while others do not readily convert. These distinctions were exploited to identify genes that correlate with resistance to an EndoMT and to elucidate transcriptional changes that underpin the transition. We believe the eAEPs may be useful not only as tractable tools for biological or pathological studies, but also as platforms for drug discovery. Overall design: Examination of eAEPs and eMPs, their mature progeny, and control vascular cells by RNA-seq.	Co-expression
SRP125109	RNAseq analysis of ruxolitinib treated breast cancers	We performed RNA sequencing analysis on fresh-frozen biopsies of metastatic triple-negative breast cancer prior to undergoing therapy with ruxolitinib, or after 2 cycles of therapy in a subset of patients. Overall design: Seventeen samples were successfully sequenced, including two pairs of baseline and cycle 2, two unmatched cycle 2 samples, and eleven unmatched baseline samples.	Co-expression
SRP125125	RNA-Seq profiling of 29 immune cell types and peripheral blood mononuclear cells	We performed RNA-Seq transcriptome profiling on 29 immune cell types consituting peripheral blood mononuclear cells (PBMCs) sorted from 4 Singaporean-Chinese individuals (S4 cohort). We also performed RNA-Seq and microarray transcriptome profiling of PBMCs from an extended cohort of 13 individuals (S13 cohort). The data was used first to characterize the transcriptomic signatures and relationships among the 29 immune cell types. Then we explored the difference in mRNA composition in terms of transcripts proportions and abundance. Lastly, we performed deep deconvolution for both microarray and RNA-Seq technologies. Overall design: Total RNA of 29 immune cell types (from 4 individuals) and peripheral blood mononuclear cells (PBMCs, from 13 individuals) was extracted for gene expression profiling. The 13 PBMCs samples were processed with both microarray and RNA-Seq platforms.	Co-expression
SRP125141	TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [RNA-seq]	We report the gene expression profiles of TRPS-depleted and YAP 5SA overexpressing breast cancer cell lines. Overall design: Investigation of TRPS1- and YAP-dependent transcriptional programs.	Co-expression
SRP125153	single cell RNA-seq raw reads of estrogen-stimulated breast cancer cell line MCF7	Single-cell RNA-seq reveals dynamic estrogen-stimulated metabolic reprogramming in breast cancer cell lines	Co-expression
SRP125154	single cell RNA-seq raw reads of estrogen-stimulated breast cancer cell line T47D	Single-cell RNA-seq reveals dynamic estrogen-stimulated metabolic reprogramming in breast cancer cell lines	Co-expression
SRP125165	Homo sapiens Transcriptome or Gene expression	Transcriptional reprogramming of macrophages upon Mycobacterium tuberculosis (Mtb) infection is widely studied; however, the significance of alternate splicing (AS) in shaping cellular responses to mycobacterial infections is not yet appreciated. Alternate splicing can influence transcript stability or structure, function and localization of corresponding proteins thereby altering protein stoichiometry and physiological consequences. Using comprehensive analysis of a time-series RNA-seq data obtained from human macrophages infected with virulent or avirulent strains of Mtb, we show extensive remodeling of alternate splicing in macrophage transcriptome. The global nature of this regulation was evident since genes belonging to functional classes like trafficking, immune response, autophagy, redox and metabolism showed marked departure in the pattern of splicing in the infected macrophages. The systemic perturbation of splicing machinery in the infected macrophages was apparent as genes involved at different stages of spliceosome assembly were also regulated at the splicing level. Curiously there was a considerable increase in the expression of truncated/non-translatable variants of several genes, specifically upon virulent infections. Increased expression of truncated transcripts correlated with a decline in the corresponding protein levels. We verified the physiological relevance for one such candidate gene RAB8B; whose truncated variant gets enriched in H37Rv infected cells. Upon tweaking relative abundance of longer or shorter variants of RAB8B transcripts by specialized transduction, mycobacterial targeting to lysosomes could be promoted or blocked respectively, which also resulted in corresponding changes in the bacterial survival. Our results show RAB8B recruitment to the mycobacterial phagosomes is required for phagosome maturation. Thus the abundance of truncated RAB8B variant helps virulent Mtb survival by limiting the RAB8B levels in the cells, a mechanism which we subsequently verified in human primary macrophages. Taken together we demonstrate alternate splicing as a new locus of intervention by Mtb and provide attractive alternative to exploit for novel drug targets against Mtb.	Co-expression
SRP125175	Tafazzin Regulates Cell State by Modulating Phosphatidylethanolamine and Phosphatidylserine levels	Inhibiting tafazzin a cardiolipin remodeling enzyme reduces stemness of AML by modulating the level of phosphatidylserine Overall design: Gene expression analysis upon knock-down of TAZ by two independent shRNAs	Co-expression
SRP125179	Natural Killer cells control tumor growth by sensing a growth factor	Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRß signaling. By screening a secretome library, we found that the human immunoreceptor NKp44 encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of IFN-? and TNF-a that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell cycle genes correlated with NCR2 and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, whilst cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. Overall design: RNAseq of NK cell and tumor cell samples in reponse to various stimuli	Co-expression
SRP125208	MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia [inhibitor MRT199665]	In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that transgenic Mef2cS222A/S222A mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, induced by MARK kinases in cells, and blocked by selective MARK inhibitor MRT199665, which caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C. These findings identify signaling-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease. Overall design: RNA-sequencing of human leukemia cell line with treatment of MARK inhibitor MRT199665.	Co-expression
SRP125231	Transcriptome analysis of HGC-27 after infection with Sendai virus	To better understand the interactions between Hippo signaling and antiviral signaling at transcription level, a high-throughput RNA-seq technology was utilized in gastric cancer cells HGC-27  at 48 hours after Sendai virus (SeV) infection. Overall design: The SeV-infected and non-infected cells were collected at 48 hours.  Each group had 2 biological replicates.	Co-expression
SRP125237	Total RNA deep sequencing (ribosomal depleted) of human umbilical vein endothelial cells exposed to hypoxia (0.2%) for 12h and 24h or kept under normoxic conditions.	Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is up-regulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-?2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function. Overall design: Human umbilical vein endothelial cell ribo-minus RNA deep sequencing. We used two replicate samples per 12h and 24h of normoxic and hypoxic conditions.	Co-expression
SRP125262	Gene expression profiling by RNA-seq in hTert-HME1 cell line treated with control or BRCA2 siRNAs and grown with or without EGF (epithelial growth factor)	Mammary epithelial cells were treated with control or BRCA2 siRNAs, then allowed to recover for 4 passages, then grown in mammary epithelial growth media supplemented with or without EGF (epithelial growth factor) for 2 passages (6 days). Overall design: Control siRNA transfection grown in media +EGF (3 replicates), control siRNA transfection grown in media -EGF (2 replicates), BRCA2 siRNA transfection grown in media +EGF (3 replicates), BRCA2 siRNA transfection grown in media -EGF (3 replicates)	Co-expression
SRP125274	single cell RNA-seq raw reads of normal growing MCF7	NA	Co-expression
SRP125275	single cell RNA-seq raw reads of normal growing MCF7, T47D and MDA-MB-231	NA	Co-expression
SRP125321	Circular RNA profiling reveals the different distribution/characteristic and possible transport mechanism among the subcellular fractions	We systemically investigated the circRNA profiles among the subcellular fractions of HepG2 cell, including nucleus, cytoplasm, mitochondria, ribosome, cytosol and exosome. Our studies reveals the wide distribution of circRNAs among the subcellular fractions except the mitochondria. Further comparative analysis indicate the differential subcellular distributions in expression, length, GC content, classification, alternative circularization and function of the parental genes. Through analyzing the binding motifs distribution of the transport-related RBPs among the subcellular circRNAs, we found that the different subcellular distribution characteristics of circRNAs might be resulted from the RBP-mediated selective transportation. It also implies that the circRNAs may follow the same transportation mechanism as linear RNAs: the RBPs specially recognize, bind to and transport the RNAs with the corresponding binding motifs, regardless of circular or linear RNAs. Our researches not only facilitate better understanding of the life history and molecular behavior of circRNA in cell, but also contribute to the exploration for new biological functions of circRNA. Overall design: Examined seven fractions of HepG2 (cell, nucleus, cytoplasm, ribsome, cytosol, exosome, mitochodria) and each has two repeats	Co-expression
SRP125326	Whole genome RNA-seq analysis of Wild type or Elf4-/- peritoneal macrophages and whole genome RNA-seq analysis of 293T cells transfected with miR-221 or empty vector.	Wild type or Elf4-/- peritoneal macrophages were infected with VSV, followed by whole genome RNA-seq analysis. 293T cells were transfected with miR-221 or empty vector, followed by whole genome RNA-seq analysis. Conclusions:Overexpression of miR-221 in cells facilitated viral infection and  inhibited the production of IFNß. Overall design: Wild type or Elf4-/- peritoneal macrophages were infected with VSV for 4 hours. Cells were harvested followed by whole genome RNA-seq analysis. 293T cells were transfected with miR-221 or empty vector. 6 hours later the cells were were harvested followed by whole genome RNA-seq analysis.	Co-expression
SRP125334	Triple vectors expand AAV transfer capacity in the retina	Maddalena et al. showed that the limited DNA transfer capacity (~4.7kb) of adeno associated viral (AAV) vectors can be expanded up to 14kb with triple AAV vectors for the efficient expression of the therapeutic CDH23 (10.1kb) and ALMS1 (12.5kb) genes. Overall design: cells infected with triple AAV vectors carrying 2 different transgenes in 3 biological replicates; RNA extracted from WT cells was used as control .	Co-expression
SRP125343	SEUSS: A scalable screening platform to assess transcriptomic and fitness effects of transcription factor overexpression	Understanding the complex effects of genetic perturbations on cellular state and fitness in human pluripotent stem cells (hPSCs) has been challenging using traditional pooled screening techniques which typically rely on unidimensional phenotypic readouts. Here, we use barcoded open reading frame (ORF) overexpression libraries with a coupled single-cell RNA sequencing (scRNA-seq) and fitness screening approach, a technique we call SEUSS (ScalablE fUnctional Screening by Sequencing), to establish a comprehensive assaying platform. Using this system, we perturbed hPSCs with a library of developmentally critical transcription factors (TFs), and assayed the impact of TF overexpression on fitness and transcriptomic cell state across multiple media conditions. We further leveraged the versatility of the ORF library approach to systematically assay mutant gene libraries and also whole gene families. From the transcriptomic responses, we built genetic co-perturbation networks to identify key altered gene modules. Strikingly, we found that KLF4 and SNAI2 have opposing effects on the pluripotency gene module, highlighting the power of our method to characterize the effects of genetic perturbations. From the fitness responses, we identified ETV2 as a driver of reprogramming towards an endothelial-like state. Overall design: Pooled transcription factor overexpression screens with scRNA-seq in ~35,000 cells across ten screens: 61 pluripotency/lineage TFs in hPSC media with five replicates, endothelial media with one replicate, multilineage media with two replicates; MYC mutant overexpression in hPSC media with one replicate; KLF family TF overexpression in hPSC media with one replicate.	Co-expression
SRP125359	pNF Cell Culture Data Portal	Diverse high throughput data was collected from cell lines cultured fromplexiform neurofibromas	Co-expression
SRP125394	Next Generation Sequencing assesses E2F7-regulated gene expression profiling	The goal of this experiment is to analyze global gene expression profiles during the cell  cycle after acute depletion of E2F7. Overall design: RNA was  isolated at three time-points following exit from cell cycle arrest, which represent G1/S  transition (0h), S phase (3h) and G2/M boundary (12h) of the cell cycle in cells transfected with siRNAs specific for  E2F7 (siE2F7) or with non-target control siRNAs (siNT)	Co-expression
SRP125396	Developmental differences between neonatal and adult human erythropoiesis	Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood- and peripheral blood-HSPC induced towards erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC and differentiated them in vitro. We observed that cells derived from cord blood proliferate 4.5 times more than cells derived from peripheral blood. However, these cells present a delay in their differentiation pattern due to increased quantities of progenitors, notably CFU-E. Using our method of immunophenotyping for the study of erythroid progenitors, we document the presence and maintenance of a specific population in peripheral blood-derived erythroid progenitors. This population, defined as IL3R-GPA-CD34+CD36+, has the ability to form both BFU-E and CFU-E colonies in colony-forming assays, reflecting a higher potential. To further understand the differences between cord blood- and peripheral blood- HSPC, we sorted all stages of erythropoiesis from both sources and compared their transcriptome. We document differences at the CD34, BFU-E, poly- and orthochromatic stages. Among the genes presenting the highest differences in expression, many are involved in the regulation of the cell cycle and autophagy. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis and highlight functional differences, critical to our understanding of the impact of the developmental origin of HSPCs on erythroid differentiation. Overall design: RNA was extracted from FACS-sorted cells at 8 distinct stages of erythropoiesis, derived from CB- and PB-CD34+ cells. cDNA libraries were prepared using the Illumina TruSeq kit and sequenced on the Illumina HiSeq 2500 (Epigenomics Core of Weill Cornell Medical College, New York). This sequencing strategy produced ~15-80 million 50bp single end reads per sample. For each distinct stage of erythropoiesis, 3 biological replicates were obtained from independently cultured and sorted samples from different donations. Quality control of reads was performed and low-quality reads removed. Reads were aligned to the hg19 reference genome using HISAT2. Raw read counts were extracted from the aligned reads using the featureCounts program. Differential expression analysis was done at each stage comparing the two original sources of CD34+ cells using the DESeq2 bioconductor package. Using gene expression data from each stage, the subset of genes differentially expressed as a function of HSPC source was clustered using divisive hierarchical clustering and split into 10 clusters. Gene ontology enrichment analysis of the biological process gene sets was then performed on each cluster using the cluster Profiler R package with the gene background of all genes expressed across all stages in both sources.	Co-expression
SRP125403	Global transcriptional responses to KI-MS2-008 treatment and Myc inactivation via doxycycline addition	The Myc/Max heterodimer has crucial roles in normal cellular processes such as cell proliferation, metabolism, apoptosis, and differentiation, but its activity is often deregulated in a majority of human cancers. In an effort to explore alternative modes of Myc perturbation, we identified KI-MS2-008 as a small molecule that binds Max and modulates Myc-driven transcription, and in some cellular contexts, KI-MS2-008 treatment leads to a decrease in c-Myc protein levels. As the Myc/Max heterodimer controls many cellular processes, we expected that treatment with this small molecule would cause changes in the transcriptome. We found that treatment with 10 µM KI-MS2-008 resulted in global alterations in the transcriptome, mimicking direct Myc inactivation with doxycycline in P493-6, a B cell line with a Tet-Off system for c-Myc expression. We also discovered enrichment of various Myc target gene sets in the genes downregulated in response to KI-MS2-008 treatment in P493-6 cells. This trend was also observed in ST486 cells, but not in P3HR1 cells, which were chosen as non-engineered B cell lines that were sensitive and insensitive, respectively, toward KI-MS2-008 in cell viability assays. Overall design: RNA-seq characterizing three B cell lines: P493-6 (an engineered, KI-MS2-008 sensitive cell line), ST486 (a non-engineered, KI-MS2-008 sensitive cell line), and P3HR1 (a non-engineered, KI-MS2-008 insensitive cell line). P493-6 cells were treated with 0.1 µg/mL doxycycline, 1 µM KI-MS2-008, 10 µM KI-MS2-008, or 0.4% DMSO for 45 minutes or 8 hours. ST486 cells were treated with 1 µM KI-MS2-008, 10 µM KI-MS2-008 or 0.4% DMSO for 45 minutes or 8 hours. P3HR1 cells were treated with 10 µM KI-MS2-008 or 0.4% DMSO for 8 hours. 4 replicates were performed for each condition.	Co-expression
SRP125416	The splicing factor SRSF1 regulates the radio-resistance of cancer cells through modulating the alternative splicing of PTPMT1	RNA-seq was performed on H1299 cells that stably knocking down SRSF1 or control, as well as these cells that were treated with ionizing radiation, in order to profile the alternative splicing events that were regulated by SRSF1 upon ionizing radiation. Overall design: Examination of different alternative splicing events in 4 types of cells	Co-expression
SRP125422	Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renal phenotype	Purpose: A proof of concept study examining the disease modelling capabilities of patient iPSC derived kidney organoids. Methods: A proband was diagnosed by genome sequencing with compound heterozygous IFT140 mutations. A one-step reprogramming/gene-editing protocol of proband fibroblasts was used to derive both uncorrected patient and isogenic gene-corrected induced pluripotent stem cells (iPSC) which were differentiated to kidney organoids. Organoids were examined by immunofluorescence. Additionally, epithelial cells magnetically sorted from whole kidney organoids underwent transcriptional profiling and spheroid culture. Results: Differential expression analysis of organoid epithelial cell fractions demonstrated apicobasal polarity, cell-cell junction and dynein motor assembly downregulation in patient organoids. Defective ciliary morphology and spheroid culture were rescued in gene corrected organoids. Conclusions: This study validates patient iPSC-derived kidney organoids as a novel, faithful and patient-specific model to further the study of inherited renal disease in regenerated, human, in vitro tissue. Overall design: RNA-seq of three replicates each of uncorrected (IFT140 compound heterozygous) and gene-corrected (IFT140 heterozygous) the epithelial cells isolated from patient iPSC derived kidney organoids.	Co-expression
SRP125430	Proteotranscriptomic profiling of potential E6AP targets in prostate cancer cells	Prostate cancer is a common cause of cancer-related death in men. E6AP, an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressor targets of E6AP, promyelocytic leukemia protein and p27. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approaches. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were significantly altered upon knockdown of E6AP. Pathway analyses supported the known phenotypic effects of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein, commonly deregulated in prostate cancer, was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight into the potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP. Overall design: Examination of candidate targets regulated by E6AP at transcript level	Co-expression
SRP125441	Comprehensive analysis of Long non-coding RNA expression in dorsal root ganglion reveals cell type specificity and dysregulation following nerve injury [human iPS]	Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron specific expression profiling of both known and novel Long Non-Coding RNAs (LncRNAs) in rodent DRG following nerve injury. We have identified a large number of novel LncRNAs expressed within rodent DRG, a minority of which were syntenically conserved between mouse and rat and which including both- intergenic and antisense LncRNAs. We have also identified neuron type-specific LncRNAs in mouse DRG, and LncRNAs that are expressed in human IPS cell-derived sensory neurons. We show significant plasticity in LncRNA expression following nerve injury, which in mouse is strain dependant. This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both naïve and injured DRG. Overall design: RNA-seq Illumina HiSeq4000 of IPSC and IPS derived sensory neurons	Co-expression
SRP125490	DNA methylation state is associated with the formation of loops and links in hematopoietic stem cells [RNA-seq]	We present the high resolution HiC study of genome folding in primary hematopoietic stem and progenitor cells. We investigated the relationship of chromosomal contacts with other epigenetic marks, particularly DNA methylation which is known to be important for appropriate stem cell differentiation. Overall design: We use RNA-Seq to probe relationship of chromosomal contacts and gene expression changes in hematopoietic stem cell	Co-expression
SRP125571	RNA-Seq of iPSC-derived neurons	Induced pluripotent stem cells (iPSC)-derived neurons were used to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) to mimic neural activity and its effects were assessed by RNA sequencing. Our results revealed the involvement of both protein-coding and long non-coding RNAs as well as a subset of human-specific genetic variants in response to neuronal activation. This study helps validate iPSCs as a valuable resource for the study of human neuronal networks.Because there is a strong association between cannabis use and schizophrenia, we treated neurons derived from hiPSCs with ?9- tetrahydrocannabinol (THC) either in a single dose (acute treatment) or 5 doses (chronic treatment) and followed this by activating treated and untreated neurons with KCl. RNA sequencing analyses revealed that THC administration severely dampened the neuronal transcriptional response following KCl treatment. The blunted response in THC-treated neurons closely resembles that previously observed in schizophrenia-associated iPSC-derived neurons. Results may help explain the significant phenotypic association between cannabis use and schizophrenia.	Co-expression
SRP125592	Gene induction by the USP6 oncogene in response to interferon	We examined the role of the USP6 oncogene in the patient-derived immortalized ewing sarcoma cell line RD-ES. RNA-sequncing revealed that USP6 induces numerous genes that overlap with genes induced by interferon treatment. When USP6-expressing cells were treated with IFN, many of the overlapping genes were synergistically upregulated, indicating an overlap in signaling pathways. Overall design: Examine the effects of USP6 and/or IFN on gene induction in RD-ES cells	Co-expression
SRP125594	Long noncoding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells	Long non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner where they function in various aspects of cell biology, often as key regulators of gene expression. In this study we established a role for lncRNAs in chondrocyte differentiation. Using RNA sequencing we identified a human articular chondrocyte repertoire of lncRNAs from normal hip cartilage donated by neck of femur fracture patients. Of particular interest are lncRNAs upstream of the master chondrocyte transcription factor SOX9 locus. SOX9 is an HMG-box transcription factor which is essential for chondrocyte development by directing the expression of chondrocyte specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of MSCs. Depletion of one of these lncRNA, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNAi disrupted MSC chondrogenesis, concomitant with reduced cartilage-specific gene expression and incomplete matrix component production, indicating an important role in chondrocyte biology. Specifically, SOX9 induction was significantly ablated in the absence of ROCR, and overexpression of SOX9 rescued the differentiation of MSCs into chondrocytes. Our work sheds further light on chondrocyte specific SOX9 expression and highlights a novel method of chondrocyte gene regulation involving a lncRNA. Overall design: Human neck of femure fracture hip cartilage chondrocyte mRNA profile generated by RNA-seq	Co-expression
SRP125636	Transcriptome of CCR1+CD14+ monocytes	To unravel the difference between monocytes recruited by HCC and monocytes in blood by RNA-Seq	Co-expression
SRP125640	Clean sequence reads of RNA-seq (transgenic cells +/- NAEK)	Investigation the effects of natural termination codons encoding	Co-expression
SRP125679	Concomitant BCORL1 and BRAF mutations in vemurafenib-resistant melanoma cells	BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current front-line therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAFV600E locus, and a missense point mutation of the transcriptional repressor BCORL1, in vemurafenib-resistant A375 melanoma cells. Functional data confirmed that truncated p47BRAFV600E and mutant BCORL1Q1076H both contribute to resistance. Interestingly, either endogenous BCORL1 silencing or ectopic BCORL1Q1076H expression mimicked the effects of a CRISPR/Cas9-edited BCORL1Q1076H locus, suggesting a change-of-function mutation. Transcriptomic data confirmed this hypothesis. Finally, we show that the pan-RAF inhibitor sorafenib is not affected by expression of BRAF deletion variant and effectively synergizes with vemurafenib to block resistant cells, suggesting a possible intervention for this class of mutants. Overall design: Nine total samples: 3 parental plus 3 BCORL1-WT and 3 BCORL1-MUT overexpressing cells	Co-expression
SRP125683	Gene expression profile of human placenta from T. Cruzi infected mothers	Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers.   Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected.  Results.  Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated.   Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response  could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease.    Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers.   Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected.  Results.  Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated.   Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response  could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Overall design: Serodiagnosis of pregnant women was done by means of conventional serological methods and carried out by the respective health centres based on routine assays. In maternal and umbilical cord blood samples T. cruzi presence was tested using multiplex Real Time PCR as previously described [6]. Maternal infection with other pathogens that produce congenital transmission and adverse pregnancy outcome were considered as exclusion criteria, as well as missing data or incorrect sampling.  Fresh normal placentas were obtained after labour from vaginal or caesarean deliveries and placed within 24 hours at 4°C. Each placenta was dissected and the middle section [7] at 2 cm distance from the umbilical cord was isolated and placed into RNAlater solution (Applied Biosystems, Foster City, CA). Total RNA was extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and stored at -80°C until used.   Transcriptomic studies. A RNA-Seq experiment was done in 9 pools of 2 different placental RNA samples each: 3 pools (C1, C2 and C3) belonging to placentas from seronegative mothers (SN) and 6 pools (TC4 to TC9) from seropositive mothers (SP). Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. The cDNA Libraries were prepared according to Illumina''s TruSeq Stranded Total RNA with Ribo-Zero Gold for Human and a Hiseq 2.500 Illumina platform with 100 bp paired-end reads was used for sequencing	Co-expression
SRP125710	Rett Syndrome in a dish model	Several recent studies have suggested that genes that are longer than 100 kb are more likely to be misregulated in neurological diseases associated with synaptic dysfunction, such as autism and Rett syndrome. These length-dependent transcriptional changes are modest in Mecp2 mutant samples, but, given the low sensitivity of high-throughput transcriptome profiling technology, the statistical significance of these results needs to be re-evaluated. Here, we show that the apparent length-dependent trends previously observed in MeCP2 microarray and RNA-Sequencing datasets, particularly in genes with low-fold changes, disappeared when compared to randomized control samples. As we found no similar bias with Nanostring technology, this bias seems to be particular to PCR amplification-based platforms. Transcriptional alterations with large fold-change values, however, can reveal an authentic long gene bias. Discriminating authentic from artefactual length-dependent trends requires establishing a baseline from randomized control samples. Overall design: RNA-Seq iPSC, NPC and Neuron dataset of Rett Syndrome	Co-expression
SRP125752	Mitochondrial translation requires folate-dependent tRNA methylation	This study investigates the role of folate one-carbon metabolism in mitochondrial physiology. In particular it highlights the need for SHMT2-derived 5,10-methylene-THF to modify mitochondrial tRNAs, which is crucial for mitochondrial translation and therefore oxidative phosphorylation.	Co-expression
SRP125806	Circular RNAs are super abundant in cervical tumor and plasma detected by high throughput microarray [RNA-Seq]	Circular RNAs (circRNAs) are a new class of endogenous and regulatory non-coding RNAs, but their expressions in tumor and plasma are largely unknown. Here, our study firstly suggested that microarray should be more efficient than RNA sequencing for circRNA profiling. Then, we detected ~80,000 circRNAs expressed in cervical tumors and matched normal tissues by microarray, and ~23,000 of them are differently expressed. The numbers of up- and down-regulated circRNAs during tumorigenesis are almost equal. In addition, we discovered that the expression of different circRNA isoforms from the same linear RNA also different. Strikingly, as much as ~18,000 circRNAs could be robustly detected in plasmas, and ~8,000 circRNAs show different expression after surgery of tumor removal. Altogether, taking advantage of the huge number of circRNAs detected in tumor and plasma, we provide strong evidence for circRNA expression, regulation and potential clinical application as non-invasive biomarkers. Overall design: The circRNA expression in Universal Human Reference RNA (UHRR, 2 replicated samples) was compared to circRNA expression in Ambion's Human Brain Reference total RNA (HBRR, 2 replicated samples) from the Microarray Quality Control (MAQC) project; The circRNA expression in cervical tumor (10 samples) was compared to circRNA expression in adjacent normal tissue (control, 10 samples) of 10 patients; The mRNA expression in cervical tumor (10 samples) was compared to mRNA expression in adjacent normal tissue (control, 10 samples) of 10 patients; The circRNA expression in preoperative plasma samples (control,7 samples) was compared to circRNA expression in postoperative plasma samples (14 samples) of 8 out of 10 cervical cancer patients.Microarray based circRNA expression profiles were acquired using CapitalBio circRNA Human Gene Expression Microarray V1.0 screening for 87,935 distinct human circRNA candidates.	Co-expression
SRP125822	TGFß1-mediated functional inhibition of mesenchymal stromal cells in MDS and AML	Mesenchymal stromal cells (MSC) are involved in the pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but how they contribute to the expansion of malignant cells and hematopoietic failure is poorly understood. To further characterize the pathological phenotype we performed RNA sequencing of MSC from patients with MDS and AML. Data analysis revealed a specific molecular signature with a significant overlap of genes commonly deregulated in all MDS subtypes and in AML. Pathway analysis revealed a strong enrichment of genes related to osteogenesis, senescence, inflammatory processes and inhibitory cytokines thereby reflecting the structural and functional deficits of MDS- and AML-derived MSC on a molecular level. Further analysis identified TGFß1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to TGFß1 healthy MSC adopted a phenotype reminiscent of that observed in primary patient-derived MSC which was characterized by impaired growth potential, osteogenic differentiation capacities, a specific gene expression profile and diminished stromal hematopoietic support. These suppressive effects of TGFß1 on MSC functionality were abrogated by SD-208, an established inhibitor of TGFß receptor signalling. Blockade of TGFß signalling by SD-208 also restored the osteogenic differentiation capacity of patient-derived MSC, thus confirming the role of TGFß1 in the bone marrow microenvironment of patients with MDS and AML. Our findings establish TGFß1 as a relevant trigger causing functional inhibition of MSC in MDS and AML and identify SD-208 as a candidate for the reversal of these effects Overall design: RNA sequencing of MSCs from 3 Healthy, 3 RCMD, 3 RAEB and 3 AML patients	Co-expression
SRP125842	Global Transcriptional analysis of human spinal cord and neocortical neuroepithelial stem (NES) cells	We report the transcriptional profile of human spinal cord and neocortical neuroepithelial stem cells (SC-NES and NCX-NES cells) to identify potential engraftment markers in the lesioned spinal cord. We report that cells with a homologous neuroanatomical origin robustly integrate in the host tissue compared to cells with a different regional identity. Specifically, we describe that SC-NES cells display elective integration properties in the lesioned spinal cord compared to NCX-NES cells and that these properties are due to a combination of intrinsic and extrinsic factors. Upon transplantation, SC-NES cells differentiate into neurons and glial cells and extend lond-distance axons, whereas NCX-NES cells remain undifferentiated and display poor integration properties. SC-NES cell upregulate genes related to neurogenesis. In particular. we emphasize the upregulation of MTURN (maturin), ATCAY, PTN (pleiotropin), KAL1 (anosmin), SYT4 and SYT13. Overall design: We handled 6 samples, 3 for SC-NES cells and 3 for NCX-NES cells. Each sample was handled in triplicate for a total of 18 samples. For SC-NES cells we had:  undifferentiated cells in vitro (SC-NES), differentiated for 2 months in vitro (SC-Neurons) and differentiated for two months in vivo upon tranplantation (SC-Graft). Similarly, we had three samples for NCX-NES cells: undifferentiated NCX-NES cells, differentiated in vitro for two months (NCX-Neurons) and differentiated for two months in vivo after transplantation (NCX-Graft)	Co-expression
SRP125882	Transcriptomic analysis to map mechanisms of viral replication control in HIV-1 positive Elite Controllers	In order to understand the underlying mechanisms, which ensure that disease progression is prevented in EC, a comprehensive analysis of clinical phenotypes coupled to genetics and biomolecular mechanisms is required. The rapidly increasing accessibility of genetic and biomolecular expression data from new high-throughput technologies is the foundation to shift the traditional phenotype-first approach to explorative genetic or molecular data-first approaches. In this study, we aimed to explore a comprehensive analysis of host transcriptomics and proteomics data coupled to clinical phenotypes in a well-defined Swedish EC cohort with up to 20 years of clinical follow-up data.	Co-expression
SRP125893	RNA G-quadruplex secondary structure promotes alternative splicing via the RNA binding protein hnRNPF	It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex forming capacity promote exon inclusion. Destroying G-quadruplex forming capacity while keeping G-tracts intact abrogates exon inclusion. Analysis of RNA binding protein footprints revealed that G-quadruplexes are enriched in hnRNPF-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an EMT-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA datasets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G-quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression. Overall design: PolyA-RNA-sequencing of two non-specific shRNA and two shhnRNPF HMLE cell lines	Co-expression
SRP125932	RNA-seq for U937 cells with or without 3 day differentiation with PMA and recovery	Sequencing data related to our manuscript "Systematic identification of general and context-specific regulators of phagocytosis using magnetic genome-wide CRISPR screens" Overall design: Two groups of U937 cells were sequenced before and after PMA differentiation. One group carried Streptococcus pyogenes Cas9 and a safe-harbor control sgRNA, and the second group was a clonally expanded U937 line expressing GFP. Each group was separated into eight separate wells at d0, and half of the wells were treated with 50 nM PMA. At day 3, undifferentiated cells were split to prevent overcrowding, and differentiated cells were trypsinized and replated. Cells were allowed to recover for 2 additional days before cells were lysed for RNA harvest and sequencing.	Co-expression
SRP125944	IMP3 regulated gene expression in breast cancer cells	IMP3 (IGF2-mRNA binding protein 3) is a member of a family of IGF2-mRNA binding proteins that function in RNA stabilization, trafficking and localization.  It exhibits the properties of an oncofetal protein and its expression correlates with the aggressive behavior of many tumors.  In breast cancer, IMP3 is associated with the highly aggressive triple-negative subtype (TNBC) The challenge is to identify specific proteins and functions that are regulated by IMP3. As an approach to this problem, we compared the mRNA expression profile of SUM-1315 cells, a TNBC cell line, to the same cells that had been depleted of IMP3. Overall design: SUM-1315 breast cancer cells were were infected with lentivirus for control shRNA and two different IMP3 shRNAs and processed for RNA-sequencing	Co-expression
SRP125952	HMGA2 Promotes Long-Term Engraftment and Myelo-Erythroid Differentiation of Human Hematopoietic Stem and Progenitor Cells	Identification of determinants of fate choices in hematopoietic stem cells (HSCs) is essential in order to improve the clinical use of HSCs and to enhance our understanding of the biology of normal and malignant hematopoiesis. Here we show that high mobility group AT hook 2 (HMGA2), a non-histone chromosomal binding protein, is highly and preferentially expressed in HSCs and the most immature progenitor cell subsets of fetal, neonatal and adult human hematopoiesis. Knockdown of HMGA2 by shRNA impaired the long-term hematopoietic reconstitution of cord blood (CB) derived CB CD34+ cells. Conversely, overexpression of HMGA2 in CB CD34+ cells led to an overall enhanced reconstitution in serial xenotransplantation assays accompanied by a skewing towards the myeloerythroid lineages. RNA-Seq analysis showed that enforced HMGA2 expression in CD34+ cells induced gene expression signatures associated with differentiation towards megakaryocyte-erythroid and myeloid lineages, as well as signatures associated with growth and survival, which at the protein level were coupled with a strong activation of AKT. Taken together our findings demonstrate a key role of HMGA2 in regulation of both proliferation and differentiation of human HSPCs. Overall design: RNA-Seq  on control and HMGA2 transduced CD34+ cells.	Co-expression
SRP125954	Mapping human pluripotent stem cell differentiation pathways via high throughput single-cell RNA-sequencing	Human pluripotent stem cells (hPSCs) provide both powerful models for studying cellular differentiations, and unlimited sources of cells for regenerative medicine. However, a comprehensive single cell level differentiation roadmap for hPSCs has not been achieved yet. Here, we used high throughput single-cell RNA-sequencing (scRNA-seq) method, based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body (EB) system. We presented a cellular landscape for hPSC early differentiations covering different cellular lineages, including neural cell, muscle cell, endothelial cell, stromal cell, liver cell, and epithelial cell. Through pseudotemporal analysis, we constructed the differentiation trajectories of these progenitor cells and revealed the gene expression dynamics in the process of differentiation. We reset Primed H9 into Na誰ve-like H9 and studied cell state transition process via scRNA-seq. We found that mesendoderm genes are enriched in Na誰ve-like H9. Functionally, Na誰ve-like H9 showed better potency for differentiation into the hematopoietic lineages. We constructed the differentiation landscape of hPSC early differentiation by scRNA-seq analysis. We offer new insights into molecular pathways of early embryonic lineages that can be harnessed for optimization of differentiation protocols. (Pipeline for C1 data demultiplex : https://github.com/bioeauty/sccpipe) Overall design: scRNA-seq analysis of na誰ve and primed human pluripotent stem cells and embryoid bodys	Co-expression
SRP125959	The human blood-nerve barrier transcriptome	We report the application of whole exome sequencing to comprehensively deduce the normally conserved transcript profile of endoneurial endothelial cells that form the adult human blood-nerve barrier by combining in vitro and in situ analyses Overall design: Examination of early and late passage primary human endoneurial endothelial cells combined with laser capture microdissected endoneurial microvessels from 4 histologically normal cryopreserved adult sural nerve biopsies	Co-expression
SRP125960	Transcriptome analysis of SKI knock-out in HL60 cells	Whole transcriptome for SKI knock-out and control HL60 cells was sequenced. SKI control and knockout samples were compared to find differentially expressed genes. Differentially expressed genes were further analysed to find the significance of SKI in HL60 cells. Overall design: Examining of SKI dependent transcriptome in HL60 cells using RNAseq.	Co-expression
SRP125961	UC Colon RNAseq subset analysis	RNAseq was used to confirm findings from microarrays and identify additional genes different between inflamed and non-inflamed tissue Overall design: Multiple biopsies were taken from UC subjects to better understand the variability of gene expression	Co-expression
SRP125962	Novel Targeting of Transcription and Metabolism in Glioblastoma	Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become effective therapeutics for GBM patients. Experimental Design: To investigate TG02, an agent with known penetration of the Blood-Brain Barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We utilized human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02.  Mechanistic studies included TG02-induced transcriptional regulation, apoptosis and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays. Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of anti-apoptotic proteins, and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue. Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Overall design: The RNA sequencing was carried out to analyze the profile of RNA expression following 0.1% of DMSO (control), TG02, TMZ, and TG02/TMZ treatment, in duplicate, in GSC923 cells.	Co-expression
SRP125977	Transcriptome analysis of PRMT6 knock-out in NT2/D1 cells	Whole transcriptome for PRMT6 knock-out and control NT2/D1 cells with and without ATRA (all-trans retinoic acid) was sequenced. These samples were compared to each other to find differentially regulated genes and PRMT6-dependent transcriptome in pluripotency and differentiating cells. Overall design: Examining of PRMT6-dependent transcriptome in NT2/D1 cells using RNAseq.	Co-expression
SRP125992	Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors	DNA methylation is thought to contribute to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements (TEs). In this study, we used CRISPR/Cas9 technology to delete DNMT1, the key maintenance DNA methyltransferase in human neural progenitor cells (hNPCs). Surprisingly, and in contrast to previous findings in mouse somatic cells, inactivation of DNMT1 in hNPCs resulted in viable proliferating cells despite the global loss of DNA CpG-methylation. DNA demethylation led to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of TEs remained silent. The activated L1s acted as alternative promoters for many protein-coding genes involved in neuronal functions, revealing a hominoidspecific L1-based transcriptional network controlled by DNA methylation that influences neuronal protein-coding genes. Our results give a novel mechanistic insight into the role of DNA methylation in silencing TEs in somatic human cells, as well as further implicating L1s in human brain development and disease. Overall design: CRISPR/Cas9 mediated disruption of DNMT1 in human neural progenitor cells. Guides targeting LacZ as control. Three replicates per condition. 2X125 paired-end RNA-sequencing. 2x150bp WGBS. 1x50bp ChIP-seq. Please note that the hEmbryo_PE150.hg38*.txt processed data files are associated with the GSM2940637-GSM2940642 samples.	Co-expression
SRP125998	Dissecting the transcriptome landscape of human neural retina and retinal pigment epithelium by Single-cell RNA sequencing analysis	The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle and ligand-receptor interaction related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies. Overall design: Here we performed single cell RNA-seq analysis for human embryonic neural  retina and retinal pigment epithelium, covering the developmental stages of 5-24 weeks after gestation.	Co-expression
SRP126048	Effect of CBL0137 on nascent transcription in HT1080 cells [RNA-seq]	Small molecule curaxin CBL0137 has broad anti-cancer activity in different preclinical models. It interferes with histone-DNA interactions via binding to DNA without causing DNA damage. It resposents first in class "chromatin damaging" agent without genotoxic properties. Its effect on the transcription in human tumor cells was evaluated. DNA-targeting small molecules are widely used for anticancer therapy based on their ability to induce cell death, presumably via DNA damage. DNA in the eukaryotic cell is packed into chromatin, a highly-ordered complex of DNA, histones, and non-histone proteins. These agents perturb chromatin organization. However, the mechanisms, consequences, and impact of the alterations of chromatin structure in relation to their anti-cancer activity is unclear because it is difficult to separate DNA damage and    chromatin damage    in cells. We recently demonstrated that curaxins, small molecules with broad anticancer activity, bind DNA without causing detectable DNA damage by interfering with histone/DNA interactions and destabilizing the nucleosome. Chromatin unfolding caused by curaxins is sensed by histone chaperone FACT. FACT binds unfolded nucleosomes, which leads to    chromatin trapping    or c-trapping. In this study, we investigated whether other DNA-targeting small molecules disturb chromatin and cause c-trapping. We found that only compounds directly binding DNA induce    chromatin damage    and c-trapping. Chromatin damage may occur in the absence of DNA damage and is dependent on the mechanism of compound binding to DNA and its ability to bind chromatinized DNA in cells. We show that FACT is sensitive to a plethora of nucleosomes perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Most importantly, the cytotoxicity of DNA-binding small molecules correlates with their ability to cause    chromatin damage   , but not DNA damage. Overall design: HT1080 cells were treated with CBL0137 for 1 hour at 1uM. EU was added for the last 15 minutes. Newly synthesized RNA was isolated using Click-iTâ„¢ Nascent RNA Capture Kit (Invitrogen, cat#C10365) according to manufacturer instruction.	Co-expression
SRP126064	transcriptomic profiling of HEK293 cells upon individual knockdown of the splicing factors  RBM17, U2SURP or CHERP	We found that the core spliceosomal proteins RBM17, U2SURP and CHERP form a protein complex regulating alternative splicing and expression of a whole network of RNA binding proteins Overall design: RNA sequencing of triplicate RNA samples from HEK293 cells treated with siRNAs against RBM17, U2SURP , CHERP or SCRAMBLE sequence	Co-expression
SRP126075	Low carbohydrate diet study for non-alcoholic fatty liver disease patients	We performed a short-term dietary intervention with a low-carbohydrate diet in obese subjects with NAFLD Overall design: Transcriptomes were generated from liver biopsies of seven non-alcoholic fatty liver disease patients before/after low carbohydrate diet	Co-expression
SRP126077	Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network	In this study we explore the gene set that is selectively expressed in chondrocytes and therefore determines the unique properties and functions of cartilage tissue. Through identification of cartilage-selective transcription factors, lncRNAs, enhancers and protein-coding genes, we address the determinants of cartilage-selective gene expression, including interactions among the regulatory molecules and selectively active promoters, which define the pattern of gene expression and ultimately chondrocyte biology. Among 34 previously undescribed cartilage selective lncRNAs, one particular lncRNA was found to be co-expressed with and reciprocally regulated by SOX9, the master transcriptional regulator of chondrogenesis, revealing a new aspect of the regulation of the gene for this critical determinant of chondrocyte function. Finally, we relate cartilage-selective gene expression to the human and mouse skeletal disorders that result from mutations in many of the selectively regulated genes, providing clinical context to the basic biological discoveries. Overall design: Identification of cartilage-selective genes in human fetal cartilage by RNA-seq	Co-expression
SRP126099	Regulation of alternative splicing induced by paclitaxel in human non-small cell lung cancer	RNA-seq was performed on A549 cells treated with paclitaxel or control, in order to profile the alternative splicing events that were regulated upon paclitaxel treatment. Overall design: Examination of different alternative splicing events in 2 types of cells	Co-expression
SRP126108	Gene expression changes in human iPSC-derived cardiomyocytes after X-ray irradiation	Within the present study we evaluated hiPSC-CMs as a possible methodological extension for the assessment of organ specific responses to ionizing radiation regarding gene expression changes. We aimed to review the feasibility of hiPSC-CMs as a valid testing model for gene expression changes and to determine alterations within the gene expression pattern of hiPSC-CMs after exposure to X-ray radiation, subsequently. Overall design: 2 samples with 3 biological replicates, one sham irradiated, one irradiated with 5 Gy x-ray radiation	Co-expression
SRP126128	RNA sequence of ISL1-MSCs and Ctrl-MSCs	The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed as a marker of cardiovascular progenitor cells. This study investigated whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) improves myocardial infarction (MI) treatment outcomes. The lentiviral vector EF1a-ISL1 was constructed using the Multisite Gateway System, and used to transduce hMSCs.	Co-expression
SRP126155	Homo sapiens	Nasal epithelial cells were exposed to air, cigarette smoke, and heated tobacco aerosols. The RNA was extracted and sequenced to compare the transcriptional response of the aerosol treatments vs air ctl.	Co-expression
SRP126169	Cancer-Associated Long Noncoding RNA SMRT-2 Controls Epidermal Differentiation	Characterization of a squamous cell carcinoma specific lncRNA	Co-expression
SRP126174	RNASEQ Analysis of sh-TRC and sh-MIR100HG in the triplex negative breast cancer	Purpose:The goals of this study are using next generation sequencing to identify differentially expressed genes by analyzing knockdown of MIR100HG in triple-negative breast cancer Overall design: Knockdown MIR100HG with two shRNAs in triple negative breast cancer MDA-MB231 cells	Co-expression
SRP126189	RTP determination in cell lines	Nine cell lines were analyzed for transcriptomics and proteomics analyses. We wanted to measure the ratio between protein and mRNA in different cell lines and see if it is conserved across them. Overall design: We performed parallel transcriptomics and proteomics analyses in three different biological replicates in nine cell lines derived from different organs.  This series contains only the transcriptome data.	Co-expression
SRP126212	Homo sapiens Transcriptome or Gene expression	Gene expression profiling of healthy skin tissue.	Co-expression
SRP126244	Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation	RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs).   Analysis from the TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of bladder cancers.  Here we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers.  Structure-function studies indicate the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs.  In urothelium, we find PPAR agonism is sufficient to drive growth factor independent growth, but only after deletion of the tumor suppressors Kdm6a and Trp53.  Similarly, mutant RXRA stimulates growth factor independent growth, in a manner reversible by PPAR inhibition.  These studies reveal a pro-tumorigenic interaction between loss of tumor suppressors and PPAR activation and implicate PPARs as targetable drivers of bladder cancer. Overall design: Two independent bladder cancer cell lines, JMSU-1 and 575A, were transfected with retrovirus to generate stable cell lines expressing either human wild-type RXRA (RXRAwt) or a mutant form of RXRA, RXRA S427F (RXRAS427F).  RNA-seq was performed in biological triplicate on RXRAwt-expressing cells treated with vehicle or the PPARG agonist pioglitazone (pio), and RXRAS427F-expressing cells treated with vehicle.  Fragments were sequenced on an Illumina HiSeq-2500 or HiSeq-3000.  Transcriptomes in the wild-type and S427F conditions were compared to establish a causal role of the RXRA hot-spot mutation S427F in the hyper-activation of PPAR singling.	Co-expression
SRP126247	Identification of PRMT5-dependent genes in ESA+CD24lowCD44+ MCF7 cells	PRMT5 has been associated with poor prognosis in breast cancer. Here, we identify genes which are dependent on PRMT5 expression in MCF7 ESA+CD24lowCD44+ breast cancer stem cells by RNA-seq Overall design: RNA-seq profiling of ESA+CD24lowCD44+ cells from MCF7 shCTRL or shPRMT5 cell lines. Three independent ESA+CD24lowCD44+ cell populations from MCF7 shCTRL or shPRMT5 cells were isolated by flow cytometry.	Co-expression
SRP126260	Alternative splicing of differentiated myeloid cell transcripts after infection by Anaplasma phagocytophilum impacts a selective group of cellular programs	Eukaryotic proteome diversity exceeds that encoded within individual genes, and results in part from alternative splicing events of pre-messenger RNA. The diversity of these splicing events can shape the outcome in development and differentiation of normal tissues, and is important in pathogenic circumstances such as cancer and some heritable conditions. A role for alternative splicing of eukaryotic genes in response to viral and intracellular bacterial infections has only recently been recognized, and plays an important role in providing fitness for microbial survival, while potentially enhancing pathogenicity. Anaplasma phagocytophilum survives within mammalian neutrophils by reshaping transcriptional programs that govern cellular functions. We applied next generation RNAseq to ATRA-differentiated HL-60 cells established to possess transcriptional and functional responses similar to A. phagocytophilum-infected human neutrophils. This demonstrated an increase in transcripts with infection and high proportion of alternatively spliced transcript events (ASEs) for which predicted gene ontology processes were in part distinct from those identified by evaluation of single transcripts or gene-level analyses alone. The alternative isoforms are not on average shorter, and no alternative splicing in genes encoding spliceosome components is noted. Although not evident at gene-level analyses, individual spliceosome transcripts that impact nearly all spliceosome components were significantly upregulated. How the distinct GO processes predicted by ASEs are regulated by infection and whether they are relevant to fitness or pathogenicity of A. phagocytophilum should be addressed in more detailed studies. Overall design: RNAseq analysis of gene expression, transcript expression and transcript isoform expression in differentiated HL-60 cells infected or not by A. phagocytophilum.	Co-expression
SRP126273	Single cell profilng of hCS derived from hiPSC cultured in feeder-free conditions	Single cell gene expression profilling of hCS derived from iPSC at day 105 of differentiation Overall design: 3 samples of hiPSC cultures, each derived from a donor	Co-expression
SRP126289	Impact of regulatory variation across human iPSCs and differentiated cells [RNA-seq]	Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. Here we investigate the use of iPSCs and iPSC-derived cells to study the impact of genetic variation across different cell types and as models for the genetics of complex disease. We established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring RNA, chromatin accessibility and DNA methylation. Regulatory variation between individuals is lower in iPSCs than in the differentiated cell types, consistent with the intuition that developmental processes are generally canalized. While most cell-type- specific regulatory effects lie in chromatin that is open only in the affected cell-types, we find that 20% of cell-type specific effects are in shared open chromatin. Finally, we developed deep neural network models to predict open chromatin regions in these cell types from DNA sequence alone and were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on tissue-specific chromatin accessibility. Our results provide a framework for using iPSC technology to study regulatory variation in cell types that are otherwise inaccessible. Keywords: Expression profiling by high throughput sequencing Overall design: Immortalized lymphoblastoid cell lines from 58 African individuals were reprogrammed into induced pluripotent stem cells	Co-expression
SRP126310	Bulk RNA sequencing of kidney tubuloids and the tissue that the tubuloids were derived from	Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from	Co-expression
SRP126311	Single cell RNA sequencing of kidney tubuloids and the tissue that the tubuloids were derived from	Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated single cell transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from	Co-expression
SRP126344	Transcriptomes of human monocytes after ex vivo exposure to uric acid	Innate immune memory, also refered to as trained immunity (TRIM) is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components.  In this study  we exposed monocytes from healthy donors to uric acid ex vivo, and analyzed the effect of this exposure on gene expression changes. After 'uric acid' or 'media only' treatments, monocytes were exposed to LPS for 4 hours to measure they response to this pyrogen. Overall design: Monocytes from healthy donors were cultured in the presence of uric acid for 24 hours and then exposed to LPS for 4 hours. Cells were then collected for RNA-seq.	Co-expression
SRP126371	Ribothrypsis, a novel process of canonical mRNA decay, mediates ribosome-phased mRNA endonucleolysis.	By developing Akron-Seq, a novel approach that captures native 3' and 5' ends of capped and polyadenylated RNAs respectively, we show that canonical human mRNAs are subject to repeated, cotranslational, ribosome-phased, endonucleolytic cuts in a process that we term ribothrypsis. Overall design: Capturing native 3' ends of capped and 5' ends of polyadenylated mRNAs	Co-expression
SRP126417	RNA-sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA	We report RNA-sequencing data of 80 tumor-educated blood platelet (TEP) samples isolated from 39 patients with lower-grade glioma (LGG) and 41 healthy donors (HD). This dataset can be employed as input for the thromboSeq source code (available via GitHub: https://github.com/MyronBest/) to reproduce the thromboSeq drylab pipeline. Overall design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the humane reference genome using STAR, and intron-spanning reads were summarized using HTSeq.	Co-expression
SRP126422	RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin	Keratinocyte (KC) hyper-proliferation and epidermal thickening are characteristic features of psoriasis lesions, but the specific contributions of KCs to plaque formation are not fully understood. This study used RNA-seq to investigate the transcriptome of primary monolayer KC cultures grown from lesional (PP) and non-lesional (PN) biopsies of psoriasis patients and control subjects (NN). Whole skin biopsies from the same subjects were evaluated concurrently. RNA-seq analysis of whole skin identified a larger number of psoriasis-increased differentially expressed genes (DEGs), but analysis of KC cultures identified more PP- and PN-decreased DEGs. These latter DEG sets overlapped more strongly with genes near loci identified by psoriasis genome-wide association studies and were enriched for genes associated with epidermal differentiation. Consistent with this, the frequency of AP-1 motifs was elevated in regions upstream of PN-KC-decreased DEGs. A subset of these genes belonged to the same co-expression module, mapped to the epidermal differentiation complex, and exhibited differentiation-dependent expression. These findings demonstrate a decreased differentiation gene signature in PP/PN-KCs that had not been identified by pre-genomic studies of patient-derived monolayers. This may reflect intrinsic defects limiting psoriatic KC differentiation capacity, which may contribute to compromised barrier function in normal-appearing uninvolved psoriatic skin. Overall design: Samples were obtained from lesional skin of psoriasis patients (PP), uninvolved skin of psoriasis patients (PN), and normal skin from control individuals (NN). RNA was extracted from full-thickness skin biopsies of keratinocytes (KCs) grown as monolayer cutures. Samples were obtained from 4 psoriasis patients (individuals 1 - 4) and 4 control subjects (individuals 5 - 8).	Co-expression
SRP126429	Paired Heavy and Light Chain Immunoglobulin Reconstruction in Single-Cell RNA-Seq Data	We generated scRNA-Seq data for 20 human plasmablasts induced by seasonal flu vaccination.To reconstruct the paired heavy and light chain antibody genes, we developed several different in silico filtering strategies to enrich immunoglobulin transcripts, and then applied de novo assembly. This method successfully reconstructed productive IgH and IgL chains in 100% of cells analyzed. The accuracy of clonotype-assignment of individual cells was 94.5-98%, as validated by comparing BCR sequences reconstructed from NGS to those obtained by conventional single-B cell cloning methodology. This makes it possible to link the transcriptional programming of individual B cell clones at critical developmental stages with the eventual fate of the clonal lineage in vivo.	Co-expression
SRP126442	Homo sapiens Transcriptome or Gene expression	Transcriptome sequencing analysis of KG-1a cells transfected with lentivirus-empty vector (CTRL-KG-1a) or lentivirus-miR-34c-5p vector (34cOE-KG-1a).	Co-expression
SRP126485	Metformin Regulates Metabolic and Non-Metabolic Pathways in Skeletal Muscle and Subcutaneous Adipose Tissues of Older Adults	Administration of metformin increases healthspan and lifespan in model systems and evidence from clinical trials and observational studies suggests that metformin delays a variety of age-related morbidities. Although metformin has been shown to modulate multiple biological pathways at the cellular level, these pleiotropic effects of metformin on the biology of human aging have not been studied. We studied ~70-year-old participants (n=14), in a randomized, double-blind, placebo-controlled, crossover trial in which they were treated with 6 weeks each of metformin and placebo. Following each treatment period, skeletal muscle and subcutaneous adipose tissue biopsies were obtained, and a mixed-meal challenge test was performed. As expected, metformin therapy lowered 2-hour glucose, insulin AUC, and insulin secretion compared to placebo. Using FDR<0.05, 647 genes were differentially expressed in muscle and 146 genes were differentially expressed in adipose tissue. Both metabolic and non-metabolic pathways were significantly influenced, including pyruvate metabolism and DNA repair in muscle and PPAR & SREBP signaling, mitochondrial fatty acid oxidation and collagen trimerization in adipose. While each tissue had, a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFß1 and miRNA-29b, that may explain tissue-specific transcriptomic changes in response to metformin treatment. This study provides the first evidence that, in older adults, metformin has metabolic and non-metabolic effects linked to aging. These data can inform the development of biomarkers for the effects of metformin, and potentially other drugs, on key aging pathways. Key words: Aging, biguanides, gene expression, metabolism, upstream regulators Overall design: This study 'MILES: Metformin in Longevity Study'' (ClinicalTrials.gov identifier: NCT02432287) is a randomized, double-blind, placebo controlled, crossover study. 14 men and women aged 60 and older, with impaired glucose tolerance based on 75g Oral Glucose Tolerance Test completed the study. Following a screening visit, the study consisted of two randomly assigned 6-week treatment periods (metformin and placebo). Metformin was introduced at 500 mg twice daily, and increased incrementally to 2000 mg daily at the end of 2 weeks to minimize gastrointestinal side effects. At the end of each 6-week treatment period, skeletal muscle and subcutaneous adipose biopsies were obtained. The samples were immediately homogenized in Trizol, frozen in liquid nitrogen and stored at -80°C for subsequent mRNA extraction. Total RNA was extracted using QIAGEN's RNeasy Mini kit. Samples showing minimal degradation, as measured by RIN > 7 were processed for library preparation and sequenced in two/three technical replicates using multiplexed 100bp paired-end sequencing on Illumina HiSeq2500. Raw sequence reads were preprocessed using WASP 3.0, and FastQC was used for quality control. The raw FASTQ files were trimmed for adapter sequences using Trim Galore! RSEM algorithm (v1.2.25) in conjunction with STAR aligner (v2.4.2a) were used to quantify the raw reads to GRCh38 build of the reference human genome with transcript annotations from GENCODE. The raw counts matrix was exported from RSEM to edgeR, normalized using TMM normalization and used for differential expression analysis.	Co-expression
SRP126487	Differential RNASeq of human bronchial epithelial cells stimulated with RIG-I ligand SLR14	The purpose of this study was to assess transcriptome changes in primary human airway epithelial cells following stimulation with RIG-I ligand. Overall design: MRNA profiles were generated from primary human airway epithelial cells at rest or following stimulation with RIG-I ligand.	Co-expression
SRP126489	Differential RNASeq of human nasal epithelial cells stimulated with RIG-I ligand SLR14	The purpose of this study was to assess transcriptome changes in primary human airway epithelial cells following stimulation with RIG-I ligand. Overall design: MRNA profiles were generated from primary human airway epithelial cells at rest or following stimulation with RIG-I ligand SLR-14.	Co-expression
SRP126505	RNA sequence of ISL1-MSCs and Ctrl-MSCs	The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed as a marker of cardiovascular progenitor cells. This study investigated whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) improves myocardial infarction (MI) treatment outcomes. The lentiviral vector EF1a-ISL1 was constructed using the Multisite Gateway System, and used to transduce hMSCs. Overall design: Examination of  mRNA in ISL1-MSCs and Ctrl-MSCs	Co-expression
SRP126511	Global transcriptional changes in U87MG glioblastoma cells upon shRNA-mediated TRIM52 knockdown	shRNA-mediated ablation of the RING-finger protein TRIM52 from multiple glioblastoma cell lines reduces proliferation and tumorigenesis. To identify gene signatures underlying this phenomenon, transcritional profile of TRIM52 knockdown cells was compared to control cells. Upon TRIM52 ablation, we find 278 differentially regulated genes. Gene ontology analysis reveals that many of the upregulated genes are associated with glycolysis and biosynthetic processes. Overall design: U87MG glioblastoma cells were stably transduced with doxycycline-inducible shRNA constructs targeting TRIM52 (two different shRNAs) or controls (two different non-targeting shRNAs). Knockdown was induced for five days using 2µg/ml doxycycline. shRNA expressing cells were sorted based on shRNA-coupled GFP expression via flow cytometry. mRNA sequening was performed in duplicate per shRNA cell line.	Co-expression
SRP126516	Transcriptome response of human skeletal muscle to divergent exercise stimuli	While acute aerobic and resistance exercise stimulate a number of shared genes, each exercsie mode stimlutes a number of  uniquely responsive genes, thus highlighting that different forms of exercise facilitate distinct molecular responses in skeletal muscle. Overall design: Randomized, counter-balanced, cross-over design (n=6) in which subjects performed an acute bout aerobic and resistance exercise separated by ~1 week.	Co-expression
SRP126547	Pancreatic tumor microenvironment confers highly malignant properties on pancreatic cancer cells	Tumor microenvironment plays a pivotal role in cancer progression; however, little is known regarding how differences in the microenvironment affect characteristics of cancer cells. Here, we investigated the effects of tumor microenvironment on cancer cells by using mouse tumor models. After 3 cycles of inoculation and extraction of human pancreatic cancer cells, including SUIT-2 and Panc-1 cells, from tumors, distinct cancer cell lines were established; 3P cells from the pancreas obtained using the orthotopic tumor model, and 3sc cells from subcutaneous tissue obtained using the subcutaneous tumor model. On cell re-inoculation of these cells, the 3sc cells and, more prominently, the 3P cells, exhibited higher tumorigenic activity than the parental cells. The 3P cells specifically exhibited low E-cadherin expression and high invasiveness, suggesting that they were endowed with the highest malignant characteristics. RNA-sequence analysis demonstrated that distinct signaling pathways were activated in each cell line and that the 3P cells acquired a cancer stem cell-like phenotype. Among cancer stem cell-related genes, those specifically expressed in the 3P cells, including NES, may be potential new targets for cancer therapy. The mechanisms underlying the development of highly malignant cancer cell lines were investigated. Individual clones within the parental cells varied in tumor-forming ability, indicating the presence of cellular heterogeneity. Moreover, the gene expression profile of each clone changed after orthotopic inoculation. The present study thus suggests that both selection and education processes are involved in the development of highly malignant cancer cells. Overall design: Expression of mRNA in the highly malignant sublines of SUIT-2 and Panc-1 cells xenografted into mice.	Co-expression
SRP126560	Disruption of Autism Spectrum Disorder-Susceptibility Genes Predominantly Reduces Functional Connectivity of Isogenic Human Neurons	Autism Spectrum Disorder (ASD) is phenotypically and genetically heterogeneous, but genomic analyses have identified candidate susceptibility genes. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NEUROG2)-directed differentiation of iPSCs allowed production of cortical excitatory neurons, and mutant proteins were not detectable. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory post-synaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2- and SCN2A-null neurons. RNAseq revealed convergence of several neuronal networks. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity. Overall design: RNAseq profile of 1 control sample and 10 isogenic knokout human induced pluripotent stem cells (iPSCs) samples with 2-4 replicates per sample, as well as their corresponding 28-day old differentiated glutamatergic neuron samples with 3-5 replicates per sample.	Co-expression
SRP126561	RING-finger protein 6 amplification activates JAK/STAT3 pathway by modifying SHP-1 ubiquitylation and associates with poor outcome in colorectal cancer	To elucidate whether  RNF6 plays a role in  colorectal cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of  RNF6 siRNA and control siRNA transfectants. Overall design: RNA-seq was performed in HT29  colorectal cancer cells after RNF6 knock down	Co-expression
SRP126580	A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Berry_London]	Whole blood transcriptional signatures distinguishing patients with active tuberculosis from asymptomatic latently infected individuals have been described but, no consensus exists for the composition of optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Overall design: We undertook RNA Sequencing (RNA-Seq) of our earlier Berry et al. 2010 (GSE19444 and GSE19442) cohorts and additionally set up a prospective cohort study at Leicester (UK) in subject groups of incident TB and recent TB contacts, respectively. In the Leicester cohort, we performed systematic longitudinal sampling and clinical characterisation first, to validate our TB signature using RNA-Seq in a new and independent cohort of individuals with active TB and LTBI, and secondly to provide longitudinal data in a low TB incidence setting. All samples in this series were re-analyzed from GSE19444. There are links on each sample page to the original sample.	Co-expression
SRP126582	A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Berry_South Africa]	Whole blood transcriptional signatures distinguishing patients with active tuberculosis from asymptomatic latently infected individuals have been described but, no consensus exists for the composition of optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Overall design: We undertook RNA Sequencing (RNA-Seq) of our earlier Berry et al. 2010 (GSE19444 and GSE19442) cohorts and additionally set up a prospective cohort study at Leicester (UK) in subject groups of incident TB and recent TB contacts, respectively. In the Leicester cohort, we performed systematic longitudinal sampling and clinical characterisation first, to validate our TB signature using RNA-Seq in a new and independent cohort of individuals with active TB and LTBI, and secondly to provide longitudinal data in a low TB incidence setting. 43 of the 47 samples in this series were re-analyzed from GSE19442. These samples include links to the original sample at the foot of the page.	Co-expression
SRP126583	A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Leicester non-progressor]	Whole blood transcriptional signatures distinguishing patients with active tuberculosis from asymptomatic latently infected individuals have been described but, no consensus exists for the composition of optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Overall design: We undertook RNA Sequencing (RNA-Seq) of our earlier Berry et al. 2010 (GSE19444 and GSE19442) cohorts and additionally set up a prospective cohort study at Leicester (UK) in subject groups of incident TB and recent TB contacts, respectively. In the Leicester cohort, we performed systematic longitudinal sampling and clinical characterisation first, to validate our TB signature using RNA-Seq in a new and independent cohort of individuals with active TB and LTBI, and secondly to provide longitudinal data in a low TB incidence setting.	Co-expression
SRP126623	A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia [RNA-Seq]	We demonstrate a promising approach to identify robust molecular markers for targeted treatment of acute myeloid leukemia. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately. Finally, we identify SMARCA4 as a marker and driver of sensitivity to topoisomerase II inhibitors, mitoxantrone and etoposide, in AML by showing that cell lines transduced to have high SMARCA4 expression reveal dramatically increased sensitivity to these agents. Overall design: We measured the gene expression of samples from 30 different AML patients with acute myeloid leukemia in order to identify reliable gene expression markers for drug sensitivity. We used this dataset for validation. This Series represents 12 patient samples.	Co-expression
SRP126626	Genome wide analysis of TLR2- and TLR4-activated SZ95 sebocytes	Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in chemotaxis, wound healing and cell proliferation and thus reflecting a more complex cytokine and chemokine regulation than previously known. Importantly, lipid metabolism, the primary feature of sebocytes, was affected only at a later time point (24 hours) indicating that sebocytes prioritize to exert a pro-inflammatory phenotype when confronted with a danger signal. Supporting the biological relevance of our results, a meta-analysis revealed that the genes showing the strongest up-regulation were also found up-regulated in acne. Of these genes, serum amyloid A 1/2 (SAA1/2) was confirmed to be a suitable protein marker for in vivo activated sebocytes, underlining their immune-competence, which is structurally defined within sebaceous glands of acne and rosacea skin samples. Altogether our findings demonstrate that sebocytes are not only positioned at the end point of inflammation but are actively involved in shaping the inflammatory response with putative diagnostic and therapeutic relevance.	Co-expression
SRP126639	Microenvironmental-derived Regulation of HIF-Signaling Drives Transcriptional Heterogeneity in Glioblastoma Multiforme	The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes such as transcriptional and metabolic reprograming play an important role in the development of tumor heterogeneity. The present study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multi-regional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment. Creatine treatment and metabolism was further shown to promote a synergistic effect through up-regulation of the glycine-cleavage system and chemical regulation of Prolyl-Hydroxylase Domain (PHD). Consequently, creatine maintained a reduction of reactive oxygen species and change of the a-ketoglutarate/succinate ratio leading to an inhibition of the HIF-signaling in primary tumor cell lines. These effects shifted the transcriptional pattern toward a proneural subtype and reduced the rate of cell migration and invasion in vitro. Overall design: For metabolic treatment, different metabolites were supplemented into the medium. Creatine-enriched environment was simulated by 15 mMol creatine supplementation. Cells were cultured under normoxic (21% O2) or hypoxic (3% O2) conditions.	Co-expression
SRP126658	Whole Transcriptome sequencing of U-2 OS cell lines expressing HPV16 E6 and/or E6* isoforms	Whole transcriptome comparison of U-2 OS cell lines stably expressing HPV16 E6, E6*I and E6*II isoforms or expressing only HPV16 E6*I against control parental U-2 OS and U-2 OS transfect with empty vector.Study goal was to uncover E6*I isoform effect on cellular genome expression dependent or undependent of full length E6 isoform.	Co-expression
SRP126664	The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma [RNA-Seq Tumor]	Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate a SS transcriptional signature we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. Overall design: RNA was harvested from patient samples of synovial sarocoma (SS) and sequenced for further analysis.	Co-expression
SRP126667	Genome-wide association analysis identifies 13 novel susceptibility loci for Carpal Tunnel Syndrome	Carpal tunnel syndrome (CTS) is a common and disabling condition of the hand caused by entrapment of the median nerve at the level of the wrist. It is the commonest entrapment neuropathy, with estimates of prevalence ranging between 5-10%1–3. We undertook the first GWAS to date of an entrapment neuropathy, using 12,106 CTS cases identified in UK Biobank and 387,347 controls. We discovered 13 novel susceptibility loci for CTS with p=5x10-8. We identified likely causal genes in the pathogenesis of CTS, including ADAMTS17, ADAMTS10 and EFEMP1, and demonstrated expression of these genes in surgically resected tenosynovium from CTS patients. We suggest that variants within genes implicated in growth and extracellular matrix architecture contribute to the genetic predisposition to CTS. Overall design: RNA-seq Illumina HiSeq4000	Co-expression
SRP126672	Integrative molecular and clinical analysis of intrahepatic cholangiocarcinoma reveals two prognostic subclassees	Intrahepatic cholangiocarcioma has two molecular classification of intrahepatic CCA with distinct clinical, pathological, biological and prognostic differences Overall design: Examination of 2 different cluster of intrahepatic cholangiocarcinoma based on RNA sequencing by NGS	Co-expression
SRP126674	Extreme heterogeneity of influenza virus infection in single cells	Viral infection can dramatically alter a cell''s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in production of viral gene transcripts -- viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells. Overall design: Dataset consists of a total of five single-cell datasets generated using the 10x Genomics Chromium Single Cell 3'' Solution platform. All samples were generated from a tissue culture infection model using A549 cells from ATCC and Influenza A/WSN/1933 virus. Uninfected control sample identically processed. Infected samples were generated from cells infected for 6, 8, and 10 hours with a single replicate at 8 hours.	Co-expression
SRP126680	Gene expression kinetics for human and mouse T cells following few hours stimulation	Adoptive cell therapy is a type of cancer immunotherapy in which T cells (possibly engineered with a T cell receptor specific to a tumor antigen) are stimulated and expanded ex vivo, and then infused into the patient. This project focused on understanding the optimal conditions for the ex vivo preparation of those T cells. A goal was to maximize functional activation while minimizing phenotype differentiation.	Co-expression
SRP126681	Expression data in LoVo cells treated with MEK inhibitor	We analyzed publicly available mucosal gene expression data from Crohn''s disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Gene expression profile was performed to analyze the gene modulation induced by a highly selective MEK inhibitor, and to evaluate whether it normalized reference residual CD signature in vitro. Overall design: LoVo, a human colorectal cancer cell line, was treated with MEK inhibitor for 24 hours across ten dose response conditions (0.03–1,000 nM), and amplicon sequencing was performed on the Ion Torrent platform. Effects of MEK inhibitor were compared with that of DMSO-treated control. MEK inhibitor (compound 33 in Bioorg. Med. Chem. Lett. 22 (2012) 2411   2414))	Co-expression
SRP126691	A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Leicester progressor]	Whole blood transcriptional signatures distinguishing patients with active tuberculosis from asymptomatic latently infected individuals have been described but, no consensus exists for the composition of optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Overall design: We undertook RNA Sequencing (RNA-Seq) of our earlier Berry et al. 2010 (GSE19444 and GSE19442) cohorts and additionally set up a prospective cohort study at Leicester (UK) in subject groups of incident TB and recent TB contacts, respectively. In the Leicester cohort, we performed systematic longitudinal sampling and clinical characterisation first, to validate our TB signature using RNA-Seq in a new and independent cohort of individuals with active TB and LTBI, and secondly to provide longitudinal data in a low TB incidence setting.	Co-expression
SRP126705	Homo sapiens Raw sequence reads	Comparison of DEGs in MucilAir cells of nasal origin exposed to cigarette smoke (1R6F) and Air control	Co-expression
SRP126741	Global transcriptomic analysis of human pancreatic islets [RNAseq]	RNA sequencing in 88 human pancreatic islet donors Overall design: mRNA profiles of human pancreatic islets from 88 donors. The data were generated by deep sequencing using Illumina HiSeq 2000.	Co-expression
SRP126765	Early response of human ovarian and fallopian tube surface epithelial cells to norepinephrine	The purpose of this study is to understand the effects of adrenergic signaling on the transcriptome of cell line models postulated to be the cells of origin of epithelial ovarian cancers using RNA-Seq. Here we explored the effects of the stress-related hormone, norepinephrine, on normal human ovarian and fallopian tube surface epithelial cellss. We investigated the early transcriptional response to norepinephrine in normal immortalized ovarian surface epithelial cells and fallopian tube secretory cells. RNA-Seq data of treated and untreated cells were analyzed to identify genes with differential expression. Overall design: RNA-seq data from ovarian surface epithelial cells and fallopian tube epithelial cells after treatment with 1µM norepinephrine for 1 hour (or mock-treatment). Three independent replicates were performed for each condition and cell line.	Co-expression
SRP126790	Enzyme-free digital counting of endogenous circular RNA molecules in Formalin-Fixed Paraffin-Embedded tissues from patients with B-cell malignancies	Circular RNAs (circRNAs) are covalently closed endogenous RNA molecules with tissue- and disease specific expression patterns, which have potential as diagnostic and prognostic biomarkers in cancer. The landscape of circRNA expression has not been characterized in B-cell malignancies. We quantified circular RNA expression by total RNA sequencing of four different Mantle Cell Lymphoma cell lines, REC-1, Granta-519, Z138 and UPN2 and the Multiple Myeloma cell line, H929. Overall design: High quality RNA samples were depleted for ribosomal RNA and sequenced on a HiSeq 4000 from Illumina, no replicates were done. CircRNA quantification was done using the bioinformatics algorithms known as Find_circ and CIRI2. The data was used for designing a panel of NanoString assays for specific circRNAs	Co-expression
SRP126825	Impact of ERBB inhibitors on erythroid progenitors	RNA-seq was performed to determine the genome-wide changes in expression upon treatment with different classes of ERBB inhibitors Overall design: treatment with different classes of ERBB inhibitors	Co-expression
SRP126844	Gene expression analysis upon TNF stimulation combined with TPCA-1 or MRT67307	The study aims at determining the function of the IKK-related kinases TBK1 and IKK epsilon in TNF-induced signalling	Co-expression
SRP126849	Identification of Differentially Expressed Splice Variants by the Proteogenomic Pipeline Splicify	Proteogenomics, i.e. comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers. To this end, we developed a proteogenomic pipeline, Splicify, which is able to detect differentially expressed protein isoforms. Splicify is based on integrating RNA massive parallel sequencing data and tandem mass spectrometry proteomics data to identify protein isoforms resulting from differential splicing between two conditions. Proof of concept was obtained by applying Splicify to RNA sequencing and mass spectrometry data obtained from colorectal cancer cell line SW480, before and after siRNA-mediated down-modulation of the splicing factors SF3B1 and SRSF1. These analyses revealed 2172 and 149 differentially expressed isoforms, respectively, with peptide confirmation upon knock-down of SF3B1 and SRSF1 compared to their controls. Splice variants identified included RAC1, OSBPL3, MKI67 and SYK. One additional sample was analyzed by PacBio Iso-Seq full-length transcript sequencing after SF3B1 down-modulation. This analysis verified the alternative splicing identified by Splicify and in addition identified novel splicing events that were not represented in the human reference genome annotation. Therefore, Splicify offers a validated proteogenomic data analysis pipeline for identification of disease specific protein biomarkers resulting from mRNA alternative splicing. Splicify is publicly available on GitHub (https://github.com/NKI-TGO/SPLICIFY) and suitable to address basic research questions using pre-clinical model systems as well as translational research questions using patient-derived samples, e.g. allowing to identify clinically relevant biomarkers. This dataset corresponds to a publication in Molecular & Cellular Proteomics 16: 10.1074/mcp.TIR117.000056, 1850–1863, 2017, PMID: 28747380. Mass spectrometry data corresponding to this entry is available at ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD006486. Overall design: Down-modulation of splicing factors SF3B1 (48h) and SRSF1 (72h) was performed in CRC cell line SW480 three times. The knock-downs and the paired non-targeting (NT) controls were subjected to RNA-sequencing and LC-MS/MS tandem mass spectrometry. Down-modulation of SF3B1 was repeated in a separate experiment, including PacBio Iso-Seq sequencing of full length transcripts. Differential mRNA splice variants were identified for down-modulation vs the non-targeting control.	Co-expression
SRP126861	Genome-Wide DNA Methylation Encodes Cardiac Transcriptional Reprogramming in Human Ischemic Heart Failure [RNA-Seq]	Background – Epigenetic alterations are stable modifications to  chromatin structure that occur in response to environmental cues such as hypoxia  or altered nutrient delivery. DNA methylation is a well-established and dynamic DNA modification that contributes to the regulation of gene expression. In the current study, we test the hypothesize that ischemic heart failure is defined by a distinct signature of DNA methylation that corresponds with altered expression of genes involved in cardiac ventricular dysfunction. Methods and Results – Using a methylation array, we quantified genome-wide DNA methylation of endomyocardial samples acquired from patients  with ischemic (n = 6) or non-ischemic (n = 5) heart failure. RNA-sequencing analysis was performed in the same samples to identify transcriptomic changes (Fold Change > 1.5, Q < 0.05, FPKM > 2) associated with differential methylation (|Percent Change| > 5%, p < 0.05). Of the promoter-associated CpG Islands, which are well-established regions of negative transcriptional regulation, we identified a signature of robust hypermethylation. The methylation changes linked to significantly decreased transcripts included key fatty acid metabolic regulators (e.g. KLF15, AGPAT9, APOA1, and MXD4). Among the few hypomethylated and induced genes was PFKFB3, which encodes for the rate-limiting enzyme of glycolysis. Gene set enrichment analysis  identified TGFß  as a nodal upstream regulator of the methylation changes, potentially supporting a role of DNA methylation in the increased fibrosis and apoptosis that accompanies ischemic heart failure.  Conclusions – Our data identify  that the DNA methylation signature recapitulates the pathologic hallmarks of ischemic heart failure. Furthermore, we show that differential DNA methylation of CpG islands within the promoter depict alterations in metabolic substrate utilization known to occur in ischemic heart failure, and may govern a return to the fetal-like metabolic program. Overall design: RNA Sequencing analysis of left ventricle samples in 11 subjects with end-stage heart failure.	Co-expression
SRP126899	Homo sapiens associated  Transcriptome	Identifying the novel candidate pathways and targets, and thus yield further insight into elderly sepsis	Co-expression
SRP126923	Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients	Total RNA sequencing was performed on CD141+ DC isolated from peripheral blood of healthy individuals (n=4), synovial fluid of patients with inflammatory arthritis (n=5) and peripheral blood of patients with inflammatory arthritis (n=7). Cd1c+ DC were also sequenced from peripheral blood of healthy individuals (n=3). Overall design: One RNA sample per subject was analyzed without replicates	Co-expression
SRP126938	HDAC Inhibitor-Induced Acetylation of KRAS Confers A Pro-Oncogenic Effect Limiting Treatment Response in Colorectal Cancer	The limited clinical utility of HDAC inhibitors for the treatment of colorectal cancer (CRC) has until now remained an unresolved conundrum. Our findings provide comprehensive mechanistic insight into the ineffectiveness that defines HDAC inhibitors as a monotherapy for CRC. We identified that inhibition of HDAC2 promotes the emergence of a super-oncogenic KRAS by inducing K5 acetylation that fosters a previously undiscovered electrostatic interaction with R67 conserved in RAF kinases. This post-translational modification facilitates an increase in the binding affinity to this family of downstream RAS effectors, which translates into an immediate and persistent hyperactivation of the downstream MAPK-signaling. The concomitant instability of its co-conspirator c-MYC enables cells selectively harboring oncogenic KRAS to enter a protective state of reversible cell cycle arrest characterized by a senescence-like phenotype. Demonstratively, preventing this phenomenon from taking place provides a compelling alternative strategy for improving the prospects of HDAC inhibitor treatment for CRC. Overall design: CaCO-2et KRAS G12V and CaCO-2et KRAS WT were treated with doxycycline to induce an ectopic expression of KRAS G12V and WT respectively. Cells were also treated with either DMSO or MS-275 for the specified duration (1, 6, 24 and 72hrs).	Co-expression
SRP126942	The RNA exosome adaptor protein ZFC3H1 functionally competes with nuclear export activity to retain target transcripts	Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short-lived due to their nuclear degradation by the ribonucleolytic RNA exosome.  Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with 'pA-tail exosome targeting (PAXT) connection' components MTR4, ZFC3H1 and PABPN1, but no overlap with known nuclear structures, such as Cajal bodies, speckles, paraspeckles or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear RNA retention factor, counteracting nuclear export activity. Overall design: Nuclear poly(A) selected RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control) and RNA exosome core factor RRP40	Co-expression
SRP126945	RNA sequencing on LNCaP cells	RNA sequencing on LNCaP cells was carried out to study how tunicamycin-induced gene expression is affected by knockdown of EIF2AK3 and ATF4. Overall design: Samples from the below setup (treatments protocol) were harvested from four independent experiments. RNA integrity of total RNA samples was assessed by Bioanalyzer. All samples had RIN = 9.7.	Co-expression
SRP126999	Beta-catenin maintains lung epithelial progenitors after lung specification	We performed RNA-seq on human embryonic stem cells raised in an established condition to produce 95% Nkx2.1 cells, with and without withdrawal of Wnt-agonist CHIR99021 or addition of Wnt-inhibitor IWP2 Overall design: Human lung progenitors were derived from RUES2 as described in Huang et al 2014, Huang et al 2015. Wnt agonist withdrawal or addition of Wnt inhibitor was done at day 12, with cell harvest for RNA-seq at day 12 (control) and day 15 (control and treatment)	Co-expression
SRP127016	Thyroid State Regulates Gene Expression in Human Whole Blood Cells	Context: Despite the well-recognized clinical features due to insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of TRa-expressing cells. Methods: We performed next-generation RNA sequencing on whole blood samples from 8 athyroid patients (4 females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene co-expression network analysis (WGCNA) was applied to identify thyroid state-related networks. Results: We detected 486 differentially expressed (DE) genes (fold-change above 1.5; multiple testing corrected P-value <0.05), of which 76 % were positively and 24 % were negatively regulated. Gene ontology (GO) enrichment analysis revealed that 3 biological processes were significantly overrepresented of which the process translational elongation showed the highest fold enrichment (7.3 fold, P=1.8 x 10-6). Comparative transcriptome analysis revealed significant overlap with DE-genes in muscle samples upon different thyroid state (1.7-fold enrichment; P=0.02). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO-analysis suggested that thyroid state regulates platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRa-expressing leukocytes. In addition, TH may regulate gene expression in platelets. Whole blood samples might potentially be used as a proxy for other TRa-expressing tissues in humans. Overall design: Transcriptome profiling (RNA-Seq) of 8 thyroidectomized human whole blood samples, sequenced first in hypothyroid state and after levothyroxine supplementation sequenced in a hypothyroid (mild thyreotoxic state) state on a Illumina HiSeq 2500 system.	Co-expression
SRP127021	Long-term Functional Maintenance of Primary Human Hepatocytes In Vitro	Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types. Overall design: Total of 29 samples were analyzed, which included primary human hepatocytes (PHHs) cultured in different condition in vitro. To figure out how terminally differentiated cells rapidly lose their function in vitro, two PHHs samples were compared, which included 24h-Cultured hepatocytes and fresh primary human hepatocytes (F-PHHs) [GSM2893923 and GSM2893924]. For comparison of global gene expression of primary human hepatocytes (PHHs) maintained with small molecules or sandwich culture for different time periods, sample3-29 were analyzed [GSM2893935 - GSM2893963][GSM3629857-GSM3629862].	Co-expression
SRP127035	Analysis of gene expression profile in the control and CHD7-knockdown hiPSC-derived lt-NES cells (scRNA-Seq)	CHARGE syndrome is a congenital disorder caused by mutations in Chromodomain Helicase DNA-binding domain 7 (CHD7) gene. We performed single cell RNA-seq analysis in CTRL and CHD7-knockdown lt-NES cells. Overall design: Single cell RNA-Seq profiling of control (shCTRL) and CHD7-knockdown (sh410 or sh411) cells.	Co-expression
SRP127169	Subtype-specific regulatory network rewiring in acute myeloid leukemia [RNA-seq]	Acute myeloid leukemia is a heterogeneous disease which is subdivided into different categories defined by disease-causing mutations in transcription factors, epigenetic regulators and signalling molecules. How different mutant regulators establish AML-specific transcriptional networks is unclear. Here we performed a comprehensive analysis of mutation-specific sets of cis-regulatory elements driving gene expression in AML blast cells from a carefully selected group of patients with alterations in genes encoding transcription factors (RUNX1, CEBPA) and signalling molecules (FTL3-ITD, RAS, NPM1). We show that each mutant regulator establishes a specific transcriptional and signalling network unrelated to normal cells driving the expression of unique sets of genes required for AML survival. Overall design: RNA-seq expreiments have been used to study the chromatin landscape of AML with different mutations	Co-expression
SRP127179	Cell hashing enable sample multiplexing, multiplet identification and super-loading on droplet-based single cell RNA-sequencing platforms	We reasoned that by using a distinct set of oligo-tagged antibodies against ubiquitously expressed proteins, we could uniquely label multiple populations of cells, multiplex them together, and use the barcoded antibody signal as a fingerprint. We refer to this approach as cellular "hashing", as our set of oligos defines a "look up table" to assign each multiplexed cell to its original sample. We demonstrate application of the technique to combine eight samples and run them simultaneously in a single droplet based scRNA-seq run. We show that cell hashtags allow sample multiplexing, confident multiplet identification and super-loading in the context of a commonly used droplet-based scRNA-seq method to drive down the per-cell cost of large-scale scRNA-seq experiments Overall design: We chose a set of monoclonal antibodies directed against ubiquitously and highly expressed immune surface markers (CD45, CD98, CD44, and CD11a) and combined these antibodies into eight identical pools (pool A-H), and subsequently conjugated each pool to a distinct hashtag oligonucleotide (henceforth referred to as HTOs). The HTOs contain a unique 10- or 12-bp barcode that could be read out and linked to the cellular transcriptome, through minor modifications to standard scRNA-seq protocols.	Co-expression
SRP127185	Colorectal Adenomas and Consensus Molecular Subtyping	Consensus molecular subtyping in adenomatous and serrated polyps Overall design: 5 samples. Colonic tubular adenoma from patient with Lynch Syndrome (LS)	Co-expression
SRP127187	RNA deep sequencing analysis of glioma stem cells(GSCs) and non-GSCs	To explore potential molecular mechanisms underlying the temporal process of DNA damage and repair in CSCs, we utilized deep RNA sequencing to analyze the expression of DNA damage and repair-associated genes at the transcriptome level. Our gene set analysis of CSCs and matched non-CSCs revealed a stemness-associated upward trend of global gene expression, particularly in NHEJ, mismatch excision repair (MMR) and HR pathways. Overall design: The RNA profiles of IN528, T3961, and T4121 CSCs and matched non-CSCs were generated by deep sequencing.	Co-expression
SRP127251	Derivation of kidney organoids from human pluripotent stem cells [RNA-Seq: Data Set 1]	We have developed a robust methodology for the derivation of kidney organoids from human pluripotent stem cells further vascularized taking advantage of several in vivo approaches. Our methodology suffices for the generation of kidney derivatives transcriptomically comparable with 22 weeks of gestation kidney tissues and highlight the use of longer periods of exposure to 3D in order to promote renal differentiation in a time frame of 15 days. Overall design: mRNA profiles of undifferentiated and differentiatig cells were generated by deep sequencing, in duplicate, using Illumina system.	Co-expression
SRP127252	Derivation of kidney organoids from human pluripotent stem cells [RNA-Seq: Data Set 2]	We have developed a robust methodology for the derivation of kidney organoids from human pluripotent stem cells further vascularized taking advantage of several in vivo approaches. Our methodology suffices for the generation of kidney derivatives transcriptomically comparable with 22 weeks of gestation kidney tissues and highlight the use of longer periods of exposure to 3D in order to promote renal differentiation in a time frame of 15 days. In order to ascertain the impact of extracellular matrix microenvironment in renal differentiation undifferentiated human pluripotent stem cells were further cultured in compliant substrates mirroring embryo-ECM microenvironment (1kPa) in order to promote renal differentiation and compared these conditions in front of rigid substrates (60 kPa) mimicking hard substrates normally used when differentiating human pluripotent stem cells Overall design: mRNA profiles of undifferentiated and differentiatig cells were generated by deep sequencing, in duplicate, using Illumina system.	Co-expression
SRP127318	Development of Specific Covalent MALT1 Inhibitors and Biomarkers for B-cell Lymphomas	The MALT1 paracaspase plays an essential role in Activated B-cell like Diffuse Large B-cell Lymphoma (ABC DLBCL) downstream of B-cell and Toll-like receptor pathway genes mutated in these tumors. Although MALT1 is considered to be a compelling therapeutic target, development of tractable and specific MALT1 protease inhibitors has thus far been elusive. Herein, we developed a target engagement assay that provides a quantitative readout for specific MALT1 inhibitory effects in living cells. This enabled a structure-guided medicinal chemistry effort culminating in a novel class of substrate-mimetic compounds that bind MALT1 active site and, constitute the first pharmacologically tractable irreversible MALT1 inhibitor. We confirmed MALT1 targeting is effective at suppressing ABC DLBCL cells in vitro and in vivo. We show that reduction in serum IL10 levels exquisitely correlates with drug PK and degree of MALT1 inhibition in vitro and in vivo and constitutes a useful pharmacodynamic biomarker to evaluate these compounds in clinical trials. Our new inhibitor revealed insights into the biology of MALT1 in ABC DLBCL, such as driving JAK-STAT signaling and suppressing type I interferon (IFN) response and MHC class II expression, suggesting that MALT1 inhibition could prime lymphomas for immune recognition by cytotoxic immune cells. Overall design: ABC-DLBCL cell lines treated with MALT1 inhibitor compound #3	Co-expression
SRP127319	SAKE (Single-cell RNA-Seq Analysis and Klustering Evaluation) Identifies Markers of Resistance to Targeted BRAF Inhibitors in Melanoma Cell Populations [Bulk RNA-Seq]	The goal of this study is to apply the SAKE algorithms to identify drug-resistant cellular populations as human melanoma cells respond to targeted BRAF inhibitors. Single-cell RNA-Seq data from both the SMART-seq/Fluidigm and 10x Genomics platforms were analyzed to dissect this problem at multiple scales. Data from both platforms indicate that BRAF inhibitor resistant cells can emerge from rare populations already present before drug application, with SAKE identifying both novel and known markers of resistance Overall design: Two Melanoma cell lines were treated with BRAF inhibitor for 6 weeks to derived a parental and resistant cell states. Bulk and single-cell RNA-Seq were generated using Illumina Hiseq 2000 to study cell response after drug treatment.	Co-expression
SRP127325	Patient-derived organoids (PDOs) model treatment response of metastatic gastrointestinal cancers.	We report RNAseq data from subsequent passages of five organoid cultures. Overall design: RNA extracted from subsequent PDO passages was subjected to RNAseq.	Co-expression
SRP127343	Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [RNA-Seq]	Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers. Overall design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.	Co-expression
SRP127362	Conventional and neo-antigenic peptides naturally processed and presented by beta cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors	Human CD8+ T cells are the final mediators of autoimmune ß-cell destruction in type 1 diabetes. However, their target epitopes have not been demonstrated to be naturally processed and presented by ß cells. We therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased ß-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known ß-cell antigens and several insulin granule proteins. Preproinsulin yielded multiple previously described HLA-A2-restricted epitopes. Secretogranin V (SCG5/7B2), proconvertase-2, urocortin-3 and the insulin gene enhancer protein ISL-1 were identified as novel ß-cell antigens, which were processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative mRNA splice isoform (SCG5-009) and from an islet amyloid polypeptide transpeptidation product. This first description of the ß-cell HLA peptidome opens new avenues to understand the antigen processing pathways employed by ß cells and provides a valuable tool for developing T-cell biomarkers and tolerogenic vaccination strategies. Overall design: 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)	Co-expression
SRP127372	miR-942-overexpressing human renal cell carcinoma cells	RNA sequencing was performed on overexpressed miR-942 OS-RC-2 cell lines using miR-942 mimic transfection and compared with negative controls.	Co-expression
SRP127395	A Reproducibility-Based Computational Framework Identifies An Inducible, Enhanced Antiviral Dendritic Cell State In HIV-1 Elite Controllers (TLR perturbation Bulk RNA-Seq)	Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-Seq to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. We discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. We identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells (PBMCs) from healthy individuals in vitro. Overall design: Bulk RNA-seq profiling of TLR-perturbed cDCs and controls from a healthy donor for comparison with gene expression programs associated with cell-intrinsic HIV-1 immune recognition.	Co-expression
SRP127409	4 NSCLC cell lines treated with GDC-0973, AZ-628 or a combination of both	RNA was purified cancer cell lines. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0013114 Overall design: RNA from NSCLC cell lines after treatment with either DMSO, GDC-0973, AZ-628 or the combination of AZ-628 and GDC-0973 all at 0.1 micro-molar concentration.	Co-expression
SRP127411	RNA sequencing of hPSC-derived cardiac progenitors and endocardium	We utilized a dual reporting hPSC line that identified cells expressing NKX2.5 and endothelal cells to characterize discrete milestones during cardiac and vascular differentiaiton. Comparing populations that express either or both reporters to human umbilical vein endothelial cells, we document a unique molecular phenotype in hPSC-derived endocardium that points toward an important role for Wnt signaling during vascular specification of cardiac progenitors. Overall design: Sequencing mRNA from biological triplicate samples of: 1) hPSC derivatives expressing NKX2.5 alone; 2) hPSC derivatives expressing NKX2.5 and endothelial markers; and 3) hPSC derivatives expressing only endothelial markers.	Co-expression
SRP127511	In vitro modeling of human germ cell development   using pluripotent stem cells	In this study, we developed a feeder-, serum-, and animal product-free culture condition, and successfully induced high percentage of SLCs from human PSCs. Genome-wide expression analyses demonstrated a significant upregulation of germ cell specific genes in SLCs derived from PSCs compared to in vivo isolated human CD90+ SSCs. And furthermore, under this optimized feeder-free condition SLCs have went through meiosis and formed putative round spermatids. Our data demonstrated a robust feeder-, serum- and xeno-free protocol to induce differentiation of PSCs to SLCs from which putative haploid spermatids may develop. Overall design: Examination of genome-wide genes expression  in PSCs, SLCs and putative haploid spermatids types.	Co-expression
SRP127513	Rescue of Fragile X syndrome neurons by DNA methylation editing of the FMR1 gene [RNA-seq]	Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by silencing of the FMR1 gene by hypermethylation of the CGG expansion mutation in the 5'UTR region of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/sgRNA switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state restoring a persistent expression of FMR1 in FXS iPSCs. Neurons derived from methylation edited FXS iPSCs rescued the electrophysiological abnormalities and restored a wild-type phenotype upon the mutant neurons. FMR1 expression in edited neurons was maintained in vivo after engrafting into the mouse brain. Finally, demethylation of the CGG repeats in post-mitotic FXS neurons also reactivated FMR1. Our data establish demethylation of the CGG expansion is sufficient for FMR1 reactivation, suggesting potential therapeutic strategies for FXS. Overall design: RNA-seq of FXS iPSC and neurons derived from FXS iPSC infected with lentiviruses expressing dCas9-Tet1-P2A-tBFP (dC-T) and a mCherry-expressing sgRNA targeting CGG repeats.	Co-expression
SRP127521	KDM5 histone demethylases repress innate immune response via suppression of STING	Tri-methylation on histone H3 lysine 4 (H3K4me3) is enriched near transcription start sites and correlates with active transcription. Like other histone marks, methylation on H3K4 is catalyzed by the respective methyltransferases and erased by demethylases. Lysine demethylase 5 (KDM5) family of Fe (II) and a-ketoglutarate-dependent dioxygenases removes the methyl groups from H3K4me3. All four family members of KDM5 demethylases (KDM5A-D) share sequence identity, have similar in vitro kinetic parameters, and display functional redundancy. To determine the effects of complete depletion of KDM5 activity, we treated MCF7 cells with DMSO, or two pan-KDM5 specific inhibitors, KDM5-C70 (our lab code 443) and CPI-48 (our lab code 278) and performed RNA sequencing to determine gene expression changes after KDM5 inhibitor treatment. Overall design: RNA sequencing of MCF7 cells treated with DMSO or KDM5 inhibitors.	Co-expression
SRP127547	mRNA sequencing to assess RfxCasR and matching shRNA specificity	Matching sets of RfxCasR and shRNAs targeting ANXA4 and B4GALNT1 plus non-targeting (NT) controls were profiled by mRNA sequencing to compare non-specific transcriptome perturbations  for both shRNA and RfxCasR technologies. Overall design: Three biological replicates for 3 shRNAs and 2 RfxCasR guide RNAs plus 2 RfxCasR arrays expresssed in HEK 293FT cells	Co-expression
SRP127549	Disruption of the TFAP2A regulatory domain causes Branchio-Oculo-Facial Syndrome (BOFS) and illuminates pathomechanisms for other human neurocristopathies [RNA-seq data set 1]	BOFS is a rare congenital syndrome that arises due to defects during neural crest (NC) development and is thus considered as a human neurocristopathy. All reported BOFS cases are caused by heterozygous mutations within TFAP2A. Here we describe a unique BOFS patient carrying a de novo heterozygous inversion in which one of the breakpoints is located 40 kb downstream of TFAP2A. Using in vitro and in vivo NC developmental models, we uncovered that TFAP2A is located within a large Topologically Associating Domain (TAD) containing enhancers essential for TFAP2A expression in NC cells (NCC). Importantly, using patient-specific hiPSC lines, we showed that the inversion causes a loss of physical interactions between the inverted TFAP2A allele and its cognate enhancers, leading to TFAP2A monoallelic and haploinsufficient expression in human NCC. More generally, our results highlight potential etiological mechanisms for other human neurocristopathies and illustrate how TAD disruption can lead to a loss of enhancer gene-interactions and, consequently, to pathological changes in gene expression. Overall design: Gene expression profiles were generated in WT p2hNCC (two different cell lines) and BOFS p2hNCC (three different cell lines) using RNA-seq	Co-expression
SRP127563	IRF5 and IRF3 regulate distinct immune programs in plasmacytoid dendritic cells	Transcriptomic analyses of pDCs show that the partitioning of TLR/IRF5 and RLR/IRF3 pathways confers differential gene expression and immune cytokine production in pDCs, linking IRF5 with immune regulatory and proinflammatory gene expression. Overall design: mRNA-seq profiling of plasmacytoid dendritic cells treated with TLR7/8 agonist R848 vs. vehicle; also PAMP (pU/UC) and controls (xRNA) vs. no RNA	Co-expression
SRP127569	Isolated Iliac Cryptococcosis in an Immunocompetent Patient	Cryptococcal osteomyelitis is an infrequent infection which is usually associated with disseminated cryptococcosis or underlying immunocompromised conditions. Here we described a rare case with isolated iliac cryptococcosis in an immunocompetent patient. Through histological, microbial, and molecular biological examinations, the pathogen was finally identified as C. neoformans VNI genotype, which likely originated from environmental bird droppings. The clinical isolate was hypomelanized but fully virulent in mouse infection model. The patient displayed lower CD4+-T lymphocyte ratio, reduced serum IFN-? and IL-12, and dysregulated transcriptional profile of blood leukocytes compare with healthy host. After surgical excision and 34 weeks' antifungal treatment, the patient got clinical cured. Our study suggested that cryptococcosis development was closely associated with the interaction of fungal agent and host immunity. Accurate diagnosis of bone cryptococcosis depends mainly on histological and fungal examinations. A combination of antifungal agent treatment regimen and surgery were quite effective for resolving bone cryptococcosis. Overall design: mRNA profiles of an Immunocompetent Patient and  normal control''s blood were generated by deep sequencing, using Illumina HiSeq 2500	Co-expression
SRP127579	Immortalized breast epithelial cell lines from normal breast with luminal and intrinsic subtypes – enriched gene expression	The cell-type origin has long been suspected to determine molecular features of tumors but has proven difficult to experimentally validate in human breast cancers because of deficiencies in culturing methods that allow propagation of three major cell types of the breast including stem/basal, luminal-progenitor and mature/differentiated cells. We have created immortalized cell lines from core breast biopsies of ancestry-mapped healthy women that are enriched for luminal gene expression including hormonally sensitive ERa-FOXA1-GATA3 transcription factor network. Gene expression pattern followed by intrinsic subtype classification identified these cell lines as “normal” counterpart to luminal A, basal, and normal-like subtypes of breast cancers. We have also created cell lines from CD201+/EpCAM- cells that are likely “normal” counter part of claudin-low subtype of breast cancers. These cell lines serve as good resources as “normal” cell line controls for breast cancer-related studies. Overall design: We propagated breast epithelial cells from breast core biopsies of healthy women using the epithelial reprogramming assay (Nakshatri et al., Scientific Reports, 5:13526). Primary cells were immortalized using human telomerase (hTERT). RNA from immortalized cells in triplicates was subjected to RNA-seq and results are included. hTERT immortalized HME cells from Horizon Discovery, MCF10A cells from ATCC and MCF7 breast cancer cells from ATCC were used as controls for comparison. 1505-10B corresponds to immortalized cells with germ line BRCA2 mutation. KTB40 and KTB42 differ from the rest of the cell lines with respect to cell surface markers profiles. These cells are CD201+/EpCAM-, whereas the remaining cells are CD201+/EpCAM+ or CD201-/EpCAM+. KTB40 and KTB42 are phenotypically fibroblastic or display features of epithelial to mesenchymal transition, whereas the remaining KTB (Komen Tissue Bank) cell lines display luminal features. This series also includes RNA-seq data for non-immortalized cell lines.	Co-expression
SRP127581	Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscleÂ	The circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans. Overall design: 10 candidates with 6 biopsies each for a total of 57 samples being sequenced. Together with GSE109825, part of the same study described above.	Co-expression
SRP127586	Single-cell RNA-seq reveals differentiation of bona fide human pDCs and cDC1s in cultures of cord blood CD34+ progenitors, and a newly identified terminal differentiation step of cDC1s	CD34+ cord blood hematopoietic progenitors were expanded in vitro as previously described (Balan et al., J Immunol, 2014) and then differentiated on a mixed feeder layer of OP9 cells expressing or not the Notch ligand Delta-like 1, with FLT3-L, TPO and IL-7. At the end of the cultures, single live Lin- HLA-DR+ cells were index sorted in 96-well plates containing lysis buffer, and snap frozen. Four putative cell types were sorted according to their expression patterns of key combinations of cell surface markers: putative pDCs, putative cDC1s, putative pre-cDC2s and putative cDC2s. Single cell RNA-sequencing libraries were subsequently generated for 90 single cells and 6 control wells using an adaptation of Smart-Seq2 (Villani et al., Science, 2017). Cells were sequenced at a depth of 1-3M reads/cell. Overall design: A total of 90 single cells and 6 controls from one culture were processed using a protocol adapted from Smart-Seq2 protocol (Villani et al., Science, 2017), which allows for the generation of full-length single cell cDNA, and sequencing libraries were generated using Illumina Nextera XT DNA library preparation kit. A few samples (10) were profiled but excluded from the processed data since they were either bulk (5) or blank (1) control samples or excluded due to QC (4). Therefore, there are 86 samples included here.	Co-expression
SRP127642	Transcriptome Analysis of wild type and SMARCB1 knock down HL60 leukemia cell line by Next Generation Sequencing	We have used lentiviral mediated knock down of SMARCB1, a subunit of the mammalian SWI/SNF complex in HL60, an acute promyelocytic leukemia cell line followed by high throughput mRNA sequencing to identify differentially expressed genes. We have used this data to identify genes affected by SMARCB1 depletion, and thus understand contribution of SMARCB1 towards leukemogenesis.	Co-expression
SRP127658	Genes altered in expression by knockdown of PTK2 in breast cancer cell lines	PTK2 was knocked down by doxycycline-dependent expression of small hairpin RNA against PTK2 in Breast cancer cell lines. Overall design: mRNA expression profiles of the breast cancer of Homo sapiens with or without expressing PTK2 were examined by Illumina Hi-seq 2500.	Co-expression
SRP127665	RNA sequencing for transcriptome comparison between HTLV-1 Tax(-) and Tax(+) cells in Adult T-cell leukemia cell lines (MT-1 and KK-1)	Initially, ATL cell lines (MT-1 or KK-1) were stably transfected  with reporter plasmid for HTLV-1 Tax expression, and single clones were isolated . This reporter in composed of Tax responsive element upstream of d2EGFP fluorescent protein. d2EGFP is expressed upon Tax expression in any individual cell. To compare transcriptomes of Tax(-) and Tax(+) cells, FACS sorting was done for d2EGFP(-) and d2EGFP(+) populations and RNA sequencing was performed. Overall design: Two ATL reporter cell lines were used in this study (MT1GFP and KK1GFP). For Each cell line, two samples were analyzed:  d2EGFP(-) and d2EGFP(+). In total 4 samples were used in this study.	Co-expression
SRP127720	Mitochondrial Proteostatic Stress Induces Aggrephagy to Triage Unimported Proteins	We report the results of overexpression of the wildtype and mutant ANT1 (SLC25A4) gene in human embryonic kidney 293T (HEK293T) cells from the cytomegalovirus (CMV) promoter. Libraries were prepared from three independent replicates per condition using stranded RNA sequencing and run at 2 x 75 read length at a targeted output of 60 million paired-end reads per sample. We found only a limited number of nuclear genes whose expression is altered by wildtype ANT1-overexpression. Among the most upregulated genes is the zinc-finger proteins Egr1, a transcriptional factor with diverse cellular functions, including the repression of genes encoding mitochondrial inner membrane protein. The upregulation of EGR1 likely serves as a retrograde mechanism to reduce protein loading on the IMM and to alleviate mPOS.  Overexpression of the triple and quadruple mutant alleles altered the expression of 206 and 560 genes, respectively, with 32 commonly up-regulated in both. These include EGR1, ZCCHC12 and SFPQ, which were also upregulated in cells overexpressing the wild-type ANT1. The 32 up-regulated genes are involved in functions including RNA-processing, autophagy/intracellular structure/trafficking, transcriptional control, ribosomal biogenesis/translational control, chaperones/proteasomal function and mitochondrial biogenesis. Upstream regulator analysis subsequently revealed 42 pathways predicted to be either activated or inhibited by these genes, including PPARGC1A, ATF4, Heat Shock Factor 1 (HSF1), mechanistic Target of Rapamycin (mTOR), Myc, EGFR and HMGA1. Overall design: Examination of effects of overexpression of wildtype and mutant ANT1 alleles in HEK293T cells	Co-expression
SRP127737	Widespread Changes in Transcriptome Profile of Human Mesenchymal Stem Cells Induced by Two-Dimensional (2D) Nanosilicates	Two-dimensional (2D) nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by monitoring change in transcriptome profile uncovers key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes is observed due to nanosilicate exposure as more than 4,000 genes are differentially expressed. The change in mRNA expression levels reveal clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to cell membrane and subsequent cellular internalization activate stress-responsive pathways such as mitogen activated protein kinase (MAPK), which subsequently directs hMSC differentiation towards osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial-cell interactions, illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment.  Overall design: Examination of affect of 2D nanosilicates on hMSCs	Co-expression
SRP127751	Effects of Acute Aerobic Exercise on Skeletal Muscle Transcriptomics in Lean vs Overweight/Obese Men	Acute aerobic exercise has been shown to improve skeletal muscle mitochondrial function and completeness of fatty acid ß-oxidation which contributes to reduction in lipid accumulation. We hypothesize that epigenetic regulation of mitochondrial genes due to exercise may lead to increased mitochondrial function in overweight/obese (Ov/Ob) individuals. 30 men, aged 19-30 years, were recruited and divided into two groups: lean (BMI<25, 18.5- 24.1 kg/m2, n=15) and Ov/Ob (BMI=25, 25.5- 36.9 kg/m2, n=15). Four hours after eating a standardized high-carbohydrate breakfast (7 kcal/kg; 60% carbohydrate, 25% fat, 15% protein), they performed an acute bout of cycling exercise (50% VO2max, spending ~650 kcal). Thirty minutes before eating the breakfast, vastus lateralis muscle biopsy samples were collected (Pre). Biopsy samples were also collected immediately after (Post) exercise. In skeletal muscle, gene expression was determined by RNA-seq via the Illumina platform. For analysis, TopHat was used for sequence alignment and Cuffdiff for differential gene expression analysis. ~97% of all sequenced reads from RNA-seq aligned to the genome. As per RNA-seq analysis, in both lean and Ov/Ob, genes upregulated following exercise were enriched for GO terms related to lipid metabolism, mitochondrial biogenesis, function and insulin signaling. Pathway analysis revealed that the AMP-activated protein kinase (AMPK) signaling pathway was one of the pathways enriched in both lean Post and Ov/Ob Post. We found that exercise led the -1N nucleosome to repositioning away from the transcription start site in PGC-1a promoter in both lean and Ov/Ob in association with alterations in gene expression of genes involved in lipid metabolism and mitochondrial adaptations. Overall design: Skeletal muscle samples (n=14 for lean pre and lean post and n=15 for Ov/Ob pre and Ov/Ob post) were pooled to give three pooled samples (n=5 per pooled sample, except for one pooled sample each in the lean pre and lean post groups, where n=4) per group for RNA-seq	Co-expression
SRP127770	Meso-Endothelial bipotent progenitors from human placenta display distinct molecular and cellular identity.	The existence of bipotential precursors for both mesenchymal and endothelial stem/progenitor cells in human postnatal life is debated. Here, we hypothesized that such progenitors are present within the human term placenta. From a heterogeneous placental single cell suspension, directly flow-sorted CD45-CD34+CD144+CD31Lo population uniquely differentiated into both endothelial and mesenchymal colonies in limiting dilution culture assays. Of interest, these bipotent cells were in vessel walls but not in contact with the circulation. RNA sequencing and functional analysis demonstrated that Notch signalling was a key driver for endothelial and bipotential progenitor function. In contrast, the formation of mesenchymal cells from the bipotential population was not affected by TGFbeta receptor inhibition, a classical pathway for Endothelial-Mesenchymal Transition. This study reveals a bipotent progenitor phenotype in the human placenta at the cellular and molecular level, giving rise to endothelial and mesenchymal cells ex-vivo.RNA-sequencing was performed on the three placental populations with high colony forming potential, mesenchymal stem/stromal cells (CD45-CD34+CD31-), Meso-Endothelial bipotent progenitors (CD45-CD34+CD31Low), and endothelial colony forming cells (CD45-CD34+CD31Int).	Co-expression
SRP127783	Homo sapiens Transcriptome or Gene expression	RNA-Seq analysis was performed to identify differentially expressed transcripts in primary AML bone marrow derived mononuclear cells compared to healthy (normal) peripheral blood mononuclear cells.	Co-expression
SRP127787	Activation of the p53-MDM4 regulatory axis defines the anti-tumour response to PRMT5 inhibition through its role in regulating cellular splicing.	Here we describe broad anti-proliferative activity of potent, selective, reversible inhibitors of protein arginine methyltransferase5 (PRMT5) including GSK3326595 in human cancer cell lines representing both hematologic and solid malignancies. Interestingly, PRMT5 inhibition activated the p53 pathway via the induction of alternative splicing of MDM4. The MDM4 isoforms witch and subsequent p53 activation are critical determinants of the response to PRMT5 inhibition suggesting that the integrity of the p53-MDM4 regulatory axis defines a subset of patients that could benefit from treatment with GSK3326595. Overall design: RNA-seq from PRMT5 inhibitor treated or control (DMSO) treated lymphoma cell lines performed in duplicate post 3 and 6 days. ** Please note that processed data was generated from control and GSK595 sample pairs and linked to the corresponding GSK595 sample records.	Co-expression
SRP127809	Novel Transcriptional Activity and Extensive Allelic Imbalance in the Human MHC Region	The MHC region encodes HLA genes and is the most complex region in the human genome. The extensive polymorphic nature of the HLA hinders accurate localization and functional assessment of disease risk loci within this region. Using targeted capture sequencing and constructing individualized genomes for transcriptome alignment, we identified 908 novel transcripts within the human MHC region. These include 593 novel isoforms of known genes, 137 antisense strand RNAs, 119 novel long intergenic noncoding RNAs, and 5 transcripts of 3 novel putative protein-coding human endogenous retrovirus genes. We revealed allele-dependent expression imbalance involving 88% of all heterozygous transcribed single nucleotide polymorphisms throughout the MHC transcriptome. Among these variants, we show that the genetic variant associated with Behc ¸et's disease in the HLA-B/MICA region, which tags HLA-B*51, is within novel long intergenic noncoding RNA transcripts that are exclusively expressed from the haplotype with the protective but not the disease risk allele. Further, we showed that the transcriptome within the MHC region can be defined by 14 distinct coexpression clusters, with evidence of coregulation by unique transcription factors in at least 9 of these clusters. Our data suggest a very complex regulatory map of the human MHC, and can help uncover functional consequences of disease risk loci in this region. Overall design: RNA-Seq in human MHC region	Co-expression
SRP127811	Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling	Despite recent advances in understanding macrophage activation, little is known regardinghow human alveolar macrophages in health calibrate its transcriptional response to canonicalTLR4 activation. In this study, we examined the full spectrum of LPS activation and determinedwhether the transcriptomic profile of human alveolar macrophages is distinguished bya TIR-domain-containing adapter-inducing interferon-ß (TRIF)-dominant type I interferon signature.Bronchoalveolar lavage macrophages were obtained from healthy volunteers, stimulatedin the presence or absence of ultrapure LPS in vitro, and whole transcriptomic profilingwas performed by RNA sequencing (RNA-Seq). LPS induced a robust type I interferon transcriptionalresponse and Ingenuity Pathway Analysis predicted interferon regulatory factor(IRF)7 as the top upstream regulator of 89 known gene targets. Ubiquitin-specific peptidase(USP)-18, a negative regulator of interferon a/ß responses, was among the top up-regulatedgenes in addition to IL10 and USP41, a novel gene with no known biological function but withhigh sequence homology to USP18.We determined whether IRF-7 and USP-18 can influencedownstream macrophage effector cytokine production such as IL-10.We show thatIRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocytederivedmacrophages, and USP-18 overexpression attenuated LPS-induced production ofIL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10,and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes. Theseresults suggest that IRF-7 and predicted downstream target USP18, both elements of a typeI interferon gene signature identified by RNA-Seq, may serve to fine-tune early cytokineresponse by calibrating IL-10 production in human alveolar macrophages.	Co-expression
SRP127823	Rhesus iPSC-CMs response to anoxia, comparing with human iPSC-CMs	RNA-Seq to compare hypoxia responses between human and rhesus macaque iPSC-CMs Overall design: Both rhesus and human iPSC-Cardiomyocytes were subjected to anoxia condition, followed by RNA-Seq	Co-expression
SRP127947	Luminal lncRNAs Regulation by ERa-controlled Enhancers in a Ligand-independent Manner in Breast Cancer Cells	Estrogen receptor-a (ERa) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal breast cancer phenotype. Recently, we demonstrated that ERa binds chromatin in absence of ligand (apoERa) regulating transcription of protein-coding genes and several lncRNAs. Noteworthy, apoERa-regulated lncRNAs marginally overlap estrogen-induced transcripts representing a signature of luminal breast cancer genes. DSCAM-AS1 is a paradigmatic example of apoERa activity since its expression is largely unaffected by estrogenic treatment despite an E2-induced increment of ERa binding on its promoter. Analysing H3K27ac ChIP-Seq performed in hormone-deprived MCF-7, we identified a set of Super Enhancers (SEs) occupied by apoERa including one mapped in proximity of DSCAM-AS1. Using ChIP-qPCR, we validated ChIP-Seq signal of apoERa, p300 and CTCF at both DSCAM-AS1 TSS and at its associated SE. Furthermore, analysing MCF-7 ChIA-PET data and performing a 3C experiment, we confirmed a long range chromatin interaction between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF binding downstream to DSCAM-AS1 shows an enrichment in hormone-depleted medium as compared to other experimental conditions, indicating that CTCF demarcates enhancer actions at DSCAM-AS1 locus. The analysis of this lncRNA provides a paradigm of transcriptional regulation of a luminal specific apoERa regulated lncRNA. Overall design: The RNA-seq datasets were obtained from libraries generated with the TruSeq stranded library preparation kit (Illumina) using as input material poly(A+) RNA depleted of ribosomal RNAs fractions. Pool of 6 libraries (pooled at equimolar concentration) was generated, quantified and run on the HiSeq2000 (Illumina) sequencer in 75 nts paired-end sequencing mode following manufacturer instruction. A total of 6 datasets, with an average depth of 91.5 million paired-end reads, were obtained, composed of triplicates of two MCF-7 culture conditions: i) hormone-deprived cells treated with ESR1 mRNA (siRNA) (48h) or hormone-deprived cells treated with control siRNA (siCTR).	Co-expression
SRP127953	Gene expression analysis of human CD8+ T cells treated with a DOT1L inhibitor	Adoptive T cell therapy (ACT) is a promising therapeutic approach for cancer patients.  The use of allogeneic T cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled.  Through extensive chemical probe screening, we found that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviated allogeneic T cell responses.  DOT1L inhibition with SGC0946 selectively ameliorated low-avidity T cell responses but not high-avidity antitumor T cell responses mediated by the high-affinity T cell receptor or chimeric antigen receptor.  The inhibition of DOT1L in T cells prevented the development of graft-versus-host disease while retaining potent antitumor activity in xenogeneic ACT models.  These results suggest that DOT1L inhibition may enable the safe and effective use of allogeneic antitumor T cells by suppressing unwanted immunological reactions in ACT. Overall design: To investigate how DOT1L inhibition modulates the T cell activation signal, we compared gene expression profiles between SGC0946-treated or DMSO-treated (control) T cells by RNA-sequencing analysis.  Human CD8+ T cells derived from three different healthy donors were cultured in the presence of SGC0946 or DMSO.  Total RNA was collected from each sample and gene expression profiles were analyzed by RNA-sequencing using an Illumina HiSeq 2500 sequencer.	Co-expression
SRP127959	Homo sapiens isolate:clone WS236 Genome sequencing	Gene expression levels of unaffected control human myoblasts transfected with empty plasmid (pCINeo), and test miRNA's (mi405 and mi1155) were compared for a in vitro toxicity study to monitor potential off-target effects of the test therapeutics.	Co-expression
SRP127964	Transcriptome analysis of VMRC-LCD cells following ASCL1 knockdown	ASCL1 is a master transcription factor for neuroendocrine differentiation. RNA-sequencing analysis on VMRC-LCD cells following ASCL1 knockdown revealed a subset of genes possibly regulated by ASCL1. Overall design: VMRC-LCD cells were transfected with siRNAs for ASCL1, and RNA-sequencing was performed using Illumina HiSeq.	Co-expression
SRP128036	High-dimensional transcriptional analyses of UC Colon comparing RNALater to DMSO collection method	Simultaneous analyses of peripheral and mucosal immune compartments can yield insight into the pathogenesis of mucosal-associated diseases. Although methods to preserve peripheral immune cells are well established, studies involving mucosal immune cells have been hampered by lack of simple storage techniques. We provide a cryopreservation protocol allowing for storage of gastrointestinal (GI) tissue with preservation of viability and functionality of both immune and epithelial cells. Overall design: Multiple biopsies were taken from UC subjects to and placed into different collection media to compare the ability to extract total RNA and use total RNAseq to study the difference between inflamed and non-inflamed tissue	Co-expression
SRP128040	Discovery of inhibitors of the HSP90-Calcineurin-NFAT pathway against glioblastoma	We report the application of mRNA sequencing technology for high-throughput profiling of genes expression changes in U87 glioblastoma cells after treatment with compound YZ129 that we identified in our screen. By analyzing the total mRNA sequencing between YZ129 treatment group and the DMSO control group, we identified that 181 genes were significantly downregulated (changed >2 folds), while 226 genes were significantly upregulated (changed >2 folds). The downregulated genes were mainly associated with hypoxia (ALDOC, TMEM45A, F3, FOS, GFBP1, etc), glycolysis (SLC2A1, ANGPTL4, ENO2, LDHA, PGM, PFKFB3, etc.), PI3K/AKT/mTOR pathway (AK4, SLC2A1, PDK1, PGM1, PLOD2, TUBA4A, etc.), EMT (epithelial-mesenchymal transition) (VEGFA, ID2, COL1A1, FOXC2, LOXL2, etc.), G2/M checkpoint (UBE2C, FBXO5 (Emi1), TOP2A, MCM5/6), etc. some of the upregualted genes may contribute to the possible chemoresistance, such as FOSB, INHBA, EDN1, IRS2, KDM6B. This study yields a global view on molecular response to YZ29 treatment in GBM cells at mRNA level. Overall design: Examination of gene expression changes in U87 glioblastoma cells after treatment with drug YZ129 (versus DMSO control)	Co-expression
SRP128458	Expansion of adult human pancreatic tissue yields organoids harbouring progenitor cells with endocrine differentiation potential	Gene expression profiles from ALDH high cells sorted from expanded adult human pancreatic organoids are more similar to fetal pancreatic tissue and ALDH high cells sorted from expanded fetal human pancreatic organoids than to adult human islets or adult islet-depleted exocrine tissue. Overall design: RNA was isolated from ALDHhi cells sorted from organoids after 7 days expansion derived from human adult pancreatic tissue, ALDHhi cells sorted from organoids after 7 days expansion derived from human fetal pancreatic tissue, primary fetal pancreatic tissue, adult human islets from different donors and adult exocrine (islet-depleted) pancreatic tissue from different donors.	Co-expression
SRP128490	RNA sequencing to study transcriptomic changes in DLD-1 (colorectal adenocarcinoma) cells exposed to soft polyacrylamide matrices (~2 kPa and ~55 kPa) for short time scale of 90 minutes	Aim: To examine transcriptional changes in DLD-1 cells exposed to softer matrices (2 kPa and 55 kPa) and identify the chromosomes that are enriched with maximmally deregulated genes Methods: DLD-1 cells (otherwise growing on stiff tissue culture plastic substrates) were exposed to softer matrices for 90 minutes and to collagen coated glass coverslips (served as control) served as control) Results: RNA sequencing revealed nearly equivalent transcriptional deregulation in cells on both the polyacrylamide matrices (783 genes up and 872 genes down on 2 kPa, 649 genes up and 783 genes down on 55 kPa) when compared to cells on glass. Additionally, GO classification revealed that unique sets of transcriptionally deregulated genes (log fold=2) belonged to pathways associated with transcription regulation, chromatin organization, cell cycle and DNA damage/repair Results: We identified chromosomes 1, 2, 3, 6, 7, 10, 12, 14, 17 and 19 to be maximally enriched with the deregulated genes on softer matrices (log fold=2), while chromosomes 13, 18 and 21 showed minimal enrichment of deregulated genes. We also examined the spatial organization of chromosome 1, 18 and 19 territories in cells on softer matrices (using 3D-FISH) and observed that these chromosomes were mislocalized away from their conserved nuclear locations Conclusions: Our study reports the transcriptomic changes in DLD-1 cells upon lowering of extracellular substrate stiffnes and its impact on the spatial positioning of chromosome territories Overall design: RNA Seq profiles for DLD-1 cells on soft polyacrylamide matrices of ~2 kPa and ~55 kPa (reference - glass) were generated across 2 independent biological replicates using Illumina HiSeq platform	Co-expression
SRP128491	RNA-seq analysis of miR-324-5p overexpression upon H5N1 infection in A549 cells	The goals of this study are to compare NGS-derived whole transcriptome profiles (RNA-seq) of H5N1 infected A549 cells overexpressing either negative control mimic or miR-324-5p mimic Overall design: A549 cells were either mock transfected or transfected with either negative control or mir-324-5p mimic. After 12 hours cells were either mock infected (mock transfected cells) or infected with A/duck/India/02CA10/2011 - H5N1 virus (negative control and miR-324-5p overexpressing cells)	Co-expression
SRP128499	RNA-seq of cultured human kidney peritubular microvascular endothelial cells following exposure to cyclosporine A	This study represents the first time human kidney endothelial cells were exposed to cyclosporine A (CsA), a calcineurin inhibitor known to contribute to nephrotoxicity with symptoms including microvascular injury. This toxicity has been found to be unique to human trials and human kidneys are particularly susceptible to injury. We found that human kidney peritubular microvascular endothelilal cells (HKMECs) that were exposed to CsA exhibited transcriptomic changes around genes important to VEGF signaling and endothelial inflammation. Overall design: HKMECs from three donors were cultured then exposed to CsA or control for 1 hour and lysed for RNA collection after 18 hours, these were performed in duplicate	Co-expression
SRP128505	Gene Expression Profiling of WT and KDM3A Knocked out Cell	We identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes.  We found that H3K27ac upregulation is highly correlated with gene activation, but not H3K4me3; and transcription repression of certain TEAD1 target genes, such as BBC3, is important for the pathway function. KDM3A knockout caused upregulation of H3K9me2 mainly on TEAD1-binding enhancers rather than gene bodies, leading to decrease of H3K27ac and TEAD1 binding on enhancers and impaired transcription. Overall design: KDM3A was knocked out in HCT116 and the gene expression profile was studied by RNA sequencing Please note that, in the sample titles, M represents Mock, which means cell cultureed in normal state. S represents Starvation, which mens cells growed up in normal culture in a due time, then change the nomal culture into no-serum culture. S+F means addition of FBS into the no-serum culture after cell-starved for for 24 hours.	Co-expression
SRP128510	RNA-sequencing of human tendon after injury	RNA-sequencing for 6 samples Overall design: Examing 2 conditions, each with 3 replicates	Co-expression
SRP128545	Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells	Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. Here, we used comparative transcriptomics to provide a data resource that can be used toidentify cellular responses that might allow bats to survive filovirus infections. We generated RNA-Seq data of Ebola and Marburg virus infected Homo sapiens HuH7 and Rousettus aegyptiacus R06E-J cell lines at three different time points (3h, 7h, 23h) post infection.	Co-expression
SRP128579	Novel Atherogenic Pathways from the Differential Transcriptiome Analysis of Diabetic Epicardial Adipose Tissue	In this study we performed transcriptome sequencing on the Subcutaneous Adipose Tissue and Epicardial Adipose Tissue of both diabetic and nondiabetic human patients. Overall design: Examination of transcriptome in human fat samples	Co-expression
SRP128608	Next-generation sequencing of human dermal fibroblasts transdifferentiated towards the otic lineage	We report the RNAseq analysis of human dermal fibroblasts which have been treated by protocols to stimulate their differentiation towards the otic lineage. This was achieved by transfection with different transcription factors with the aim to induce an initial reprogramming of the cells and was followed by growth factor treatments known to promote otic differentiation. The results show that a partial differentiation towards the otic lineage is achieved by these protocols. Overall design: RNAseq profiles were obtained from human dermal fibroblasts  with two different protocols. Prior to treatment with growth factors stimulating differentiation, the samples were either transfected with the transcription factors OCT4 or a combination of ATOH1, POU4F3 and GFI1.	Co-expression
SRP128610	C1 single-cell RNA-seq of Adult Human spermatoognia	To reveal distinct transcriptomes associated with spermatogonial stem cell renewal vs. initiation of differentiation, single-cell transcriptomes from Adult Human spermatogonia were subdivided into subpopulations based on the levels of ID4 mRNA (determined in this experiment). This correlates with distinct fates of corresponding mouse spermatogonia when assayed by transplantation, with ID4-EGFPbright cells highly enriched for SSCs, and ID4-EGFPdim cells enriched for progenitors. We used the Fluidigm C1 instrument to capture individual spermatogonia for SMART-Seq2 single-cell RNA-seq. Overall design: Nine replicate preparations of Adult Human spermatogonia were used for this study. Data are from a total of 635 cells. Cells were binned into quartiles according to ID4 mRNA levels (Q1 = ID4-high, Q4=ID4-low, Q2 and Q3 have intermediate ID4 mRNA levels) to facilitate comparisons.	Co-expression
SRP128622	Caspase-dependent apoptosis gene in gliomas	Gliomas are the most common malignant tumors of the brain. The aim of this study is to identify caspase-dependent apoptotic genes and uncover their potential regulatory mechanism in glioma progression. Human glioma cell line U251 was used. Three experiment groups were set as control group, H2O2 group (treated with H2O2) and caspase inhibitor group (treated with caspase inhibitor).	Co-expression
SRP128653	Human iPS-derived astroglia from a stable neural precursor state; improved functionality compared to conventional astrocytic models	Characterization of different astrocytes soruces was done using RNAseq including samples from human primary adult brain, astrocytoma, and hiPSC derived astrocytes including neural stem cell origin Overall design: Full RNAseq (>200nt) of biological triplicates isolated with Illumina TrueSeq Stranded mRNA LT Sample Prep Kit and sequenced using Illumina NextSeq 500 sequencer	Co-expression
SRP128693	The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [RNA-seq]	Gene fusions arising from chromosomal translocations are key oncogenic drivers in soft tissue sarcomas but little is known about how they exert their oncogenic effects. Our study explores the molecular mechanisms by which the SS18-SSX fusion oncoprotein subverts epigenetic mechanisms of gene regulation to drive synovial sarcoma. Using functional genomics, we identify KDM2B – a histone demethylase and core component of a non-canonical Polycomb Repressive Complex 1 (PRC1.1) – as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands genome-wide. Via KDM2B, SS18-SSX binds and aberrantly activates expression of a series of developmentally regulated transcription factors that would otherwise be targets of polycomb-mediated repression, which is restored upon KDM2B depletion leading to irreversible mesenchymal differentiation. Thus, SS18-SSX de-regulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression. Overall design: RNA-Seq of  human synovial sarcoma cells (HS-SY-II) in control cells (Ren.173) and upon knockdown of SS18-SSX1 (SS18.273 and SSX.1274) or of KDM2B (KDM2B. 4395 and KDM2B.4835) in duplicates.	Co-expression
SRP128699	RNAseq analyze global transcriptome of changes between siIRF3 and siYAP in Gastric cancer cells	Purpose: To investigate the signal crosstalk between IRF3 and YAP, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by the knockdown of IRF3 or YAP in HGC-27 cells. Methods: Total RNA was extracted from HGC-27 cell after transfection with negative control siRNA (n.c.), IRF3 siRNA (siIRF3) or YAP siRNA (siYAP). Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina  HiSeq 2500 platform. Results: Approximately approximately one thousand transcripts showed differential expression between the siIRF3/siYAP and n.c., with a Fold-change>=2 and q-value <= 0.05. Gene ontology (GO) and gene set enrichment analysis (GSEA) showed a significant negative enrichment of YAP target genes identified by three independent studies in IRF3-knockdown condition. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding the signal crosstalk between IRF3 and YAP. Overall design: RNA was extracted from HGC-27 cells transfected with siRNAs for 48 h. The quality assessed on the Agilent 2100 and sequencing on the Illumina Hiseq2500.	Co-expression
SRP128828	Novel calcineurin A (PPP3CA) mutation in NPCs and NGN2 neurons of patient with epileptic encephalopathy and dysmorphy.	Gene expression studies of neuron and neuron precursor cells of unhealthy individual.	Co-expression
SRP128859	RNA-seq of shEZH2 cells	Downregulation of EZH2 Leads to Cellular Senescence with Features of SASP Overall design: Cells were infected with a lentivirus vector expressing shRNA against EZH2 and harvested at 4 and 8 days after infection. Total RNA was harvested from cells using Trizol reagent (Invitrogen) and further purified using the Purelink RNA Mini kit (Invitrogen) with DNase I digestion. RNA library preparation with polyA selection and Illumina HiSeq 2x150bp sequencing was performed by GeneWiz Inc. Paired-end reads were quality trimmed using Trim galore v0.4.0 and subsequently aligned to the human reference genome, hg19, using HISAT2 v2.1.0. Reads mapping to annotated genes were quantified using featureCounts (Liao et al., 2014). Differential gene expression was determined using DESeq2 v1.12.4 (Love et al., 2014) and significance was defined as FDR-corrected p-values of <0.05. The log2 fold change for each gene was used to rank the list of genes for GSEAPreranked analysis (Subramanian et al., 2005). FPKM values were calculated using DESeq2 and Z-scores were generated from FPKMs	Co-expression
SRP128876	Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq.	Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels. Over-representation and gene set enrichment analysis corresponded well and revealed that TBOEP treatments resulted in an upregulation of genes involved in protein and energy metabolism, along with DNA replication. Such increases in cell and macromolecule metabolism could explain the increase in mitochondrial activity at lower TBOEP concentrations. In addition, TBOEP affected a wide variety of biological processes, the most notable one being the general stress response, wound healing. Finally, TBOEP showed effects on steroid hormone biosynthesis and activation, regulation, and potentiation of immune responses, in agreement with other studies. As such, this study is the first study investigating genome-wide changes in gene transcription in response to TBOEP in human cells. Overall design: HepG2 cells were treated with low (2.5 uM) or high (125 uM) concentrations of Tris (2-butoxyethyl) phosphate (TBOEP) in 0.1% DMSO. For control purposes cells were exposed to 0.1% DMSO alone. Treatment lasted for 72 hours. All treatments were conducted in triplicates, involving separate seeding of cells. RNA was isolated with Trizol (Invitrogen, USA) and RNeasy Kit (Qiagen, GER). Libraries were prepared with the TruSeq Stranded mRNA Sample Preparation Kit (Illumina, USA). 50bp long paired-ends reads were sequenced using the HiSeq(R) 1500 platform (Illumina, USA). Alignement to the UCSC hg19 assembly of the human genome, mapping and annotation was performed with CLC Genomics Workbench (CLC Bio, DEN). Samples were normalised by quantile normalisation. Differential expression p-values were generated using Baggerly''s test statistic. These p-values were subsequently corrected with the Benjamini-Hochberg procedure to limit the false discovery rate (FDR) to 5% of the significant genes .	Co-expression
SRP128898	Sex Differences in the Late First Trimester Human Placenta Transcriptome	This study is the first characterization of the first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long term adult health. Overall design: Examination of gene expression in Males vs. Females	Co-expression
SRP128903	The dynamic landscape of coding and non-coding RNAs in the innate immune response to microbial pathogens	We performed a systematic analysis of the coding and non-coding transcriptomes of human macrophages after stimulation with ligands to TLR2/6  (FSL), TLR 1/2  (Pam3CSK4), and TLR4 (LPS) Overall design: Transcriptome of THP1 derived macrophages without and with treatment with 3 different TLR ligands for 8hrs	Co-expression
SRP128918	A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [HSC and PROG RNA-seq]	While gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs. Overall design: RNA-seq of hematopoietic stem cells (HSC) and progenitor cells (PROG) from fetal liver (FL), cord blood (CB) and bone marrow (BM) and control HPC cells differentiated from IPSC cells.	Co-expression
SRP128920	A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [BM low-input mRNA-seq]	While gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs. Overall design: RNA-seq of BM-HSC cells transduced with a control (CTRL), HMGA2-S+3''UTRwt (SHORT) or CLK3 lentiviral over-expression vectors.	Co-expression
SRP128940	Sex Differences in the Late First Trimester Human Placenta Transcriptome	This study is the first characterization of the first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long term adult health. Overall design: Examination of gene expression in Males vs. Females.	Co-expression
SRP129004	Mucosal transcriptome of rectal biopsies in treatment-naïve, pediatric ulcerative colitits patients	Using recal mucosal biopsies, collected prior to treatment in new-onset pediatric ulcerative colitis patients, we performed RNAsequencing to generate transcriptomic profiles linked to pathogenesis, severity, and treatment response. Overall design: Biopsies were obtained from 206 new-onset patients during diagnostic colonoscopy, using the Qiagen AllPrep RNA/DNA MiniKit. PolyA-RNA selection, fragmentation, cDNA synthesis, adaptor ligation, TruSeq RNA sample library preparation (Illumina, San Diego, CA), and paired-end 75bp sequencing was performed.  Reads were quantified by kallisto [32], using Gencode v24 as the reference genome and Transcripts per Million (TPM) as an output. We included 14,085 protein-coding mRNA genes with TPM above 1 in 20% of the samples in our downstream analysis.	Co-expression
SRP129007	hnRNP L protects mRNAs from nonsense-mediated mRNA decay	Identification of RNAs differentially expressed upon treatment with nontargeting siRNA, hnRNP L siRNA, UPF1 siRNA, or hnRNP L and UPF1 siRNAs together. Overall design: Paired-end high throughput RNA sequencing of total RNA from HEK-293 cells treated with siRNAs against hnRNP L, UPF1, or a non-targeting control (NS).	Co-expression
SRP129026	Comparison of transcriptional changes after CD28/CD3z and 4-1BB/CD3z chimeric antigen receptor ligation	The adoptive transfer of chimeric antigen receptor- (CAR) modified T cells is revolutionizing the treatment of B cell malignancies and has the potential to be applied to other diseases. CARs redirect T cell specificity by linking an antigen recognition domain to T cell signaling modules comprised of CD3z to provide signal 1, and CD28 or 4-1BB to provide costimulation. CD28/CD3z and 4-1BB/CD3z CARs confer differences in effector function and cell fate that affect clinical efficacy and toxicity. These differences may result from activation of divergent transcriptional programs. To gain this insight, we analyzed changes in gene expression in stimulated and resting CD28/CD3z or 4-1BB/CD3z CAR T cells. CD28/CD3z CAR stimulation initiated more marked early transcriptional changes with greater fold increases in the expression of effector molecules including GZMB, IFNG, IL2, TNF, and IL6. Direct comparison of CD28/CD3z and 4-1BB/CD3z samples stimulated for 6 hours identified 1,673 differentially expressed genes. Of these, the memory T cell-associated genes KLF2, IL7R, and FAM65B were expressed at lower levels in CD28/CD3z CAR T cells. KLF2 and IL7R are FOXO transcription factor family targets and we found that FOXO4 expression was similarly reduced in CD28/CD3z CAR T cells. CD28/CD3z CAR stimulation induces an effector T cell-like transcriptional profile that may underlie the decreased persistence and increased risks of toxicities observed with CD28/CD3z CAR T cells in early clinical trials. Overall design: Purified CD28/CD3z and 4-1BB/CD3z CAR T cells were prepared from healthy donors and stimulated by incubation with anti-CAR beads, or left unstimulated by incubation with control beads. Total RNA was harvested 6 or 24 hours after treatment. Three biological replicates for each treatment condition were prepared, yielding 24 total samples for analysis. A42 and A44 denote 4-1BB/CD3z CARs, A43 and A45 denote CD28/CD3z CARs.	Co-expression
SRP129578	Homo sapiens Raw sequence reads	HEK293 cells were treated with single or mixture of OTA and CTN and sRNA and transcriptome sequencing were performed to explore molecular signatures mediating cytotoxic outcomes	Co-expression
SRP130149	Maternal plasma cell-free RNA sequencing for prematurity initiative	cfRNA-seq: We used cfRNA-seq to identify differentially expressed gene-specific cfRNA transcripts between women who delivered spontaneous preterm (n=8) and women who delivered at full-term (n=7). Overall design: cfRNA-seq was used for gene-specific cfRNA transcript discovery. RT-qPCR (available through Github link) was used for validation, and the development of a heuristic to predict spontaneous preterm delivery up to two months in advance of labor.	Co-expression
SRP130621	Investigation of molecular mechanism of severe viral infections in humans	It's intriguing that many common viruses infect the general human population, however only a few of them develop severe diseases. We aim to search for human gene mutations which could eventually explain their diseases. We also aim to understand the underlying molecular mechanisms.	Co-expression
SRP130653	Mutational signatures reveal the role of RAD52 in p53-independent p21 driven genomic instability	Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential to design appropriate therapeutic strategies. In a recent study we reported an unexpected oncogenic property of p21WAF1/Cip1 showing that its chronic expression, in a p53-deficient environment, causes genomic instability by deregulating the replication licensing machinery.	Co-expression
SRP130768	Homo sapiens bisulfite and mRNA sequencing of blood T cells and LCM collected lung cells	Raw sequencing reads of Homo sapiens bisulfite and mRNA sequencing of blood T cells and LCM collected lung cells.	Co-expression
SRP130901	High-Depth Transcriptomic Profiling Reveals the Temporal Gene Signature of Mesenchymal Stem Cells During Chondrogenesis	Cartilage tissue engineering seeks to replace degenerated or damaged cartilage following disease or injury. Mesenchymal stem/stromal cells (MSCs) provide an attractive cell source for cartilage repair; however, the underlying molecular pathways that drive chondrogenesis of these pools of adult stem cells remains poorly understood. Here, we generated a rich data set of high throughput RNA sequencing of human MSCs throughout chondrogenesis at six different time points. Our data is consisted of 18 libraries with three individual donors as biological replicates, each library possessing a sequencing depth of 100 million reads. We also performed flow cytometric, histological, and biochemical analyses in parallel to validate the quality of our in vitro engineered cartilage. Differential gene expression and gene ontology analyses identified dynamic changes in multiple biological pathways, namely downregulation in cell cycle and proliferation, and upregulation in extracellular matrix synthesis. Weighted gene correlation network analysis also identified an important chondrogenic gene subset, whose functional characterization promises to further harness the potential of MSCs for cartilage tissue engineering. Furthermore, we created a graphic user interface encyclopedia built with the goal of producing an open resource of transcriptomic regulation for additional data-mining and pathway analysis of the process of MSC chondrogenesis. The tool can be accessed at: http://msc-browser.guilaklab.com Overall design: High throughput RNA sequencing following mesenchymal stem cells throughout chondrogenesis at six different time points with 3 donors as biological replicates	Co-expression
SRP130907	A Reproducibility-Based Computational Framework Identifies An Inducible, Enhanced Antiviral Dendritic Cell State In HIV-1 Elite Controllers (Sorted Bulk RNA-Seq)	Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-Seq to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. We discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. We identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells (PBMCs) from healthy individuals in vitro. Overall design: Bulk RNA-seq profiling of sorted cDC subsets associated with cell-intrinsic HIV-1 immune recognition.	Co-expression
SRP130947	Single cell RNA-Seq of E18.5 developing mouse kidney and human kidney organoids	These files represent single cell RNA-Seq data generated on a 10x Chromium genomics platform from three biological replicates from the embryonic day (E)18.5 developing mouse kidney and three biological replicates of iPSC-derived human kidney organoids differentiated according to our published protocol (Takasato et al., Nature Protocols 2016). When aggregated, the mouse data represents >6000 cells that passed our QC, containing most major cell types known to exist in the developing mouse kidney. The aggregated human organoid data contains of >7000 cells that passed our QC and contains populations representing endothelial cells, podocytes, stroma, nephron, and off-target populations with similarity to neurons. Overall design: Examination of the celular composition of human kidney organoids by comparison to mouse embryonic kidney	Co-expression
SRP130953	Differential miRNA Expression in B Cells/T Cells Associated with Inter-individual Differences in Humoral Immune Response to Measles Vaccination	Through Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells isolated from high and low antibody responders to measles vaccination, we identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) associated with measles-specific antibody response after vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found. DIANA tool was used for gene/target prediction and pathway enrichment analysis and this yielded several biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, that were significantly associated with neutralizing antibody titers after measles vaccination.   This study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may potentially serve as predictive biomarkers of vaccine response. Overall design: Examination of miRNA expression differences in/between purified B and CD4+ T cells of high and low responders to measles vaccination.	Co-expression
SRP130955	Response of HEK293 Freestyle cells to 36 h of culture in Zn(II)-depleted Freestyle medium	We describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the “A12-resin,” that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids including human sera. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293T cells cultured in medium depleted of Zn(II) using S100A12. Our data indicate that dividing cells can maintain a constant pool of free Zn(II), even under conditions of severe Zn(II) deprivation. We expect that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis in biological settings, uncovering novel roles for Zn(II) in biology. Overall design: Defining the response of a cell line to Zn(II) starvation	Co-expression
SRP130969	CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9orf72 dipeptide repeat protein toxicity	Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). The nucleotide repeat expansions are translated into dipeptide repeat (DPR) proteins, which are aggregation-prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene knockout screens for suppressors and enhancers of C9orf72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA processing pathways, and in chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9orf72 DPRs in neurons, and improved survival of human induced motor neurons from C9orf72 ALS patients. Together, this work demonstrates the promise of CRISPR-Cas9 screens to define mechanisms of neurodegenerative diseases. This dataset contains the RNA-sequencing data used to support the conclusions from this study. Overall design: Differential gene expression derived from RNA-sequencing data, analyzed using DESeq2. 3 independent experiments were performed for this study, each had 6 samples per experiment (3 biological replicate controls and 3 biological replicate experimental conditions). Experiment #1 = K562 cells treated with 10uM synthetic PR20 peptides compared to untreated controls (samples GSM2934784 - GSM2934789). Experiment #2 = primary mouse cortical neuron cultures from Cas9+ mice with control sgRNAs or TMX2 targeting sgRNAs, both groups expressing PR50 (samples GSM2934790 - GSM2934795). Experiment #3 = primary mouse cortical neuron cultures treated with a control GFP lentivirus or a lentivirus expressing PR50 (samples GSM2934796 - GSM2934801).	Co-expression
SRP130971	Transcriptome sequencing wide functional analysis of human mesenchymal stem cells with PolyIC treatment	Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs polyIC (10 ug/ml). Overall design: Examination of effects of PolyIC-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500 (101 cycles PE lane).	Co-expression
SRP130972	RNA-seq analysis of IL-1B and IL-36 responses in epidermal keratinocytes identifies a shared MyD88-dependent gene signature	IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B or IL-36G. We identified some early IL-1B-specific responses (8 hours post-treatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 hours post-treatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 hours) followed by no response or repression (24 hours). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 + 24 hours). These involved up-regulation of ligands (IL1A, IL1B, IL36G) and activating proteases (CTSS), but also up-regulation of inhibitors such as IL1RN and IL36RN. Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, IBD, primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses. Overall design: Cultures were treated with truncated recombinant human IL-1B, IL-36A, IL-36B or IL-36G (10 ng/ml for IL-1B; 2000 ng/ml for IL-36 cytokines). Three cell lines were used (lines A, B and C) with samples processed in 4 batches. Samples within the same batch are comparable. Experiments were performed with 8 and 24 hours of cytokine treatment (n = 2-3 per time point).	Co-expression
SRP130975	Transcriptome analysis of iPSC-derived keratinocytes with or without a disease-associated TP63 mutation	Induced pluripotent stem cells (iPSC) were generated from two patients affected by ankyloblepharon ectodermal dysplasia and clefting (AEC), an ectodermal dysplasia caused by mutations in TP63. The two TP63mutations(I537T and R598L) were corrected using Crispr/Cas9- mediated homologous recombination. The resulting conisogenic iPSC pairs were differentiated into keratinocytes and subjected to RNA-sequencing. Overall design: 2 conisogenic pairs of AEC and gene-corrected iPSC-derived keratinocytes were analyzed (4 samples total)	Co-expression
SRP131002	Necroptosis inhibition protects from dopaminergic neuronal cell death in OPA1 mutant Parkinson's disease patient neurons and MPTP treated mice	Dysfunctions in mitochondria dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). Recently, it was shown that an inherited form of PD and dementia is caused by new mutations in the OPA1 gene, which encodes for a key player of mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1 mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectively rescued this survival deficit. Additionally, dampening necroptosis in MPTP treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both the early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a promising therapeutic target for PD. Overall design: 3 replicates for control and 3 replicates for OPA1 F38D mutant cells	Co-expression
SRP131004	RNA-Seq in human T-cell lymphoblastic lymphoma samples and control thymuses	Precursor T-cell lymphoblastic neoplasms are aggressive haematological neoplasm that most often manifest with extensive marrow and blood affectation (T-cell acute lymphoblastic leukaemia or T-ALL) or less commonly as a thymic mass with limited bone marrow infiltration (T-cell lymphoblastic lymphoma or T-LBL). Here we show data from RNA-Seq in a sample series of T-LBL from Spanish patients.The goal was to determine the levels of expression of coding genes and microRNAs, and to identify all genetic variants including SNVs, indels, and fusion transcripts. Overall design: Expression data were determined by comparson of each tumour sample with two control thymuses (404 and 405). Genetic variants were determined by comparison of tumour sequences with canonical ENSEMBL normal-references of each gene.	Co-expression
SRP131025	Bioinformatics analysis of transcriptome related to blood stasis syndrome in diabetes mellitus patients	In traditional Chinese medicine (TCM), blood stasis syndrome (BSS) is mainly manifested by the increase of blood viscosity, platelet adhesion rate and aggregation, and the change of microcirculation, resulting in vascular endothelial injury. It is an important factor in the development of diabetes mellitus (DM). According to the differences in the internal and external environment of the individual disease, BSS were divided into qi-deficiency and blood stasis syndrome (QDBS), qi-stagnation and blood stasis syndrome (QSBS), cold-coagulation and blood stasis syndrome (CCBS), heat-accumulation and blood stasis syndrome (HABS). The aim of this study was to screen out the potential candidate mRNAs in DM patients with BSS by high-throughput sequencing (HTS) and bioinformatics analysis. CRL-1730 human umbilical vein endothelial cells (HUVECs) were incubated with 10% human serum to establish models of DM with BSS, DM without BSS (NBS) and normal control (NC). Total RNA of each sample was extracted and sequenced by the Hiseq2000 platform. Differentially expressed mRNAs (DE-mRNAs) were screened between samples. On the basis of mRNA expression profiles, four comparisons were made, including QDBS vs NBS and NC, QSBS vs NBS and NC, CCBS vs NBS and NC, HABS vs NBS and NC. Then, comparisons with P values <0.05 (Fisher''s exact test), false discovery rates (FDR) <0.01 and |log2 ratios|=1 were considered as DE-mRNAs in BSS. This study screened out the DE-mRNAs in DM patients with BSS by HTS and bioinformatics analysis. Overall design: Bioinformatics analysis of transcriptome in DM patients with BSS by establishing cell models of DM with BSS.	Co-expression
SRP131028	RNA seq_PDX2_SHP099	RNA seq data of PDX2 treated with vehicle of SHP099 --> to check senescence and SASP gene expression signatures Overall design: PDX2 KRAS mut NSCLC tumors implanted in 12 different mice, 5 treated with vehicle, 7 with SHP099, during 19 days.	Co-expression
SRP131037	Using Next-Generation Sequencing Transcriptomics to Determine Markers of Post-traumatic Symptoms  - preliminary findings from a post-deployment cohort	Post-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Overall design: Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)	Co-expression
SRP131052	Transcriptomes of human monocytes and monocyte-derived macrophages with or without glucocorticoid treatment	Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases due to their potent immune suppressive properties. Overall design: Monocytes from healthy donors and the respective monocyte-derived macrophages were cultured in the presence of triamcinolone acetonide (TA) for 4 hours. Cells were then collected for  RNA-seq.	Co-expression
SRP131065	Effect of NORAD shRNA on A549 cells treated with TGF-beta	We evaluated the effect of NORAD (also known as LINC00657 or LOC647979) shRNA on TGF-beta induced changes in the gene expression in A549 cells by RNA-seq. Overall design: mRNA expression was determined in a lung adenocarcinoma cancer cell line A549 infected with NORAD shRNA-expressing lentiviral vector and treated with TGF-beta.	Co-expression
SRP131083	ROP: Dumpster Diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues	High-throughput RNA sequencing technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), a tool for discovering the source of all reads originating from complex RNA molecules. We apply ROP to samples across 2630 individuals from 54 diverse human tissues. Our approach can account for 99.9% of 1 trillion reads of various read length. Additionally, we use ROP to investigate the functional mechanisms underlying connections between the immune system, microbiome, and disease. ROP is freely available at http://smangul1.github.io/rop/. Overall design: 19 nasal epithelium RNA-Seq, 9 ashmatic, 10 normal/control. 18 peripheral blood RNA-Seq, 9 ashmatic, 9 normal/control. Please note our analysis identifies the origin of unmapped read, hence Read Origin Protocol, by aligning the unmapped reads to elements that are not on human reference genome. The elements include bacterial and viral genome database as well as immune variable regions, and repeat elements.	Co-expression
SRP131089	Regenerating hair cells in human vestibular sensory epithelia	To investigate alterations in gene expression after Ad2-ATOH1-GFP transduction of human supporting cells, we measured transcriptome changes by RNA-seq. We compared gentamicin-treated tissue (to kill the hair cells) transduced with Ad2-ATOH1-GFP (to promote hair cell production) cultured for 5 days, versus control tissues only treated with gentamicin (cultured for 2 days, 8 days and 14-18 days). Overall design: Human utricle mRNA profiles after treatement with gentamycin alone or incombination with Atoh1 and untreated controls.	Co-expression
SRP131095	Transcriptional changes after overexpression of proliferation drivers in human mammary epithelial cells.	Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of human cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes tested regulate proliferation, many performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in SCNAs (somatic copy number changes) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue type-specific genetic network architectures underlie SCNA selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive new insights about the genetic network architecture of aneuploidy in tumors. KRTAPs are a class of human genes that promote proliferation in mammary epithelial cells (HMEC), but the mechanism is not understood. We performed RNAseq to study transcriptional changes associated with oeverxepression of KRTAPs and other oncogenes in hTERT-immortalized human mammary epithelial cells. GSEA analysis revealed the top enriched pathways upregulated by KRTAP expression are E2F-mediated regulation of DNA replication, G1-S specific transcription, cell cycle, translation and ribosome. KRTAP-induced mRNA changes are most closely related to those due to CCND1 expression, including induction of E2F1 transcription factor. Overall design: Analysis of whole transcriptome in HMEC overexpressing different human genes.	Co-expression
SRP131103	A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects	Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2. We identified that compared to other flame retardants, TCEP and TCIPP had little cytotoxicity. Treatment with sub-cytotoxic concentrations of the two compounds revealed that both chemicals elicited similar effects; both compounds were found to affect genes involved in immune responses and steroid hormone biosynthesis, while also affecting xenobiotic metabolism pathways in a similar manner. Specifically for effects on immune responses, both compounds were shown to alter the expression of the receptor of the potent and pleiotropic complement component, C5a. Additionally, expression of genes encoding for effector proteins involved in the complement cascade along with other potent inflammatory regulators were found altered in response to TCEP and TCIPP, further emphasizing their potential effects on immune function. Taken together, given that TCIPP elicited similar effects compared to TCEP, and at lower concentrations, the potential health effects of TCIPP need to be further studied for a complete risk assessment of the compound. Overall design: HepG2 cells were treated with low (25 uM) or high (250 uM) concentrations of tris(2-chloroethyl) phosphate (TCEP), low (2.5 uM) or high (25 uM) concentrations of tris(2-chloroisopropyl) phosphate (TCIPP). For control purposes, cells were exposed to 0.1% DMSO alone. Treatment lasted for 72 hours. Treatments were done in triplicate for each condition involving separate cell seeding, cell growth, treatments and RNA extractions per triplicate. RNA was isolated with Trizol (Invitrogen, USA) and RNeasy Kit (Qiagen, GER). Libraries were prepared with the TruSeq Stranded mRNA Sample Preparation Kit (Illumina, USA). 50bp long paired-ends reads were sequenced using the HiSeq(R) 1500 platform (Illumina, USA). Alignment, mapping and annotation of sequenced reads were performed using the CLC Genomics Workbench (CLC Bio, Aarhus, Denmark). Samples were normalized by quantile normalization before being mapped and annotated using the human reference hg19 genome.	Co-expression
SRP131116	Transcriptional profiling at the DLK1/MEG3 domain explains clinical overlap between imprinting disorders	we performed transcriptomic profiling on fibroblasts cultures from controls, TS14 and SRS patients in order to study the effect of hypomethylation at imprinted loci on genes expression Overall design: RNA seq was perfromed from fibroblasts mRNA of: 4 controls. 4 TS14 patients, 5 SRS patients and one SRS/TS14 patient	Co-expression
SRP131119	GEO accession GSE109483 is currently private and is scheduled to be released on Jan 24, 2018.	If GEO accession GSE109483 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP131120	GEO accession GSE109484 is currently private and is scheduled to be released on Jan 24, 2018.	If GEO accession GSE109484 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP131125	A compendium of long non-coding RNAs transcriptional fingerprint in multiple myeloma	Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells (PCs) characterized by highly heterogeneous genetic background and clinical course, and whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis and invasion. Although still in its infancy, the knowledge of the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts.  Herein, we assessed the lncRNAs expression profiling by RNA-sequencing in a cohort of 30 MM patients, aimed at defining a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. We identified 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship. Overall design: Total RNA samples from highly purified plasma cells of 30 MM cases at onset	Co-expression
SRP131141	Survey of Human Fetal Kidney Development Through Single Cell RNA Sequencing Analysis	Human kidney is a major metabolic organ, which plays a crucial role in regulating homeostasis of human body. However, gene expression characterizations of human fetal kidney development is still not fully explored. Here, we used single-cell RNA-seq to analyze more than 3,000 individual renal cells of human fetal kidneys covering over four months of development in vivo.We found co-expression of self-renewal and differentiation genes in cap mesenchyme, progenitors differed from that of mouse as they persistently express SIX1 throughout the renal morphogenesis. Besides, we recapitulated the transcription factors and signaling pathways potentially important for segmentation of nephron tubule. Furthermore, we explored the human specific features of the heterogeneous collecting duct epithelium. We also dissected the metabolism signatures of fetal kidney as well as the extracellular matrix composition of glomerulus mesangium. Eventually, we identified novel markers for renal tubules. Our study highlights the gene expression features of human fetal kidney development, which will contribute to dissecting the mechanisms of renal dysplasia and congenital nephrotic disease. Overall design: Here we sequenced 3,543 single cells and 3,023 of them passed the screening criteria, which we set the expressed gene number and transcripts in each cell should respectively above 1000 and 5000.And then we constructed the gene expression landscape throughput kidney organogenesis.	Co-expression
SRP131149	Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia	In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing the surrounding vasculature network. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines responded strikingly different to hypoxia. We demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response. Overall design: 16 paired-end samples in total: 4 different cell lines sequenced in duplicate across 2 conditions each.	Co-expression
SRP131169	GEO accession GSE109528 is currently private and is scheduled to be released on Jan 24, 2018.	If GEO accession GSE109528 has been cited in a publication, please notify us at geo@ncbi.nlm.nih.gov to initiate the public release of associated data.	Co-expression
SRP131173	scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3' mRNA profiling	We present sc-FTDseq, a microchip platform for single-cell freeze-thaw lysis directly toward 3' mRNA sequencing. It offers format flexibility with a much simplified, widely adoptable workflow that reduces the number of preparation steps and hands-on time, with the quality of data and the cost per sample matching that of the state-of-the-art scRNA-seq platforms. Freeze-thaw, known as an unfavorable lysis method resulting in RNA fragmentation, turns out to be fully compatible with single-cell 3' mRNA sequencing, which detects only ~50 bases at the 3' end. We applied it to the profiling of mixed populations including whole tumors for distinguishing all major cell types and to the profiling of circulating follicular helper T cells implicated in systemic lupus erythematosus pathogenesis. Our results delineate the heterogeneity in the transcriptional programs and effector functions of these rare pathogenic T cells. Overall design: mRNA sequencing libraries are prepared after lysing the cells using three cycles of freeze-thaw. Open-surface and closed-environment formats refer to how a microwell array is used for co-loading cells and uniquely barcoded beads for mRNA capture. In closed-environment format, the microwell array is bonded with a channel on top of the array, and the cells and beads are introduced into the microwells through the channel. In open-surface format, microwell arrays are used without a channel on top, and cells and beads are introduced onto the array using a pipette.	Co-expression
SRP131185	Circular RNAs sequencing in patients with HBV-positive hepatocellular carcinoma	This work illustrates that clusters of circRNAs are aberrantly expressed in HBV-related hepatocellular carcinoma (HCC), which might provide potential targets for the early diagnosis of this disease and new genetic insights into HCC.	Co-expression
SRP131198	Xeno-free and Chemically Defined Human System for Culturing Human Epidermal Keratinocytes	Developing an effective xeno-free and defined system for human keratinocyte culture has been one of the fundamental measures in current cellular therapy. For keratinocytes, in particular, such system will not only fulfill clinical safety and quality criteria, it will allow for the management of less severe burns and other skin injuries such as chronic wounds. To date, the expansion of autologous keratinocytes in the clinical settings still relies on 3T3 feeder co-culture system. Here we report a completely xeno-free and defined culture system by using human recombinant laminins as feeder replacement. We have thoroughly characterized the cells cultured in this new system both in vitro and in vivo. We found that laminin-511/-521, and the unanticipated laminin-411/-421, but not -332, -111, -121, -211, or LN-221 support adult human skin keratinocytes and could maintain their self-renewal properties comparable to the 3T3 system. We believe our new culture method should facilitate broader use of cultured epithelial cell products for today's regenerative medicine. Overall design: RNA sequencing and analysis on whole adult human skin or freshly cultured human keratinocytes using two different methods: co-cultured with 3T3 feeder and laminin-coated tissue culture plates.	Co-expression
SRP131216	Gene Expression Profiling of Cutaneous CD30+ Lymphoproliferative Disorders by RNA-seq	Cutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs, whereas other CD30+LPDs didn't express SATB1 at all. To elucidate the underlying molecular events in CD30+LPDs with differential SATB1 expression, we subjected 4 SATB1+ and 3 SATB1- CD30+LPDs skin biopsies to second-generation RNA-sequencing (RNA-seq). These data provide a significant resource for studies of CD30+LPDs. Overall design: 200ng total RNA samples were extracted and purified from 7 CD30+LPDs skin lesions (4 SATB1+, 3 SATB1-) to establish RNA library. Then the library was qualified through Agilent 2100 bioanalyzer instrument (Agilent Technologies, Santa Clara, CA) and Quantitative real-time polymerase chain reaction. The qualified library was sequenced on an Illumina HiSeqTM 2000 platform using paired-end reads. 10G raw data for each sample were obtained. The reads were aligned to the hg19 genome with SOAPaligner/SOAP2. Gene expression levels were calculated by reads per kilobase transcriptome per million mapped reads(RPKM)method.	Co-expression
SRP131220	Transcriptome of organotropic metastatic cancer cells	Characterization of organ-targeting metastatic cancer cells	Co-expression
SRP131243	IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors [mRNA]	The oncofetal IGF2 mRNA binding protein (IGF2BP) family modulates tumor cell properties but IGF2BP paralogue-specific roles remain poorly understood. We demonstrate that phenotypic roles of IGF2BPs vary in a cancer cell-dependent manner. However, only IGF2BP1 shows oncogenic potential in all cancer cells analyzed. Consistently, only IGF2BP1 expression is associated with poor prognosis in ovarian carcinoma and promotes all oncogenic properties analyzed in ovarian cancer-derived tumor cells. Despite a substantial overlap of candidate target mRNAs of IGF2BP paralogues proposed by CLIP analyses, the paralogue-specific depletion of IGF2BPs induces strikingly distinct deregulation of mRNA abundance. Transcripts decreased by IGF2BP1 depletion or knockout are enriched for IGF2BP1- as well as AGO-CLIP hits conserved in distinct cell lines, are prone to targeting by highly abundant miRNAs and comprise significantly longer 3'UTRs. Downregulation of target mRNAs upon IGF2BP1 depletion is abrogated when miRNAs are expressed at low levels or depleted by DICER/DROSHA knockdown. Strikingly, the depletion of all 12 randomly selected miRNA-prone target mRNAs impairs at least one analyzed IGF2BP1-modulated tumor cell property. These findings indicate that IGF2BPs serve distinct roles in cancer-derived cells and suggest that IGF2BP1's main role is the post-transcriptional, miRNome-dependent enhancement of factors promoting oncogenic tumor cell properties. Overall design: total RNA-Seq of ES-2 cells transfected with either control siRNAs (siC) or siRNAs directed against IGF2BP1/IGF2BP2/IGF2BP3.	Co-expression
SRP131252	Neonatal neutrophil immune regulatory functional analysis	Neutrophils are one of key innate immune cells which play an important role in pathogen clearance. Neutrophils can also exert immunoregulatory functions via direct or indirect means, particularly on T cell responeses. However, there is little study for its role on T cell differentiation, especially whether neutrophils regulate human neonatal T cell differentiation is not clear. In the current study, we have demonstrated that human neonatal neutrophils can initiate the de novo Th2 cell differentiation. Besides, neonatal neutrophils showed an immature and less differentiated phenotype compared to adult neutrophils. RNAseq results indicated that the gene expression profiles of neonatal neutrophils were quite different from those of adult neutrophils. Specifically, the gene pathways related to eliminating microbes were impared in neonatal neutrophils, which could be another reason contributing to the high susceptibility to pathogens at neonatal stage.	Co-expression
SRP131319	Transcriptome sequencing indentifies novel BMP5 downstrem genes and network in HT-29 cells	Although BMP5 belongs to BMPs(TGF-ß)/Smad signaling pathway, the downstream network induced by BMP5 is far from clear. Our transcriptome sequencing results discovered a novel pathway BMP5 transduces through, the Jak-STAT signaling. Overall design: mRNA profiles of HT-29 (control) and BMP5-expressing HT-29 cells were generated by deep sequencing, in triplicate, using Ion  Proton.	Co-expression
SRP131322	Toll-Like Receptor 7 Agonist GS-9620 Induces Prolonged Inhibition of HBV in Human Hepatocytes via a Type I Interferon-Dependent Mechanism	TLR7 induced transcriptional change in HBV-infected primary human hepatocytes Overall design: RNA-Seq was conducted in two independent primary human hepatocyte (PHH) donors. After day 13 post-infection, primary human hepatocytes (PHH) were infected with HBV and treated with GS-9620, with media from human peripheral blood mononuclear cells (PBMCs) treated with GS-9620 (GS-9620 conditioned media; GS-9620-CM)	Co-expression
SRP131324	Transcriptome profiling of HepG2 cells upon treatment of the menin-MLL inhibitor MI-503 or DMSO	Hepatocellular carcinoma (HCC) accounts for the majority of malignant liver tumors and results in many deaths each year, emphasizing the need for new therapies. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Therefore, we performed RNA sequencing experiment to determine the transcriptome change in the HepG2 cells upon treatment of MI-503, a small molecule inhibitor of the menin-MLL1 interaction with optimized drug-like properties Overall design: HepG2 cells were plated in the 12-well plates at the initial concentration of  0.4x106 cells/ml and treated with 3 µM MI-503 or DMSO (0.25%) in triplicates. After 3 days of  treatment viable cell number was adjusted to the original concentration in the DMSO treated  samples and the same dilution factor was used to adjust cell number in the MI-503 treated cells.  Media was changed and compound or DMSO was re-supplied at that time. Cells were harvested  after 3 more days of incubation.	Co-expression
SRP131326	WNK1-dependent transcriptome in decidualized human endometrial stromal cells	We report the transcriptomic profile of primary human endometrial stromal cells subjected to 48-hour transfection with control non-targeting siRNA or siRNA targeting WNK1 followed by 3-day in vitro decidualization treatment. Overall design: RNA-Seq analysis of HESCs at day 3 of EPC treatment following siNT or siWNK1 treatment	Co-expression
SRP131337	RNA Seq analysis of pancreatic beta cell transcriptome during dedifferentiation	We report RNA Seq analysis using Illumina nextSeq500 of human beta cells EndoC-BH1 treated with FGF2 to induce dedifferentiation. FGF2 treatment induced dedifferentiation of EndoC-BH1 cells. Indeed, we observed a strong decrease in expression of ß-cell markers, (INS, MAFB, SLC2A2, SLC30A8 and GCK).  Opposingly, we identifed positive markers of human ß cell dedifferentiation, as attested by increased expression of mature ß-cell disallowed transcription factors (MYC, HES1, SOX9 and NEUROG3). Interestingly, our temporal analysis revealed that loss of expression of ß cell specific markers preceded the induction of ß cell disallowed genes. Overall design: human beta cells EndoC-BH1 were treated with FGF2 (100ng/L) during 4, 24, 72 and 144h. RNA was isolated post treatment, along with the non-treated controls, and RNA Seq was performed using Illumina nextSeq500  to generate a full transcriptome analysis of gene   expression during dedifferentiation of pancreatic beta cells.	Co-expression
SRP131347	Transcriptional profile in dermal fibroblasts from patients with collagen VI related muscular dystrophy	Objectives:  The collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies, but the pathogenesis, including the role of mutant collagen VI in the matrix is poorly understood. To better define the pathways disrupted by mutations in collagen VI, we have used a transcriptional profiling approach with RNA-Seq to identify differentially expressed genes in COL6-RD patients from controls. Methods:  We have used RNA-Seq to identify differentially expressed genes in cultured dermal fibroblasts from 13 COL6-RD patients (8 dominant negative and 5 null) and 6 controls.  Sequence reads were analyzed using the TopHat/Cufflinks pipeline. Results:  Differentially expressed transcripts between COL6-RD patient and control fibroblasts include upregulation of ECM components and downregulation of factors controlling matrix remodeling and repair.  DN and null samples are differentiated by downregulation of genes involved with DNA replication and repair in null samples Overall design: Expression profiles of dermal fibroblasts from 13 COL6-RD patients with dominant negative (8) or null (5) mutations compared to 6 control fibroblasts.	Co-expression
SRP131373	Inflammatory Response and Host-Donor Chimerism Defined by Single Cell RNA-Seq of Allograft Biopsy	Kidney transplantation offers the best survival and quality of life for patients' with end-stage kidney disease. The major barrier to successful long-term transplantation is the host's immune response to alloantigens' causing rejection of the transplant. The complexity of this immune response in kidney transplantation is still not fully understood and effective treatment strategies are needed. To better understand rejection at the molecular and cellular level we characterized 4,487 cells from a single biopsy core from a kidney transplant undergoing mixed rejection using single cell RNA sequencing. Overall design: InDrop was used to generate single cell profiles from a allograft kidney biopsy	Co-expression
SRP131375	Identification of transcriptome and metabolome signatures of fatty liver disease in HepaRG cells exposed to PCB 126 and glyphosate	We provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of the polychlorinated biphenyl (PCB) 126, one of the most potent chemical inducing NAFLD. Additionnally, three concentration of the pesticide active ingredient glyphosate were tested. This ultimately suggested sensitive biomarkers of exposure. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. Our study provides grounds for the development of molecular signatures of fatty liver diseases to rapidly assess toxic effects of chemicals in the HepaRG cell line. Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the PCB were then tested from day 8 to day 14, in order to cover a wide range of biological effects, starting from low environmental exposures (100 pM) to high concentrations of (1 uM), with an intermediate concentration (10 nM). Three concentrations of glyphosate, or one concentration of the Roundup herbicide (Grand Travaux +) were also tested in the same system.	Co-expression
SRP131390	Single-Cell RNA Sequencing Reveals Metallothionein Heterogeneity during hESC Differentiation to Definitive Endoderm [RNA-Seq]	Differentiation of human pluripotent stem cells toward definitive endoderm (DE) is the critical first step for generating cells comprising organs such as the gut, liver, pancreas and lung. This in-vitro differentiation process generates a heterogeneous population with a proportion of cells failing to differentiate properly and maintaining expression of pluripotency factors such as Oct4. RNA sequencing of single cells collected at four time points during a 4-day DE differentiation identified high expression of metallothionein genes in the residual Oct4-positive cells that failed to differentiate to DE. Using X-ray fluorescence microscopy and multi-isotope mass spectrometry, we discovered that high intracellular zinc level corresponds with persistent Oct4 expression and failure to differentiate. This study improves our understanding of the cellular heterogeneity during in-vitro directed differentiation and provides a valuable resource to improve DE differentiation efficiency. Overall design: H9 human ES cells undergoing DE differentiation were collected daily (day 0-4) for RNA sequencing. Experiments were performed in triplicates.	Co-expression
SRP131419	Differential gene expressions of human pluripotent stem cells derived cells in different culture system	Human pluripotent stem cells (H9s) were differentiated into endothelial cells (ECs), neural stem cells (NSCs) and vascular smooth muscle cells (VSMCs) in 2 dimentional, 3 dimensional PEG hydrogel and alginate hydrogel culture system, and we compared their differential gene expression in different culture system, respectively. Overall design: RNA deep sequencing H9s were maintained in E8 medium for routine culture. Then H9s were differentiated into ECs, NSCs and VSMCs in 2D, 3D PEG hydrogel and alginate hydrogel cell culture system according to their differentiation protocol. mRNAs were sequenced.	Co-expression
SRP131422	Cell transplantation strategies for acquired and inherited disorders of peripheral myelin	Objective: To investigate transplantation of rat Schwann cells or human iPSC-derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage. Methods: Primary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation.  Human induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells (NCSC), and subsequently toward a Schwann cell lineage via two different protocols.  Protocol 1 = treated with MesenPRO with Heregulin. Protocol 2 = coculture with iPSC-derived Motor Neurons. Cell types were characterized using flow cytometry, immunocytochemistry and transcriptomics. Rat Schwann cells and human iPSC-derivatives were transplanted into (i) nude rats pretreated with lysolecithin to induce demyelination or (ii) a transgenic rat model of dysmyelination due to PMP22 overexpression. Results: Rat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration.  Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal appearing myelin.  Human iPSC-derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin. Interpretation: These results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve.  However, lack of reliable technology for generating human iPSC-derived Schwann cells for transplantation therapy remains a barrier in the field. Overall design: RNA-seq of iPSC-derived Neural Crest Stem Cells in three conditions: 1) untreated 2) treated with MesenPRO with Heregulin 3) cocultured with iPSC-derived Motor Neurons	Co-expression
SRP131480	RNA-seq analysis on high altitude exposure	30 samples were collected from 15 subjects at two time points (at plain and at high altitude). Significance was determined by comparing the expression profiling at high altitude with that of plain. Overall design: 15 volunteers traveled to an area of 5300m from the starting point of the 1400m within 4 days. The intact clinic phenotype data of heart rate (HR), oxygen saturation (SpO2), Lake Louise score (LLS), blood pressure (BP), hemoglobin (HB) were collected before and after high altitude exposure (5300m).	Co-expression
SRP131486	Transcriptome analysis of VCaP xenografts resistant to dual therapy with abiraterone and enzalutamide	We report RNA sequencing data on serial biopsies of prostate cancer VCaP xenografts as the tumors pass from androgen-sensitivity (Pre-Cx), to castration resistance (CRPC, castration resistant prostate cancer), onto resistance to dual therapy with abiraterone plus enzalutamide (AER). From comparison of these RNAseq data sets, we were able to determine differentially expressed genes between the AER/CRPC and Pre-Cx states that could mediate resistance to androgen deprivation therapies. Overall design: RNA sequencing of the transcriptome of serial biopsies (Pre-Cx, CRPC, and Abi/Enza resistant) of 4 VCaP xenograft tumors.	Co-expression
SRP131497	MULTIPLE SCN5A ENHANCERS MODULATE CARDIAC GENE EXPRESSION AND QT INTERVAL VARIATION	Genome-wide association studies (GWAS) have suggested that sequence variation in cis-regulatory elements (CREs) modulate common disease risk and trait variation. However, identification of the majority of these causal variants and their mechanism of action have remained significant challenges. We used reporter assays for all common variants at the QT interval associated SCN5A GWAS locus with the goal of identifying causal variants for the association. A target region of ~500kb containing SCN5A was defined based on recombination hotspots (rate>10cM/Mb; estimated from HapMap) flanking the 5 independent QT interval GWAS hits. Within this region, all common variants (minor allele frequency >5%), from the 1000 Genomes European ancestry populations, in moderate linkage disequilibrium (LD; r2>0.3) with any of the 5 sentinel hits, were selected for analyses. Of a total 121 variants selected, 112 variants in 104 amplicons passed primer design (amplicon size 256-617bp; median 397bp), with both alleles of 106 variants successfully cloned along with flanking sequences into 98 amplicons upstream of a minimal promoter-driven firefly luciferase gene in pGL4.23. Cardiomyocyte cells, AC16 (human) and HL1 (mouse), were transfected with test constructs and Renilla luciferase vector (for transfection normalization) in triplicate; luciferase assays were performed 24h later. All cloning and reporter assays were performed in 96- and 24-well plates. In reporter assays across the two cell lines, compared to empty vector, 37 amplicons showed enhancer activity (z-score>99 %tile), with a concordance rate of ~70%. Of these 37 enhancer CREs, 9 overlapped open chromatin regions (DNase-seq peaks) observed in adult human heart tissue, largest among all human tissues evaluated by the RoadMap Epigenomics project. Of these 37 enhancer CREs, 12 showed allelic difference in reporter activity (P<0.05), thus identifying at least one enhancer CRE variant in high-to-moderate LD with each of the 5 sentinel hits. Using GTEx heart left ventricle (n=190) gene expression data, we showed correlation between SCN5A expression and the number of QT interval prolonging alleles across the 5 index SNPs. We are currently assessing the binding of cardiac nuclear factors at the 12 enhancer CRE variants by gel-shift assays and the effect of CRISPR-Cas9 mediated CRE deletion on SCN5A expression in AC16 and HL1 cells, an analyses helped by evaluation of AC16 and HL1 cells by RNA-seq, ATAC-seq and karyotyping. Thus, independent of the publicly available epigenomic data, which are of limited cell-type relevance, an unbiased in vitro reporter screen for CREs overlapping all common variants associated with QT interval at the SCN5A GWAS locus identified 12 common cis-regulatory variants that map to cardiac open chromatin regions and correlate with SCN5A cardiac expression. Overall design: RNA-seq and ATAC-seq in AC16 and HL1 cell lines	Co-expression
SRP131498	Enhancing human kidney organoid differentiation from pluripotent stem cells with high-throughput automation	Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. In this study, single-cell RNA sequencing identify within organoids previously-undetected parietal and interstitial compartments. We discovered that addition of vascular endothelial growth factor (VEGF) during the differentiation process resulted in an approximately ten-fold increase in endothelial cells, without compromising the formation of the organoids. Although VEGF clearly increased the number of endothelial cells by immunofluorescence, relatively few endothelial cells were captured by scRNA-seq and only a modest increase in endothelial cells was observed. This suggested that either a substantial number of endothelial cells were lost or destroyed before sequencing, or that a spectrum of maturation states was present in the cultures. Overall design: We have used DropSeq to perform single cell sequencing on  human kidney organoids.Organoids included in this analysis were generated by treatment  with and without VEGF. We did a bulk RNA analysis on the organoids treated with and without VEGF	Co-expression
SRP131505	Telomerase-mediated Strategy for Overcoming Non-Small Cell Lung Cancer Targeted Therapy and Multi-drug Chemotherapy Resistance	Standard and targeted therapies almost universally fail due to tumor heterogeneity/plasticity leading to intrinsic or acquired drug resistance. We used the telomerase substrate precursor 6-thio-2'-deoxyguanosine (6-thio-dG) to target telomerase-expressing targeted therapy and platin-doublet chemotherapy resistant cells. We observed that erlotinib, paclitaxel/carboplatin and gemcitabine/cisplatin resistant cells are sensitive to 6-thio-dG in xenograft, syngeneic immunocompetent and genetically engineered mouse models. We also show sensitivity to 6-thio-dG on a large panel of non-small cell lung cancer cell lines (73 of 77). The 4 resistant NSCLC lines clustered together, providing a molecular signature for patients that may not respond to 6-thio-dG. We find SLC43A3 as a top candidate in this molecular signature. Thus, 6-thio-dG may prolong disease control of therapy-resistant lung cancer patients.	Co-expression
SRP131506	LINE-1 elements are derepressed in senescent cells and elicit a chronic Type-I Interferon response	It is not known to what extent retrotransposable elements contribute to the development of age-associated diseases. Here we show that during cellular senescence L1s become transcriptionally derepressed and trigger a type-I interferon (IFN-1) response. We propose that RTE activation is an important component of the sterile inflammation that is a hallmark of aging, and that L1 reverse transcriptase is a relevant target for the development of drugs to treat associated disorders. Overall design: Human normal diploid lung fibroblast cells from proliferative, early senescent and late senescent stages were used to observe relative changes in gene expression and type-I interferon induction	Co-expression
SRP131516	RNA Sequencing analysis of different genetically characterized lung cancer cell lines	We performed RNA sequencing to assess changes in gene expression in lung cancer cell lines with MET genetic alterations with or without co-occurrence of JAK2 inactivating mutations. Different treatments have been administrated to activate or inhibit selected pathways in order to define MET signature and IFNg (or JAK/STAT) signature. Overall design: Differential expression analysis of RNA sequencing of 4 different lung cancer cell lines with MET genetic alterations  treated with different treatements to activate or inhibit selected pathways	Co-expression
SRP131518	RB tumor suppressor promotes cancer immunity through downregulating PD-L1 expression	Aberrant expression of immune checkpoint protein programmed death ligand-1 (PD-L1) promotes immune tolerance in cancer. RB is a tumor suppressor known to regulate the cell cycle, DNA damage response, and differentiation. Here, we demonstrate transient knockdown or homozygous deletion of RB markedly induces PD-L1 mRNA expression. RB binds to NF?B protein p65 and serine-249/threonine-252 (S249/T252) phosphorylation of RB is important for its interaction with p65 and suppression of PD-L1 expression. RNA-seq analysis identifies a subset of NF?B pathway genes including PD-L1 are selectively upregulated by RB knockdown. S249/T252-phosphorylated RB inversely correlates with PD-L1 expression in patient samples. Expression of a RB-derived S249/T252 phospho-mimicking peptide blocks radiation-induced PD-L1 expression and increases the anti-cancer efficacy of radiation in mice. Our findings reveal a previously unappreciated tumor suppressor function of hyperphosphorylated RB in inhibition of NF?B activity and PD-L1 expression, suggesting this regulatory module can be exploited to overcome cancer immune evasion. Overall design: Examination of RNA expression in PC-3 cells  knocked down endogenous RB or treated cells with the CDK4/6 inhibitor palbociclib	Co-expression
SRP131524	Synergy from Gene Expression and Network Mining (SynGeNet) method predicts genotype-specific synergistic drug combinations in melanoma	Using our computational method SynGeNet to evaluate genomic and transcriptomic data characterizing four major genomic subtypes of melanoma, we selected the top ranked drug combination for BRAF-mutation melanoma for subsequent validaiton. Here we present drug-induced gene expression data from the BRAF-mutant A375 melanoma cell line in response to four treatment conditions: vehicle control (DMSO), vemurafenib alone, tretinoin (ATRA) alone and vemurafenib+tretinoin combination. Overall design: Gene expression profiles of A375 melanoma cells were generated by RNAseq (Illumina HiSeq 4000) under the following treatment conditions: vehicle control (DMSO),  vemurafenib, tretinoin and vemurafenib + tretinoin combination.	Co-expression
SRP131607	Compare RNA expression of Old Fibroblast to RNA expression of Young Fbroblast	Analyze of RNA expression of Old Fibroblast and Young Fibroblast. Compare RNA expression of Old Fibroblast to RNA expression of Young Fbroblast	Co-expression
SRP131659	Compare RNA expression of UVA fibroblast to sham fibroblast	we analysis of sham fibroblast and UVA fibroblast RNA expression using RNA sequencing and compare RNA expression.	Co-expression
SRP131681	Gene expression in mature and immature human ES-derived beta cells, and sorted beta-cells from adult islets	This submission comprises RNA-Seq profiling of in vivo differentiated pancreatic beta cells types and primary islet-derived pancreatic beta cell sources. The study reports that re-aggregation of immature beta-like cells (d20Beta) and removal of progenitor cells leads to further maturation in vitro resulting in beta-cells (eBCBeta) that are closer to human primary islet-derived beta-cells(IsletBeta). As a control stem cell derived spheres were dissocated, reassociated and taken through till the end of the protocol (NECBeta). Overall design: 2 samples each of eBCBeta, NECBeta, d20Beta and IsletBeta were for RNA-seq by using SMARTer Stranded Total RNA Sample Prep Kit – Low Input Mammalian Kit (Clontech) kits for library preparation after RNA integrity was confirmed. Sequencing was carried out on the Illumina platform	Co-expression
SRP131684	Comparative Transcriptomics of Triple Negative Breast Cancer Stem Cells and Differentiated Tumor Cells Identifies Teneurin-4 as a Potential Therapeutic Target	BACKGROUND: Triple-negative breast cancer (TNBC) is insensitive to the most effective therapies for other breast cancers, including endocrine and Her2-directed therapies, thus the lack of specific treatments prompted us to search for new TNBC-associated molecules to be used as targets for cancer therapy. As patients with TNBC usually experience a quicker relapse and metastatic progression compared to other breast cancer subtypes, we hypothesized that cancer stem cells (CSC) could play a central role in TNBC. We thus directed our focus on genes differentially expressed between CSC and differentiated cancer cells of TNBC cell lines. RESULTS: We established tumorsphere cultures from mouse and human mammary cancer cell lines to enrich the CSC population. RNA-Seq was used to identify differences in gene expression between tumorspheres and their monolayer counterparts. Seventy-four transcripts were found up-regulated in the tumorspheres, while forty-two genes were down-regulated. Enrichment analysis of biological processes showed an up-regulation in genes involved in regulation of apoptosis in tumorspheres, and a down-regulation in genes involved in lipid metabolism and cell cycle regulation. By focusing on up-regulated genes coding for cell membrane-associated proteins, we selected Teneurin-4 (TENM4) as a candidate for further studies. Meta-analysis of publicly available datasets revealed that TENM4 mRNA is up-regulated in both lobular and ductal invasive carcinoma specimens compared to normal breast, and that high expression of TENM4 in TNBC patients shows a trend of correlation with a shorter relapse-free survival. 4T1 tumorspheres treated with a siRNA specific to TENM4 showed a decrease in TENM4 mRNA and protein levels, which was reflected by a significant impairment of tumorsphere-forming ability. TENM4 silencing also led to a decrease in Focal Adhesion Kinase (FAK) phosphorylation, which has been previously linked to CSC biology, thus strengthening the possible link between TENM4 and a CSC-like phenotype. CONCLUSIONS: Overall, our results indicate that the stem-like status of TNBC cells is accompanied by altered regulation of apoptosis, cell cycle and lipid metabolism pathways. Furthermore, we identified TENM4 as a potential novel player in CSC biology, and its potential role as a novel target to improve the outcome of TNBC patients in the future. Overall design: 4T1 and HCC1806 cell lines as model for TNBC in mouse and human, respectively. Based on culture conditions previously established for these and other breast cancer cell lines, we successfully generated tumorspheres from the parental cells. For both cell lines three replicates were done for the cell grown in RPMI-1640 supplemented with 10% fetal bovine serum (FBS, Sigma-Aldrich) and Penicillin/Streptomycin solution at 1x dilution (Sigma-Aldrich) (bulk), and those grown in DMEM/Nutrient Mixture F-12 Ham (Sigma-Aldrich) supplemented with 0.4% bovine serum albumin (BSA, Sigma-Aldrich), 20 ng/mL bFGF (PeproTech EC Ltd., London, UK), 20 ng/mL EGF (Sigma-Aldrich) and 5 µg/mL insulin (Sigma-Aldrich).  (spheroids)	Co-expression
SRP131693	Transcriptome profiling of HCC1937 vector and wtBRCA1 cell lines which were treated with OTX-015	Purpose: To compare the transcriptomes of HCC1937 vector and wtBRCA1 cells which were treated with OTX-015. Methods: HCC1937 vector and wtBRCA1 cells were treated with 5 micromolar OTX-015 for 24 hours. Total RNA was extracted and processed with NEBNext Ultra Directional RNA Library Prep Kit for cDNA library preparation. The data are in duplicate and raw data were generated by Illumina 2500 sequencer. The Fastq format data were then processed with Tophat for genome mapping. After getting the bam files, they were further analyzed with cuffdiff for gene expression of different groups. Results: From the transcriotome profiling and analysis, we got gene expression data of DMSO control group and OTX-015 treatment group for the HCC1937 BRCA1 isogenic cell lines. Conclusion: The gene expression data revealed the transcriptome variation by OTX-015 treatment. Overall design: OTX-015 treated HCC1937 BRCA1 isogenic cells were used for RNA extraction and RNAseq analysis for transcriptome profiling	Co-expression
SRP131744	RNAseq of undifferentiated small round cell sarcomas	We identified a novel gene fusion in undifferentiated round cell sarcomas through high-throughput RNA-seq analysis.	Co-expression
SRP131755	Telomere length and telomerase activity in T-cells are biomarkers of high performing centenarians	With the goal of identifying genes and pathways potentially involved in the process of healthy aging and longevity, this series of studies was designed to characterize and compare the stimulation-induced responses in T-cells from young (23-39 years old), middle-aged (50-66 years old), old (67-83 years old) and centenarians (100+ years old). In addition, we compared whole genome expression profiles by RNA-sequencing in stimulated T-cells from the study groups listed above. Based on these studies we are now able to separate low performing from high performing centenarians providing novel biomarkers of healthy aging.	Co-expression
SRP131761	Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations	Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining tissue integrity. We have previously shown that mouse skin connective tissue, the dermis, is comprised of functionally distinct fibroblast lineages. However, the extent of fibroblast heterogeneity in human skin is unknown. Here, using a combination of spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts, we show that there are at least four distinct fibroblast populations in adult human skin. We define markers permitting prospective isolation of these cells and show that although marker expression is rapidly lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, T cell communication and the ability to support human epidermal reconstitution in organotypic culture. Furthermore, while some fibroblast subpopulations are spatially segregated, others are not. These findings have profound implications for normal wound healing and diseases characterized by excessive fibrosis, and suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications. Overall design: Spatial RNA sequencing of human papillary versus reticular dermis for 3 individuals, and single cell RNA sequencing of dermal fibroblasts for a single individual.	Co-expression
SRP131762	Expression levels of genes of NKG2C+ NK cells after in vitro treatment	RNA-Seq and comparison of gene expression levels was performed of FACS-sorted viable CD56+ NKG2C+ NK cells after in vitro treatment with peptide-pulsed RMA-S/HLA-E/LFA-3 target cells in the presence of or absence of IL-12 and IL-18 Overall design: NK cells of HCMV-seronegative healthy individiuals were FACS-sorted for viable CD3- CD56dim cells. CD56dim NK cells were co-cultured for 7 days with RMA-S/HLA-E/LFA-3 target cells either pulsed with VMAPQSLLL or VMAPRTLFL peptide in the presence of 10 ng/mL IL-15. 10 ng/mL IL-12 and 100 IL-18 were either present or not during the initial 20 h of culture.	Co-expression
SRP131763	Temporal RNA-seq analysis of human skeletal myotubes synchronized in vitro	The circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans. Overall design: 100 samples from 2 donors. Together with GSE108539, part of the same study described above.	Co-expression
SRP131775	A novel CD4+ T cell population expanded in Systemic Lupus Erythematosus (SLE) blood provides B cell help through IL10 and succinate	A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell 'helper' population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 2 independent datasets; dataset1: total 9 samples (3 subjects, 3 groups, 3 replicates); dataset2: total 20 samples, 2 samples(PD1POS, Tfh) from each of 10 SLE patients	Co-expression
SRP131787	transcriptome studies of BRD4 inhibitor BDF-1253 on renal clear carcinoma 786-O cells	As an epigenetic reader, BRD4 is important for the recognition of acetylated lysines and regulation of transcription. As BRD4 regulates the expression of several survival genes, such as c-Myc and Bcl-2, which is vital for the survival of tumor cells, then it is closely involved in various kinds of cancers. Accumulating evidence has proven that BRD4 could serve as a novel anti-cancer pharmaceutical target, and small-molecular BRD4 inhibitors have promising potentials in the treatment of BRD4-related cancers and other diseases. In this study, a novel category of BRD4 inhibitors, which are originated from an approved drug Nitroxoline and its analogues, were synthesized and evaluated by biochemical and cellular assays, as well as the method of crystallography and xenograft mice models. In renal cell carcinoma cell lines, these compounds exhibited efficient inhibition against the expression and protein abundance of BRD4 downstream genes. Moreover, the complex crystal structures of several compounds in this series with the first bromodomain of BRD4 were solved, which revealed the binding mechanism of this novel category of BRD4 inhibitors and facilitated further structural modifications. This series of novel BRD4 inhibitors is promising to become drug candidates for the treatment of renal cell carcinoma after further development and assessments. Overall design: RNA-Seq in renal clear carcinoma cells in the presence or absence of BRD4 inhibitor BDF-1253	Co-expression
SRP131796	Clinical and genomic crosstalk between glucocorticoid receptor and estrogen receptor a in endometrial cancer [RNA-seq]	Steroid hormone receptors are simultaneously active in many tissues and capable of altering each other's function. Estrogen receptor ? (ER) and glucocorticoid receptor (GR) are expressed in the uterus and their ligands have opposing effects on uterine growth. In endometrial tumors expressing high levels of ER, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is significantly altered by estradiol with GR recruited to ER bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol, but with novel regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. Overall design: ChIP-seq, ATAC-seq, and RNA-seq data collected from endometrial cancer cell lines induced with dexamethasone, estradiol, or the combination	Co-expression
SRP131806	The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma [RNA-seq Cell lines]	RNA-Sequencing Analysis was performed on 7 Head and Neck Squamous Cell Carcinoma Cells Lines in order to examine their overall gene expression profiles. Overall design: In order to understand the transcriptomic heterogeneity that exists between different Head and Neck Squamous Carcinoma (HNSCC) Cell Line Models, RNA-Seq analysis was performed on a cohort of 7 different cell lines.  These profiles were assessed for their overall variance in gene expression profile via unsupervised clustering analysis and were shown to match established intrinsic subtypes of HNSCC such as the Atypical, Basal and Mesenchymal classes of tumors.	Co-expression
SRP131807	The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma [RNA-seq knock-down]	RNA-Sequencing Analysis of gene expression changes due to ablation of Ets1 in SCC25 Cells. Overall design: Global transcriptomic characterization of the effects of Ets1 knockdown in SCC25 Head and Neck Squamous Cell Carcinoma cells was performed via RNA-Seq Analysis.  The knockdown of ETS1 was performed using transient siRNA based approach as well as stable cell lines were generated with targeted shRNA. As controls, we used SCC25 cells transduced with siRNAs and shRNAs with non-silencing control hairpin sequences that do not match any known mammalian genes and hence are not expected to not target any gene product.	Co-expression
SRP131871	TAD cliques shape the 4-dimensional genome during dual lineage terminal differentiation	How genomic information is selectively utilized to direct spatial and temporal gene expression patterns during differentiation remains to be elucidated but it is clear that regulated changes in higher-order genomic architecture plays a fundamental role. Specifically, long range interactions within and between chromosomes and the position of chromosome territories in the nucleus are controlled by TADs and LADs respectively, but the relationship between these genomic organizers remains poorly understood Overall design: We analyzed the large-scale spatial reorganization of chromatin by generating matched Hi-C and nuclear lamin-chromatin contact datasets throughout a dual adipose/neuronal induction of human primary adipose stem cells.  We have mapped Hi-C (TADs) and lamin-associated domains (LADs) in multiple steps during adipose stem cell differentiation to characterize the spatial and temporal link between genomic architecture and gene expression. We identify a new level of 4D genomic organization involving a long-range clustering of individual TADs or TAD pairs into TAD cliques. LADs appear to regulate their formation. (ASCs). We unveil a lineage-specific dynamic assembly and disassembly of repressive cliques of linearly non-contiguous TADs, and a time course-coupled relationship between TAD clique size and lamina association. Our findings reveal a new level of developmental genome organization and provide an overview of large-scale changes in the 4D nucleome during lineage-specific differentiation.	Co-expression
SRP131910	Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer [RNA-seq]	Transcriptome levels of matched patient-derived xenograft (PDX) in vitro-in vivo models. Overall design: Comparison of gene expression levels between matched patient-derived xenograft in vitro-in vivo models.	Co-expression
SRP131953	Human cytotrophoblast organoids	Human cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB). Overall design: We employed QuantSeq method to analyzed the global expression profile of the cytotrophoblast organoids (4 replicates, CTB-ORG 1-4) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (3 replicates, vCTB 1-3) as well as to in vitro differentiated syncytiotrophoblast (3 replicates, STB1-3) and placental fibroblasts (2 replicates, FIB 1-2).	Co-expression
SRP131959	Single-Cell RNA Sequencing Reveals Metallothionein Heterogeneity during hESC Differentiation to Definitive Endoderm [scRNA-Seq]	Differentiation of human pluripotent stem cells toward definitive endoderm (DE) is the critical first step for generating cells comprising organs such as the gut, liver, pancreas and lung. This in-vitro differentiation process generates a heterogeneous population with a proportion of cells failing to differentiate properly and maintaining expression of pluripotency factors such as Oct4. RNA-sequencing of single cells collected at four time points during a 4-day DE differentiation identified high expression of metallothionein genes in the residual Oct4-positive cells that failed to differentiate to DE. Using X-ray fluorescence microscopy and multi-isotope mass spectrometry, we discovered that high intracellular zinc level corresponds with persistent Oct4 expression and failure to differentiate. We further show that differentiation-arrested phenotype is inversely correlated with zinc concentration in the differentiation media. This study improves our understanding of in-vitro DE differentiation and provides actionable options to improve DE differentiation efficiency. Overall design: RNA-sequencing of 329 single cells collected at four time points during a 4-day DE differentiation to identify mechanisms leading to cellular heterogeneity during differentiation	Co-expression
SRP131980	Induction of Myelinating Oligodendrocytes in Human Cortical Spheroids	Organoid technologies provide an accessible system in which to examine the generation, self-organization,and 3-dimensional cellular interactions during development of the human cerebral cortex. However, oligodendrocytes, the myelinating glia of the central nervous system and third major neural cell type, are conspicuously absent from current protocols. Here we reproducibly generate human oligodendrocytes and myelin in pluripotent stem cell-derived cortical spheroids. Transcriptional and immunohistochemical analysis of the spheroids demonstrates molecular features consistent with maturing human oligodendrocytes within 14 weeks of culture, including expression of MyRF, PLP1, and MBP proteins. Histological analysis by electron microscopy shows initial wrapping of human neuronal axons with myelin by 20 weeks and maturation to compact myelin by 30 weeks in culture. Treatment of spheroids with previously identified promyelinating drugs enhances the rate and extent of human oligodendrocyte generation and myelination. Furthermore, generation of spheroids from patients with a severe genetic myelin disorder, Pelizaeus-Merzbacher disease, demonstrates the ability to recapitulate human disease phenotypes, which were in turn improved with both pharmacologic and CRISPR-based approaches. Collectively, these 3-dimensional, multi-lineage cortical spheroids provide a versatile platform to observe and perturb the complex cellular interactions   that occur during developmental myelination of the brain and offer new opportunities for disease modeling and therapeutic development in human tissue. Overall design: RNAseq profiles comparing neuro-cortical spheroids and oligo-cortical spheroids	Co-expression
SRP132018	In-vitro stimulation of healthy donor blood with IL-3 cytokine	This experiment was designed to look for in vitro IL-3 gene signature in donor blood at two different time points (6 and 24 hours). RNA from lysed whole blood cells was used for the sequencing. Overall design: Lysed whole blood from seven healthy donors was stimulated with recombinant human IL-3 for 6 hours, or 24 hours, prior to RNA extraction for next-generation sequencing on the Illumina HiSeq platform. Unstimulated samples were included as controls.	Co-expression
SRP132039	Generic drug screen identifies paracetamol as 5-aza-2'-deoxycytidine sensitizer in head and neck squamous cell carcinoma cells	Aberrant DNA methylation (5mC) is one of the key characteristics of many cancers including head and neck squamous cell carcinoma (HNSCC). The DNA demethylating agent 5-aza-2'-deoxycytidine (DAC) has anti-cancer therapeutic potential, but its clinical efficacy is currently hindered by dose-limiting side effects. Here we investigated the potential use of DAC in the treatment of HNSCC and show that its efficacy is primarily dependent on the ability of DAC to demethylate DNA. In order to establish whether HNSCC cells can be sensitized to DAC, a panel of 100 generic drugs were screened in combination with DAC. While the 100-drug panel did not sensitise DAC-resistant HNSCC cell lines to DAC treatment, the screen identified that paracetamol (acetaminophen), valproic acid and zinc acetate significantly enhanced DAC efficacy in the DAC-responsive cell lines. DAC and paracetamol were established to work in synergy, allowing DAC to be used at therapeutically relevant low doses (below 500nM). The mechanisms underlying the DAC-paracetamol synergy are multifactorial and encompass both effects of DAC on paracetamol action (alterations in the cyclooxygenase (COX) pathway and mimicry of paracetamol overdose) as well as decreased DNA methylation by paracetamol.   Therefore, we propose DAC to be a potential therapeutic in a subset of HNSCC patients with its efficacy significantly increased by use of the common analgesic paracetamol. The DAC-paracetamol synergy should also be considered in cancers with an approved DAC treatment regime. Overall design: There are four RNA-seq samples. VU40T squamous cell cacrcinoma cells were treated for 96h with 500nM 5-aza-2''-deoxycytidine (DAC), 132.3µM Paracetamol (Para), or both and compared to the untreated cells (control). For each sample three biological replicates were pooled for each RNA-seq library.	Co-expression
SRP132065	Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction	Purpose: Evaluate the transcriptional profile of genes involved in fungus-host interactions using RNA sequencing Methods: T. rubrum and HaCat cells line were co-cultured in RPMI medium supplemented with 5% of fetal bovine serum and were incubated for 24 h  at 37ºC in a humidified atmosphere containing 5% CO2  , followed RNA by extraction of both organisms, libraries construction and sequence. Results: Our data demonstrated the induction of specific genes that may improve the assimilation of nutrients and fungal survival in the host and genes encoding keratinolytic proteases that are important for T. rubrum virulence during infection. In HaCat cell lines it were induced genes encoding antimicrobial activity , cell migration and epithelial barrier repair. Futhermore, the genes KRT1 and FLG involved in epithelial barrier integrity were repressed Conclusions: This mixed transcriptome analysis showed the modulation of important genes involved in the mechanism of T. rubrum infection and in the defense and maintenance of cell homeostasis of keratinocytes, which could represent potential antifungal targets for new therapeutic approaches to the treatment of dermatophytoses Overall design: The transcriptional profile of T. rubrum and keratinocytes co-culture was assessed using the RNA-sequencing technique in order to provide new insights about fungal-host interaction.	Co-expression
SRP132083	RNA Ligation Procedes U6 snRNA/LINE1 Retrotransposition	Long INterspersed Element-1 (L1) amplifies via retrotransposition. Active L1s encode two proteins (ORF1p and ORF2p) that bind their encoding transcript to promote retrotransposition in cis. ORF1p and/or ORF2p also can promote the retrotransposition of Small INterspersed Element RNAs, non-coding RNAs, and messenger RNAs in trans. A class of L1-mediated retrotransposition events consist of a copy of U6 small nuclear RNA conjoined to a variably 5''-truncated L1, but how U6/L1 chimeras are formed requires elucidation. Here, we report that: U6/L1 chimeric RNAs are present in human cell lines; the RNA 2'',3''-cyclic phosphate ligase protein can ligate U6 RNAs ending in a 2'',3''-cyclic phosphate to L1 RNAs containing a 5''-OH group in vitro; and retrotransposition of the ligated RNAs leads to U6/L1 pseudogene formation. Thus, we have uncovered a mechanism for U6/L1 chimera formation and suggest that U6 snRNA and RtcB have biological roles in addition to their essential functions in mRNA and tRNA splicing, respectively.	Co-expression
SRP132172	A practical evaluation of alignment algorithms for RNA variant calling analysis	We performed RNA-seq with ten pieces of breast cancer (invasive ductal carcinoma; luminal B type) tissue and three pieces of adjacent normal tissue from a single patient. These RNA-seq data were used to evaluate the performance of splice-aware aligners. Overall design: RNA-seq was performed with 10 pieces of  breast cancer tissue and 3 pieces of adjacent normal tissue obtained from a single patient	Co-expression
SRP132182	Suppression of glioblastoma by a drug cocktail inducing tumor cells toward a neuronal fate	Glioblastoma (GBM), the most common and aggressive malignant tumor in adult brain, is a notoriously fatal tumor. For many years, surgical resection and postoperative radiotherapy had been used for the treatment of GBM, which resulted in a poor median survival of about 12 months. Currently, Temozolomide (TMZ) as a clinically meaningful chemotherapy drug has become the standard first-line treatment for GBM, but with an increase of the median survival for about only 2.5 months. In this study, encouraged by previous findings that human astrocytes could be converted into neuronal cells with small molecules and that human GBM cells could be induced into neuronal like cells by transcription factors, we intended to test whether GBM cells could be induced into neuronal like cells by a cocktail of approved drugs and whether this drug cocktail help to suppress GBM in patient derived xenograft (PDX). Here we screened and identified TMZ, Tranilast, and Fasudil, three approved clinical drugs (TTF), to induce GBM cells toward a neuronal fate. Both serum and serum-free cultured GBM cells exhibited neuronal morphology and expressed neuronal genes under TTF treatment. Malignant properties including uncontrolled proliferation and intensive invasion of GBM cells were also attenuated with TTF treatment. Most importantly, when administrated in PDX, TTF cocktail significantly suppressed GBM growth in vivo and prolonged the survival of tumor-bearing mice, as compared to TMZ alone. Our study indicated that using the approved drug cocktail to induce tumor cells toward a neuronal fate might be a clinically promising strategy for GBM treatment. Overall design: In this data set, we include RNA-Seq data of human glioblastoma cells treated with a drug cocktail (TMZ, Tranilast, and Fasudil) for 0, 2, and 10 days, as well as human neurons	Co-expression
SRP132194	Differential expression in wild type and mutant HAP1 cells [RNA-seq I]	using RNA-seq we characterized gene expression changes occuring upon knockout of BAP1, ASXL1, ASXL2, ASXL1/2 or Polycomb genes RING1B and EZH2. We also investigated the response to retinoic acid treatment in wild-type and BAP1 KO cells. Overall design: Examination of transcript abundance in wild-type HAP1 cells and in 9 different HAP1-mutated cell lines as well as upon retinoic acid treatment in wild-type and BAP1 KO cells. Two biological replicated were performed for each condition.	Co-expression
SRP132239	Transcriptomic analysis of multiple myeloma cell lines	We found that a small molecule inhibitor of PRMT4 inhibited cell growth of a subset of multiple myeloma cell lines. To identify biomarkers that predict the sensitivity of myeloma cells to PRMT4 inhibition, we performed transcriptomic analysis of multiple myeloma cell lines. Overall design: Amplicon sequencing of thirteen multiple myeloma cell lines was performed on the Ion Torrent platform. Steady-state gene expression profile of sensitive cells were compaired with that of insensitive cells.	Co-expression
SRP132263	RNA-seq analysis of BAP1-depleted uveal melanoma cells	OCM-1A uveal melanoma cells were infected with lentivirus carrying shRNA expression constructs specific for BAP1 or GFP (control), and placed under selection for 6 days. RNA-seq was performed. Overall design: Samples represent three independent experiments treated with control or BAP1 shRNA	Co-expression
SRP132285	Whole transcriptome targeted gene quantification provides new insights on pulmonary sarcomatoid carcinomas	Pulmonary sarcomatoid carcinomas (PSCs) are rare and aggressive histological types of non-small cell lung cancer (NSCLC) with a median overall survival of about 9-12 months. In detail, PSCs comprise five different histological subtypes: pleomorphic carcinoma (PLC), giant cell carcinoma (GCC), spindle cell carcinoma (SCC), carcinosarcoma (CS) and pulmonary blastoma (PB). Preoperative pathological diagnosis may fail to identify these tumors and therapeutic options are still limited. PSCs have been scarcely characterized from a molecular point of view because of their rarity, and to date no specific markers have been found for PSCs in comparison with other NSCLC types. In this study a highly sensitive amplicon based whole transcriptome quantification analysis was performed, using the Ion AmpliSeq Transcriptome Human Gene Expression Kit (Life Technologies) on a selected series of 14 PSCs (1 PB, 4 CS, 2 SCC, 2 GCC, 5 PLC) and 3 samples of normal lung parenchyma. PSCs expression data were then compared with transcriptome data of lung adenocarcinoma and squamous cell carcinoma available on The Cancer Genome Atlas database. Thirty-eight genes specifically deregulated in PSC samples were identified. Among these, IGJ and SLMAP were validated by immunohistochemistry on an independent cohort (30 PSCs, 31 lung adenocarcinoma and 31 squamous cell carcinoma cases). Furthermore, a pathway enrichment analysis, performed on differentially expressed genes, revealed that FOXO signalling and Fanconi Anemia pathways, playing a pivotal role in cancer development and progression, are enriched in PSC tumors. The description of peculiar molecular profiles besides increasing our knowledge on PSCs biology may suggest new diagnostic and therapeutic strategies. Overall design: Whole transcriptome targeted gene quantification analysis was perfomed on a selected series of 14 pulmonary sarcomatoid carcinomas (1 pulmonary blastoma, 4 carcinosarcomas, 2 spindle cell carcinomas, 2 giant cell carcinomas, 5 pleomorphic carcinomas) and 3 samples of normal lung parenchyma, using the Ion AmpliSeq Transcriptome Human Gene Expression Kit ( Life Technologies).	Co-expression
SRP132296	USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells	Gain-of-function p53 mutants such as p53-R175H form stable aggregates that accumulate in cells and play an important role in cancer progression. Selective degradation of gain-of-function p53 mutants has emerged as a highly attractive therapeutic strategy to target cancer cells harboring specific p53 mutations. We identified a small molecule called MCB-613 to cause rapid ubiquitination, nuclear export, and degradation of p53-R175H through lysosome-mediated pathway leading to catastrophic cancer cell death. In contrast to its effect on the p53-R175H mutant, MCB-613 causes slight stabilization of p53-WT and has weaker effects on other p53 gain-of-function mutants. Using state-of-the-art genetic and chemical approaches, we identified the deubiquitinase USP15 as the mediator of MCB-613's effect on p53-R175H and established USP15 as a selective upstream regulator of p53-R175H in ovarian cancer cells. These results confirm that distinct pathways regulate the turnover of p53-WT and the different p53 mutants and open new opportunities to selectively target them. Overall design: Comparison between the RNAseq data between NSC632839 (a deubiquitinase inhibitor) treated and MCB613 treated MCF7 breast cancer cell	Co-expression
SRP132298	Targeting CREBBP/EP300 bromodomains in cancer	Changes in gene expression caused by CREBBP/EP300 bromodomain inhibitors in a CML cell line Overall design: K562 cells were treated with CBP30 and I-CBP112 and changes in gene expression were evaluated by RNA-seq	Co-expression
SRP132313	Multi-platform single cell transcriptomic profiling as a benchmarking resource	We generated those datasets to provide a publicly available resource for scRNA-seq, hoping that this resource serves as a starting point to systematically compare and benchmark different sequencing protocols. Two popular model cell lines were selected as starting materials, considering that there are also other types of datasets generated under different experimental perturbations.	Co-expression
SRP132340	Gene expression profiling of cutaneous T cell lymphoma cell lines and primary tumor samples treated with mechlorethamine and romidepsin.	In this study, we demonstrated the synergistic effect of the mechlorethamine-romidepsin combination in cutaneous T cell lymphoma cell lines and CD4+ T cells derived from patients with Sezary Syndrome. We identify the signaling pathways specifically perturbed under treatment with mechlorethamine-romidepsin combination. Overall design: Gene expression profiling by RNA sequencing of cutanieous T cell lymphoma cell lines SeAX, HH, and Hut78 as well as cells isolated from 6 primary tumor samples upon treatment with vehicle control or mechlorethamine and romidepsin individually and in combination.	Co-expression
SRP132366	Sequencing of freshly produced RNA following exposure of cells to DNA damage-inducing UV mimetic 4-hydroxyaminoquinolone (4-NQO)	We used Illumina-HiSeq4000 to sequence 4sU-labelled RNA samples isolated from unchallenged and DNA damaged HeLa Flp-In cells, which revealed the nature of transcriptional response folowing genotoxic stress and the contribution of P-TEFb kinase in DNA damage-induced gene transcription. Overall design: We mock treated or treated HeLa Flp-In cells for 1 or 2 hr with DMSO, 4-NQO, or 4-NQO + flavopiridol (FP) as indicated below. During the last 30 minutes of the treatments, we labeled the RNA or not with the nucleoside analogue 4-thiouridine (500µM 4sU) for 30 minutes.	Co-expression
SRP132370	Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid	We aimed to determine the characteristic of IL-10-producing ILCs induced from ILC2s by RA. We found that IL-10-producing ILCs has distinct characteristic compared to IL-10 negative ILCs. Overall design: mRNA profile of IL-10 positive ILCs and IL-10 negative ILCs genarated from ILC2s	Co-expression
SRP132414	Molecular Signature of CAID Syndrome: Noncanonical Roles of SGO1 in Regulation of TGF-ß Signaling and Epigenomics. [RNA-seq]	RNA sequencing of human dermal fibroblasts from CAID patients passage 8 and passage 14 Overall design: RNA sequencing was perfomed on 3 wild type controls and 3 CAID patients fibroblast cell lines at cell passages 8 and 14. Sequencing was performed on Illumina Hiseq4000, 8 samples/lanes, paired-end.	Co-expression
SRP132520	Proximity-CLIP provides a snapshot of occupied cis-acting elements on RNA in different subcellular compartments on a transcriptome-wide scale	Many cellular RNAs localize to specific subcellular compartments. Currently, methods to systematically study subcellular RNA localization are limited and lagging behind proteomic approaches. Here, we combined APEX2-mediated proximity biotinylation of proteins with PAR-CLIP to simultaneously profile the proteome and the transcriptome bound by RNA binding proteins in any given subcellular compartment. Our approach is fractionation-independent and does not rely on additional RNA manipulation and labeling steps, thus making it easy to apply. Furthermore, it enables to study the locali-zation of RNA processing intermediates, as well as the identification of regulatory RNA cis-acting elements occupied in different cellular compartments. In a proof-of-concept study we studied RNA and protein localization in the nucleus, cytoplasm and at cell-cell interfaces using Proximity-CLIP. These experiments revealed among other in-sights frequent transcriptional readthrough continuing for several kilobases down-stream of the canonical cleavage and polyadenylation site, a differential binding pat-tern of nuclear and cytoplasmic mRNAs, as well as the localization of mRNAs contain-ing 3'UTR CUG sequence elements at cell-cell interfaces, of which many encode regulatory proteins. Overall design: Proximity-CLIP takes advantage of the occupancy of cellular RNAs by RBPs throughout their life cycle. An APEX2 fusion protein is targeted to a cellular compartment, and cellular RNAs are labeled with 4SU. Cells are incubated with biotin-phenol (BP) for 30 min, before APEX2-mediated BP oxidation is activated by addition of hydrogen peroxide, followed by reaction quenching and 4SU-dependent protein-RNA crosslinking by UV illumination. BP radicals are created locally and either covalently tag proximate proteins or decay. Compartment-specific RNPs are captured by Streptavidin affinity chromatography. Eluted RNA is analyzed either by RNAse treatment followed by small RNA cDNA library preparation of RBP-protected footprints, analogous to PAR-CLIP, or by standard RNAseq. Data also includes RNAseq analysis of the input, i.e. total cell extract RNA prior to Streptavidin chromatography.	Co-expression
SRP132529	Pro-inflammatory cytokine and high doses of ionizing radiation have similar effects on the expression of NF-kappaB-dependent genes [RNA-seq]	The NF-?B transcription factors are activated via diverse molecular mechanisms in response to various types of stimuli. A plethora of functions associated with specific sets of target genes could be regulated differentially by this factor, affecting cellular response to stress including an anticancer treatment. Here we aimed to compare subsets of NF-?B-dependent genes induced in cells stimulated with a pro-inflammatory cytokine and in cells damaged by a high dose of ionizing radiation (4 and 10 Gy). The RelA-containing NF-?B species were activated by the canonical TNFa-induced and the atypical radiation-induced pathways in human osteosarcoma cells. NF-?B-dependent genes were identified using the gene expression profiling (by RNA-Seq) in cells with downregulated RELA combined with the global profiling of RelA binding sites (by ChIP-Seq), with subsequent validation of selected candidates by quantitative PCR. There were 37 NF-?B-dependent protein-coding genes identified: in all cases RelA bound in their regulatory regions upon activation while downregulation of RELA suppressed their stimulus-induced upregulation, which apparently indicated the positive regulation mode. This set of genes included a few “novel” NF-?B-dependent species. Moreover, the evidence for possible negative regulation of ATF3 gene by NF-?B was collected. The kinetics of the NF-?B activation was slower in cells exposed to radiation than in cytokine-stimulated ones. However, subsets of NF-?B-dependent genes upregulated by both types of stimuli were essentially the same. Hence, one should expect that similar cellular processes resulting from activation of the NF-?B pathway could be induced in cells responding to pro-inflammatory cytokines and in cells where so-called “damage-induced inflammation” response was initiated by ionizing radiation Overall design: We sequenced mRNA from wild type U2OS cells and cells transiently transfected using siRNA specific for RELA gene or control siRNA. Cells were untreated (control) or stimulated using TNFalpha cytokine for specific time or subjected to ionizing radiation with subsequent recovery. Three biological replicates were performed and sequenced.	Co-expression
SRP132553	NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination	Accumulating evidence suggests that molecularly targeted therapies, which were originally developed to target  the underlying cell autonomous genetic drivers of tumorigenesis, can provoke tumor specific immune  responses. Using immunocompetent mouse models of KRAS mutant lung adenocarcinoma, we show that a  combination of MEK and CDK4/6 inhibitors can induce natural killer (NK) cell immune surveillance that is  necessary for its full anti-tumor effect. Mechanistically, we show that the drug combination – but neither agent  alone – drives RB-mediated cellular senescence induction leading to potent cell cycle arrest and activation of  the immunomodulatory senescence-associated secretory phenotype (SASP). This, in turn, leads to an increase in  tumor-specific NK cell ligand expression and secretion of TNF-a that provokes NK cell-mediated targeting of  senescent tumor cells, culminating in tumor regressions and long-term survival in genetically engineered mouse  models of lung cancer. These studies identify a means and method of invoking a unique form of NK cell  mediated immune surveillance in lung tumors through molecularly targeted therapies that induce senescence. Overall design: For RNA-seq analysis of transcriptional changes after drug treatment of human KRAS mutant lung and pancreas cancer cell lines, total RNA was extracted using the RNeasy Mini Kit (Qiagen) from cell lines following 8 day treatment with vehicle (DMSO), trametinib (25 nM), palbociclib (500nM), or both in combination. For RNA-seq analysis of transcriptional changes in Natural Killer (NK) cells in vivo, total RNA was extracted as described above from CD45+CD3-NK1.1+ NK cells sorted from the lungs of tumor bearing KP transplant mice following 1 week treatment with vehicle or combined trametinib (1 mg/kg body weight) or palbociclib (100 mg/kg body weight). PolyA mRNA was selected using beads coated with polyT oligonucleotides. Purified polyA mRNA was subsequently fragmented, and first and second strand cDNA synthesis performed using standard Illumina mRNA TruSeq library preparation protocols. Double stranded cDNA was subsequently processed for TruSeq dual-index Illumina library generation. For sequencing, pooled multiplexed libraries were run on a HiSeq 2500 machine on RAPID mode. Approximately 10 million 76bp single-end reads were retrieved per replicate condition. Resulting RNA-Seq data was analyzed by removing adaptor sequences using Trimmomatic (29), aligning sequencing data to GRCh37.75(hg19) with STAR (30), and genome wide transcript counting using HTSeq (31) to generate a RPKM matrix of transcript counts.	Co-expression
SRP132594	Exploring the effects of different sample preparation factors on RNA sequencing	We investigated the effects of different sample preparation factors on RNA-seq experiments, including RNA concentration, library storage time, and cryopreserved condition, by comparing their sequencing biases, gene expression profiles, and biological function using primary B cell and CD4+ cell blood samples in healthy subjects. Overall design: The effects of RNA concentration, library storage time, and cryopreserved condition for RNA-seq experiments	Co-expression
SRP132630	Profiling in vivo Bone Lesion (IVBL) and Orthotopic tumors by Next Generation Sequencing	Based on RNA-seq, we performed transcriptomic profiling to examine the differences between Orthotopic and IVBL (in vivo bone lesion). We found Calcium signalling is upregulated in IVBL and correlated to the expression of gap junctions. Overall design: Orthotopic tumors and Bone lesions, all developed by MCF-7, are subject to NGS and then analyzed.	Co-expression
SRP132632	Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [RNA-seq]	The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers.  ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity.  EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations.  However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown.  Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells. Overall design: Parental TOV21G cell line and and resistant to EZH2 inhibitor GSK126 treatment clones were assayed by RNA-seq and BRG1 CHIP-seq	Co-expression
SRP132699	Immunophenotype and Transcriptome Profile of Patients with Multiple Sclerosis Treated with Fingolimod. Setting Up a Model for Prediction of Response in a 2-Year Translational Study	No description.	Co-expression
SRP132709	Whole blood transcriptome analysis of Septic shock patients according to early therapy response	Septic shock is the most severe complication of sepsis, associated with high mortality. The patient's response to supportive therapy is very heterogeneous and the underlying mechanisms are still elusive. In order to identify which are the actors (genes and pathways) that play a role in establishing the response, we investigate the whole blood transcriptome in septic shock patients with positive and negative responses to early supportive hemodynamic therapy, assessed by changes in SOFA scores within the first 48 hours from ICU admission. We pinpointed genes and pathways that are differently modulated and enriched respectively within 48hrs between responders and non-responders. Overall design: We analyzed 31 patients (17 Responders and 14 Not Responders to early therapy). For each patient, 2 samples were collected. In particular the first sample (T1) collected within 16 hours from ICU admission whereas the second (T2) collected within 48 hours from ICU admission. Experimental groups (Responders and Not Responders) are defined accordingly with SOFA scores improvements within 48 hours.	Co-expression
SRP132711	Aberrant hyperediting of myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis	We constructed strand-specific cDNA libraries of 23 total RNA samples (human cell lines and patient samples) and sequenced the libraries using Hiseq 4000 platform. More than 80 millions of mappable reads for each sample have been obtained. Overall design: The clinical importance of RNA editing in myeloma disease pathogenesis was elucidated by comparing the global editing events in the primary clinical samples. RNA was extracted from the plasma cells of the healthy volunteers and myeloma patients (from different disease stages) and paired end, 100bp RNA sequencing was conducted. Only high confidence editing events (at least 20 reads count and more than 10% absolute editing frequency) were considered for downstream analyses. Functional importance of ADAR1 in RNA editing was investigated by looking at the effects of differential ADAR1 expression after knocking down and overexpressing ADAR1 in myeloma cell lines. Likewise, only high confidence editing events were included into the analyses.	Co-expression
SRP132715	Characterization of gene regulation and protein interaction networks for Matrin 3 encoding mutations linked to amyotrophic lateral sclerosis and myopathy	To understand how mutations in Matrin 3 (MATR3) cause amyotrophic lateral sclerosis (ALS) and distal myopathy, we used transcriptome and interactome analysis, coupled with microscopy. Over-expression of wild-type (WT) or F115C mutant MATR3 had little impact on gene expression in neuroglia cells. Only 23 genes, expressed at levels of >100 transcripts showed =1.6-fold changes in expression by transfection with WT or mutant MATR3:YFP vectors. We identified ~123 proteins that bound MATR3, with proteins associated with stress granules and RNA processing/splicing being prominent. The interactome of myopathic S85C and ALS-variant F115C MATR3 were virtually identical to WT protein. Deletion of RNA recognition motif (RRM1) or Zn finger motifs (ZnF1 or ZnF2) diminished the binding of a subset of MATR3 interacting proteins. Remarkably, deletion of the RRM2 motif caused enhanced binding of >100 hundred proteins. In live cells, MATR3 lacking RRM2 (?RRM2) formed intranuclear spherical structures that fused over time into large structures. Our findings in the cell models used here suggest that MATR3 with disease-causing mutations is not dramatically different from WT protein in modulating gene regulation or in binding to normal interacting partners. The intra-nuclear localization and interaction network of MATR3 is strongly modulated by its RRM2 domain. Overall design: RNA-seq of untransfected cells or cells with overexpression of YFP, WT MATR3, or ALS mutation MATR3	Co-expression
SRP132719	Single cell RNA sequencing of multiple myeloma II	To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss-of-heterozygosity in individual cells from single-cell RNA-sequencing data. By combining allele frequency and expression magnitude deviations, HoneyBADGER is able to infer the presence of subclone-specific alterations in individual cells and reconstruct subclonal architecture. Also HoneyBADGER to analyze single cells from a progressive multiple myeloma (MM) patient to identify major genetic subclones that exhibit distinct transcriptional signatures relevant to cancer progression. Overall design: We performed single cell RNA sequencing (RNA-seq) for multiple myeloma from the bone marrow and/or extramedullary sites from 3 patients. Data contain 173 and 1,339 single-cell RNA-seq from Fluidigm C1  and 10x Genomics respectively.	Co-expression
SRP132721	Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following anti-angiogenic treatment	To understand tumor stromal cell heterogeneity focusing on tumor endothelial cells and tumor-associated fibroblasts, we isolated single cells from COLO205 tumor xenograft grown sub-cutaneously in SCID mice. To enrich stromal cell content, we removed vast majority of tumor cells by a depletion protocol using anti-CD24 and anti-E-Cadherin antibodies. The remaining single cells were profiled by single cell RNAseq Overall design: Tumors were dissociated, sorted into single cells, and profiled by 1 chromium. Single cell 3'' library, Gelbeads and multiplex kit were made by using 10x Genomics platform.	Co-expression
SRP132740	Integrating single-cell transcriptomic data across different conditions, technologies, and species	Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple datasets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq datasets based on common sources of variation, enabling the identification of shared populations across datasets and downstream comparative analysis. Implemented in our R toolkit Seurat (http://satijalab.org/seurat/), we use our approach to align scRNA-seq datasets of peripheral blood monocytes (PBMCs) under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across datasets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq datasets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution. Overall design: Human PBMCs were profiled using ddSeq and bulk RNA-seq.  The ddSeq experiment was performed on unperturbed PBMCs. The bulk RNA-seq experiments were performed on both unperturbed and IFN-beta stimulated PBMC-derived populations (cDCs and pDCs) with three technical replicates.	Co-expression
SRP132774	The long non-coding RNA MALAT1 contributes to the pathogenesis of multiple sclerosis through alternative splicing and backsplicing regulation	Since we found an upregulation of the long non coding RNA MALAT1 in Multiple Sclerosis (MS) patients, we decided to explore the global effect of MALAT1 modulation on transcriptome. We hence performed high-coverage RNA-seq experiments of MALAT1 knockdown in Jurkat E6-1 T cells to analyze gene expression, alternative splicing (AS), and backsplicing profiles. We found 107 differentially expressed genes, 1114 dysregulated AS events, and 49 circular RNAs that were modulated by MALAT1. These results highlighted the role of MALAT1  in splicing and backsplicing regulation. Overall design: Jurkat E6-1 cells were incubated with 500 nM GapmeR targeting MALAT1 (kd) or 500 nM GapmeR negative control (mock)	Co-expression
SRP132791	RNA sequencing in hBMSCs with DEPTOR knockdown	As an endogenous inhibitor, DEPTOR played an important role in cellular activities, while its role and effect in osteogenic differentiation remains unclear. To investigate the underlying mechanisms of DEPTOR, we conducted a RNA sequence to determine the expression profiles with DEPTOR knockdown in hBMSCs.	Co-expression
SRP132792	Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile (RNA-seq data set)	Screening and surveillance of colorectal cancers (CRCs) using advanced colonoscopy technologies have significantly reduced the incidence and mortality rates of CRCs in recent years. However, a significant portion of CRCs are still remained undiagnosed, especially those involving sessile serrated adenomas/polyps (SSA/P), most likely due to their flat shape and the excessive amounts of secreted mucin that cover the polyps, making them invisible for colonoscopy. Here, a potential alternative solution is the application of molecular markers enabling unambiguous characterization of SSPs. However, full implementation of this strategy requires availability of robust markers which are still lacking. In this work by comprehensive molecular analysis of several malignant and normal samples at the genome, methylome and transcriptome levels we show that activating mutation of BRAF-V600E drives the generation of a unique SSP-specific DNA methylation profile. As the result a robust set of DNA methylation markers showing significant (~3 to 30 fold) increase in their methylation levels, exclusively in SSP samples, are introduced. These markers can be of important clinical relevance, especially in early diagnosis of SSPs using non-invasive approaches such as fecal DNA testing. Overall design: To study the effect of BRAF-V600E mutation on gene expression profile we performed high-throughput RNA sequencing (RNA-Seq) on BRAF-V600E positive and negative samples. The RNA-Seq was performed on all available samples, from the exact same list of samples we evaluated their DNA methylation profile in our study.	Co-expression
SRP132822	High-throughput RNA sequencing on circular RNA profiles of human pancreatic cancer cell lines and gemcitabine resistant pancreatic cancer cell lines.	Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR) cell lines and compared the circular RNAs (circRNAs) profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Overall design: Examing 2 conditions, each with 3 replicates	Co-expression
SRP132830	T CELL-INDUCED TUMOR VULNERABILITY DISCOVERY IN AN IFN?-INDEPENDENT GENOMIC LANDSCAPE	No description.	Co-expression
SRP132872	Targeted mutagenesis recapitulates brain tumor initiation in cerebral organoids (RNA-seq data set: 130d)	Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids Overall design: Comparison of abundances (TPM) from different brain tumor organoid groups	Co-expression
SRP132875	Characterization of missense mutations in the tetratricopeptide region of O-GlcNAc transferase found in patients with X-linked intellectual disability	Dfferential transcriptomics analysis of RUES-1 human embryonic stem cells edited using Crispr/Cas9 to contain four mutations in OGT found in certain patients with X-linked intellectual disability reveals changes in the gene expression profile associated with ectoderm and mesoderm development in all four mutant cell lines compared to the wild type control. Overall design: The steady state global gene expression profiles of four mutant cell lines are compared with that of a control wild type cell line using Illumina mRNA-sequencing.	Co-expression
SRP132889	RNA sequencing data from triple-negative breast cancer patient-derived xenografts (PDX)	RNAseq was performed on WHIM2 and WHIM30 PDX mammary tumors, brain metastases, and single cell suspensions over time. Overall design: Comparison of gene expression profiles between two PDX models of triple-negative breast cancer, and between primary tumors, cell suspensions, and brain metastases within the PDX lines.	Co-expression
SRP132924	Transcriptional profiles of normal human mature B cells	Mature B cells leave the bone marrow  as naïve B cells and migrate to the secondary lymphoid organs where they encounter the antigen for the first time. This interaction stimulates B cells to rapidly grow and form characteristic histological structures called germinal center. In the germinal centers, B cells are targeted by mechanisms of genetic editing of the immunoglobulin loci, namely somatic hypermutation and class switch recombination, undergo selection for high affinity immunoglobulin receptors and are committed to differentiate into memory B cells or plasma cells. GCs display two histological areas the dark and the light zone that have been characterized as functionally distinct compartments through which B cells recycle multiple times during the germinal center reaction. Overall design: Naïve, germinal center and memory B cells were isolated from three independent donors each.	Co-expression
SRP132928	RNA-sequencing of isogenic primary, pre-malignant immortalized, and Ras-transformed human mammary epithelial cells	Understanding changes in gene expression during tumor initiation and progression is critical to understanding how genetic alterations drive malignancy. We used a genetically defined cell culture model to study the progression of normal human mammary epithelial cells (HMECs) to malignancy. Primary HMECs were immortalized through the expression of hTERT, p53DD, cyclin D1, CDK4R24C and c-MYCT58A. This immortalization conferred limitless replicative potential as well as migratory capacity. These pre-malignant cells were subsequently HRASG12V transformed, which converted the immortalized cells to a fully tumorigenic state with significantly increased invasive capacity. We analyzed the cells using RNA-sequencing, and we report dramatic mRNA expression changes during the pre-malignant immortalization of primary cells, and very few mRNA expression changes occurring during oncogenic Ras transformation. RNA signatures in pre-malignant immortalized and Ras-transformed cells are consistent with previously reported epithelial-to-mesenchymal transition (EMT) signatures. Overall design: RNA-sequencing in biological triplicate of three cell types (Primary HMECs, Immortalized HMECs, Transformed HMECs); Illumina HiSeq 2000 125bp PE (1 replicate) and Illumina HiSeq 4000 150bp PE (2 replicates)	Co-expression
SRP132939	Low density granulocytes and their gene signature associate with vascular inflammation and coronary atheroclerosis in systemic lupus erythematosus patients	Patients with systemic lupus erythematosus (SLE) display an increased risk of cardiovascular disease that is not fully explained by traditional risk factors. This study correlated RNA sequencing data from whole blood of patients with SLE and healthy controls with markers of cardiovascular risk including coronary plaque measured by CT angiogram and vascular inflammation by FDG-PET CT. Overall design: This dataset includes a total of 53 individual samples from two independent RNAseq runs. This study sought to compare healthy controls to SLE patients and to determine transcriptomic differences in patients that developed vascular damage to those without vascular impairments. The first run compared SLE patients with high noncalcified plaque burdens (NCB) (>1.5 standard deviations of healthy control mean), measured by coronary CT angiography, and patients that had NCB comparable to healthy controls (within 1.5 standard deviations of healthy control mean). The second run validated these findings and compared patients with high vascular inflammation (>1.5 standard deviations of healthy control mean), as measured by target:background ratio (TBR) on FDG-PET/CT scans, to patients with vascular inflammation comparable to healthy controls (within 1.5 standard deviations of healthy control mean).	Co-expression
SRP132967	PolyA+ RNA-seq in ALL-SIL upon TLX1 knockdown	T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the 'T-cell leukemia homeobox 1' TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL. Overall design: polyA+ RNA-seq data was generated for the T-ALL cell line ALL-SIL upon TLX1 knockdown	Co-expression
SRP132968	PolyA+ RNA-seq in a primary T-ALL patient cohort	T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the 'T-cell leukemia homeobox 1' TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL. Overall design: polyA+ RNA-seq data was generated for a primary T-ALL patient cohort	Co-expression
SRP132970	Total RNA-seq in ALL-SIL upon TLX1 knockdown	T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the 'T-cell leukemia homeobox 1' TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL. Overall design: Total RNA-seq data was generated for the T-ALL cell line ALL-SIL upon TLX1 knockdown	Co-expression
SRP132971	Total RNA-seq in a primary T-ALL patient cohort	T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the 'T-cell leukemia homeobox 1' TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL. Overall design: total RNA-seq data was generated for a primary T-ALL patient cohort	Co-expression
SRP132977	RNA-seq of GSK-J4 Treated Neuroblastoma Cell Lines	High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential with tumors refractory to retinoic acid differentiation based therapies. Here, we leverage high-throughput drug screening of epigenetic targeted therapies across a large and diverse tumor cell line panel to uncover the hypersensitivity of neuroblastoma cells to GSK-J4, a small molecule dual inhibitor of H3K27 demethylases UTX and JMJD3. Mechanistically, GSK-J4 induced neuroblastoma differentiation and ER stress with accompanying upregulation of PUMA and apoptosis induction. Retinoic acid (RA)-resistant neuroblastoma cells were sensitive to GSK-J4. Additionally, GSK-J4 was effective at blocking the growth of chemorefractory and patient-derived xenograft models of high-risk neuroblastoma in vivo. Further, GSK-J4 and RA combined to induce differentiation, ER-stress and limit the growth of neuroblastomas resistant to either drug alone. In MYCN-amplified neuroblastoma, which is the most prevalent driver gene alteration in the refractory population, PUMA induction by GSK-J4 sensitized tumors to the BCL-2 inhibitor venetoclax, demonstrating that epigenetic targeted therapies and BH3 mimetics can be rationally combined to treat high-risk subset of neuroblastoma. Therefore, H3K27 demethylation inhibition is a promising therapeutic target to treat high-risk neuroblastoma, and H3K27 demethylation can be part of rational combination therapies to induce robust anti-neuroblastoma activity. Overall design: Four neuroblastoma cell lines were untreated or treated with GSK-J4 for 72 hours. Each cell line and condition was performed in triplicate.	Co-expression
SRP133058	Comparison of single hWJSCs and hBMMSCs	The Wharton's jelly of the human umbilical cord contains a population of mesenchymal stem cells that are unique and possess significant clinical utility. Known as human Wharton's jelly stem cells (hWJSCs), they have broad differentiation potential, are proliferative and available in large numbers from discarded cords thus requiring minimum ex vivo expansion. They are safe and non-tumorigenic and maintain stemness properties for prolonged periods in culture. Besides their potential to produce tissues for cell based therapies, it has been demonstrated that they have anti-cancer and wound healing properties and provide cues for expansion of hematopoietic stem cells for treatment of hematopoietic malignancies. They are thus an attractive alternative source of MSCs of therapeutic value compared to bone marrow MSCs (hBMMSCs). We aimed to characterise the differences in gene expression profiles between these two stem cell types using single cell RNA sequencing to determine which pathways are involved in conferring hWJSCs with their unique properties. Overall design: One hundred and three hWJSCs and sixty-three hBMMSCs. There are no replicates.	Co-expression
SRP133068	Single-cell transcriptomics of human oocytes: environment-driven metabolic competition and compensatory mechanisms during oocyte maturation	Aim: The mechanisms coordinating maturation with an environment-driven metabolic shift, a critical step in determining the developmental potential of human in vitro matured (IVM) oocytes, remains to be elucidated. Here, we explored the key genes regulating human oocyte maturation using single-cell RNA sequencing and illuminated the compensatory mechanism from a metabolic perspective by analyzing gene expression. Results: Three key genes that encode CoA-related enzymes were screened from the RNA sequencing data. Two of them, ACAT1 and HADHA, were closely related to the regulation of substrate production in the Krebs cycle. Dysfunction of the Krebs cycle was induced by decreases in the activity of specific enzymes. Further, the activator of these enzymes, the calcium concentration, was also decreased because of the failure of influx of exogenous calcium. Although release of endogenous calcium from the endoplasmic reticulum and mitochondria met the requirement for maturation, excessive release resulted in aneuploidy and developmental incompetence. High nicotinamide nucleotide transhydrogenase expression induced NADPH dehydrogenation to compensate for the NADH shortage resulting from the dysfunction of the Krebs cycle. Importantly, high NADP+ levels activated DPYD to enhance the repair of DNA double-strand breaks to maintain euploidy. Innovation: The present study shows for the first time that exposure to the in vitro environment can lead to the decline of energy metabolism in human oocytes during maturation but that a compensatory action maintains their developmental competence. Conclusions: In vitro maturation of human oocytes is mediated through a cascade of competing and compensatory actions driven by genes encoding enzymes. Overall design: Investigated the transcriptome characteristics of human oocytes matured in vitro and in vivo to gain a transcriptome-level understanding of how oocytes mature and to illuminate the differences between human IVM and in vivo (IVO) matured oocytes at the transcript level.	Co-expression
SRP133072	Nudt12 is an mRNA DeNADding Enzyme	The 5´-end 7-methylguanosine cap structure has long been known as a signature feature of eukaryotic cellular and viral mRNAs that confers mRNA stability and efficient translation.  Recent findings in diverse organisms have demonstrated that RNAs can additionally possess a non-canonical cap structure consisting of a nicotinamide adenosine dinucleotide (NAD+) at their 5´ end in place of m7G.  It has been shown that 5´ end-NAD+ cap promotes rapid decay of the RNA at least in part by the DXO family of proteins in mammalian cells.  This observation led to the hypothesis that mammalian cells harbor additional deNADding enzymes that may function in distinct pathways.  Here we report Nudt12 efficiently removes NAD+ caps and functions as alternate cellular deNADding enzyme that targets NAD+-capped RNAs distinct from DXO.  Importantly, with the use of an NAD-Cap Detection (NAD-CapD) approach that utilizes enzymatic properties to release intact NAD+/NADH from the 5´ end of NAD-capped cellular RNAs and a colorimetric NAD Quantitation to detect released NAD+/NADH, we can follow total cellular NAD+ cap levels.  Removal of Nudt12 or DXO deNADding enzymes from cells significantly increased levels of NAD+-capped cellular RNAs.  Moreover, fungal Rai1 and Dxo1, previously demonstrated to possess deNADding activity in vitro, can also function as deNADding enzymes in yeast cells.  Double disruption of Rai1 and Dxo1 in yeast cells lead to accumulation of NAD+-capped RNAs, indicating that both enzymes function to clear NAD+ from the 5´ end of RNAs.  Finally, our findings established that alterations in cellular NAD+ levels impact NAD+-capped RNA levels implying NAD+ capping is a modulated process that may be linked to the metabolic state of the cell. Overall design: Three replicates each of HEK293T-Nudt12-KO (N12-KO) cell RNA were prepared and enriched by NAD-Capture for sequencing library preparation and seqeuencing.  Results were compared with previously-published samples of HEK293T-WT and HEK293T-DXO-KO prepared by identical methods.	Co-expression
SRP133095	Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [RNA-Seq]	To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).	Co-expression
SRP133178	NCI60 Transcriptome	MRNA sequencing of the NCI60 cell lines	Co-expression
SRP133187	RNA-seq profiling identifies Androgen Receptor-regulated genes in prostate cancer cells	The goal of this analysis is to profile AR-regulated genes, especially non-coding RNAs in three androgen sensitive prostate cancer cell lines, MDA-PCA-2B, LNCaP and VCaP. The two cell lines were serum-starved first, followed by dihydrotestosterone (DHT) stimulation or treated with Enzalutamide (AR inhibitor) without starvation. Transcriptome profiling was generated by RNA-sequencing from polyA-selected RNA. These experiments are followed by knock-down experiments of AR and ARlnc1 in MDA-PCA-2B, and also Enzalutamide (anti-androgen) treatment of LNCaP cells. Overall design: Identification of Androgen Receptor regulated transcriptome in three prostate cancer cell lines.	Co-expression
SRP133205	Abnormal neutrophil signature in the blood and pancreas of pre-symptomatic and symptomatic type 1 diabetes	Analysis of neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls. Overall design: Subjects were classified into four groups based on type 1 diabetes (T1D) risk or diagnosis. Healthy control subjects with no family history of T1D (N=16) were donors undergoing surgery. Patients with family history of T1D were enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention Trial; these subjects were divided into pre-symptomatic T1D (N=8) or at risk of T1D (N=13) based on the presence/absence (respectively) of 2 or more T1D-related autoantibodies. Symptomatic T1D subjects had clinical diagnosis of T1D, with first insulin injection no more than 10 days prior to the blood draw.	Co-expression
SRP133209	Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [RNA_seq_Whole]	To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).	Co-expression
SRP133211	The role of CFTR in islet function	Cystic fibrosis (CF)-related diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting ~35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of b cell CFTR deletion, and normal and CF human pancreas and islets. Specific deletion of CFTR from murine b cells did not affect b cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein/electrical activity was not detected. Isolated CF/CFRD islets demonstrated appropriate insulin and glucagon secretion with few changes in key islet-regulatory transcripts. Furthermore, ~65% of b cell area was lost in CF donors, compounded by pancreatic remodeling and immune infiltration of the islet. These results indicate that CFRD is not caused by intrinsic islet dysfunction from CFTR mutation, but rather, by b cell loss and intra-islet inflammation in the setting of a complex pleiotropic disease Overall design: Human samples 3351-ACP-005, -0017, -0020, -0027, -0036 are isolated islets from normal healthy individuals. 3362-ACP-0011, -0012,-0013,-0014,-0015 are isolated from individuals with cystic fibrosis. 12 samples from mouse.	Co-expression
SRP133227	RNA Seq data: A375, A375R, A375DR vorinostat treated, and biopy samples from patients pre- and post- treated with Vorinostat	BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here. Overall design: one replicate of RNA Seq data A375, A375R, A375DR vorinostat treated and patient samples pre- post- vorinostat treatment	Co-expression
SRP133231	Solid phase chemistry to covalently and reversibly capture thiolated RNA	Here, we describe an approach to enrich newly transcribed RNAs from primary mouse neurons using 4-thiouridine (s4U) metabolic labeling and solid phase chemistry. This one-step enrichment procedure captures s4U-RNA by using highly efficient methane thiosulfonate (MTS) chemistry in an immobilized format. Like solution-based methods, this solid-phase enrichment can distinguish mature RNAs (mRNA) with differential stability, and can be used to reveal transient RNAs such as enhancer RNAs (eRNAs) and primary microRNAs (pri-miRNAs) from short metabolic labeling. Most importantly, the efficiency of this solid-phase chemistry made possible the first large scale measurements of RNA polymerase II (RNAPII) elongation rates in mouse cortical neurons. Thus, our approach provides the means to study regulation of RNA metabolism in specific tissue contexts as a means to better understand gene expression in vivo. Overall design: s4U metabolic labeling of RNA in K562 cells and mouse cortical neurons, followed by biochemical enrichment of labeled RNA with solid-phase activated disulfides, and RNA sequencing	Co-expression
SRP133266	Transcriptome assemblies 10 vertebrate species	2 types of content: a) Raw RNA-seq files from cell lines of 10 vertebrate species (human, mouse, cow, tasmanian devil, chicken, duck, zebra finch, xenopus, medaka and zebrafish), 4 replicates per species. b) Refined transcriptomes after combining with paired proteomics data and data curation.	Co-expression
SRP133278	RNA sequencing of B cell subsets (CD11c hi IgD+ B cells, CD11c hi IgD- B cells, Memory B cells and Naïve B cells) from healthy subjects and subjects with Systemic lupus erythematosus (SLE) or Rheumatoid arthritis (RA)	CD11c+ B cells (IgD+ and IgD-) are pathogenic B cells expanded in autoimmune disease. The purpose of this study is to identify the pathways unique to IgD+ CD11c B cells and IgD- CD11c B cells. Overall design: B cell subsets were isolated from peripheral blood and RNA sequencing was performed with Hiseq 2000 platform	Co-expression
SRP133294	RNA-Seq profiling of iPSC-derived ventricular and atrial cardiomyocytes	We profiled RNA expression in human iPSC-derived ventricular and atrial cardiomyocytes Overall design: 4 biological replicates of human iPSC-derived ventricular cardiomyocytes and 4 biological replicates of iPSC-derived atrial cardiomyocytes (from 3 individual iPSC lines)	Co-expression
SRP133303	Integrative analysis of mRNA and lncRNA profiles identified pathogenetic  lncRNAs  in esophageal squamous cell carcinoma	Systems biology approaches can help understand pathogenesis of complex human diseases like cancers for identification of potential new therapeutic targets. Here in this study, we performed genome-wide screening for mRNA and lncRNA profiles in esophageal cancer to identify the novel cancer-related mRNA and lncRNA in esophageal squamous cell carcinoma (ESCC). We identified 3000 up-regulated/2517 down-regulated mRNAs and 402 up-regulated/741 down-regulated lncRNAs. Further functional analysis revealed differentially expressed genes (DEGs) of mRNA and lncRNA are related to different pathways. mRNA pathways are mainly involved in cell cycles while lncRNA pathways are for regulation and metabolic procession. Differentially expressed mRNAs/lncRNAs were validated with qPCR. At last, mRNA and lncRNA co-expression network were built and highly-connected networks were identified, which may provide a mechanism of mRNA expression regulation by lncRNA. To our knowledge, this is the first study to explore the co-expression networks and the lncRNA-mRNA networks could be therapeutic targets for ESCC treatments. Overall design: we performed genome-wide screening for mRNA and lncRNA profiles in 7 pairs (S1 nomal S2 Tumor, S1 and S2 paired, S3 normal S4 tumor, S3 and S4 paired, etc.) of esophageal cancer and normal tissues to identify the novel cancer-related mRNA and lncRNA in ESCC. Then we build a co-expression network for all of these mRNA and lncRNA to build the relationship between mRNA and lncRNA.	Co-expression
SRP133314	Chromatin mapping and single-cell immune profiling defines the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia [scRNA-seq]	Chronic lymphocytic leukemia (CLL) is a genetically, epigenetically, and clinically heterogeneous disease. Despite this heterogeneity, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for the vast majority of CLL patients. To define the underlining regulatory program, we analyzed high-resolution time courses of ibrutinib treatment in closely monitored patients, combining cellular phenotyping (flow cytometry), single-cell transcriptome profiling (scRNA-seq), and chromatin mapping (ATAC-seq). We identified a consistent regulatory program shared across all patients, which was further validated by an independent CLL cohort. In CLL cells, this program starts with a sharp decrease of NF-?B binding, followed by reduced regulatory activity of lineage-defining transcription factors (including PAX5 and IRF4) and erosion of CLL cell identity, finally leading to the acquisition of a quiescence-like gene signature which was shared across several immune cell types.  Nevertheless, we observed patient-to-patient variation in the speed of its execution, which we exploited to predict patient-specific dynamics in the response to ibrutinib based on pre-treatment samples. In aggregate, our study describes the cellular, molecular, and regulatory effects of therapeutic B cell receptor inhibition in CLL at high temporal resolution, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring. Overall design: 12 scRNA-seq samples of peripheral blood mononuclear cells from chronic lymphocytic leukemia patients	Co-expression
SRP133349	High definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms	Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed Helicase-like Transcription Factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses. Overall design: 9 samples comprising three sets of three replicates (0h, 24h, 72h)	Co-expression
SRP133374	The commensal-derived metabolite butyrate imprints an antimicrobial program in macrophages	The balance between tolerogenic and inflammatory responses determines immune homeostasis in the gut. Dysbiosis and a defective host defense against invading intestinal bacteria can shift this balance via bacterial-derived metabolites and trigger chronic inflammation. We show that the short chain fatty acid butyrate modulates monocyte to macrophage differentiation by promoting antimicrobial effector functions. The presence of butyrate modulates antimicrobial activity via a shift in macrophage metabolism and reduction in mTOR activity. This mechanism is furthermore dependent on the inhibitory function of butyrate on histone deacetylase 3 (HDAC3) driving transcription of a set of antimicrobial peptides including calprotectin. The increased antimicrobial activity against several bacterial species is not associated with increased production of conventional cytokines. Butyrate imprints antimicrobial activity of intestinal macrophages in vivo. Our data suggest that commensal bacteria derived butyrate stabilize gut homeostasis by promoting antimicrobial host defense pathways in monocytes that differentiate into intestinal macrophages. Overall design: Paired samples of control and butyrate-treated macrophages prepared from two individuals.	Co-expression
SRP133401	Expression profiling by RNA-Seq of breast cancer samples from patients in walnut-consuming and control groups	Consumption of walnuts has slowed breast cancer growth and/or reduced the risk of breast cancer in mice. The significantly reduced mean tumor size or numbers of tumors was associated with changing the expressions of many genes that are associated with cancer growth, survival and metastasis. Many women treated for breast cancer are interested in reducing the risk for recurrence. The study was a non-placebo, two-arm, clinical trial. Women with lumps large enough for research and pathology biopsies were recruited to the trial. One or two additional biopsies were taken for gene expression analyses using next generation RNA Sequencing methods. The subjects randomized to the walnut group immediately began to consume 2 ounces of walnuts per day until follow-up surgery, if surgery were needed. At follow up surgery, additional biopsies were taken from the surgically removed, cancerous tissue for additional gene expression analyses. Changes in gene expression compared to baseline were determined in tumors of each individual woman in walnut-consuming and control groups. Overall design: Gene expression profiles of two samples from each of ten breast cancer patients were obtained via RNA-Seq in a 2x50bp paired-end design. The first sample was obtained from biopsy; the second sample was taken at the time of surgery 2-3 weeks later. Five patients consumed two one-ounce packets of walnuts daily between the biopsy and surgery, while the other five remained on their regular diet.	Co-expression
SRP133437	The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN	Human telomerase RNA (hTR) is transcribed as a precursor that is then posttranscriptionally modified and processed.  A fraction of the transcripts is oligoadenylated by TRAMP and either processed into the mature hTR or degraded by the exosome.  Here, we characterize the processing of 3' extended forms of varying length by PARN and RRP6. We show that tertiary RNA interactions unique to the longer precursor forms favor RNA degradation, whereas H/ACA RNP assembly stimulates productive processing. Interestingly, the H/ACA complex actively promotes processing in addition to protecting the mature 3' end.  Processing occurs in two steps with longer forms being trimmed by RRP6 and shorter forms being preferentially processed by PARN.  These results reveal how RNA structure and RNP assembly affect the kinetics of processing and degradation and ultimately determine the amount of functional telomerase produced in cells. Overall design: We cloned and sequenced 3' ends by 3' RACE coupled with high-throughput sequencing to gain further insights into hTR processing.	Co-expression
SRP133438	Hominin-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis	Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and a determinant of neuronal number in the mammalian cortex. We find three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation. Furthermore, NOTCH2NL genes provide the breakpoints in typical cases of 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism, and deletions with microcephaly and schizophrenia. Thus, the emergence of hominin-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger hominin neocortex accompanied by loss of genomic stability at the 1q21.1 locus and a resulting recurrent neurodevelopmental disorder. Overall design: H9 embryonic stem cells were used for directed differentiation towards cortical organoids. Using the CRISPR/Cas9 system, H9 control and H9 NOTCH2NL knockout lines were generated. Comparative analysis of RNA-seq at week 4 of differentiation was done to assess the effect of NOTCH2NL KO on cortical neurogenesis. Mouse 46C ES cell stable lines were generated, overexpressing either EV control, or NOTCH2NL-Sh_T197I cDNA. Mouse 46C stable cell lines were differentiated into cortical organoids, and gene expression level was compared by RNA-Seq at day 6 of differentiation.	Co-expression
SRP133442	Distinct Transcriptomic and Exomic Abnormalities within Myelodysplastic Syndrome Marrow Cells	Prior studies using DNA microarray platforms have shown alterations of gene expression profiles (GEPs) of marrow cells in myelodysplastic syndromes (MDS). Using the increased sensitivity and accuracy of high-throughput RNA sequencing (RNA-Seq) for detecting and quantifying mRNA transcripts, our study has demonstrated novel significant differences in GEPs between MDS and normal CD34+ marrow cells with 41 genes identified as disease classifiers. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable (sMDS) vs patients whose illness transformed to acute myeloid leukemia within 12 months (tMDS). The genes whose expression was associated with disease outcome were involved in functional pathways and biologic processes highly relevant for MDS. Exomic analysis identified MDS-associated pathogenic mutations in virtually all patients tested. MDS subgroups with spliceosome mutations demonstrated distinct differential isoform usage and expression and consequent dysregulation of distinct biological functions. This combination of clinical, transcriptomic and exomic findings provides valuable molecular insights into the mechanisms underlying MDS and its progression to a more aggressive stage and also facilitates prognostic characterization of MDS patients. Overall design: RNA-Seq was performed on CD34+ hematopoietic stem cells derived from healthy individuals and patients with myelodysplastic syndrome.	Co-expression
SRP133455	Transcriptome analysis of anti-cancer adaptions in cancer-resistant species	This study provides multiple new insights into anti-cancer mechanisms in cancer-resistant species	Co-expression
SRP133497	Gain-of-function mutations in DNMT3A in patients with paraganglioma	Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq	Co-expression
SRP133555	Next Generation Sequencing Facilitates Quantitative Analysis of Retinoblastoma Transcriptomes	Methods:  mRNA profiles of retinoblastoma samples and para-tumor were generated by deep sequencing, in triplicate, using Illumina. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Overall design: Retinoblastoma mRNA of retinoblastoma were generated by deep sequencing, using Illumina.	Co-expression
SRP133573	Identification of Transcription Factor Relationships Associated with Androgen Deprivation Therapy Response and Metastatic Progression in Prostate Cancer	Background: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived, and responses are variable. ADT failure results in castration-resistant prostate cancer (CRPC), that inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis.   Results: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT. We found that all patients lost AR-dependent subtype (PCS2) transcriptional signatures. The high impact group maintained the more aggressive subtype (PCS1) signal, while the low impact group more resembled an AR-suppressed (PCS3) subtype. Computational analyses identified transcription factor coordinated groups (TFCGs) enriched in the high impact group network. Leveraging a large public dataset of over 800 metastatic and primary samples, we identified 33 TFCGs in common between high impact group and metastatic lesions, including SOX4/FOXA2/GATA4, ERF/ETV5/ETV3/ELF4, and a TFCG containing JUN, JUNB, JUND, FOS, FOSB, and FOSL1. The majority of metastatic TFCGs were subsets of larger TFCGs in the high impact group network, suggesting refinement of critical TFCGs in prostate cancer progression.   Conclusions: We have identified TFCGs associated with pronounced initial transcriptional response to ADT, aggressive signatures, and metastasis. Our findings suggest multiple new hypotheses that could lead to novel combination therapies to prevent development of CRPC following ADT. Overall design: Sequence alignment and gene level expression quantifications were obtained using the STAR read aligner. We obtained an average of 91,077,364 reads (sd: 41,923,139) with a mean transcriptome coverage of 64x (83% mapping to exons).	Co-expression
SRP133589	Genome wide characterization of a STAT1-independent antiviral and immunoregulatory transcriptional program induced by IFNß and TNFa reveals non-canonical STAT2 and IRF9 pathways	Interferon (IFN) ß and Tumor Necrosis Factor (TNF) a are key players in immunity against pathogens as well as in the development of autoinflammatory and autoimmune diseases. Accordingly, their molecular pathways have attracted much interest as therapeutic targets. Compelling evidence has shown that the antiviral and inflammatory transcriptional response induced by IFNß is reprogrammed by crosstalk with TNFa. IFNß typically induces interferon-stimulated genes by the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway leading to activation of the canonical ISGF3 transcriptional complex, composed of STAT1, STAT2 and IRF9. The signaling pathways engaged downstream of the combination of IFNß and TNFa remain elusive, but previous observations suggested the existence of a response independent of STAT1. Here, using genome-wide transcriptional analysis by RNASeq, we observed a broad antiviral and immunoregulatory response initiated in the absence of STAT1 upon IFNß and TNFa costimulation. Additional stratification of this transcriptional response with respect to the role of STAT2 and IRF9 revealed that they mediate the expression of a wide spectrum of genes. While a subset of genes was regulated by the concerted action of STAT2 and IRF9, other gene sets were independently regulated by STAT2 or IRF9. Collectively, our data supports a model in which STAT2 and IRF9 act through non-canonical parallel pathways to regulate distinct pool of genes in response to IFNß and TNFa. This study provides novel insights into the molecular pathways leading to antiviral and immunoregulatory gene expression in conditions where elevated levels of both IFNß and TNFa are present. Overall design: To investigate the transcriptional program triggered by IFNß and TNFa independently of STAT1, the human STAT1-deficient U3A cell line (derived from the 2ftGH fibrosarcoma cell line, McKendry R, et al.Proc Natl Acad Sci U S A. 1991;88(24):11455-9) were efficiently transfected with Control (Ctrl), STAT2 or IRF9 targeting RNAi and further left untreated or stimulated with a combination of IFNß (1000U/ml) +TNFa (10ng/ml) for 24h. Total RNA was isolated and analyzed by RNA sequencing (n=3 for each group) on an Illumina HiSeq2500 platform. Bioinformatics analysis was performed to determine genes differentially regulated upon IFNß and TNFa costimulation. Moreover, the role of STAT2 and IRF9 in the regulation of these genes was analyzed. Results of RNASeq were validated by qRT-PCR.	Co-expression
SRP133590	Homo sapiens Transcriptome or Gene expression	BCBL1 derived exosomes added to HUVEC culture over time	Co-expression
SRP133591	The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 KO]	To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: knock out ELL2 in L363 cells using CRISPR-Cas9	Co-expression
SRP133615	The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 rescue]	To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: Reconstitution of ELL2 expression in L363-ELL2-knockout cells	Co-expression
SRP133658	RNA sequencing of LNZ308 glioma cells treated under differential conditions including monotherapies, dual therapy and synergistic triple regimen employing ?-irradiation, temozolomide and oncolytic measles virus.	The synergistic regimen CT-VT-RT triggers proinflammatory antiviral signalling with activation of apoptotic cascades resulting in tumor cell death. Overall design: The experiment was designed to elicit individual treatment effects using monotherapies to understand the combinatorial sequential effect of dual and triple regimen using appropriate controls.	Co-expression
SRP133668	Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma (RNA-Seq)	Purpose: Identification of core transcriptional regulatory programs and bromodomain and extraterminal (BET) protein dependency in liposarcoma (LPS) Methods: ChIP-seq and RNA-seq were performed on LPS cells. Antibodies against H3K27ac, H3K4me1, H3K4me3, RNA-Pol2, BRD2, BRD3, BRD4, FOSL2, pan-RUNX, and DDIT3 (FUS-DDIT3) were used for ChIP-seq assays. The transcriptome responses of LPS141 and MLS402 cells to OTX015 and ARV-825 were compared. Result: We generated genome-wide chromatin-state maps of LPS cells. By charting the super-enhancer structures, we identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. This study also provides a framework for discovering and targeting of core oncogenic transcriptional programs. Overall design: ChIP-seq and RNA-seq were performed on LPS cells.	Co-expression
SRP133685	Global transcriptome analysis of HAP1 cells	We analyzed the global change in transcription upon CHD3-KO and SENP1-KO compared to control HAP1 cells. Overall design: CRISPR-Cas9-generated knockout HAP1 cells for CHD3 and SENP1 compared to HAP1 control cell line were profiled for changes in transcriptome-wide expression using RNA-seq. Three biological replicates were used for RNA sequencing, where 150 bp PE-reads were obtained using Illumina Hiseq 4000 sequencer	Co-expression
SRP133748	mRNA sequencing of the mouse and human Hep-Orgs, Chol-Orgs and primary hepatocytes	The mammalian liver possesses a remarkable regenerative ability. 1) The 'oval cell' response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. 2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). We establish a long-term 3D organoid culture system from mouse and human fetal/pediatric/adult hepatocytes that retain key morphological and functional features of hepatocytes fate. We report the mRNA and single cell sequencing of Hep-Orgs from different donors in different passages. We compared Hep-Orgs with primary hepatocytes, proliferative hepatocytes or Chol-Orgs derived from Epcam+ biliary cells. By analyzing, we determine similar gene expression profile of Hep-Orgs with primary hepatocytes and make genes lists distinguished with undamaged hepatocytes as well. We find the Hep-Orgs resemble proliferative damage-response of hepatocytes after partial hepatectomy while Chol-Orgs express high cholangiocytes markers. The sequencing data constitutes a valuable resource to understand liver organoids especially Hep-Orgs. Overall design: We generated transciptome data [1] from hepatocytes unbiasely sorted from the labeled mice liver three days after 2/3 partial heptectomy [2] from mouse and human Hep-Orgs and compare them with primary undamaged hepatocytes, proliferative hepatocytes and Chol-Orgs Please note that the processed *csv files contains extra data columns which do not belong to the current samples. The submitter provided the 'readme.txt' file indicating which column the corresponding data is included.	Co-expression
SRP133763	Neuronal Development And The Onset Of Electrical Activity In The Human Enteric Nervous System	Objective: To assess the development of neuronal subtypes and the emergence of evoked electrical activity within the developing human ENS. Methods: Human foetal gut samples were obtaining via the MRC-Wellcome Trust Human Developmental Biology Resource (UK). Characterisation of the developing ENS was performed by immunohistochemistry, calcium imaging, RNAseq and qRT-PCR Results: Human foetal colon samples displayed robust Tuj1 immunohistochemistry by embryonic week (EW) 12 with a dense neuronal network at the level of the myenteric plexus. At EW12 expression of excitatory neurotransmitter markers (VAChT and Sub P) was observed. By contrast, inhibitory neurotransmitter markers (nNOS and VIP) were not observed until EW14. Co-labeling with synaptic markers (SYN1/SNAP-25) demonstrated the development of synaptic contacts by EW12. However, electrical train stimulation (40V,2s,20Hz of 300?s electrical pulses) did not evoke activity within the myenteric plexus of EW12 foetal gut (n=0/3). Similarly, the majority of EW14 gut tissues assessed (80%), demonstrated no response to electrical stimulation (n=4/5). Interestingly, at EW16 Tuj1+ expression, in the myenteric plexus, was observed within discrete ganglia and was combined with the emergence of calcium transients (F/F0=1.273±0.024;n=3), upon electrical stimulation (n=3/3), which were abolished after the addition of 1uM TTX (n=3/3). RNAseq and qRT-PCR analysis between EW12-16 revealed increases in expression in genes involved in neurotransmission and action potential generation including SCN9A and KCNQ3. Conclusion: Here we demonstrate the temporal development of human enteric neuronal subtypes from EW12-14 and the subsequent emergence of coordinated electrical activity within the human foetal ENS at approximately EW16. Overall design: total RNA was isolated from three human embryonic colon samples. Three technical replicates/timepoint were sequenced.	Co-expression
SRP133768	Large-scale expansion of human iPSC-derived skeletal muscle cells for disease modeling and cell-based therapeutic strategies	Although skeletal muscle cells can be generated from human iPSCs, transgene-free protocols include only limited options for their purification and expansion. In this study we found that FACS-purified myogenic progenitors generated from healthy controls and Pompe disease iPSCs can be robustly expanded as much as 5 x 1011 fold. At all steps during expansion, cells could be cryopreserved or differentiated into myotubes with a high fusion index. In vitro, cells were amenable to maturation into striated and contractile myofibers. Insertion of the acid alpha glucosidase cDNA into the AAVS1 locus in iPSCs using CRISPR/cas9 prevented glycogen accumulation in myotubes generated from a patient with classic infantile Pompe disease. In vivo, the expression of human-specific nuclear and sarcolemmar antigens indicated that myogenic progenitors engraft into murine muscle to form human myofibers. This protocol is useful for modeling of skeletal muscle disorders and for using patient-derived, gene-corrected cells to develop cell-based strategies. Overall design: Myogenic progenitors were expanded for ~15 days and harvested either in proliferation conditions or after 4 days of differentiation as described previously (van der Wal et al., 2017b). RNA was extracted using the RNeasy minikit with DNAse treatment (Qiagen, Germantown, MD). Sequencing libraries were prepared using TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, California, USA) according to the manufacturer's instructions. Libraries were sequenced on a HiSeq2500 sequencer (Illumina, San Diego, California, USA) in rapid-run mode according to the manufacturer's instructions. Reads 50 base-pairs in length were generated. The RNA-sequencing datasets listed in table S3 were downloaded and aligned with the datasets generated in this study using the 'new Tuxedo' pipeline (Pertea et al., 2016). The processed data file includes the analysis of 30 additonal Samples from other research groups, partly from GEO and partly from other sources such as ENCODE and ENA. The header table linked below lists the origin of the other Samples.	Co-expression
SRP133779	Transcriptome analysis to investigate the role of EDC3 in a neuronal cell line	We knocked down EDC3 using an siRNA-based approach in the human neuroblastoma cell line SKNBE and carried out RNA sequencing.	Co-expression
SRP133789	Development and Verification of an RNA-Seq Assay for the Detection of Gene Fusions in Tumors	Purpose: Assessment of the performance characteristics of an RNA-Seq assay designed to detect gene fusions in 573 genes to aid in the management of cancer patients. Methods: Polyadenylated RNA was converted to cDNA which was then used to prepare NGS libraries that were sequenced on a HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. Results: The assay identified 38 of 41 (93%) gene fusions previously detected by a different laboratory using FISH, RT-PCR, or RNA-Seq for a sensitivity of 93%. No false positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA-Seq in a different laboratory (100% specificity).  The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods.  Nineteen of the 22 fusions had not previously been described. Good intra- and inter-assay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion positive cases with fusion negative RNA.  Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. The assay identified 38 of 41 (93%) gene fusions previously detected by a different laboratory using FISH, RT-PCR, or RNA-Seq for a sensitivity of 93%. No false positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA-Seq in a different laboratory (100% specificity).  The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods.  Nineteen of the 22 fusions had not previously been described. Good intra- and inter-assay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion positive cases with fusion negative RNA.  Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. This assay should be useful for identifying cancer patients that may benefit from both FDA-approved and investigational targeted therapies. Overall design: Sequencing data was generated using Hiseq 2500 with a library of 101 paired end reads in the rapid run mode	Co-expression
SRP133808	Homo sapiens Transcriptome or Gene expression	RNA-Seq analysis of intestinal integrity-relevant genes in Caco-2 cell line exposure to aflatoxins M1 and ochratoxin A	Co-expression
SRP133817	Systematic perturbation of retroviral LTRs reveals widespread long-range effects on human gene regulation [RNA-seq]	Recent work suggests extensive adaptation of transposable elements (TEs) for host gene regulation. However, high numbers of integrations typical of TEs, coupled with sequence divergence within families, have made systematic interrogation of the regulatory contributions of TEs challenging. Here, we employ CARGO, our recent method for CRISPR gRNA multiplexing, to facilitate targeting of LTR5HS, a higher primate-specific class of HERVK (HML-2) LTRs that is active during early development and present in ~700 copies throughout the human genome. We combine CARGO with CRISPR activation or interference to, respectively, induce or silence LTR5HS en masse, and demonstrate that this system robustly targets the vast majority of LTR5HS insertions. Remarkably, activation/silencing of LTR5HS is associated with reciprocal up- and down-regulation of hundreds of human genes. These effects require presence of retroviral sequences, but occur over long genomic distances, consistent with a pervasive function of LTR5HS elements as early embryonic enhancers in higher primates. Overall design: Identify transcriptional changes of CARGO-CRISPRa/CRISPRi by RNA-seq CRISPR dCas9 fusions to target transposable elements in the genome; 'VPR' and 'KRAB' refer to the name of the dCas9 fusion protein expressed in the given sample. 'Sp' and 'Sa' refer to the gRNA scaffold species for the CRISPR targeting construct, and 'LTR5HS' and 'nontarget' refer to the class of transposable element (or none at all) that the CRISPR targeting construct aims to target.	Co-expression
SRP133840	NA	No description.	Co-expression
SRP133849	Unique features and clinical importance of acute alloreactive immune responses	By 2 weeks after stem cell transplantation, there was differentiated changes in T cell phenotype between autograft and allograft. RNA-seq was used to reveal the different transcription profiles of these T cells at week 2 after SCT. Overall design: Compare the transcription profile of the T cells in allograft and autograft transplantation patients.	Co-expression
SRP133851	6mer seed toxicity in tumour suppressive microRNAs	6mer seed toxicity in tumour suppressive microRNAs Overall design: Samples of human ovaries were generated by deep sequencing, using Illumina HiSeq4000.  HeyA8 cells treated with Doxorubicin, Carboplatinum, Etoposide. We provide evidence that miR-34a is toxic to cancer cells mostly through its toxic 6mer seed sequence. RNA isolated from HeyA8 cells 48 hrs after transfection with either a nontargeting siRNA (siNT2), miR-34a Seed, pre-miR-NC, or pre-miR-34a was subjected to deep sequencing, using Illumina HiSeq4000.	Co-expression
SRP133853	ZC3H11A RNAseq data	Transcriptome analysis of WT and ZC3H11A-/- HeLa cells after adenovirus infection.	Co-expression
SRP133877	RNA-seq analysis of RALD iPSCs after in vitro differentiation	We investigated roles of KRAS on stemness maintenance and differentiation propensity in the context of induced pluripotent stem cells (iPSCs) using isogenic KRAS mutant (G13C/WT) and wild-type (WT/WT) iPSCs from the same RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD) patients. RNA-seq analysis was conducted to compare gene expression profiles of WT/WT and G13C/WT iPS cells after in vitro differentiation. We found some differences of gene expression profiles regarding stemness and linage markers in the two genotypes. Overall design: To investigate the changes of stemness and linage markers between KRAS mutant and wild-type iPSCs after differentiation, the iPSCs were differentiated for 16 days . Two clones were used for each genotype (WT/WT and G13C/WT) before and after differentiation, resulting in total 8 conditions.	Co-expression
SRP133891	Discovery Korean specific gastric cancer genes and targeted cancer drugs	Gastric cancer is one of the leading cause of cancer related deaths among Koreans. Pathogenetic mechanisms related to carcinogenesis has not been clearly defined, yet. Targeted therapy approach may be the promising approach exploring the pathogenetic mechanism of gastric cancer and candidate search for anti cancer drugs. The goal of this study was to investigate the gene regulation of Korean specific gastric cancer and seeking for the novel regulatory candidate drug.	Co-expression
SRP133949	circRNA profile in hypopharyngeal cancer	3 normal samples and 3 tumor samples were sequenced Overall design: RNA-seq to profile circRNA in normal hypopharynx and hypopharyngeal cancer	Co-expression
SRP134014	SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis [Quant-Seq]	Defining direct targets of transcription factors and regulatory pathways is key to understanding their role in physiology and disease. Here we combine SLAM-seq, a novel method for direct quantification of newly synthesized mRNAs, with pharmacological and rapid chemical-genetic perturbation to interrogate primary transcriptional targets of BRD4 and MYC and define the response to BET bromodomain inhibitors (BETi). While BRD4 acts as a global co-activator of Pol2-dependent transcription in a BET bromodomain-dependent manner, therapeutic BETi doses deregulate a small set of hypersensitive target genes. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator that controls basic metabolic processes such as ribosome biogenesis and de-novo purine synthesis across diverse cancer contexts. Beyond defining primary regulatory functions of BRD4 and MYC in cancer, our study establishes a simple, robust and scalable approach to dissect direct transcriptional targets of any gene or pathway. Overall design: Baseline gene expression profiling of clonal cell lines engineered to express AID-tagged proteins and unedited controls by 3''mRNA sequencing.	Co-expression
SRP134015	Single-cell transcriptome dynamics in stabilized pituitary gonadotrope cells [mini_dropseq]	Studying dynamic transcripts in single cells (SC) requires large numbers of timed samples. We report an easy to use protocol to stabilize RNA in intact SCs without perturbing transcriptional patterns, and demonstrate its applicability for SC transcriptome assays with cells and tissue. We identify a gene-specific hierarchical pattern of all-or-none transcript induction elicited by different concentrations of pulsatile hormone stimuli in pituitary gonadotropes. Overall design: SC Mini Drop-seq experiments were performed on two samples from dissociated human cortical tissue: one is neocortex from a glioblastoma multiforme (GBM, tumor), the other is normal neocortex adjacent to the tumor.	Co-expression
SRP134043	RNA-seq of MLLT3-overexpressing cultued HSPC, compared to non-overexpressing and uncutured FL-HSPC [RNAseq_MLLT3_OE]	MLLT3 preserves the FL-HSPC gene expression signature in culture Overall design: FL-HSPC were infected with Control or MLLT3-OE lentivirus and cultured for 4 weeks on OP9M2. sorted HSPC were profiled before (n=3) or after (n=6) culture	Co-expression
SRP134044	Multi-omic measurements of heterogeneity in HeLa cells across laboratories	Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells. Overall design: Multi-omic (genome, transcriptome, proteome, protein turnover) analysis of 14 HeLa cell lines obtained from different laboratories but grown under the same conditions.	Co-expression
SRP134089	PARN and TOE1 constitute a 3' end maturation module for nuclear non-coding RNAs	Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). scaRNAs are strongly downregulated when PARN and TOE1 are compromised together, leading to defects in small nuclear RNA (snRNA) pseudouridylation. They also function redundantly in the biogenesis of telomerase RNA component (TERC), which shares sequence motifs found in H/ACA box scaRNAs. Our findings extend the knowledge of nuclear ncRNA biogenesis, and they provide insights into the pathology of PARN/TOE1-associated genetic disorders whose therapeutic treatments are currently unavailable. Overall design: RNA-seq of short non-coding RNAs in siRNA-transfected HeLa cells	Co-expression
SRP134092	Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines	Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines. Hek293T cells treated with DFMO or Spermidine. Overall design: DFMO vs. Spermidine treatment	Co-expression
SRP134098	mRNA sequence  Analysis of Apocynin treated MKN45	Noxo1, a component of NADPH oxidase 1 (NOX1) complex, is upregulated in gastric cancer cells in a inflammation-dependent manner, and plays an important role in tumorigenesis (Oncogene, 33: 3820, 2014). To examine the mechanism of NOX1/ROS signaling in tumorigenesis, MKN45 gastric cancer cells were treated with apocynin, an inhibitor for NOX, and their gene expression was examined by RNA sequencing. Based on expression data, Sox2 was shown to be suppressed by apocynin, suggesting a role of Sox2 in a inflammation-associated gastric tumorigenesis. Overall design: Total mRNA expression profiles of Apocynin administrated MKN45 in 2 trials.	Co-expression
SRP134127	Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [scRNA-seq]	Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction.  Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: Single-cell RNA sequencing (SMARTSeq2) of 373 human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected	Co-expression
SRP134128	Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [bulk RNA-seq]	Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction.  Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: RNA-seq of mini-bulks (5000 cells) of human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected	Co-expression
SRP134188	APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa	RNA-sequencing of RDEB SCC tumors and RDEB normal skin Overall design: RNA was isolated from fresh frozen samples and used for RNA-sequencing	Co-expression
SRP134191	Neural progenitors derived from Tuberous Sclerosis Complex patients exhibit attenuated PI3K/AKT signaling and delayed neuronal differentiation	Tuberous Sclerosis Complex (TSC) is a disease caused by autosomal dominant mutations in the TSC1 or TSC2 genes, and is characterized by tumor susceptibility, brain lesions, seizures and behavioral impairments. The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin (mTOR) in complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. TSC1/2 loss of heterozygosity (LOH) and the subsequent complete loss of TSC regulatory activity in null cells causes mTORC1 dysregulation and TSC-associated brain lesions or other tissue tumors. However, it is not clear whether TSC1/2 heterozygous brain cells are abnormal and contribute to TSC neuropathology. To investigate this issue, we generated induced pluripotent stem cells (iPSCs) from TSC patients and unaffected controls, and utilized these to obtain neural progenitor cells (NPCs) and differentiated neurons in vitro. These patient-derived TSC2 heterozygous NPCs were delayed in their ability to differentiate into neurons. Patient-derived progenitor cells also exhibited a modest activation of mTORC1 signaling downstream of TSC, and a marked attenuation of upstream PI3K/AKT signaling. We further show that pharmacologic AKT inhibition, but not mTORC1 inhibition, causes a neuronal differentiation delay, mimicking the patient phenotype. Together these data suggest that heterozygous TSC2 mutations disrupt neuronal development, potentially contributing to the disease neuropathology, and that this defect may result from dysregulated AKT signaling in neural progenitor cells. Overall design: Two replicates each of TSC#1 and CON#1 NPC cell RNA were prepared for sequencing library preparation and seqeuencing.	Co-expression
SRP134192	Transcriptomic responses to hypoxia in endometrial stromal fibroblasts and decidual stromal cells	We sequenced mRNA from hypoxia treated endometrial stromal fibroblasts and decidual stromal cells in order to better understand endometrial hypoxia responses Overall design: We sequenced mRNA from hypoxia treated (1% O2 , 24 hours) endometrial stromal fibroblasts (2 biological replicates) and decidual stromal cells (2 biological replicates) and compared these to the corresponding normoxic samples that were made available earlier (GSM1556296, GSM1556297, GSM1556298, GSM1556299)	Co-expression
SRP134235	Poly(A)+ RNA-seq from H226 cells expressing doxycycline-inducible Control (non-targeting) and p63-targeting shRNAs	To determine the impact of ?Np63a knockdown on steady-state mRNA levels, we performed poly(A)-enriched RNA-seq analysis of lung squamous cell carcinoma line H226 (inducible shControl and shp63) in the presence of 1µg/mL doxycycline to induce shRNA expression. Overall design: Poly(A)+ RNA for two independent biological replicates was purified  from H226 cells (inducible shControl and shp63) incubated treated for six days with 1 µg/mL doxycycline. a TruSeq Stranded mRNA Library Prep Kit (Illumina). Libraries were sequenced on an Illumina HiSeq 2000 system at the University of Colorado Cancer Center Genomics and Microarray Core facility. Reads were aligned (TopHat2) to the Human reference genome (GRCh37/hg19) and gene-level counts (HTseq-count) were used for differential expression analysis (DESeq2).	Co-expression
SRP134274	Gene expression profiling in human nasal epithelial cells (HNEpCs) stimulated with eosinophil-derived neurotoxin (EDN)	The goal of this study is to evaluate the function of eosinophil-derived neurotoxin (EDN) in eosinophilic chronic rhinosinusitis (ECRS) pathogenesis and assess its potential as a disease activity marker. Overall design: To determine the pathological role of eosinophil-derived neurotoxin (EDN) in eosinophilic chronic rhinosinusitis (ECRS), we performed RNA sequencing to analyze gene expression in human nasal epithelial cells (HNEpCs) stimulated with EDN.	Co-expression
SRP134387	Transcriptome analysis of U87 cells upon LINC00152 knockdown	To understand the global changes in genes expression after knockdown of LINC00152, we compared transcriptomes of control cells (treated with siGL2) and LINC00152 knockdown cells (treated with si00152). Overall design: U87 cells were transfected during two rounds of transfection. First, cells were reverse transfected with a combination of two LINC00152 siRNAs or a nonspecific siGL2 control siRNA using Lipofectamine RNAiMAX transfection reagent. 24 hours later, a second round of transfection was performed using the same reagents. 24 hours after the final transfection, cells were harvested and used for library preparation.	Co-expression
SRP134388	Inhibition of microRNA-138 enhances bone formation in multiple myeloma bone marrow niche	Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically delivered locked nucleic acid (LNA)-modified anti-miR-138 oligonucleotides in suppressing myeloma bone disease. We showed that expression of miR-138 was significantly increased in MSCs from MM patients (MM-MSCs) and myeloma cells compared to those from healthy subjects. Furthermore, inhibition of miR-138 resulted in enhanced osteogenic differentiation of MM-MSCs in vitro and increased number of endosteal osteoblastic lineage cells (OBCs) and bone formation rate in mouse models of myeloma bone disease. RNA sequencing of the OBCs identified TRPS1 and SULF2 as potential miR-138 targets that were de-repressed in anti-miR-138 treated mice. In summary, these data indicate that inhibition of miR-138 enhances bone formation in MM and that pharmacological inhibition of miR-138 could represent a new therapeutic strategy for treatment of myeloma bone disease. Overall design: RNA sequencing of endosteal osteoblastic lineage cells (OBCs) from 4 C57BL/KaLwRij (KaLwRij) mice treated with anti-miR-138 LNA-modified antisense oligonucleotide and 4 KaLwRij mice treated with scramble control and RNA sequencing of primary human BM–derived MSCs obtained from normal healthy donors (ND-MSCs) co-cultured with myeloma cells (OPM2) and treated with anti-miR-138 LNA-modified antisense oligonucleotide (N=3) or scramble control (N=3)	Co-expression
SRP134389	A consensus hypoxia signature in breast cancer	We exposed a panel of 32 breast cancer cell lines or normal human mammary epithelial cells to 20% or 1% O2 concentration for 24h. Total RNA was extracted from cells using TRIzol (Invitrogen) and treated with DNase I (Ambion). All samples had a RIN value of >9.0 when measured on an Agilent Bioanalyzer. Libraries for RNA-Seq were prepared with KAPA Stranded RNA-Seq Kit. The workflow consisted of mRNA enrichment, cDNA generation, end repair to generate blunt ends, A-tailing, adaptor ligation and 12 cycles of PCR amplification. Unique adaptors were used for each sample in order to multiplex samples into several lanes. Sequencing was performed on Illumina Hiseq 3000/4000 with a 150bp pair-end run. A data quality check was done on Illumina SAV. Demultiplexing was performed with Illumina Bcl2fastq2 v 2.17 program. Overall design: 32 breast cancer cell lines exposedto standard tissue culture conditions normoxic (20% O2) or hypoxic (1% O2) conditions.	Co-expression
SRP134687	The LINC01138 Drives Malignancies via Activating Arginine Methyltransferase 5 in Hepatocellular Carcinoma	Our study have demonstrated LINC01138 acts as an oncogenic driver that promotes cell proliferation, tumourigenicity, tumour invasion and metastasis through physically interacting with Arginine Methyltransferase 5 (PRMT5) in HCC cells. In order to investigate the related signaling pathways regulated by LINC01138 or PRMT5, we performed the unbiased transcriptome profiling using high-throughput RNA sequencing in SMMC-7721 cells transfected with si-LINC01138 or si-PRMT5. Here we showed the LINC01138/PRMT5 axis is an ideal therapeutic target for HCC treatment. Overall design: Illuminate the related signaling pathways and biological processes regulated by LINC01138 or PRMT5 in human liver cancer SMMC-7721 cells through high-throughput sequencing data.	Co-expression
SRP134731	R430: A potent inbibitor of DNA and RNA viruses	PURPOSE: Acyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. However, HSV-1 resistance to ACV and its derivatives is being increasingly documented, particularly among immunocompromised individuals.  The burgeoning drug resistance compels the search for a new generation of more efficacious anti-herpetic drugs. We have previously shown that 3-epi-trans-dihydrolycoricidine (R430), a lycorane-type alkaloid derivative, effectively inhibits HSV-1 infections in cultured cells. METHODS: We employed human induced pluripotent stem cells-derived neurons (hiPSC-neurons) and neural progenitor cells (hiPSC-NPCs) to investigate the antiviral activity of R430 on HSV-1 and Zika (Strain XX), respectively. hiPSC line 73-56010-02 employed in this study established at the National Institute of Mental Health (NIMH) Center for Collaborative Studies of Mental Disorders-funded Rutgers University Cell and DNA Repository (http://www.rucdr.org/mental-health) (RUCDR). hiPSC- neurons and hiPSC-NPCs were generated as previously described (D’Aiuto et al. Organogenesis. 2014;10(4):365-77).  hiPSC based assays for HSV-1 infection.  We used a genetically engineered HSV-1 KOS strain that expresses enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) under the control of immediate early and late gene promoters, respectively (33).  To determine the optimal conditions for evaluating drug effects, hiPSC-neurons cells were infected for 2 hours (multiplicity of infection, MOI=0.3), after which the inocula were replaced with media containing R430 (10 µM) or vehicle (DMSO).  Separately, cells were incubated in media containing R430 (10 µM) or vehicle in the absence of HSV-1. All assays were conducted in triplicate.  Cells were harvested after 6 hours post infection (hpi), 12 hpi, or 24 hpi, DNA was extracted using (QIAamp DNA Mini Kit, (Qiagen) and DNA conentrations were estimated. Subsequently, the EGFP locus was amplified to estimate viral copy number using custom primers (34).  A significant increase in viral copy number was noted in vehicle treated cells after 12h and 24h, but not after 6h. Substantial reduction in viral copy number was found following incubation with R430 at 12h or 24h.  The 12h incubation period was therefore selected for subsequent studies examining gene expression (see below). Overall design: We employed human induced pluripotent stem cells-derived neurons (hiPSC-neurons) to investigate the antiviral activity of R430 on HSV-1. hiPSC line 73-56010-02 employed in this study established at the National Institute of Mental Health (NIMH) Center for Collaborative Studies of Mental Disorders-funded Rutgers University Cell and DNA Repository (http://www.rucdr.org/mental-health) (RUCDR). hiPSC- neurons and hiPSC-NPCs were generated as previously described (D'Aiuto et al. Organogenesis. 2014;10(4):365-77).	Co-expression
SRP134738	Next Generation Sequencing Facilitates Quantitative Analysis of a circRNA, hsa_circ_0005505 regulated Transcriptomes in breast cancer cells (MDA-MB-231 lung metastatic cells LM2)	Purpose: hsa_circ_0005505 stably knockdown cells (circ-sh1 and circ-sh2) and its corresponing control cells (con-sh) were constructed using its specific shRNAs. Next-generation sequencing (NGS) has used to examine hsa_circ_0005505 regulated transcripts. Methods:  mRNA profiles of circsh1, circsh2 and con-sh were generated by deep sequencing using IlluminaI HiSeq 4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays Results: We found 816 and 909 transcripts downregulated in circ-sh1 and circ-sh2 cells compared with con-sh cells, respectively. But 712 and 723 transcripts upregulated in circ-sh1 and circ-sh2 cells compared with con-sh cells, respectively. The differential expression with a fold change =1.5 and p value <0.05. Conclusions: Our study represents the first detailed analysis of hsa_circ_0005505-regulated transcripts in breast cancer cells. Overall design: Next Generation Sequencing Facilitates Quantitative Analysis of a circRNA, hsa_circ_0005505 regulated Transcriptomes in breast cancer cells	Co-expression
SRP134757	Interaction between TANs and HCC cells	identifies an inflammation-associated cellular, molecular, and clinical network that controls the positive feedback loop between HCC stem-like cells and TANs,T cell immunity, tumor progression, and patient outcome. These findings support their potential for exploration as therapeutic targets for HCC.	Co-expression
SRP134954	WNT signaling memory is required for ACTIVIN to function as a morphogen	It has now become clear that the process of fate specification during early embryogenesis is mediated by a handful of key signaling pathways. However, how the temporal and spatial integration of these signals plays out to give rise to self-organization of tissues remains obscure. Here we use artificial human gastruloids and quantitative single-cell analysis to dissect the temporal integration of two key pathways WNT and ACTIVIN that along with BMP control gastrulation and primitive streak patterning in model systems. We showed that ACTIVIN elicits a transient signaling response, as well as a transient induction of differentiation. However, unlike BMP and WNT, ACTIVIN cannot induce stable primitive streak formation and mesodermal patterning. Pre-exposure to WNT switches the response of cells to ACTIVIN whereby it becomes a concentration dependent morphogen. This provides evidence for WNT signaling memory that occurs at the transcriptional level and not as a modifier of ACTIVIN signaling dynamics. Overall design: Time series RNAseq analysis of the effect of the addition of activin to a hESC culture. The study consists of 3 control samples (0, 6, 12h) and 5 activin-treated samples (collected at 1, 2.5, 4, 8, 12h). There are no replicates per timepoint/condition.	Co-expression
SRP135144	RNA-seq analysis of colorectal cancer cell line (CRC) SW1116 overexpressed POLR1D	Gene expression profiles were generated for CRC cell line SW1116 overexpressed POLR1D and empty vector to explore the effect of POLR1D on colorectal cancer cell line SW1116. Overall design: SW1116 cells were infected with lentivirus overexpressing POLR1D and negative control lentivirus. After 72h, the GFP-positive cells were isolated by FACS. POLR1D overexpression was confirmed by RT-PCR and Western blotting. Then, the total RNA of POLR1D overexpression cells and negative control cells was extracted by Trizol reagent and sequenced using Illumina HiSeqTM4000 according to the manufacturer's instructions.	Co-expression
SRP135295	Impact of shRNA-mediated KLF4 down-modulation on the transcriptome profile of human keratinocyte precursor cells	Characterization at the global transcriptome level of the gene networks ensuring the regulation of the immature status of cutaneous stem- and precursor-cells is a necessary step to further understand the concept of 'stemness' in this tissue. Moreover, considering possible clinical applications, the search for molecular targets to control stem cell characteristics and regenerative capacity is a necessary step to improve therapeutic approaches. Cutaneous cell therapy is concerned by this objective, as skin graft bioengineering requires a phase of ex vivo expansion of keratinocytes from donors, during which the preservation of a sufficient stem cell pool is critical for graft take and long-term skin regeneration. We have investigated the role of transcription factor KLF4 in native keratinocyte precursors from adult human skin. A stable lentiviral-based shRNA-mediated KLF4 knock-down (KD) approach was developed and used to study the properties of KLF4-deficient [KLF4KD] versus control [KLF4WT] native keratinocyte precursors. Using long-term cultures and clonal assays, we found that decreased KLF4 expression increased keratinocyte precursor immaturity and clonogenic potential, thus promoting self-renewal. Importantly, [KLF4KD] keratinocyte precursors exhibited an improved grafting capacity in an in vivo skin xenograft model and in serial grafting.  To analyze the biological impact of KLF4 knock-down at the molecular level, comparative transcriptome profiling of [KLF4WT] and [KLF4KD] cells was performed using next-generation RNA sequencing (RNA-seq). This set of data provides a material that permits the dissection of genetic networks modulated by KLF4 in human keratinocyte precursor cells, and controlling their immature status and epidermis regeneration capacity. Overall design: The study is based on the comparative RNA-seq analysis of human keratinocyte precursor cells corresponding to 3 cellular contexts: 1) non-transduced wild-type (WT) cells, [KLF4WT]; 2) cells transduced with a control lentiviral vector driving the expression of the reporter gene GFP, [KLF4WT]; 3) cells transduced with a lentiviral vector driving the expression of GFP and an anti-KLF4 shRNA, [KLF4KD]. For each cellular context 3 biological replicates were conducted (Bio rep), each including 3 technical replicates (Tech rep).	Co-expression
SRP135489	RNA-seq of circulating human eosinophils before and after oral prednisone administration	Glucocorticoids are first-line agents for the treatment of many eosinophil-associated disorders. However, their mechanism of action in this group of disorders remains poorly understood, including the well-known clinical observation that glucocorticoids at therapeutic doses lead to profound, transient eosinopenia within hours of administration. To gain an unbiased, genome-wide view of the early transcriptional effects of glucocorticoids on human eosinophils in vivo, and torelate them to the kinetics of glucocorticoid-induced eosinopenia, RNA sequencing was performed on purified blood eosinophils obtained before and 30, 60, and 120 minutes after administration of a single dose of oral prednisone (1 mg/kg) to healthy subjects with hypereosinophilia (hypereosinophilia of unknown significance). Overall design: Three subjects with hypereosinophilia of unknown significance were each given a single dose of oral prednisone, 1 mg/kg. Whole blood was collected before and 30 minutes, 1 hour, and 2 hours after prednisone administration. Eosinophils were purified from each peripheral blood sample. Total RNA was obtained from purified eosinophils and subject to library preparation and high-throughput sequencing.	Co-expression
SRP135523	Transcriptome of NK/T-cell lymphoma	No description.	Co-expression
SRP135671	Reactivation of Human Herpesvirus 6 (HHV-6) in Diverticulitis	Background: Diverticular disease is a significant healthcare burden in the United States. Younger diverticulitis patients are at increased risk for recurrence. How the molecular pathophysiology differs from those that develop disease at an older age is not understood. We aimed to profile the colonic transcriptome from younger versus older diverticulitis patients to identify differential biological pathways contributing to disease. Methods: We performed RNA-seq on full-thickness sigmoid colon tissue obtained at the time of surgery on diverticulitis patients (n=26) diagnosed at a younger age (<42 years old) or at an older age (>65 years old). Viral reads were identified from the RNA-seq dataset and associated with clinical metadata and the host transcriptome. HHV-6 positivity was evaluated in diverticulitis patients by PCR and immunofluorescence. Patient sera was profiled for HHV-6 using qPCR and ELISA to detect anti-HHV-6 antibodies. Results: Using RNA-seq, diverticulitis patients were profiled for differential expression associated with age of diagnosis. A subset of younger diverticulitis patients (diverticulitis colonic transcriptome-viral signature (DCT-VS)) demonstrated increased expression of anti-viral response genes. We identified viral transcripts in the RNA-seq dataset and found HHV-6 transcripts negatively correlated with DCT-VS. Younger patients more frequently displayed evidence of HHV-6 infection through DNA analysis and immunofluorescence of colonic tissue. During acute disease, HHV-6 DNA was detected in the serum but was absent during disease quiescence. Conclusions: Patients diagnosed with diverticulitis at a younger age demonstrate reactivation of HHV-6 in the sigmoid colon that remains persistent. Future studies to assess the role of pathogenicity and the use of anti-virals for acute uncomplicated diverticulitis should be considered. Overall design: Examination of full-thickness sigmoid colon tissue from 26 diverticulitis patients, including 13 diagnosed at an younger age (<42 years old) and 13 diagnosed at an older age (>65 years old)	Co-expression
SRP135684	The transcriptomic profile of stem-cell derived neurons in 3D culture conditions and stem-cell derived astrocytic cells	Understanding neurological diseases requires tractable genetic systems. Three-dimensional (3D) neural tissue systems are an attractive choice, but it is not well understood how the transcriptome profile of these tissues is affected by encapsulating materials. Here we characterize the effect of different culturing conditions on the transcriptomic profile of induced neuronal cells and develop a method for  rapid generation of 3D co-cultures of neuronal and astrocytic cells from hESCs. We perform transcriptome analysis of cells resulting from astrocytic cell differentiation. Using single-cell sequencing, we find that our system recapitulates transcriptional patterns of cell types in the human brain. Overall design: Refer to individual samples.	Co-expression
SRP135686	NCOA5 knockout suppresses epithelial-to-mesenchymal transition (EMT) impairing cell proliferation and migration in Hepatocellular Carcinoma cells	Nuclear receptor coactivator 5 (NCOA5) is an AF2-independent coactivator that contains both transcriptional activation and repression domains. Previous studies have shown that NCOA5 plays an important role in the development of a variety of malignancies. However, the underlying mechanisms remain unclear. In our study, we successfully generated the NCOA5 knockout liver cancer cell lines by CRISPR/Cas9 -mediated genome editing and found that NCOA5 knockout inhibited the proliferation and migration of hepatocellular carcinoma (HCC) cells significantly, meanwhile led to a marked decrease in tumor microsphere formation. Furthermore, mechanistic analyses indicated that NCOA5 knockout can inhibit the EMT process. In this study, knocking out NCOA5 in hepatoma cells LM3 with CRISPR/Cas9 provides an important cellular model for studying role of NCOA5 in HCC. In conclusion , Oour study provides new insights and evidence that NOCA5 was significantly correlated with the progression of HCC and was particularly involved in EMT. Overall design: Hepatocellular Carcinoma cells  mRNA profiles of wide type(WT) and NCOA5 knockout LM3 cells were generated by deep sequencing, using Illumina HiSeq.	Co-expression
SRP135702	RNA-Seq of Circulating Tumor Cells in Stage II-III Breast Cancer	BACKGROUND: We characterized the whole transcriptome of circulating tumor cells (CTCs) in Stage II-III breast cancer to evaluate correlations with primary tumor biology. METHODS: CTCs were isolated from peripheral blood (PB) via immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE-FACS). CTCs, PB and fresh tumors were profiled with RNA Seq. Formalin-fixed, paraffin-embedded (FFPE) tumors were subjected to RNA Seq and NanoString PAM50 assays with Risk of Recurrence (ROR) scores. RESULTS: CTCs were detected in 29/33 (88%) of patients. We selected 21 cases to attempt RNA Seq (median number of CTCs=9). 16 CTC samples yielded results that passed quality control metrics. These samples had a median of 4,311,255 uniquely mapped reads, less than PB or tumors. Intrinsic subtype predicted by comparing estrogen receptor (ER), progesterone receptor (PR) and HER2 versus PAM50 for FFPE tumors was 85% concordant. However, CTC RNA Seq subtype assessed by the PAM50 classification genes was highly discordant both with the subtype predicted by ER/PR/HER2 as well as by tumor PAM50. Two patients died of metastatic disease - both had high ROR scores and high CTC counts. We identified significant genes, canonical pathways, upstream regulators and molecular interaction networks comparing CTCs by various clinical factors. We identified a 75-gene signature with highest expression in CTCs and tumors taken together that was prognostic in The Cancer Genome Atlas and METABRIC datasets. CONCLUSION: It is feasible to use RNA Seq of CTCs in non-metastatic patients to discover novel tumor biology characteristics. Overall design: 6 peripheral blood samples from healthy individuals (negative controls) were compared to circulating tumor cells from n=16 patients, with comparison to the primary tumors available for n=12 of these patients	Co-expression
SRP135716	RNA-seq analysis of normal and NMD-inhibited human erythroblasts	This experiment was designed to study a component of the erythroblast alternative splicing program that is normally masked by nonsense-mediated decay (NMD). CD34+ cells from cord blood were cultured under conditions that promote erythroblast proliferation and differentiation. RNA was isolated from proerthryoblasts / immature erythroblasts at day 9 of culture, and mature erythroblasts at day 16 of culture, and the transcriptomes of normal cells were compared with those in which NMD was inhibited by treatment with cycloheximide plus emetine. Many novel splice junctions identified in NMD-inhibited cells were located in retained introns. Experimental studies support the model that cryptic intron-internal splice sites can promote intron retention by serving as decoys that engage normal splice sites at the ends of the introns and prevent splicing at these sites.	Co-expression
SRP135729	RNA-seq of STON2 knockdown  3AO  cells	3AO cells transfected with shSton2 lentivirus or control shRNA were cultured in a serum free medium for 7 days,Total RNA from cells was prepared for RNA-seq.Three independent samples in each group	Co-expression
SRP135771	The m 6 A-methylase complex recruits TREX and regulates mRNA export.	N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Here we show that the m6A complex (WTAP, KIAA1429, METTL3/14) drives recruitment of the TREX mRNA export complex onto m6A modified mRNAs and this process is essential for the efficient export of certain mRNAs. Depletion of the core m6A complex leads to loss of TREX from mRNAs which undergo the m6A modification. We show that TREX stimulates recruitment of the m6A reader protein YTHDC1 to the mRNP and the m6A complex influences the interaction of TREX with YTHDC1. We suggest that m6A acts as a surrogate for other TREX recruitment mechanisms such as splicing and 5' capping, in long internal and final exons which may otherwise be devoid of this essential complex for mRNA export. Overall design: mRNA profiles of control and Virilizer/WTAP RNAi samples in cytoplasmic and nuclear cell fractions generated by mRNA-seq in triplicate using HiSeq 2500	Co-expression
SRP135773	Transcriptome analysis of total RNA in the Raji B cell line	RNA-seq was performed for total RNA in the Raji B cell line Overall design: Four biological replicates of total RNA in the Raji B cells were subjected to RNA-seq	Co-expression
SRP135775	Transcriptome analysis of total RNA in human osteosarcoma cell line U2OS before and after inhibition of zinc finger protein ZNF768	Inhibition of ZNF768 function was achieved by conditional over expression expression of the C-terminal zinc finger of ZNF768 for 12h. For preparation of total RNA cells were resuspended in TRIzol reagent (Life Technologies) at 0.9Mio/ml and snap-frozen.  After thawing RNA was extracted from 0.4ml of TriZol lysate using the direct-zol RNA Miniprep (Zymo Research, Irvine CA, USA) as described in the manufacturer's protocol. RNA was assessed for purity by UV-vis spectrometry (Nanodrop) and for integrity by Bioanalyzer (Agilent Bioanalyzer 2100, Agilent, Santa Clara USA)). RNA was of high purity (abs. 260/280 >1.9, abs 269/239>2.1) and integrity (Bioanalyzer RIN>9 ) and thus used for further processing. For production of RNA-seq libraries total RNA was DNAse treated (dsDNAse, Fermentas) and 100 ng of this RNA was processed with a strand-specific protocol (RNA-seq complete kit, NuGEN, San Carlos, USA). In brief the RNA was reverse transcribed to cDNA with a reduced set of hexamer primers, avoiding excessive representation of rRNA in the cDNA. Second strand cDNA synthesis was done in presence of dUTP. After ultrasonic fragmentation of the cDNA and end repair, Illumina-compatible adapter were ligated. Adapters contained uracil in one strand, allowing complete digestion of the second-strand derived DNA. After strand selection the libraries were amplified, assessed for correct insert size on the Agilent Bioanalyser and diluted to 10nM. Barcoded libraries were mixed in equimolar amounts and sequenced on an Illumina HiSeq1500 in single-read mode with a read length of 100 b. Overall design: ZNF768-deltaN	Co-expression
SRP135794	Screening in Human Cardiac Organoids Identifies a Requirement for the Mevalonate Pathway in Cardiomyocyte Proliferation	Purpose: Induction of endogenous proliferation is a promising strategy for cardiac regeneration. We find that GSK3 inhibition activates a cell cycle network whereas MST1 inhibition drives the mevalonate pathway, with synergistic activation of proliferation. However, all GSK3 inhibitors tested also reduce contractile force in hCO. We screened for small molecule activators of cardiomyocyte proliferation that did not alter contractile force in hCOs. This was overcome by screening of a boutique compound library, identifying a p38 inhibitor, which activated a cell cycle network without reducing force. The screen also identified a TGFBR inhibitor that induces the mevalonate pathway and can also synergise to activate proliferation.  RNA sequencing was performed to investigate underlying mechanisms of action. Methods: RNA samples were processed with Illumina TruSeq Stranded mRNA Library prep kit selecting for poly(A) taled RNA following the manufacturer's recommendations. Libraries were quantified with Qubit HS (ThermoFisher) and Fragment Analyzer (Advances Analytical Technologies) adjusted to the appropriate concentration for sequencing. Indexed libraries were pooled and sequenced at a final concentration of 1.8 pM on an Illumina NextSeq 500 high-output run using paired-end chemistry with 75 bp read length. The sequencing data was demultiplexed using Illumina bcl2fastq2-v2.17. The quality of the reads was assessed thanks to FastQC. The reads were then processed and mapped to the human genome hg38 using the Bcbio-nextgen framework version 1.0.3. The aligner used was HISAT2 2.0.5.  Raw counts were normalised and analysed with DESeq2. Results: Analysis of RNAseq data lead to the understanding that compound 3 regulated the cell cycle network, which was similar to GSK3 inhibitors, whereas compound 65 regulated the mevalonate network, which was similarly to MST1 inhibitors. Conclusions: The current study adds to a growing body of evidence that alterations in cardiomyocyte metabolism may be a cause rather than a consequence of cardiomyocyte cell cycle arrest. Controlling cellular metabolism is emerging as a key strategy in the fight against cancer but the same pathways may conversely be required for the development of cardiac regenerative therapies. Overall design: mRNA profiles of hCO samples (control and treated with three compounds selected from screen) were generated on an Illumina NextSeq 500 high-output run.	Co-expression
SRP135797	Single-cell transcriptomic analysis of tissue resident memory T cells in human lung cancer [ 10x genomics]	High numbers of tissue-resident memory T (TRM) cells have been associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, using single-cell and bulk transcriptomic analysis of purified populations of TRM   and non-TRM cells we characterise these populations Overall design: Population and single cell profiling of subtypes of CD8 cells isolated from human lung and lung tumour samples with flow cytometry	Co-expression
SRP135807	Patient iPSC-derived neural stem cells display progressive enlargement of lysosomes and disruptions of glycosaminoglycan pathway and autophagy in concordance with clinical severity of Mucopolysaccharidosis I	Mucopolysaccharidosis type I (MPS I) is caused by genetic defects in alpha-L-iduronidase (IDUA), a lysosomal enzyme involved in the breakdown and recycling of glycosaminoglycans (GAGs). Although an enzyme replacement therapy is available, the efficacy for the treatment of neuropathic symptoms is limited. To facilitate drug discovery and model disease pathophysiology, we have generated neural stem cells (NSCs) from MPS I patient-derived iPSCs. NSCs exhibited characteristic disease phenotypes with deficiency of alpha-L-iduronidase (IDUA), accumulation of glycosaminoglycans (GAGs) and enlargement of lysosomes, correlating with the severity of clinical symptoms. Transcriptome profiling of NSCs revealed differential expression of 429 genes that changed more extensively in the more severe Hurler syndrome subgroup compared to the Hurler-Scheie (median severe) and Scheie (less severe) subgroups. Clustering and pathway analyses demonstrated high concordance of the severity of neurological defects with marked dysregulation of GAG biosynthesis and degradation, lysosomal function and extracellular matrix. Gene Ontology (GO) analysis identified a dramatic upregulation of autophagy pathway, especially in the Hurler syndrome. Thus, GAG accumulation in the patient cells disrupts lysosomal homeostasis affecting multiple related cellular pathways which compensates for IDUA deficiency. These dysregulated process likely lead to enhanced autophagy and more severe disease states. Our studies provide useful tools for clinical biomarker development and potential targets for drug development. Overall design: Patient iPSC-derived and control neural stem cells from Scheie, Hurler-Scheie, and Hurler disease were expression profiled in triplicate using RNA-seq.	Co-expression
SRP135811	Pluripotent stem cell model of Nakajo-Nishimura syndrome untangles proinflammatory pathways mediated by oxidative stress	Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. Although dysfunction of the immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokines in NNS, the underlying mechanisms of the autoinflammation are still largely unknown. To investigate and understand the mechanisms and signal pathways in NNS, we established a panel of isogenic pluripotent stem cell (PSC) lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MT-MLs) was reduced even without stimulation compared to non-mutant-MLs. Additionally, MT-MLs showed an overproduction of inflammatory cytokines and chemokines, with elevated reactive oxygen species (ROS) and phosphorylated p38 MAPK levels. Treatment with p38 MAPK inhibitor and anti-oxidants decreased the abnormal production of cytokines and chemokines. The current PSC model revealed a specific ROS-mediated inflammatory pathway, providing a platform for the discovery of alternative therapeutic options for NNS and related immunoproteasome disorders. Overall design: RNA-sequencing was conducted to identify the genes expressed in reponse to stimulation in different manners between WT and MT cells	Co-expression
SRP135821	RUNX1 mutations lead to a myeloid differentiation block by altering the RUNX1 transcriptional program (RNA-Seq)	Mutations in the RUNX1 gene (RUNX1mut) have been established in myelodysplasia (MDS), de novo and secondary acute myeloid leukaemia (AML), and are in general associated with an unfavourable clinical outcome. Familial RUNX1 mutations are associated with familial thrombocytopenia and these patients have a predisposition to AML development. However, a number of studies have been performed so far in mice which might be distinct from the human hematopoietic system. Therefore we studied the cellular phenotypes, the RUNX1 binding pattern and expression profile induced by RUNX1mut in cord blood (CB) CD34+ cells and induced pluripotent stem cell (iPSC) and compared these findings to primary RUNX1mut AML's. Overall design: A total of nine samples were subject to RNA-Seq including RUNX1mut-transduced cord blood CD34 cells and time-course iPSCs.	Co-expression
SRP135822	An Activating Mutation of the NSD2 Histone Methyltransferase Drives Oncogenic Reprogramming in Acute Lymphocytic Leukemia?	The E1099K mutation of NSD2 leads to increased dimethylation of H3K36, activating oncogenic gene expression programs. NSD2-mutant cells acquire several malignant phenotypes and demonstrate increased invasion into mouse brain parenchyma. Identification of aberrantly expressed genes and pathways provides avenues for therapeutic intervention in NSD2-dysregulated malignancy.	Co-expression
SRP135850	Transcriptomic characterization of FTD-resistant colorectal cancer cell lines	Examination of mRNA expression levels of parental cell line and FTD resistant cell line.	Co-expression
SRP135856	Effect of chorioamnionitis exposure on neonatal monocyte transcription	We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions. Overall design: RNA-seq on 11 samples with 2-3 replicates per exposure/stimulation group (each replicate contains 3 pooled samples)	Co-expression
SRP135891	Arginine methylation controls cell proliferation by integrating E2F activity with the splicing machinery (RNA-seq data set)	Residue-specific arginine methylation (meR) on the E2F1 subunit plays an essential role in determining whether cell cycle progression or apoptosis ensues, although the molecular pathways underpinning the effects of methylation remain obscure.  We report here that the methylation events on E2F1 have a direct impact on the mechanisms which underpin gene expression control. Specifically, the PRMT5-mediated symR mark not only influences the transcription repertoire of genes targeted by E2F1, but also endows E2F1 with the ability to regulate RNA splicing. This occurs through tudor domain protein p100/TSN which reads the symR mark on E2F1, and thereby enables a distinct set of RNA to be alternatively spliced. The p100/TSN-E2F1 complex binds alternatively spliced RNAs, with many RNAs derived from E2F target genes connected with proliferation and cancer. Overall design: The U2OS Tet-ON inducle, stable cell line system was used to generate cell lines expressing WT E2F1, or meR deficient derivatives R109K and R111/113K (KK).  An empty vector cell line (pTRE) was used as a control, reference sample.  mRNA was enriched from three biological replicates and sequenced by Illumina NextSeq platform.	Co-expression
SRP135900	Transcriptomic analysis of human tonsillar TFH subsets	We used an IL4-capture assay followed by FACS sorting, to isolate IL4-secreting TFH cells from a human tonsil and compared their transcriptomic profiles with CXCR5hi PD1hi IL4-negative tonsillar TFH cells and IL4-producing CXCR5neg non-TFH cells (TH2 cells). Our studies validate the notion of functionally distinct TFH subsets and identify genes that are specifically expressed in and define the human IL-4 secreting TFH cell  subset. Overall design: T follicular helper cell subset mRNA profiles from human tonsils were generated by deep sequencing. Naive CD4 T cells, IL4-producing nonTFH CD4 T cells (i.e. TH2), and IL4-producing TFH cells and PD1hi TFH cells were analyzed. DOI: 10.26508/lsa.201800050	Co-expression
SRP135927	Efficient generation of human CA3 neurons and modeling hippocampal neuronal connectivity in vitro (single cells)	Despite widespread interest in using human stem cells in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a protocol for efficient differentiation of hippocampal pyramidal neurons and an in vitro model for hippocampal neuronal connectivity. We developed an embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)-based protocol to differentiate human CA3 pyramidal neurons from patterned hippocampal neural progenitor cells (NPCs). This differentiation induces a comprehensive patterning and generates multiple CA3 neuronal subtypes. The differentiated CA3 neurons are functionally active and readily form neuronal connection with dentate granule (DG) neurons in vitro, recapitulating the synaptic connectivity within the hippocampus. When we applied this neuronal co-culture approach to study connectivity in schizophrenia, we found deficits in spontaneous activity in patient iPSC derived DG–CA3 co-culture by multi-electrode array recording. In addition, both multi-electrode array recording and whole cell patch clamp electrophysiology revealed a reduction in spontaneous and evoked neuronal activity in CA3 neurons derived from schizophrenia patients. Altogether these results underscore the relevance of this new model in studying diseases with hippocampal vulnerability. Overall design: 4 technical replicates were used and later pooled together for the bioinformatic analysis.	Co-expression
SRP135951	Microarray analysis of the ClC-3 gene expression profile	search differential gene expression with ClC-3 knockdown	Co-expression
SRP135952	Deregulated LncRNAs Identified by RNA-Seq in Diffuse Gastric Cancer	we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.	Co-expression
SRP135973	Human iPSC-derived glomeruli provide an advanced model to interrogate podocyte biology and accurately recapitulate podocytopathy	Podocytes are highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria and glomerulosclerosis. Studies into podocyte biology and disease have previously relied on conditionally immortalised cell lines due to the non- proliferative nature of this cell type. Here we describe an advanced model to study both podocyte and glomerular biology using isolated glomeruli from kidney organoids derived from human pluripotent stem cells. Overall design: Gene expression profiling of day three 17, 21 and 26 day kidney organoid derived glomeruli respectively with heterzygous genotype for BFP tagged MAFB; gene expression profiling of  three day 25 kidney organoid derived glomeruli; gene expression profiling of three organoid-derived podocytes grown out for 3 days from day 25 kidney organoid derived glomeruli.	Co-expression
SRP135989	Next Generation Sequencing Facilitates Quantitative of Transcriptomes in Various Cells Treated with or without LD100 and siRNA of SOD1	Purpose: mRNA-sequencing has revolutionized systems-based analysis of cellular pathways. The goals of this study are to systemically research the biological functions of SOD1 in ROS signaling pathway using specific SOD1 inhibitor-LD100 and its validated siRNA. Methods: We reported the mRNA-sequencing data of HeLa cells (designated as C), LD100-treated HeLa cells (L), SOD1 knockdown HeLa cells (S), DU145 cells (DC), LD100-treated DU145 cells (DL), RWPE-1 cells (RC) and LD100-treated RWPE-1 cells (RL). All the samples were sequenced in triplicate, using Illumina HiSeq PE150. Remaining paired-end clean reads were aligned to the reference genome (GRCh38) using HISAT aligner. After calculating the reads numbers mapped to each gene by HTSeq, we estimated gene expression levels via FPKM. Differential expression analysis of two different groups was performed using the DESeq R package, which was based on a model of negative binomial distribution. Results: A total of 133,070,980 reads in the control group, 128,097,025 reads in the SOD1 knockdown group, and 129,315,055 in the LD100-treated group were mapped to the reference genome. The total of 4513 differentially expressed genes (DEGs) was identified in the knockdown group, and the total of 2650 DEGs was identified in the SOD1 inhibition group compared to the control group. A total of 170,657,327 and 175,502,302 reads in the control group of DU145 and RWPE-1, 181,591,462 and 179,503,168 reads in the LD100-treated group of DU145 and RWPE-1 were respectively mapped to the reference genome. Among them, 8806 DEGs were identified in the LD100-treated DU145 cells compared to the control, but only 1503 DEGs were identified in the LD100-treated RWPE-1 cells compared to the control. Conclusions: The global transcriptomic data on HeLa, DU145 and RWPE-1 after SOD1 inhibition using its specific inhibitor-LD100 indicated that the most changed expression upon this interruption of ROS homeostasis is the key genes in plenty of signaling pathways inside cancer cells, not inside normal cells, although mRNA levels of numerous genes are altered in three lines of cells. The modulation of gene expression leads to repression of multiple signaling pathways including ERK, PI3K and NF-KB and their crosstalk to promote cell growth and activation of the signaling pathways to cause both cell cycle arrest and apoptosis. These modulated signaling pathways constitute a ROS signaling network, and SOD1 is a master hub in modulation of the network to selectively kill cancer cells. Overall design: Examination of transcriptomes in HeLa cells (designated as C), LD100-treated HeLa cells (L), SOD1 knockdown HeLa cells (S), DU145 cells (DC), LD100-treated DU145 cells (DL), RWPE-1 cells (RC) and LD100-treated RWPE-1 cells (RL).	Co-expression
SRP135996	Transcriptomic profiling of THP-1 macrophages infected with SFG Rickettsia	Comprehensive transcriptomic profiling to elucidate early host cell responses upon infection of THP-1 macrophages with a pathogenic (R. conorii) and a non-pathogenic (R. montanensis) species of SFG Rickettsia	Co-expression
SRP136057	Whole Blood Transcriptome Profiling in Juvenile Idiopathic Arthritis and Inflammatory Bowel Disease	We report whole blood gene expression of 12 healthy controls and 190 patients with either oligoarticular (n=43), polyarticular (n=46), or systemic JIA (n=26), or Crohn''s disease (n=60) and ulcerative colitis (n=15). The subtypes of JIA are characterized by a gradient of differential gene expression ranging from controls to oligoJIA, polyJIA, sJIA, and IBD. Overall design: Whole blood samples were obtained from JIA patients age <17 years. Transcriptome profiling was performed with RNA-Seq.	Co-expression
SRP136058	Gene expression in PANC1 cells treated with Rakicidin	Cells were treated with Rakicidin A or an analogue compound BE-43547 or DMSO (control) in three replicates. Overall design: three groups in triplicates.	Co-expression
SRP136093	RNA-Seq of fibrosarcoma with ESCC case	Analysis of a fibrosarcoma with ESCC case at transcriptome level Overall design: RNA-Seq of normal esophageal tissue and esophageal squamous cell carcinoma from the same individual.	Co-expression
SRP136094	Codon usage optimization in pluripotent embryonic stem cells [RNA-seq]	The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias on regulating cell state-specific expression programs is currently debated. Here, we asked whether the gene expression program in the well-defined cell states of self-renewal and differentiation in embryonic stem cells is driven by optimized codon usage. Using ribosome and transcriptome profiling, we identified distinct codon signatures for human self-renewing and differentiating embryonic stem cells. One driver for the cell state-specific codon bias was the genomic GC-content of the differentially expressed genes and thus, determined by transcription rather than translation. However, by measuring the codon frequencies at the ribosome's active sites interacting with transfer RNAs (tRNA), we discovered that the wobble position tRNA modification inosine strongly influenced the codon optimization in self-renewing embryonic stem cells. This effect was conserved in mice and independent of the differentiation stimulus. In summary, we newly reveal how translational mechanisms based on RNA modifications can shape optimized codon usage in embryonic stem cells.  Overall design: Ribosome profiling and total RNA from self-renewing and differentiating human H9 cells, 4 biological replicates per condition	Co-expression
SRP136102	Systemic Lupus Erythematosus patient blood with controls	The experiment consists of 31 Systemic Lupus Erythematosus patient blood samples and 29 healthy donor blood samples. Overall design: Whole blood was collected in PaxGene tubes from 31 SLE and 29 healthy donors.	Co-expression
SRP136108	RNA-seq of nine primary human cell types exposed in vitro to methylprednisolone	Glucocorticoids remain the most widely used class of anti-inflammatory and immunosuppressive agents. They act primarily by binding to the glucocorticoid receptor, resulting in direct and indirect effects on gene expression. The current understanding of glucocorticoid effects on transcription in human cells is based mostly on studies of cancer cell lines, immortalized cell lines, or highly mixed populations of primary cells (such as peripheral blood mononuclear cells). To advance the understanding of the transcriptome-wide effects of glucocorticoids on highly pure populations of primary human cells, we performed RNA-seq on nine such cell populations at two time points after in vitro exposure to methylprednisolone or vehicle. Overall design: Nine cell types were studied: four hematopoietic (circulating B cells, CD4+ T cells, monocytes, and neutrophils) and five non-hematopoietic (endothelial cells, fibroblasts, myoblasts, osteoblasts, and preadipocytes). Each cell type was obtained from a separate cohort of 4 unrelated healthy human donors (4 biological replicates per cell type: BR1 - BR4). Cells form each donor were independently cultured and exposed in vitro to glucocorticoid or vehicle. Non-hematopoietic cells were incubated until the early plateau phase of growth, then exposed to methylprednisolone or vehicle. Hematopoietic cells were collected from peripheral blood, purified by magnetic selection (negative selection for B cells, CD4+ T cells and neutrophils; positive selection for monocytes). Purified B cells, CD4+ T cells, and monocytes were incubated overnight, then exposed to methylprednisolone or vehicle. Purified neutrophils were cultured for 4 hours, then exposed to methylprednisolone or vehicle. Ethanol was used as a vehicle for methylprednisolone. Estimated final concentrations were 8500 mcg/L (22.7 mcM) for methylprednisolone and 0.07% (15.57 mM) for ethanol (vehicle). For each cell type, samples were collected at two time points after treatment with methylprednisolone or vehicle: 2 hours and 6 hours. Samples were collected into TRIzol reagent and frozen at -80°C prior to RNA extraction. RNA-seq data for all samples is made available in this GEO Series.	Co-expression
SRP136132	RNASeq of total RNA isolated from self-assembling co-cultures of primary human hepatocytes (SACC-PHHs) mono-infected with HBV, co-infected with HBV/HDV, or uninfected at 8 and 28 days post-infection	Here, we examined the host response relative of SACC-PHHs infected with either hepatitis B virus (HBV) alone or both HBV/hepatitis delta virus (HDV) co-infection compared to non-infected controls. Overall design: SACC-PHHs were generated with PHHs from either a single human donor or mixed donors (in total, there were five donors) and co-cultured with 3T3J mouse non-parenchymal cells. These cultures can be persistently infected for up to 1-1.5 months post-challenge and exhibit a transcriptomic profile similar to what's observed in the 3D context of the liver. Note that not all donors and conditions have the same number of replicates.	Co-expression
SRP136156	Leukaemic alteration of IKZF1 primes stemness and malignancy programs in human lymphocytes	We uncovered upregulated stem cell program in leukaemic lymphoblasts of patients with IKZF1 alterations by analyzing the archived gene-expression profiling datasets. We then used a frequent IKZF1 deletion, IK6, as a model via transduction into human primitive haematopoietic cells, followed by xenotransplantation in mice. Immunophenotypically defined stem, pro-B, and immature/mature (IM/M)-B cells were collected from primary recipients for functional assay and transcriptome profiling. Successful reconstitution in secondary recipient mice revealed the stemness of IK6+ pro-B and IM/M-B cells. Upregulated stemness and malignancy programs in IK6+ cells confirmed IK6 effects. Interestingly, these programs corresponded to distinct canonical pathways. Remarkably, the pathway profile mapped in the modelled cells well mirrored that in patients' leukaemic cells; therefore, our study provides a seminal insight into the cancerous reprogramming of somatic cells. Overall design: Examination of gene expression in 7 cell types, triple replicates were used.	Co-expression
SRP136195	RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia patients	We compared the transcriptome of keratoconus and control epithelium using RNA-Seq. Epithelial tissues were obtained prior to surgery from keratoconus and myopia control patients, undergoing collagen cross-linking and photorefractive keratectomy, respectively. We identified major differences in keratoconus linked to cell-cell communication, cell signalling and cellular metabolism. The genes associated with the Hedgehog, Wnt and Notch1 signaling pathways were down-regulated in keratoconus. Overall design: Twenty samples were used for RNA-Seq including 10 KC and 10 controls. All 10 KC samples were from males, and there were 4 samples from females in the control group.  Samples were prepared and processed in 2 batches each with 5 control samples and 5 KC samples. The RNA samples were prepared using the TruSeq Stranded Total RNA Library Prep Kit (Illumina,USA) according to the manufacturer's instructions.  The libraries were sequenced on a NextSeq500 (Illumina) using a 75bp paired end read high output v2 run at the Ramaciotti Centre for Genomics UNSW.	Co-expression
SRP136239	RNA Misplicing in Fuchs Endothelial Corneal Dystrophy II	RNA-Seq splicing data from the  corneal endothelia of FECD patients and controls reveal hundreds  of differential alternative splicing events. These include  events previously characterized in the context of myotonic dystrophy  type 1 and epithelial-to-mesenchymal transition, as well  as splicing changes in genes related to proposed mechanisms of  FECDpathogenesis Overall design: RNA-Seq was used to compare corneal endothelial specimens from subjects with Fuchs endothelial corneal dystrophy.	Co-expression
SRP136263	Human Cellular Model of Hypoxic Brain Injury of Prematurity	Extremely premature birth is associated with an increased risk for hypoxic brain injury due to lung immaturity and this results in severe long-term neurodevelopmental impairments. The susceptible cell types in the cerebral cortex at this critical developmental time point and the molecular mechanisms underlying associated gray matter defects in premature infants are not known. Here, we used a human three-dimensional (3D) cellular system to study the effect of changes in oxygen tension on the mid-gestation human cerebral cortex. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and show that these are related to the unfolded protein response (UPR) and cell cycle changes. Moreover, we verify these findings in human primary cortical tissue and demonstrate that a modulator of the UPR pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be useful in studying other environmental and genetic factors underlying brain injury in premature infants. We investigated the transcriptional changes associated with exposure to <1% O2 by performing RNA sequencing. Overall design: RNA-seq, 101 bp singlepaired-end reads; minimum of 40 million high quality reads per sample) at 24 and 48 hours (middle and end of <1% O2 for hypoxic condition), as well as after 72 hours of re-oxygenation at 21% O2.	Co-expression
SRP136266	Integrating the Epigenome to Identify Novel Drivers of Hepatocellular Carcinoma	Gene expression, histone modification, DNA methylation, and DNA hydroxymethylation from normal, cirrhotic, and HCC livers Overall design: 10 total samples (2 normal, 4 cirrhosis, 4 HCC). Cirrhosis and HCC are from the same four patients.	Co-expression
SRP136292	MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network with PRC2 [RNA-seq]	We performed RNA-seq to identify differentially expressed genes in response to knockout of EZH2 and global miRNA knockdown (VP55 overexpressed) in T98G Glioblastoma multiforme cells. Overall design: RNA-seq in WT and EZH2-/- T98G cells and VP55 overexpressed WT and EZH2-/- T98G cells.	Co-expression
SRP136355	MKL1 augments megakaryocyte maturation by enhancing the SRF regulatory axis [RNA-seq]	SRF is a ubiquitous transcription factor that binds DNA in association with myocardin-family proteins (e.g. MKL1), or the ternary complex factor (TCF) family of ETS proteins. In primary hematopoietic cells, knockout of either SRF or MKL1 decreases megakaryocyte maturation caused thrombocytopenia, and MKL1 over-expression (MKL1OE) in the Human Erythroleukemia (HEL) cell line enhances megakaryopoiesis, but the mechanisms underlying these effects are unknown. To elucidate the role of SRF and MKL1 in megakaryopoiesis, integrated analysis was performed of anti-SRF ChIP-seq and RNA-seq data in undifferentiated and differentiated HEL cells, both with and without induction of MKL1OE. MKL1OE enhances TPA-induced megakaryopoiesis with 25% of genes upregulated, as opposed to 11% with TPA alone. MKL1OE increases SRF binding to genomic sites, and enhances expression of specific target cytoskeletal genes in response to TPA.  Genes upregulated in response to TPA are predicted to be regulated by SRF and ETS factors, whereas those upregulated in TPA plus MKL1OE lack ETS binding motifs. Using ChIP-PCR, we validated that both SRF and MKL1 have increased binding at target upregulated genes, e.g. CORO1A, with MKL1OE. We show for the first time that MKL1 increases both the genomic association and activity of SRF, and upregulates genes that enhance megakaryopoiesis. Overall design: 4 treatment groups of HEL-iMKL1 cells were studied for RNA-seq: untreated, Dox-treated (MKL1^OE), TPA-treated (TPA+), and Dox+TPA-treated (TPA+MKL1^OE).  Two replicates of each type were used.	Co-expression
SRP136360	Extracellular RNA profiles with human age	Circulating extracellular RNAs (exRNAs) are potential biomarkers of disease. We thus hypothesized that age-related changes in exRNAs can identify age-related processes. We profiled both large and small RNAs in human serum to investigate changes associated with normal aging. exRNA was sequenced in 13 young (30-32 yrs.) and 10 old (80-85 yrs.) African American women to identify all RNA transcripts present in serum. We identified age-related differences in several RNA biotypes, including mitochondrial transfer RNAs, mitochondrial ribosomal RNA, and unprocessed pseudogenes. Age-related differences in unique RNA transcripts were further validated in an expanded cohort. Pathway analysis revealed that EIF2 signaling, oxidative phosphorylation, and mitochondrial dysfunction were among the top pathways shared between young and old. Protein interaction networks revealed distinct clusters of functionally-related protein-coding genes in both age-groups. These data provide timely and relevant insight into the exRNA repertoire in serum and its change with aging. Overall design: Profiling of extracellular RNA (exRNA) from human serum in 13 young (30.9 ± 0.60 yrs) and 10 old (81.8 ± 1.87 yrs) individuals.	Co-expression
SRP136364	The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress	RNAseq of HEK293 cells with and without MOTSC expression, with and without glucose restriction.	Co-expression
SRP136411	Post-transcriptional regulation of the epithelial cell response to colitis	Aim: RNA binding proteins (RBPs) are emerging as critical regulators of gut homeostasis via post-transcriptional control of key growth and repair pathways. IMP1 (IGF2 mRNA Binding Protein 1) is ubiquitously expressed during embryonic development and Imp1 hypomorphic mice exhibit severe gut growth defects. In the present study, we investigated the mechanistic contribution of intestinal epithelial IMP1 to gut homeostasis and response to injury. Method: We evaluated IMP1 expression in patients with Crohn's disease followed by unbiased ribosome profiling in IMP1 knockout cells. Concurrently, we measured differences in histology and cytokine expression in mice with intestinal epithelial-specific Imp1 deletion (Imp1?IEC) following dextran sodium sulfate (DSS)- colitis. Based on ribosome profiling analysis, we evaluated changes in autophagy in Imp1?IEC mice as well as in silico and in vitro approaches to evaluate direct protein:RNA interactions. Finally, we analyzed the consequence of genetic deletion of Atg7 in Imp1?IEC mice using colitis and irradiation models. Results: IMP1 was robustly upregulated in Crohn's disease patients and Imp1 loss lessened DSS-colitis severity. Unbiased ribosome-profiling revealed that IMP1 may coordinate translation of multiple pathways important for intestinal homeostasis, including cell cycle and autophagy, which we verified by Western blotting. Mechanistically, we observed evidence for increased autophagy flux in Imp1?IEC mice, reinforced through in silico and biochemical analyses revealing direct binding of IMP1 to autophagy transcripts. Finally, we found genetic deletion of Atg7 reversed the phenotype observed in DSS- or irradiation-challenged Imp1?IEC mice. Conclusions: IMP1 acts as a post-transcriptional regulator of gut epithelial repair, in part through modulation of autophagy. This study highlights the need for examining post-transcriptional regulation as a critical mechanism in inflammatory bowel disease. Overall design: Ribosome-footprinting and RNA-seq samples from WT SW480 cells and IMP1-/- knockout cells	Co-expression
SRP136415	Polyamide induced gene expression changes in VCaP cells	VCaP cells were treated with 10uM of a Py-Im polyamided targeted to the DNA sequence 5''-WGWWCW-3'' for 24hrs. Gene expression changes are normalized to untreated VCaP cells.	Co-expression
SRP136473	Choline Kinase Alpha (CHKa) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors	Choline kinase a (CHKa) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKa in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKa expression, associated with differentiation. CHKa protein expression was directly correlated with sensitivity to MN58b, a CHKa inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKa knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKa inhibition and, in vitro, MN58b had additive or synergistic effects with gemcitabine, 5-fluorouracil, and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKa was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKa did not relate to survival, nuclear CHKa distribution was observed in 43% of samples and was associated with longer survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKa inhibitors, we cultured IMIM-PC-2 cells with increasingly higher concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified upregulation of ABCB1 and ABCB4 multidrug resistance transporters, and functional studies confirmed that their upregulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKa inhibition merits further attention as a therapeutic option in patients with PDAC and that expression levels may predict response. Overall design: RNAseq from parental (IMIM-PC2 cell line)) and MN58b-resistant cells by triplicate	Co-expression
SRP136481	Regional differences in mRNA and lncRNA expression patterns in the non-failing human heart	Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed.   Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples.    Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization. Overall design: 8 human hearts, 5 chambers from each	Co-expression
SRP136483	Novel risk variants affecting enhancers of TH1 and TREG cells in type 1 diabetes [RNA-seq]	We generated expression profiles of TH1 and TREG cells from T1D and healthy subjects by RNA-Seq. By integrating RNA-Seq dta with other data sets, we predicted and validated serveral T1D risk SNPs. Overall design: Effector memory TH1 and effector memory TREG cells were isolated from 6 T1D patients and mached 5 helathy controls. Gene expression profilings were generated using RNA-Seq. By integrating RNA-Seq data, ChIP-Seq and other data sets, we predicted and validated several risk SNPs for T1D.	Co-expression
SRP136484	Viral shRNA Knockdown of INS Promotor Activity in EndoC-ßH1 Cells	To inhibit INS expression, we used shRNA to target the INS promoter. We find that knocking down INS expression with such an shRNA targeting the INS promoter significantly affects expression of 259 genes. Overall design: mRNA profiles of EndoC ßH1 with or without shRNA targetting INS promoter were generated by deep sequencing, in triplicate, using Illumina Hiseq 2500.	Co-expression
SRP136521	The Promyelocytic Leukemia Zinc Finger Dependent Transcriptome during Human Endometrial Stromal Cell Decidualization	RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of PLZF Overall design: Primary human endometrial stromal cells isolated from 3 healthy volunteers. Transfected with nontargeting or PLZF siRNA. Treated with estradiol, medroxyprogesterone acetate, and cAMP (EPC) for 0 or 3 days	Co-expression
SRP136642	Polarized B -cell functions	In this study, we designed an in vitro approach to help us understand how extracellular components participate in human B cell functional plasticity and how this network might be involved in auto-immune diseases. Two activated T cell subsets were used to expose a common pool of B cells to distinct, controlled microenvironments. We showed that the same B cell population could experience two possible opposite evolutions, to either helper or suppressor functions, in a flexible manner. These cells were thus referred to as effector B cells (Eff B) or suppressor B cells (Supp B). We thus analyzed their different transcriptional programs by RNA sequencing. Overall design: B cells cultured with memory or naive T cells  were analyzed by RNA sequencing	Co-expression
SRP136693	Celll type specific gene expression from healthy human lung tissue infected with mycobacterium tuberculosis (ILC).	We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)	Co-expression
SRP136694	Celll type specific gene expression from healthy human lung tissue infected with mycobacterium tuberculosis (innate).	We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)	Co-expression
SRP136698	A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development (HPC-5F RNAseq)	While gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs. Overall design: RNA-seq of HPC-5F cells transduced with a control (CTRL), HMGA2-L (LONG), HMGA2-S (SHORT) or CLK3 ORF lentiviral over-expression vectors.	Co-expression
SRP136720	Gene expression profile in breast cancer cells	We report the gene expression patterns in MDA-MB-231 (a line selected for low metastatic ability), MDA-MB-231-1833 (its bone-tropic metastatic derivative line), MDA-MB-231p27CK-DD (a phosphomimetic cell line), MDA-MB-231-1833shp27 (p27 knockdown cell line), MDA-MB-231-1833PF1502 (PI3K inhibitor treatment). It shows that the gene expression pattern are regulated in a p27 phosphorylation-dependent manner. Overall design: Examination in 5 cell types.	Co-expression
SRP136721	Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor and estrogen receptor signalling pathways in endocrine resistant breast cancer	Our data supports the potential combination of inhibition of ERBB2/3 signalling with mTORC1 perturbation and endocrine therapy in patients who have relapsed on endocrine therapy and retain a functional ER. Overall design: RNAseq examination of gene expression changes in MCF72a-LTED tumour xenografts due to treatment with RAD001 (RAD), the pan-ERBB inhibitor neratinib (Ner) and fulvestrant ICI182780 (Ful)	Co-expression
SRP136727	Functional CRISPR Screen Identifies AP1-associated Enhancer regulating FOXF1 to modulate Oncogene-Induced Senescence	We carried out CRISPR-Cas9 functional screen focused on AP-1 bound enhancers that are activated upon oncogenic stress. The screen discovered Enh.AP1.OIS1 - an enhancer bound by AP1 that is required for activation of oncogene-induced senescence (OIS) response. We applied RNA-seq analysis to RASG12V-activated BJ cells transduced with either sgRNAs targeting AP-1 bound enhancer (sgRNA-69 or sgRNA71), or sgRNA targeting the target gene FOXF1 or non-targeting control sgRNA (sgNT) Overall design: RNA-seq was applied to oncogenic RASG12V-induced BJ cells genetically manipulated using CRISPR-Cas9	Co-expression
SRP136739	Single cell RNA-seq of CRX+ cells obtained at day 90 of retinal organoid differentiation	Death of photoreceptors and/or Retinal Pigment Epithelium (RPE) cells is a common cause of age related and inherited retinal dystrophies, thus their replenishment from renewable stem cell sources is a well sought therapeutic goal. Human pluripotent stem cells provide a useful cell source in view of their limitless self-renewal capacity and potential to differentiate into all key retinal cell types either in isolation or as part of three dimensional retinal organoids. Photoreceptor precursors have been isolated from differentiating human pluripotent stem cells either through application of cell surface markers or fluorescent reporter approaches and shown to share a transcriptional profile akin to foetal photoreceptors. In this study we investigated the transcriptional profile of CRX+ photoreceptor precursors derived from human embryonic stem cells (hESC) using single cell RNA sequencing and their engraftment capacity in an animal model of retinitis pigmentosa (C3H/rd1). Single cell RNA seq analysis revealed the presence of dominant cell cluster which displayed the hallmarks of early cone photoreceptor expression. When transplanted subretinally into the C3H/rd1 mice, the Crx positive cells settled next to the inner nuclear layer of host retina, matured into cone photoreceptors and made connections with the inner neurones of the host retina. Cellular transfer between the host retina and donor photoreceptors was investigated and shown to be minimal. Together our data provide valuable molecular insights into the transcriptional profile of human pluripotent stem cells derived CRX+ photoreceptor precursors and indicate their usefulness as a source of transplantable cone photoreceptors. Overall design: CRX-GFP human ESC line was differentiated to retinal organoids. At day 90 CRX+ and CRX- cells were purified by flow activated cell sorting and subjected to single cell RNA-seq. RNA-seq of bulk CRX+ and CRX- from the same experiment was carried out in parallel.	Co-expression
SRP136742	RNA-seq analysis identifies different transcriptomic types and developmental trajectories of primary melanomas	Recent studies revealed trajectories of mutational events in early melanomagenesis, but the accompanying changes in gene expression are far less understood. Therefore, we performed a comprehensive RNA-Seq analysis of laser-microdissected melanocytic nevi (n=23) and primary melanoma samples (n=57) and characterized the molecular mechanisms of early melanoma development. Using self-organizing maps, unsupervised clustering and analysis of pseudotime (PT) dynamics to identify evolutionary trajectories, we describe here two transcriptomic types of melanocytic nevi (N1 and N2) and primary melanomas (M1 and M2). N1/M1 lesions are characterized by pigmentation-type and MITF gene signatures, and a high prevalence of NRAS mutations in M1 melanomas. N2/M2 lesions are characterized by inflammatory-type and AXL gene signatures with an equal distribution of wild type and mutated BRAF and low prevalence of NRAS mutations in M2 melanomas. Interestingly, N1 nevi and M1 melanomas and N2 nevi and M2 melanomas, respectively, cluster together, but there is no clustering in a stage-dependent manner. Transcriptional signatures of M1 melanomas harbour signatures of BRAF/MEK inhibitor resistance and M2 melanomas harbour signatures of anti-PD-1 antibody treatment resistance. Transcriptomic signatures suggest that the epigenetic regulators SMARCA2 and SMARCA4 are differentially involved in the epigenetic programming of the two melanoma types. Pseudotime dynamics of nevus and melanoma samples reflect a switch-like immune-escape mechanism in melanoma development with downregulation of immune genes paralleled by an increasing expression of a cell cycle signature in late-stage melanomas. Taken together, the transcriptome analysis identifies gene signatures and mechanisms underlying development of melanoma in early and late stages with relevance for diagnostics and therapy. Overall design: RNA-Seq analysis of laser-microdissected melanocytic nevi and primary melanoma samples. Some Melanoma samples are NRAS and/or BRAF mutated.	Co-expression
SRP136770	Co-regulation of alternative splicing by hnRNPM and ESRP1 during EMT	The epithelial-mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome-scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they co-regulate a set of cassette exon events, with the majority showing discordant splicing regulation. hnRNPM discordantly regulated splicing events show a positive correlation with splicing during EMT while concordant splicing events do not, highlighting the antagonistic role of hnRNPM and ESRP1 during EMT. Motif enrichment analysis near co-regulated exons identifies guanine-uridine rich motifs downstream of hnRNPM-repressed and ESRP1-enhanced exons, supporting a model of competitive binding to these cis-elements to antagonize alternative splicing. The set of co-regulated exons are enriched in genes associated with cell-migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of co-regulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtypes. In conclusion, hnRNPM and ESRP1 co-regulate antagonistically a set of alternative splicing events that occur during EMT. This regulation is likely mediated through competition for the same intronic binding sites downstream of variable exons. hnRNPM and ESRP1 regulated splicing events are associated with breast cancer survival. Overall design: PolyA-RNA-sequencing of control and hnRNPM knockdown cell lines	Co-expression
SRP136781	ARID2 promotes clear cell renal cell carcinoma in the absence of functional PBRM1 [RNA-seq]	Subunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in clear cell renal cell carcinoma (ccRCC). Here, we integrate RNA-seq, ARID2 and histone mark ChIP-seq, and ATAC-seq data to show that PBAF acts to enhance or repress gene expression depending on the genomic context. At baseline, ARID2 binds to areas of open chromatin at both active enhancers and promoters. Depletion of PBRM1 leads to attenuated and redistributed ARID2 chromatin binding that correlates significantly with gene expression changes. At enhancers, ARID2 binding loss leads to diminishment of the histone mark H3K4me1 and gene downregulation. Alternatively, at a subset of promoters, ARID2 binding loss derepresses gene expression. Interestingly, ARID2, which remains bound to other PBAF subunits after loss of PBRM1, is essential for many of the pro-tumorigenic transcriptional changes observed after loss of PBRM1, whereas other core SWI/SNF components are dispensable. Upon loss of PBRM1, ARID2 positively regulates cancer-related genes and pathways, including the cancer stem cell marker ALDH1A1 and 足足足EG足F signaling, to stimulate tumor cell growth. Therefore, ARID2 is crucial for maintaining the transformed state of PBRM1-deficient ccRCC cells. In total, this study suggests a novel mechanism of transcriptional control by PBRM1, whereby its loss alters the chromatin distribution of the residual PBAF complex leading to altered transcription that promotes tumorigenesis. Overall design: RNA-seq was performed at high and low serum concentrations in the the human clear cell renal cell carcinoma cell line 786-O in which PBRM1 had been stably knocked down with two different lentiviral vectors containing shRNA targeting PBRM1 (sh1 or sh2), or with a lentiviral vector containing an off-target control shRNA (control). RNA-seq at high and low serum concentration was also performed in another human clear cell renal cell carcinoma cell line, A-704, which harbors a homozygous truncating mutation of PBRM1. These cells had been stably transduced with either an empty-vector containing retrovirus (EV) or a retrovirus containing wild-type PBRM1 with a C-terminal V5 tag (V5).	Co-expression
SRP136794	DNA methylation in neurons from post-mortem brains in schizophrenia and bipolar disorder (RNA-Seq)	We fine-mapped DNA methylation in neuronal nuclei (NeuN+) isolated by flow cytometry from post-mortem frontal cortex of the brain of individuals diagnosed with schizophrenia, bipolar disorder, and controls (n=29, 26, and 28 individuals). Overall design: Brain tissue samples (n=34 human samples, 17 case and 17 control) were lysed using QIAzol Lysis Reagent (Qiagen) and homogenized with a TissueLyser (Qiagen). Total RNA from each sample was isolated using the RNeasy Plus Universal Mini kit (Qiagen) according to manufacturer's instructions and included an enzymatic DNase (Qiagen) digestion step. RNA quality was measured on a 2100 Bioanalyzer (Agilent) and quantity was determined with a Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific). Only RNA samples with a RIN quality score >7 proceeded to RNA-seq library preparation (RIN between 7.1 to 9.4 for all samples). Libraries were prepared by the Van Andel Genomics Core from 300 ng of total RNA using the KAPA RNA HyperPrep Kit with RiboseErase (v1.16) (Kapa Biosystems). RNA was sheared to 300-400 bp. Prior to PCR amplification, cDNA fragments were ligated to Bio Scientific NEXTflex Adapters (Bioo Scientific). Quality and quantity of the finished libraries were assessed using a combination of Agilent DNA High Sensitivity chip (Agilent Technologies, Inc.), QuantiFluor® dsDNA System (Promega Corp.), and Kapa Illumina Library Quantification qPCR assays (Kapa Biosystems).  Individually indexed libraries were pooled, and 75 bp paired-end sequencing was performed on an Illumina NextSeq 500 sequencer, with all libraries run across 3 flowcells.  Base calling was done by Illumina NextSeq Control Software (NCS) v2.0 and output of NCS was demultiplexed and converted to FastQ format with Illumina Bcl2fastq v1.9.0.    Trimgalore (v0.11.5) was used for adapter removal prior to genome alignment. STAR33 (v2.3.5a) index was generated using Ensemble GRCh38 p10 primary assembly genome and the Gencode v26 primary assembly annotation. Read alignment was performed using a STAR two-pass mode. Gene counts matrix was imported into R (3.4.1) and low expressed genes (counts per million (CPM) < 1 in all samples) were removed prior to differential expression in EdgeR. Gene counts were normalized using the trimmed mean of M-values, fitted in a generalized linear model and differentially tested using a likelihood ratio test. The generalized linear model contained covariates age, sex, post mortem interval and neuronal cell composition. Cell-type compositions for each sample was accessed using CIBERSORT34 on normalized sample counts against cell-type specific markers, identifying the proportion of neurons in each samples. Benjamini Hochberg correction was used to adjust for multiple testing.	Co-expression
SRP136914	RNA transcriptome sequencing analysis of SGC-7901 cells transfected with ENST00000431060 shRNA or control shRNA	RNA transcriptome sequencing analysis was performed in SGC-7901 cells that were transfected with ENST00000431060 shRNA or control shRNA Overall design: mRNA profiles of SGC-7901 cells transfected with ENST00000431060 shRNA or control shRNA	Co-expression
SRP136927	Targeted RNA-seq of human monocytes	The purpose of this RNA-seq experiment was to perform a correlation analysis of mRNA expression levels in LPS-stimulated monocytes from patients with an IKZF1 mutant haploinsufficient phenotype (H167R-a and H167R-b are two siblings carrying IKZF1 p.H167R mutation) versus patients with an IKZF1 mutant dominant negative phenotype (C1, G1) along with five healthy normal controls (HC).	Co-expression
SRP136928	XBP1s Activation Globally Remodels N-Glycan Structure Distribution Patterns	The unfolded protein response (UPR), as its name implies, safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated, XBP1s-mediated transcriptional response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s' transcriptional output for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional consequence of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. XBP1s activity decreases sialylation of tri- and tetra-antennary N-glycans in the HEK293 membrane proteome and secretome, while substantially increasing the population of high mannose N-glycans only in the secretome. Related, but distinctive, signatures in the HEK293 N-glycome are observed when the entire UPR is activated in a stress-dependent manner using thapsigargin. In HeLa cells, stress-independent XBP1s activation increases the population of cell surface high mannose N-glycans and tetra-antennary N-glycans. mRNA profiling experiments suggest that the XBP1s-mediated remodeling of the N-glycome may re-flect a coordinated consequence of transcriptional resculpting of the N-glycan maturation pathway by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s is a master regulator of N-glycan maturation. Moreover, because the sugars on cell surface proteins or on those proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling pathways into al-tered interactions with the extracellular environment. Overall design: Three biological replicates of HeLaXBP1s cells treated with DMSO vehicle, 1 ug/ml dox or 750 nM Thapsigargin.	Co-expression
SRP136931	Next Generation Sequencing Facilitates Quantitative Analysis of Ramos and Rituximab-resistant Ramos cell Transcriptomes	The goal of this study is to screen the differential genes between Ramos and Rituximab-resistant Ramos cells, then analyze the significant pathways. Overall design: The total RNA of each group was pooled from 3 different passages separately. RNA-seq was performed using the proton sequencing process.	Co-expression
SRP136932	Gene expression signatures of innate lymphoid cells from human blood	We aimed to determine the characteristic of 3 different ILC subsets (ILC1, 2 and 3) isolated from human blood. Overall design: mRNA profile of ILC1, ILC2 and ILC3	Co-expression
SRP136939	Targeted RNA-seq of human naive CD4+ T-cells	The purpose of this RNA-seq experiment was to perform a correlation analysis of mRNA expression levels in naïve CD4+ T cells from patients with an IKZF1 mutant haploinsufficient phenotype (H167R-a carries an IKZF1 p.H167R mutation) versus patients with an IKZF1 mutant dominant negative phenotype (C1, G1) along with five healthy normal controls (HC).	Co-expression
SRP136989	Environmental toxins and colon carcinogenesis.	RNA was isolated from colorectal cancer (HCT116) and normal colon cells (HCoEpic) treated with toxic agents (bisphenol A (BPA), hexabromocyclododecane (HBCD), 4-tert-octylphenol (OP)) or Vehicle (DMSO) and then preformed NGS using Illumina protocol.	Co-expression
SRP137071	Time series integrative analysis of RNA-Seq and miRNA expression data reveals key biologic pathways during keloid formation	Keloids represent a common form of exaggerated wound scarring that cause considerable morbidity. Moreover, there are limited data on molecular mechanisms underlying keloids and effective therapies are lacking. To gain new insight in the transcriptomic alterations of wound healing in keloid-prone individuals, we followed an integrative approach of RNA-Seq and miRNA expression data analysis in serial skin biopsies of the same site (baseline and six weeks after wounding) in keloid-prone (n=8) and healthy matched control individuals (n=6). Bioinformatic analysis identified 37 miRNAs and 1449 genes that are differentially expressed specifically in keloid-prone individuals during wound healing. Pathway enrichment analysis was undertaken in the RNA-Seq data and identified NOTCH signaling, MAPK signaling, and Toll-like receptor pathways to be altered in keloid-prone individuals after wounding. In addition, dysregulation of DNA repair, p53 signalling and metabolic pathways (RNA, protein, fructose, mannose and glycerophospholipid metabolism) was highlighted during keloid formation. Gene association network analysis demonstrated divergent average expression profiles of cytokine signaling genes, as well as lipid metabolism genes between keloid-prone and healthy individuals during wound healing. In summary, our study provides a comprehensive and integrative analysis of the keloid transcriptome and miRNAome and highlights biological pathways that feature during keloid formation.	Co-expression
SRP137096	Effect of hyperfractionated irradiation (HFRT) of prostate primary basal cells (PrEPs) on the transcriptome	We irradiated PrEPs derived from four patients undergoing radical prostatectomy according to a HFRT protocol (20 single treatments). Transcriptome was analysed by NextGen sequencing. Gene expression profiling revealed a dysregulation of 3468 genes at mRNA level (1470 upregulated and 1998 downregulated). We could characterize cells surviving the lethal effects of radiation by two gene expression signatures showing that these cells have low expression of genes related to DNA damage response and Interferon signaling pathways. These findings could be exploited to develop new drugs for radiotherapy improvement. Overall design: PrEPs derived from 4 patients undergoing radical prostatectomy were irradiated with either 0.5 or 1 Gray (Gy) for 5 times a week (4 weeks in total) using a linear accelerator. An untreated control group was included. Cells were allowed to recover for one week before all groups received a final 1 Gy treatment 24 hours before harvesting total RNA and RNA sequencing. Bioinformatical analysis was conducted on irradiated samples versus control group.  Group A = 1 Gy irradiation,  group B = 0.5 Gy irradiation, group CTRL = 0 Gy irradiation.	Co-expression
SRP137147	Use single cell RNA sequencing to study the molecular siganature of primary human Megakaryocytic-erythroid progenitor	Megakaryocytic-Erythroid Progenitors (MEP) produce circulating red blood cells and platelets. Although much is known regarding megakaryocytic (Mk) and erythroid (E) maturation, detailed molecular mechanisms underlying the MEP fate decision have not been determined. Single cell RNA sequencing of highly enriched populations of primary human common myeloid progenitors (CMP), MEP, megakaryocyte progenitors (MKP) and erythroid progenitors (ERP), revealed that MEP have a distinct molecular signature with co-expression of genes otherwise expressed exclusively in CMP, MKP or ERP. Cell cycle genes are significantly differentially expressed between MEP, MKP, and ERP. We therefore tested the effects on MEP fate of genetic and pharmacologic modulation of cell cycle progression, and found that cell cycle activity mechanistically controls MEP fate decisions; cell cycle activation promotes E whereas cell cycle inhibition promotes Mk specification. The data obtained from healthy cells can now be applied to the mechanisms underlying benign and malignant disease states of Mk and E production. Overall design: To address the heterogeneity of the MEP enriched population, we performed single-cell mRNA sequencing (scRNA-seq) of FACS-enriched MEP, MKP and ERP, and CMP. Specifically, we tested whether MEP have an expression signature that is distinct from CMP, MKP and ERP. Single cells were captured and lysed using the Fluidigm C1 platform and sequenced to more accurately identify and profile the transcriptome of multi-lineage cells. On average, there were 504,984 aligned reads per cell, with an average of 5,028 genes expressed (FPKM>0.1) per cell. We first performed an analysis of the scRNA-seq data from sorted CMP, MEP, MKP and ERP populations from a single PBSC donor (donor-1, n=246 cells). Unsupervised analysis with the recently described ICGS software identified separate major gene expression clusters for each of the sorted populations along with subdivisions of the CMP, MEP, MKP and ERP. To confirm the major gene expression clusters associated with the four sorted populations, we performed scRNA-Seq analysis of cells from a different donor (donor-2, n=294 cells) sorted using a complementary gating strategy, but running 1 plate of MEPs and 1 plate of a mix of 55% MKP and 45% ERP.	Co-expression
SRP137216	Analysis of MGE Transcriptomes with or without Ctnnb1 knockout in human through RNA Sequencing	Purpose: Understand the cues that orchestrate the expansion or differentiation of medial ganglionic eminence (MGE) progenitors no matter in vivo or in vitro. Methods: Total RNA from each sample was used to prepare the library. Then the libraries were sequenced at 50bp single read on an Illumina HiSeq 2500 platform. Sequencing reads from each sample were mapped to the human reference genomes (hg38 version) by using TopHat v2.1.1. The mapped reads were further analyzed by cufflinks v1.3.0 and the expression levels for each transcript were quantified as Fragments Per Kilobase of transcript per Million mapped reads (FPKM). For differential expression analysis, sequencing counts at the gene level were obtained using HTSeq v 0.9.1. R package DESeq2 was then used to identify differential expressed genes between different conditions.Statistically enriched functional categories of genes were identified using DAVID 6.8. PPI networks were constructed by using STRING v10.0 . Results: Transcriptome profiling reveals that ablation of ß-catenin in MGE cells leads to advanced neuronal differentiation, while activation of Wnt/ß-catenin signaling keeps the MGE cells in an undifferentiated progenitor state. Conclusions: Wnt signaling is a key player in governing self-renewal vs terminal differentiation of MGE progenitors both in vivo and in vitro. Overall design: mRNA profiles of MGE cells with or without Ctnnb1 knockout were generated by RNA sequencing, using Illumina Hiseq 2500 platform.	Co-expression
SRP137776	Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs	Molecular tools to target RNA site-specifically allow recoding of RNA information and processing. SNAP-tagged deaminases, guided by a chemically stabilized guideRNA, enable the simultaneous editing of targeted adenosine to inosine in several endogenous transcripts, with high efficiency (up to 90%), high potency, sufficient duration, and high precision. We applied SNAP-ADARs for the efficient and concurrent editing of two disease-relevant signaling transcripts, KRAS and STAT1. We also show improved performance compared to the recently described Cas13b-ADAR. Overall design: Identification of off-target editing events in SNAP-ADAR cell lines by RNA-Seq, 7 samples, 2 biologically independent experiments	Co-expression
SRP137884	PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer	Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-Ras-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPa axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Se151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPa. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition. Overall design: We quantify transcription via high-throughput RNA sequencing in two human breast cancer cell lines (BT-549 and Hs578T) 72hrs after transient transfection with control (siControl) or PAK4-targetting siRNA.	Co-expression
SRP137893	Molecular characterization of neuroendocrine prostate cancer organoids and PDOX by RNA-seq	We report the generation and characterization of tumor organoids and PDOX derived from needle biopsies of metastatic lesions from neuroendocrine prostate cancer patients. Overall design: Understanding the expression profile of neuroendocrine prostate cancer tumor organoids and PDOXs.	Co-expression
SRP138008	Human Eosinophil Transcriptome	This study was performed to investigate the effect of IL-37 on the transcriptional profile of eosinophils upon co-culture with human bronchial epithelial BEAS-2B cells and peptidoglycan (PGN) stimulation.	Co-expression
SRP139120	Transcriptome-wide identification of transient RNA G-quadruplexes in human cells	We report here on G4RP-seq, which comprises of a cross-linking step, followed by chemical-affinity capture with the G4-specific small-molecule, BioTASQ and target identification using sequencing. This allows for capturing global snapshots of relative average levels of transiently folded G4-RNAs. We observed widespread G4-RNA targets indicative of transient G4 formation in several RNA entities in living human cells. G4RP-seq has also demonstrated that G4-stabilizing ligands (BRACO-19 and RHPS4) can change the G4 transcriptomic landscape, most notably in long non-coding RNAs. G4RP-seq thus provides a proof-of-principle for studying the G4-RNA landscape, as well as new ways of considering the mechanisms underlying G4-RNA formation and the activity of G4-stabilizing ligands. Overall design: Two BioTASQ-enriched samples and one input control for three different conditions (Untreated, BRACO-19-treated, and RHPS4-treated) in MCF7 cells	Co-expression
SRP139147	RNA-seq MCF10 series	We generated a set of RNA-seq data to explore the epigenetic role of PHF5A in regulating breast cancer progression.	Co-expression
SRP139556	RNA sequencing of HepG2 cells treated with estradiol or estrogen receptor agonist	We report differential expressed genes in HepG2 cells treated with control, E2, or an ER agonist Overall design: Methods: HepG2 cells treated with control, E2, PPT, or DPN for 48 hours. mRNA profiles were generated by deep sequencing, in triplicates, using Illumina NextSeq2000 sequencing system.  The sequence reads that passed quality filters were analyzed at the transcript level with DESeq2.	Co-expression
SRP139587	Transcriptome profiling of Cryptosporidium parvum infected lung and intestinal organoids	Purpose: Transcriptome profiling of Crytosporidium parvum infected lung and small intestinal organoids was performed to access the response of epithelial cells upon parasitic infection and to do a temporal analysis of the transcriptome of the parasite inside the organoid lumen. We isolated RNA from infected human lung and small intestinal organoids at 24 and 72 hour post infection. Methods: Organoids were grown in expansion or differentiation media and microinjected with equal amounts of Cryptosporidium oocysts. Media-injected organoids were used as a control .Expanding SI organoids were microinjected at 5-6 days after seeding, differentiated SI organoids were injected at 5 days after inducing differentiation. Lung organoids were incubated for 2 weeks after seeding for microinjection. RNA was extracted from 1-2 matrigel drops containing organoids. RNA was converted to cDNA and libraries were prepared using the CelSeq2 method and sequenced. Samples were sequenced on Illumina NextSeq500 by using 75-bp paired-end sequencing. Methods:    Paired-end reads from Illumina sequencing were aligned to the human transcriptome genome and C. parvum transcriptome genome (Iowa strain) by BWA. DeSeq (v1.18.0) was used for read normalization and differential expression analysis (p-value adjustment 0.05 by method Benjamini-Hochberg). Gene set enrichment analysis (GSEA) was performed using gene lists for type I interferon response and regulation against normalized RNA-seq reads of injected SI and lung organoids using GSEA software v3.0 beta2. Results: At 24 hr post-infection,GO (gene ontology)-term analysis revealed that a substantial number of genes related to 'cytoskeleton' and 'cell mobility' were up-regulated in lung organoids. This suggests that infection by the parasites and subsequent formation of the intracellular stages within 24 hrs might affects cytoskeleton structures of host cells. After 72 hrs, many genes associated with the type I interferon pathway increased dramatically in lung and intestinal organoids. Results: After 72 hrs, many genes associated with the type I interferon pathway increased dramatically in lung and intestinal organoids. Multiple C. parvum genes were differentially expressed with a large fold change between 24 and 72 hr post-injection.At 24 hr post-infection, most of the enriched genes represented ribosomal proteins and ribosomal RNA subunits in both intestinal organoids and lung organoids. By contrast, at 72 hr post-infection, multiple oocyst-wall protein genes were up-regulated, confirming that the parasites formed new oocysts within the organoids. Conclusions: RNA sequencing of injected organoids revealed host epithelial responses upon parasite infection in differentiated SI organoids as well as in lung organoids.Upregulation of genes associated with type I interferon immunity in both SI and lung organoids. Overall design: mRNA profiles of C. parvum infected human lung and intestinal organoids were generated by Deep Sequencing. Transcriptome profiles were generated from 2 human donors and samples were prepared in triplicates (Illumina NextSeq500 by using 75-bp paired-end sequencing).	Co-expression
SRP139607	Defining the transcriptome of T cells transduced with FOXP3fl or FOXP3d2	Rationale - Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective - To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3?2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease. Methods and Results - Human primary T-cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3?2. FOXP3?2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-ß to the cell membrane of activated Treg cells. RT-PCR was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of over 150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3?2 transcript usage, when comparing plaques from patients without symptoms and patients with occurrence of recent (<1 month) vascular symptoms including minor stoke, transient ischemic attack or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these two groups. Conclusions - These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3?2 controls a transcriptional program that acts protectively in human atherosclerotic plaques. Overall design: In this experiment we have analyzed 3 groups of each 3 biological repliactes equalling 9 samples in total.	Co-expression
SRP139667	Next Generation Sequencing Facilitates Quantitative Analysis of conventional and ischemia-free liver transplantation Transcriptomes	Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare the transcriptomes of conventional liver transplantation liver allografts and ischemia-free liver transplantation livers by comparing samples of post-reperfusion and at the end of preservation. Overall design: Liver allograft mRNA profiles of the end of preservation and post-reperfusion were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP139744	Seletive inhibition of CDK9 in DLBCL cell lines	Deregulation of the MYC transcription factor is a key driver in lymphomagenesis. MYC induces global changes in gene expression that contribute to cell growth, proliferation and oncogenesis by stimulating the activity of RNA polymerases. A key feature in its ability to stimulate RNA Pol II activity is recruitment of pTEFb, an elongation factor whose catalytic core comprises CDK9/cyclin T complexes. Hence, MYC expression and function may be susceptible to CDK9 inhibition. Non-specific inhibitors of multiple CDKs have shown promise in B-cell malignancies, where their pro-apoptotic effect has been attributed to a reduction in transcription and downmodulation of short lived pro-survival proteins (e.g., Mcl-1). However, they lack a defined mechanism of action. Here we selectively targeted CDK9 in a pre-clinical study in DLBCL.  Overall design: We employed gene expression profiling by RNA-Seq to determine which pathways were deregulated by AZ5576, a selective CDK9 inhibitor, in DLBCL cells. VAL cells and OCI-LY3 cells were treated with 0.3 µM AZ-5576 for 3 or 6 hours and comparisons in gene expression were made to vehicle-treated cells. Expression of 30,451 genes was detected in DLBCL cells. Using a cutoff of at least 2-fold change we identified between one and three thousand genes whose expression was significantly affected by AZ5576	Co-expression
SRP139759	A High-Throughput Screen Identifies DYRK inhibitor ID-8 that Stimulates Human Kidney Tubular Proliferation	Use NGS-transcriptome profiling (RNA-seq) to investigate deregulated genes involved in the proliferative effects of ID-8 and Harmine after hypoxia-induced damage in primary human proximal tubular epithelial cells (HPTECs) Overall design: Examination of differentially expressed genes in HPTECs treated with 1uM of ID-8; or 1uM of Harmine; or EGF in comparison to cells without treatment after 24 hours of hypoxia, in triplicates	Co-expression
SRP139787	NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence [RNA-Seq]	We decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.	Co-expression
SRP139810	Sequencing of human chain specific ribosome transcriptional group	The purpose of this study is to investigate whether the expression profile of long chain non coding RNA (lncRNA) in different concentrations of PM2.5 after treatment of normal human bronchial cells is changed. The total RNAs were extracted from 16HBE cells after exposure to either PM2.5, at concentration of 50 µg/mL and 100µg/mL, or PBS (control group) for 48h. lncRNA-sequencing, detection and analysis was performed. Fold change = 2 and p = 0.05 were used as a cutoff values to determine significant differential expression Further, cluster analyses were performed to classify lncRNAs based on their distinguishable expression in different samples. Overall design: Detection of a long chain noncoding RNA treated with cell type and different concentrations of PM2.5	Co-expression
SRP139859	Spontaneous functional network activity in organoids resembles programmed early human brain development	We describe the different cell types and their differential gene expression patterns present in six-month-old cortical organoids following single cell analysis. Overall design: Two different experimental replicates (two parallel differentiations started simultaneously) of cortical organoids of WT CVB-iPSCs.	Co-expression
SRP139891	Alternative splicing analysis in human monocytes and macrophages reveals MBNL1 as major regulator	We report the detailed transcriptomic profiles of human innate myeloid cells using RNA sequencing. Monocytes migrate from blood into infected or wounded tissue to differentiate into macrophages, and control inflammation via phagocytosis or cytokine secretion. We differentiated culture primary monocytes with either GM- or M-CSF to obtain pro- or anti-inflammatory macrophages, and respectively activated them with either LPS/IFN? or anti-inflammatory cytokines. We also treated the THP-1 monocytic cell line with PMA and similar cytokines to mimic differentiation and activation. We detected thousands of expression and alternative-splicing changes during monocyte-to-macrophage differentiation and activation, and a net increase in exon inclusion. This study provides general insights into alternative splicing in the monocyte-macrophage lineage, whose future characterization will elucidate their contribution to immune functions, which are altered in immunodeficiencies, autoimmunity, atherosclerosis and cancer.	Co-expression
SRP139916	RNA-seq across polysome gradient fractions of HeLa cellular extracts	We applied RNA-seq across the polysome gradient fractions of HeLa cell extracts, comparing extracts after cycloheximide versus puromycin treatment.	Co-expression
SRP139919	Differential responses by human respiratory epithelial cell lines to respiratory syncytial virus reflect distinct patterns of infection control	We compared constitutive gene expression between two respiratory epithelial cell lines Overall design: Examination of mRNA transcriptome by Illumina NGS	Co-expression
SRP139926	Primary T cells from cutaneous T-cell lymphoma skin explants display an exhausted  immune checkpoint profile	Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a  background of chronic inflammation. Dendritic cells (DCs) are potent T-cell stimulators; yet  despite DCs' extensive presence in skin, cutaneous T cells in CTCL do not respond with  effective anti-tumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and  dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5).  Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1,  CTLA-4, and LAG-3; and CD8+ CTCL populations comprised more T cells expressing CTLA-4  and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell  costimulator (ICOS), a marker of T-cell activation. DC émigrés from healthy or CTCL skin  biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1  expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples  from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA  expression profiles corroborated that advanced T3/T4 stage samples expressed higher levels of  checkpoint inhibition genes compared with T1/T2 stage patients or healthy controls. Exhaustion  of activated T cells is therefore a hallmark of both CD4+ and CD8+ T cells directly isolated from  the lesional skin of patients with CTCL, with a continuum of increasing expression in more  advanced stages of disease. These results justify identification of antigens driving T-cell  exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion  earlier in the treatment of CTCL. Overall design: RNA-seq correlated with tumor stages	Co-expression
SRP139931	Transcriptome of human chorioamniotic membranes of severe preterm birth	Preterm birth (PTB), defined as the delivery of an infant before 37 weeks of completed gestation, results of the interaction of both, genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the multiple causes of PTB and the numerous maternal and foetal gestational tissues that must interact to facilitate parturition. A common pathway of labour and PTB may be the activation of fetal membranes. In this work chorioamnion membranes from severe preterm and term fetus were analysed using RNA seq. The primary goal of this study was to identify differentially expressed transcripts and dilucidate molecular mechanisms distinguishing severe PTBs from term births. Overall design: Chorioamnion tissues were collected immediately after labor from women who had spontaneous severe preterm births between 24-33 weeks (n=4) and women with spontaneous term labor (>37 weeks)(n=4).	Co-expression
SRP139932	Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis	DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and preventing aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domain. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1gamma.  Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathological and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA-independent role for DGCR8 in maintaining heterochromatin organization and preventing senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders. Overall design: Transcriptional profiles of DR8dex2 and WT hMSCs	Co-expression
SRP139939	RNA-Seq with and without RNase treatment in PCa cell lines	Standard RNA analyses using microarrays and low-coverage polyadenylation enriched RNA-Sequencing (RNA-Seq) cannot fully characterize the complexity of the cancer transcriptome. To fully elucidate the transcriptome of prostate tumours, we performed ultra-deep total RNA-Seq on 144 localized prostate tumours with long-term clinical follow up. Analysis of linear RNAs identified a transcriptomic subtype associated with the aggressive intraductal carcinoma subhistology, and a fusion gene profile that differentiates localized from metastatic prostate cancers. Analysis of back-splicing events identified widespread RNA circularization, with the average tumour expressing 7,140 distinct circular RNAs. The degree of aberrant circRNA production is correlated to disease progression in multiple clinical cohorts. Loss of function screens identified 11.3% of the screened circRNAs as essential to prostate cancer proliferation, and for 93.6% of these, their parental linear genes are not required for proliferation. Follow-up studies on circCSNK1G3 revealed its role in regulating cell cycle progression. Ultra-deep transcriptome sequencing thus provides a more comprehensive view of the linear and circular transcriptional and functional landscapes of localized prostate cancer. Overall design: RNA-seq with rRNA depletion and random reverse transcription (RT) primer was performed with or without RNase R treatment in five PCa cell lines: LNCap, 22Rv1, V16A, PC-3 and 42D	Co-expression
SRP139943	Transcriptional alteration after ionizing radiation exposure in human fibroblasts, iPSCs and NPCs	RNA sequencing was performed to investigate ionizing radiation-dependent transcriptional change in human pluripotent cells and differentiated cells. Overall design: Examined 3 types of cells (fibroblasts, iPS cells and neural progenitor cells) and 2 types of treatments (non IR or IR), total 6 samples were analyzed.	Co-expression
SRP139944	Critical role for Lymphocytes in Producing FLT3LG in Tumors and Driving Checkpoint Therapy-Receptive Immune Microenvironments	Intratumoral stimulatory dendritic cells (SDCs) play an important role in locally restimulating cytotoxic T cells and driving immune responses against cancer. However, the mechanisms that control SDC numbers remain poorly understood. In human melanoma, SDC numbers correlated with intratumoral expression of the gene encoding the cytokine FLT3LG, and we subsequently found in mouse and human tumors that this cytokine was predominantly produced by lymphocytes, notably including natural killer (NK) cells. NK cells stably formed conjugates with SDCs in the mouse tumor microenvironment (TME) and genetic and cellular ablation of NK cells in mice demonstrated their importance in regulation of SDC numbers through production of Flt3L. Although anti-PD-1 “checkpoint” immunotherapy for cancer largely targets T cells, we found that NK cells correlated with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with better overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as the best prognostic tool for T cell directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis for novel therapies. Overall design: This dataset is n=11 biologically independent metastatic melanoma samples from patient tumors. There is no control dataset.	Co-expression
SRP140437	Transcriptome change after tocilizumab therapy in rheumatoid arthritis patients	We compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes. Overall design: Examination between before and after tocilizumab treatment of CD4 and CD8 T cell in rheumatoid arthritis patients	Co-expression
SRP140469	Identification and single cell functional characterization of an endodermally-biased pluripotent sub-state in human embryonic stem cells	Human embryonic stem cells (hESC) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESC we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm biased stem cell state. Overall design: Examination of 4 different cell substates within one human embryonic stem cell line as determine by the expression status of GATA6 and SSEA3	Co-expression
SRP140488	Single Cell RNA sequencing of Adult Human Breast Epithelial Cells [C1_Individual_1]	Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500	Co-expression
SRP140489	Single Cell RNA sequencing of Adult Human Breast Epithelial Cells [C1_Individual_2]	Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500	Co-expression
SRP140515	IL-6 trans-signaling induced gene expression in airway epithelial cells	Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) with asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthma is unclear. Objective: To explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthma. Methods: Primary human bronchial epithelial cell (HBEC) air-liquid interface (ALI) cultures were stimulated with IL-6 and sIL-6R to establish an IL-6TS gene signature. Two separate RNA sequencing (RNA-seq) studies were performed: The “IL-6 vs T2 study” compared gene expression after stimulation with control medium, IL-6, IL-6/sIL-6R and IL-4/IL-13, while the “JAK1-inhibition study” addressed the effect of JAK1 inhibition on IL-6TS induced gene expression.   The IL-6TS gene signature was used to stratify lung epithelial transcriptomic data obtained from asthmatics (n=103) in the U-BIOPRED cohorts by hierarchical clustering. Molecular phenotyping was based on the transcriptional profiling of epithelial brushings, pathway analysis and immunohistochemistry analysis of bronchial biopsies. Results: Activation of IL-6TS in HBEC ALI cultures reduced epithelial barrier function and induced a specific epithelial gene signature enriched in airway remodeling genes. The IL-6TS signature identified a subset (n=17) of IL-6TS High asthma patients with increased epithelial expression of IL-6TS inducible genes in absence of increased systemic levels of IL-6 and sIL-6R. The IL-6TS High subset had an increased exacerbation frequency (p=0.028), blood (>300/µl; p=0.0028) and sputum (>20%; p=0.007) eosinophilia, and submucosal infiltration of CD4 T cells, CD8 T cells (p<0.001) and macrophages (p=0.001). In bronchial brushings, TLR pathway genes were up-regulated while the expression of epithelial tight junction genes was reduced (all with q<0.05). Sputum sIL-6R levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, MMP3, IL-8 and IL-1ß (all with q<0.001). Conclusions: Local lung epithelial IL-6TS activation in absence of type 2 airway inflammation defines a novel subset of asthmatics and may drive airway inflammation and epithelial dysfunction in these patients. Overall design: Primary human bronchial epithelial cells grown and differentiated on air-liquid interface were stimulated basolaterally for 24h with cytokines corresponding to IL-6TS (IL-6 + sIL-6R), IL-6 alone, a Type 2 immune response (IL-4 + IL-13) or media alone as non-stimulated control. Each stimulation condition was done in triplicates. Cells were lysed, the RNA isolated and converted into libraries then used for next generation sequencing in order to identify genes that were up- or downregulated in response to the different stimulations.	Co-expression
SRP140536	Single Cell RNA sequencing of Adult Human Breast Epithelial Cells [C1_Individual_3]	Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we used single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produc one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides novel insights into cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. Overall design: Microfluidics-enabled Single Cell RNA sequencing libraries were generated for 3 adult human women using the Fluidigm C1 and sequenced on the Illumina HighSeq 2500	Co-expression
SRP140540	Sex differences in transcriptomic profiles in aged kidney cells of renin lineage	Renin expressing cells in the kidney's juxta-glomeruluar compartment likely also serve as progenitors for adult glomerular cells in disease. Although these cells of renin lineage (CoRL) decrease in number with advancing kidney age, accompanied by less responsiveness to typical stimuli such as ACE-inhibition, mechanisms and the impact of sex as a biological variable with age are not known. Accordingly, labeled CoRL were sorted from individual young (2m) and aged (27m) male and female Ren1cCre|ZsGreen reporter mice, and their transcriptomic profiles analyzed by RNA seq. When both aged female and male mice were combined, there were 48 differentially expressed genes (DEG) compared to young mice. However, when compared to their young sex-matched mice, aged female and male mice had 159 and 503 DEGs respectively. In addition to marked differences in individual genes between aged female and male mice, gene ontology analysis showed major pathway differences by sex. The majority of DEGs in one sex did not significantly change or changed in the opposite direction in the other sex. These results show that in CoRL of advanced age, individual genes and gene ontologies change, but differ between female and male mice, highlighting sex related differences the aging process. Overall design: We performed RNA-seq on 5 young (2 months) CoRL reporter mice (3 male, 2 female) and on 5 aged (27 months) inducible CoRL reporter mice (3 male, 2 female)	Co-expression
SRP140557	Acute viral bronchiolitis (NMS)	Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence. Overall design: The study design consisted of PBMC from infants (<18months, n=15 pairs) and pre-school children (2-5yrs, n=16 pairs) sampled during severe acute viral bronchiolitis (acute visit = AV) and following recovery during convalescence (convalescent visit = CV). RNA-Seq profiles were generated by sequencing llumina HiSeq2500, 50bp single-end reads, v4 chemistry. Samples were sequenced across two lanes and collapsed prior analysis.	Co-expression
SRP140558	Acute viral bronchiolitis (PBMC)	Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence. Overall design: The study design consisted of PBMC from infants (<18months, n=15 pairs) and pre-school children (2-5yrs, n=16 pairs) sampled during severe acute viral bronchiolitis (acute visit = AV) and following recovery during convalescence (convalescent visit = CV). RNA-Seq profiles were generated by sequencing llumina HiSeq2500, 50bp single-end reads, v4 chemistry. Samples were sequenced across two lanes and collapsed prior analysis.	Co-expression
SRP140592	High-throughput RNA sequencing on circular RNA profiles of human triple-negative breast cancer and adjacent normal tissues	In an attempt to search for metastasis-associated circRNAs, we performed RNA-sequencing on ribosomal RNA-depleted total RNA from three pairs of triple-negative breast cancer (TNBC) and adjacent normal tissues. A computational pipeline based on the anchor alignment of unmapped reads was used to identify circular RNAs. Taken together, 69,815 distinct circRNAs were found in this study and 87% were derived from exons, and the others were derived from introns, intergenic region and 3' or 5' UTR, etc. We further identified 5,033 differentially expressed circRNAs (fold change = 2 and p < 0.05). Among them, 3,726 circRNAs were significantly down-regulated and 1,307 circRNAs were significantly up-regulated in TNBC tissues compared with adjacent normal tissues. These data indicate that circRNAs are abundant in human breast tissues and dysregulation of circRNAs may contribute to breast cancer progression. Overall design: Circular RNAs profiles of three pairs of triple-negative breast cancer (TNBC) and adjacent normal tissues were generated by RNA deep-sequencing, using HiSeq3000, Illumina.	Co-expression
SRP140625	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network	We performed transcript profiling of sauchinone treated with various doses on HepG2 cells using the Illumina high-throughput sequencing platform and analyzed differential gene expression at the transcriptional level. Overall design: mRNA levels were examinated in sauchinone treated with various doses, in two biological replicates.	Co-expression
SRP140637	RNA-sequencing (RNA-seq) in BxPC-3 and S2-007 cell lines	RNA sequencing technology has been carried out in order to compare mRNA expression changes in epithelial BxPC-3 versus mesenchymal S2-007 cells. Overall design: To evaluate the changes in gene expression in BxPC-3 and S2-007 cells we have performed RNA-seq in cells growing in standard condition. Three biological replicates for each cell lines were used for expression analysis (6 samples in total).	Co-expression
SRP140640	Mechanosensitive ion channel regulates tissue stiffening to promote glioma aggression	Tissue stiffening is a physical hallmark of solid tumor. In our study, we found that the mechanosensitive ion channel PIEZO1 can be tumor cells force sensor and transducer that regulate the altered tissue mechanics. We examined the transcriptional changes modulated by depletion of PIEZO1 in two human GBM cell lines. We found that with PIEZO1 KD, the components involved in ECM organization, focal adhesion formation, cytoskeleton, and mitosis, which contribute to tissue stiffness, are down-regulated. Overall design: RNA-Seq of G508 and G532 human GBM cell lines treated with scrambled shRNA, PIEZO1 shRNA #1, PIEZO1 shRNA #2, in triplicates.	Co-expression
SRP140711	Transcriptional profile in human S. haematobium infection (II)	Genome-wide transcriptional survey in peripheral blood mononuclear cells (PBMCs) by RNA-Seq in schoolchildren living in an endemic area in Gabon, with and without Schistosoma haematobium infection before and after treatment with the anthelminthic drug praziquantel. Overall design: 26 samples; paired pre- and post-treatment for S.haemotobium-infected individuals, plus controls	Co-expression
SRP140719	Epigenetic changes induced by Bacteroides fragilis toxin (BFT) [RNA-seq]	Purpose: The goal of this study is to determine how BFT2 alters chromatin accessibility at relatively early time points in colon epithelial cells, and to correlate the changes in chromatin accessibility with changes in gene expression, transcription factor binding sites, and the location of common single nucleotide variants (SNVs) and differentially methylated regions (DMRs) in colorectal cancer. Methods: HT29/C1 cells were plated at low density and allowed to grow for 4 days at 37C and 10% CO2. Afterwards, cells were either left untreated or treated with 100ng/mL BFT2 for 24 or 48 hours. After the specified time point, cells were counted and RNA was collected in order to prepare RNA-seq libraries. RNA was collected using the Qiagen RNeasy mini kit. mRNA was enriched using the NEBNext Poly(A) mRNA Magnetic Isolation Module. Afterwards, a non-directional RNA-seq library was constructed using the NEBnext Ultra RNA Library Prep kit from Illumina. The 2nM pooled RNA-seq library was sequenced using the Illumina HiSeq. Results: After sequencing, Kallisto was used to perform pseudoalignment of the raw RNA-seq data. Then, Sleuth was used to quantify gene expression and perform differential expression analyses. After treatment with BFT2 for 24 hours, 70 genes were differentially expressed (P-value < 0.01). Of these genes, 41 showed a decrease in gene expression, while 29 showed an increase in gene expression. After BFT2 treatment for 48 hours, we found only 16 differentially expressed genes (P-value < 0.01); 3 showed a decrease in gene expression and 13 showed an increase in gene expression. Conclusions: This study adds critical knowledge to our understanding of host-microbe interactions in the gut. While scientists have begun to analyze the effect of specific bacteria on the epigenome of colon epithelial cells, to date, no other studies have surveyed the effect of a specific bacterial toxin on chromatin accessibility in colon epithelial cells. We conclude that BFT2 alters chromatin accessibility in colon epithelial cells, and that these changes correlate with subsequent changes in gene expression. Also, sites of BFT2-induced increased chromatin accessibility are associated with a lower frequency of common single nucleotide variants (SNVs) in CRC and with a higher frequency of common differentially methylated regions (DMRs) in CRC. Overall design: Gene expression in HT29/C1 cells with and without BFT2 treatment for 24 or 48 hours was assessed, in triplicate, using Illumina HiSeq.	Co-expression
SRP140795	Using RNA sequencing to examine age-dependent skeletal muscle transcriptome response to bed rest-induced atrophy, and age independent disuse-induced insulin resistance	Short-term bed rest is used to simulate muscle disuse in humans.  In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations.  Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse.  Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). Overall design: RNA was isolated and sequenced from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9) and OLD (N=18) men and women before and after five days of bed rest. Sequencing libraries (18 pM) were chemically denatured and applied to an Illumina TruSeq v3 single read flowcell using an Illumina cBot.  Hybridized molecules were clonally amplified and annealed to sequencing primers with reagents from an Illumina TruSeq SR Cluster Kit v3-cBot-HS (GD-401-3001).   Following transfer of the flowcell to an Illumina HiSeq 2500 instrument (HCS v2.0.12 and RTA v1.17.21.3), a 50 cycle single read sequence run was performed using TruSeq SBS v3 sequencing reagents (FC-401-3002). The design formula was constructed by following the section on group-specific condition effects, individuals nested within groups in the DESeq2 vignette.   The design included age + age:nested + age:time to test for differences in bed rest in old subjects, young subjects and the interaction, in this case if bed rest effects are different between the two age groups (where age is young or old, nested is patient number nested by age and time is pre- or post-bed rest).  A similar design was used to determine susceptibility to disuse-induced insulin resistance, where “susceptibility” took the place of “age”.	Co-expression
SRP140829	Differential expression of miRNAs in a cellular model of MELAS.	We investigate the participation of miRNAs in the cell response to the mitochondrial dysfunction associated with m.3243A>G mutation in mitochondrial DNA (mtDNA), which is the most common cause of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome.Through small-RNA sequencing and in silico analysis, we identified 246 differentially-expressed in a transmitochondrial cybrid model of MELAS (100% m.3243A>G mutant mitochondrial DNA), with 126 being up-regulated and 120 down-regulated. The enrichment analysis of Gene Ontology (GO) terms revealed that target genes for dysregulated miRNAs were involved in muscle and nervous system development, heart development, and signaling pathways controlling cardiac events.These data suggest that the miRNA program triggered by the MELAS m.3243A>G mutation could explain for some of the clinical manifestations of the MELAS syndrome. Overall design: Examination of dysregulated miRNAs in MELAS.	Co-expression
SRP140871	Nascent RNA sequencing in IMR-32 cells treated with THZ531 or DMSO	We performed RNA-seq analsysis of nascent transcripts obtained by 4sU labeling in IMR-32 cells treated with THZ531 for 30min and 2h and DMSO as a control Overall design: Expression of  nascent  transcripts in IMR-32 treated with THZ531 using  standard RNA-seq library kit in triplicate, for a total of 9 individual samples	Co-expression
SRP140872	PolyA-sequencing in IMR-32 cells treated with THZ531 or DMSO	We performed RNA-seq analsysis of polA transcripts in IMR-32 cells treated with THZ531 for 2 and 6h and DMSO as a control Overall design: Expression of  polA transcripts in IMR-32 treated with THZ531 using  the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen)  in duplicate, for a total of 6 individual samples	Co-expression
SRP140916	Transcriptome-wide analysis links the short-term expression of the b isoforms of T-cell intracellular antigens to protective proteostasis-mediated survival and quiescence	Control of gene expression depends on genetics and environmental factors. The T-cell intracellular antigens T-cell intracellular antigen 1 (TIA1), TIA1-like/related protein (TIAL1/TIAR) and human antigen R (HuR/ELAVL1) are RNA-binding proteins that play crucial roles in regulating gene expression in both situations. This study used massive sequencing analysis to uncover molecular and functional mechanisms resulting from the short-time expression of the b isoforms of TIA1 and TIAR and HuR in HEK293 cells. Overall design: Three comparisons (altered vs control) were carried-out using three biological replicates per sample type. RNA-seq was performed with 100 nt strand-specific and paired-ends reads. Illumina HiSeq 2000 sequencer was used.	Co-expression
SRP140918	Human intestinal biopsy gene expression after infection with Salmonella enterica serovar Typhi	This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples to analyze gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. Overall design: mRNA was collected from four control biopsies, five infected biopsies and four control bacterial samples. RNA sequencing was done using 1x50bp SR, HiSeq 2500; rapid run flow cells and analyzed using an Ergatis-based RNA-Seq analysis pipeline.	Co-expression
SRP140945	Genome-wide expression from the esophageal biopsies of subjects with and without eosinophilic esophagitis	Esophageal biopsy RNA was isolated from distal esophageal biopsy RNA from EoE patients with active disease and from unaffected controls. EoE biopsies showed active disease pathology at the time when they were taken, and all patients reported no glucocorticoid treatment at the time of biopsy.   RNA sequencing acquiring 50 million mappable 125 base-pair reads from paired-end libraries was performed at the Genetic Variation and Gene Discovery Core Facility at Cincinnati Children's Hospital Medical Center. Data were aligned to the hg19 build of the human genome using the Ensembl annotations as a guide for TopHat. Overall design: RNA sequencing of esophageal biopsy RNA	Co-expression
SRP140975	Human K562 Cell Line Raw sequence reads for small RNA analysis	The goal of this study was to evaluate CleanTag small RNA library preparation kit on RNA extracted from single K562 cells using an electrokinetic chip-based fractionation method. Single Cell total RNA fractionated using this method was compared to commercially available total RNA at 100 ng and 10 pg input as well as the total cellular material from a single cell.	Co-expression
SRP141017	DAOY-NERT2 Notch/Hypoxia Transcriptome Analysis	Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2a, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2a by Notch under normoxic conditions leads to elevated HIF2a protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma and renal cell carcinoma cell lines. The elevated level of HIF2a protein was in certain tumor cell types accompanied by down-regulation of HIF1a protein levels, indicating that high Notch signaling may drive a HIF1a-to-HIF2a switch. At the transcriptome level, the presence of HIF2a was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2a expression was knocked down by HIF2a siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2a, which may be important for future cancer therapies. Overall design: DAOY-NERT2 cells, +/- Notch induction by Tamoxifen (TMX) for 48 hours, +/- hypoxia (1% O2) treatment for 48 hours, where HIF1a or HIF2a had been knocked down by siRNA, were subjected to RNA sequencing. The quality of the cDNA libraries was tested on an Agilent 2100 bioanalyzer. The libraries were sequenced on an Illumina HiSeq 2000 system, and the reads were aligned to the human genome (assembly hg19) and a transcriptome database (RefSeq and Ensembl) using bowtie. RPKM values were generated using rpkmforgenes.	Co-expression
SRP141118	Activating Transcription Factor 4 modulated TGFb-induced aggresiveness in triple negative breast cancer vis SMAD2/3/4 and mTORC2 signaling	Based on the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFß1. ATF4 is overexpressed in triple negative breast cancer (TNBC) patients, but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on breast cancer patient survival and TNBC aggressiveness, and the relationships between TGFß and ATF4. Overall design: RNA seq analysis was carried out on 20 Triple Negative Breast Cancer Patient Derived Xenograft models	Co-expression
SRP141131	Evaluation of cross-platform and interlaboratory concordance via consensus modelling of genomic measurements [Whole RNA-Seq]	We empirically assess the measurement precision and sensitivity of a suite of gene expression technologies via a consensus modelling method called the row-linear model. Overall design: 2 Ribo-Zero libraries (1 LNCaP cell line, 1 PrEC cell line) were prepared using Epicentre (Illumina) ScriptSeq v2 RNA-Seq Library Preparation Kit. The resultant cDNA libraries were sequenced at the University of Western Sydney Next Generation Sequencing Facility	Co-expression
SRP141147	Conditional DICER1 knockout hESCs	We report the generation and characterization of DICER1-deficient hESCs. We uncover an unexpected requirement for DICER1 as well as essential pro-survival roles of members of the mir-302- 367 and mir-371- 373 clusters in hESCs. Our work provides a robust platform for interrogating microRNA function in hESC and differentiation. Overall design: For RNAsequencing, total RNA was isolated from Tra-1-60+ sorted cells from +DOX and -DOX conditions using the miRNeasy Mini Kit (Qiagen Cat. No. 217004), following manufacturer's guidelines. Three replicates were done for each sample.	Co-expression
SRP141351	ALYREF links 3'processing and nuclear export of histone mRNAs	To examine whether ALYREF can facilitate the 3'processing of RD histone mRNA,we isolated and sequenced the polyadenylated and nonpolyadenylated RNAs from control and ALYREF KD cells Overall design: Polyadenylated and nonpolyadenylated RNAs isolated from control or ALYREF KD cells were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP141364	Genome-wide transcriptional analysis of human patterned induced neurons (hpiNs)	We report that combining NGN2 programming with SMAD and WNT inhibition generates patterned induced neurons (hpiNs).Transcriptional analyses showed that hpiN cultures contained cells along a developmental continuumranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene. Overall design: RNA sequencing analysis (population and single cell) over hpiNs differentiation time (D0 through D49 after induction). Two independent iPS lines, 9 time points, three replicates each.	Co-expression
SRP141379	RNAseq Study in CC-671 Treated Cal-51 Cells	CC-671 has been identified as an inhibitor of Cdc2-like kinase 2 (CLK2) and TTK in direct enzyme assays. CLK2 is a member of the CLK family that phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex as part of a regulatory mechanism for control of pre-mRNA splicing.  SR proteins are a family of small nuclear ribonucleoprotein particle (snRNP) splicing factors involved in constitutive and alternative splicing. Monitoring specific phospho-biomarkers of CLK2 demonstrated that CC-671 inhibited phosphorylation of CLK2 substrates in cancer cells with mean IC50 of 549 nM in the triple negative breast cancer (TNBC) line CAL51.  In this study, RNA sequencing approach was used to quantify the impact of CC-671 treatment on gene transcription and global alternative splicing in CAL51 cells.  Differential exon usage analysis demonstrated that CC-671 changed alternative splicing of many genes.  In addition, different sets of genes are impacted by CC-671 at both the alternative splicing and mRNA expression. Genes impacted by alternative splicing shared a set of common pathways with genes altered by mRNA expression. This result indicates that CC-671 regulates transcription via both gene expression and alternative splicing mechanisms. Overall design: Triple negative breast cancer (TNBC) line CAL51 was grown in DMEM medium containing 10% fetal bovine serum, as recommended by vendor. The growing cells were treated by CC-671 in three biological replicates at the following concentrations and time intervals.  The treatment time points were 6 hour and 24 hour. Concentration of compounds used was 3 and 10 uM. Six million cells from each treatment were harvested and RNA was isolated by RNeasy kit. Poly-A selection and strand-specific RNA library construction were performed, followed by multiplexing indexed libraries and sequencing on the HiSeq 2500 with 2x100 bp read lengths. A total of 16 samples were included in this experiment, including 4 treatment groups with three biological replicates and 2 vehicle control groups with two biological replicates	Co-expression
SRP141444	RNAseq of Breast cancer PDX samples	RNAseq was done on Breast cancer PDX samples uisng Library protocol =llumina TruSeq Stranded Total RNA Kit with Ribo-Zero Gold , HiSeq 125 Cycle Paired-End Sequencing v4 Overall design: Paired end sequencing of PDX samples	Co-expression
SRP141453	Cockayne syndrome and rRNA variation	Cockayne syndrome (CS) is a progeria characterized by childhood onset of degenerative symptoms reminiscent of the aging body, such as loss of subcutaneous fat, alopecia, cataracts, neurological degeneration and cachexia. CS can be caused by the recessive mutation of 5 genes (CSA, CSB, XPB, XPD, XPG) that are all involved in a branch of Nucleotide-Excision Repair (NER), thus explaining the elevated UV-sensitivity of the patients. However, total loss of NER is not always followed by premature aging, suggesting that alternative functions of the CS proteins have a crucial role in the disease. This study showed that a disturbed RNA polymerase I transcription in CSA and CSB-deficient cells is followed by a decreased translational accuracy of the ribosomes. rRNA sequencing was performed to determine whether rRNA variations play a role in translational accuracy in CS cells.	Co-expression
SRP141733	Human gut derived-organoids as model to study gluten response and effects of microbiota bioproducts in celiac disease	Celiac disease (CeD) is an intestinal immune-mediated disorder caused by gluten ingestion in genetically predisposed subjects. CeD is characterized by villous atrophy, altered intestinal permeability, crypt hyperplasia and innate and adaptive immune response. This study aimed to develop and validate the use of intestinal organoids from celiac patients to study CeD. A repository of organoids from duodenum of non-celiac and celiac patients was generated and characterized accordingly to standard procedures. RNA-seq analysis was employed to study the global gene expression program of CeD (n=3) and non-CeD (n=3) organoids sets. While the three celiac derived organoids shared similar transcriptional signatures the NC samples set appeared more heterogeneous. We found 486 genes differentially expressed between the two groups. Of them, 299 genes were downregulated (FC<2; FDR<0.05) and 187 were upregulated in CeD (FC >2; FDR<0.05). We observed CeD organoids had significantly altered expression of genes associated with barrier function, innate immunity, and stem cell function. Overall design: mRNA profiles of 3 non-celiac healthy controls and 3 celiac organoids derived from duodenal biopsies.	Co-expression
SRP142249	Clinker: visualizing fusion genes detected in RNA-seq data	Genomic profiling efforts have revealed a rich diversity of oncogenic fusion genes, and many are emerging as important therapeutic targets. While there are many ways to identify fusion genes from RNA-seq data, visualising these transcripts and their supporting reads remains challenging. Clinker is a bioinformatics tool written in Python, R and Bpipe, that leverages the superTranscript method to visualise fusion genes. We demonstrate the use of Clinker to obtain interpretable visualizations of the RNA-seq data that lead to fusion calls. In addition, we use Clinker to explore multiple fusion transcripts with novel breakpoints within the P2RY8-CRLF2 fusion gene in B-cell Acute Lymphoblastic Leukaemia (B-ALL). Overall design: RNA-seq of six B-cell Acute Lymphoblastic Leukaemia (B-ALL) samples with a P2RY8-CRLF2 fusion gene.	Co-expression
SRP142279	A high-throughput screening strategy identifies regulators of alternative splicing via interaction with RNA G-quadruplexes	RNA secondary structures have been increasingly reported to serve critical regulatory roles in post-transcriptional gene regulation. RNA G-quadruplex secondary structures can serve as cis-elements to recruit splicing factors and regulate alternative RNA splicing. We recently showed that RNA G-quadruplexes play a critical regulatory role in regulating alternative splicing during the epithelial mesenchymal transition.  Due to the critical role alternative splicing plays in human health and disease, an unmet need exists to identify small molecule modulators of alternative splicing. In this study, we performed high-throughput screening using a dual-output splicing reporter to identify small molecules capable of regulating alternative splicing by interacting with RNA secondary structure G-quadruplexes. We identify emetine and its analog cephaeline as small molecules that denature RNA G-quadruplexes in a sequence and location independent manner to modify alternative splicing. Transcriptome analysis reveals that treatment with emetine globally regulates alternative splicing, including events associated with exon-proximal G-quadruplexes. These data suggest a critical role for emetine and cephealine as splicing regulators with the selective ability to disrupt RNA G-quadruplex-associated alternative splicing in vivo. Overall design: PolyA-RNA-sequencing of control and emetine treated cell lines with two biological replicates each	Co-expression
SRP142292	Identification of Nrf2 regulated genes by RNA sequencing	The transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is activated by the metabolite  itaconate during metabolic reprogramming. Activated Nrf2 then dampens the release of pro-inflammatory  cytokines and type I IFNs in response to toll-like receptor stimulation. If and how Nrf2 affects cytosolic  antiviral sensing and whether this occurs during metabolic reprogramming is currently not known. Here, we  show that Nrf2 is a negative regulator of the adaptor molecule STimulator of INterferon Genes (STING),  which signals downstream of the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS). The regulation  of STING by Nrf2 was inducible by the metabolite itaconate, specific to human cells, and sufficient to  decrease the responsiveness to STING agonists and to increase the susceptibility to infection with DNA  viruses. Mechanistically, Nrf2 regulated STING expression post-transcriptionally by increasing STING  mRNA stability. Lastly, treatment with itaconate or with the chemical Nrf2 inducer sulforaphane repressed  STING expression and the release of type I IFNs in cells from patients with the STING dependent  interferonopathy SAVI. With this report we identify Nrf2 as an important regulator of cGAS-STING  signaling pathway and link metabolic reprogramming to control of cytosolic DNA sensing. Overall design: RNA sequencing of control and Nrf2 siRNA treated A549 cells was generated by Active Motif (Carlsbad, California, USA), in triplicate, Illumina HiSeq 4000.	Co-expression
SRP142336	Specific Oxylipins Enhance Vertebrate Hematopoiesis via the Receptor GPR132	Epoxyeicosatrienoic acids (EETs) are endogenous lipid signaling molecules with cardioprotective and vasodilatory actions. We recently showed that exogenous addition of 11,12-EET enhances hematopoietic induction and engraftment in mice and zebrafish. EETs are known to signal via a G-protein coupled receptor(s), but no specific EET receptor has been identified. Identification of an EET receptor would enable genetic interrogation of the EET signaling pathway and perhaps clinical use of this molecule. We developed a bioinformatic approach to identify the EET receptor based on the expression of GPCRs in cell lines with differential responses to EETs. We found 10 candidate EET receptors that are commonly expressed in three EET-responsive human cell lines, but not expressed in an EET-unresponsive line. Of these candidates, only GPR132 showed EET-responsiveness in vitro using a luminescence-based assay for ß-arrestin recruitment. Knockdown of zebrafish gpr132b prevented EET-induced hematopoiesis, and marrow from GPR132 knockout mice showed decreased long-term engraftment capability. GPR132 has affinity for certain fatty acids in vitro, and we found that these same fatty acids enhance hematopoietic stem cell specification in the zebrafish. We conducted structure-activity relationship analyses using both in vitro and in vivo assays on diverse medium chain fatty acids. Certain oxygenated, unsaturated free fatty acids showed high activation of GPR132, while unoxygenated or saturated fatty acids had lower activity. Absence of the carboxylic acid moiety prevented activity, suggesting that this moiety is required for receptor activation. GPR132 responds to a select panel of polyunsaturated, oxygenated fatty acids to enhance both embryonic and adult hematopoiesis. Overall design: To identify potential EET receptors, we performed RNAseq on 3 EET-binding cell lines and one non-binding cell lines, then identified GPCRs expressed in common in the EET-binding lines but missing from the non-binding line.	Co-expression
SRP142391	Role of cohesin in cancer development	The aim of this project is to understand the role of cohesin in both genome instability and colorectal cancer development	Co-expression
SRP142438	DHX15 regulates CMTR1-dependent gene expression and cell proliferation	We discovered that the RNA helicase DHX15 is a regulator of the methyltransferase CMTR1.  To determine the biological consequences of this interaction we overexpressed CMTR1 or a mutated CMTR1 (2LA)that does not bind DHX15, in the human breast cancer cell line HCC1806.  To assess the effects of the DHX15-CMTR1 interaction on translation, polysomes were separated on a sucrose gradient and sequencing libraries generated from the polysomal and input RNA.  We found that the DHX15-CMTR1 interaction controls ribosome loading of a subset of mRNAs and impacts on cell proliferation. Overall design: Polysome and input RNA samples were sequenced from two replicate experiments.  In each experiment  HCC1806 cells were transfected with either pcDNA5 (vector control), pcDNA 5 HA-CMTR1 WT (wildtype CMTR1) or pcDNA 5 HA-CMTR1 2L/A mutant (mutant CMTR1 that does not interact with DHX15).	Co-expression
SRP142465	Profiling of lung tumor-infiltrating CD8 T cells according to their expression status of CD39	Human tumors are infiltrated by various immune cells, including CD8 T cells. CD8 T cells express unique receptors that can recognize peptides at the host's cells, including tumor cells. After probing the antigen specificity of ex-vivo tumor-infiltrating CD8 T cells from human tumors, we hypothesized that expression of CD39 was correlated with tumor-specificity. The present experiment aims at better characterizing ex-vivo CD39+ vs CD39- CD8 T cells. Overall design: CD39- and CD39+ CD8 T cells were FACS sorted from 8 fresh tumor samples and their RNA extracted for transcriptomic profiling.	Co-expression
SRP142468	Profiling of colorectal tumor-infiltrating CD8 T cells according to their expression status of CD39	Human tumors are infiltrated by various immune cells, including CD8 T cells. CD8 T cells express unique receptors that can recognize peptides at the host's cells, including tumor cells. After probing the antigen specificity of ex-vivo tumor-infiltrating CD8 T cells from human tumors, we hypothesized that expression of CD39 was correlated with tumor-specificity. The present experiment aims at better characterizing ex-vivo CD39+ vs CD39- CD8 T cells. Overall design: CD39- and CD39+ CD8 T cells were FACS sorted from 8 fresh tumor samples and their RNA extracted for transcriptomic profiling. Additionally, Effector memory and Naive CD8+ T cells were FACS sorted from 5 healthy donors' peripheral blood.	Co-expression
SRP142489	RNA sequencing analysis of adult mixed phenotype acute leukemia (MPAL)	RNA sequencing analysis was performed from bone marrow samples of 24 adult mixed phenotype acute leukemia (MPAL) patients Overall design: RNA expression profiles of bone marrow samples from 24 adult mixed phenotype acute leukemia (MPAL) patients were generated by RNA-Seq using HiSeq 2000 platform.	Co-expression
SRP142503	BET bromodomain dependency in EWS/ETS driven Ewing Sarcoma	The pathognomonic EWS/ETS fusion transcription factors drive Ewing sarcoma (EWS) by orchestrating an oncogenic transcription program. Therapeutic targeting of EWS/ETS has not been successful; therefore identifying mediators of the EWS/ETS function could offer new therapeutic targets. Here we describe the dependency of chromatin reader BET bromodomain proteins in EWS/ETS driven transcription and investigate the potential of BET inhibitors in treating this lethal cancer. Similar to EWS/ETS fusions, knockdown of BET proteins BRD2/3/4 severely impaired the oncogenic phenotype of EWS cells. Notably, EWS/FLI1 and EWS/ERG was found to be in a transcriptional complex consisting of BRD4. RNA-Seq analysis upon BRD4 knockdown or its pharmacologic inhibition by the BET inhibitor JQ1 revealed an attenuated EWS/ETS transcriptional signature. In contrast to other reports, JQ1 reduced proliferation, and induced apoptosis through MYC-independent mechanism without affecting EWS/ETS protein levels, which was further confirmed by depleting BET proteins using PROTAC-BET degrader (BETd). Interestingly, polycomb repressive complex 2 (PRC2) associated factor PHF19 was downregulated by JQ1/BETd or BRD4 knockdown in multiple EWS cells. ChIP-seq analysis revealed occupancy of EWS/FLI1 at a distal regulatory element of PHF19 and its subsequent knockdown resulted in downregulation of PHF19 expression. Furthermore, deletion of PHF19 by CRISPR-Cas9 system lead to a decreased tumorigenic phenotype and increased sensitivity to JQ1. Importantly, PHF19 expression was associated with worse prognosis of Ewing sarcoma patients.  In vivo, JQ1 demonstrated anti-tumor efficacy in multiple mouse xenograft models of EWS. Together, these results indicate that EWS/ETS require BET epigenetic reader proteins for its transcriptional program including PHF19 expression, which can be mitigated by BET inhibitors. Moreover, this study provides a clear rationale for the clinical utility of BET inhibitors in treating Ewing sarcoma. Overall design: Gene epxression by RNAseq in the ewing sarcoma cell lines with knockdown of EWS-FLI1, BRD4 or JQ1 treament, knockout of PHF19	Co-expression
SRP142547	Role of JMJD1A/KDM3A in HCT116 colorectal cancer cells	The goal of this study was to determine the impact of the histone demethylase JMJD1A (also called KDM3A) on gene transcription in colorectal cancer cells.	Co-expression
SRP142570	High throughout long non-coding RNA sequencing of nasopharyngeal carcinoma from chronic nasopharyngitis patients	The objective of our study was to identify a lncRNA expression profile in tissue of patients with nasopharyngeal carcinoma.	Co-expression
SRP142599	Quantitative whole transcriptomics sequencing of progeria-derived cells point to a key role of nucleotide metabolism in premature aging	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived PG and their healthy progenitor lines transcriptome profiling (RNA-seq) to proteomic methods (iTRAQ) and to evaluate these protocols for optimal high-throughput data analysis Methods: The raw RNA-Seq reads for each sample were aligned to the reference human genome browser (GRCh38.p12 assembly) using Bowtie2 and Tophat2. Results: An average of 23 million paired-end 100-bp reads was obtained per sample. After alignment, raw sequence read depths were converted to estimate transcript abundance measured as fragments per kilobase of exons per million (FPKM), and the cuffinks of differentially expressed genes and transcripts were calculate with Cuffdidd. Conclusions: Our study represents a detailed analysis of human PG lines transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell pathological line. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: The sequencing data was generated on Hiseq 1500 on a rapid mode flow cell from Illumina.	Co-expression
SRP142608	Genome-wide transcriptome profiling of NEDD9-regulated genes using RNA-seq	Purpose:This study is to examine NEDD9-regulated and aldosterone-induced gene expression to understand the roles of NEDD9 and aldosterone in pulmonary arterial hypertension and pulmonary arterial fibrosis. The hypothesis tested here is whether there is a cross-talk between NEDD9 regulation and aldosterone signaling pathway in human pulmonary artery endothelial cells. Methods: mRNA profiles of human pulmonary artery endothelial cells were generated by deep sequencing, in triplicate, using Ilumina Hiseq 2000. The sequence reads that passed quality filters were aligned to the human reference genome (hg19) using Tophat2. Results: RNA-seq based transcriptome characterization revealed a number of NEDD9-regulated and aldosterone-induced profibrotic genes. Conclusions: RNA-seq based transcriptome analysis helps to make biological discoveries and decipher complex biological functions. Overall design: Transcriptome analysis was performed on human pulmonary artery endothelial cells. Six samples were transfected with NEDD9 siRNA and treated with aldosterone or vehicle control. 12 additional samples were directly treated with aldosterone or vehicle control.	Co-expression
SRP142614	RNA-seq of CD33 KO and control HSPCs	Gene expression profile of in vitro differentiated control and CD33 KO CD34+ cells (with 70-85% CD33 KO) were analyzed by RNA-seq to exclude any major impact of CD33 loss on downstream gene expression Overall design: Primary CD34+ cells were treated with CRISPR/Cas9 to disrupt the CD33 gene and grown in culture for 5-7 days prior to analysis; mRNA profile was compared to control cells from the same donor that were also treated with Cas9 and a control gRNA; 5 different donors were evaluated (CD33 KO/control for each = total 10 samples)	Co-expression
SRP142722	EIF1AX-A113 splice and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC	Translation initiation in higher eukaryotes is orchestrated by the tight regulation of the cap binding and the 43S pre-initiation complexes (PIC). The PIC component eukaryotic initiation factor 1A (EIF1A), encoded on human chromosomes X and Y by EIF1AX and EIF1AY, respectively, is essential for recruitment of the ternary complex and for assembling the 43S PIC, which after recruitment onto capped mRNAs scans their 5'UTR and localizes the AUG to initiate translation. Recurrent EIF1AX mutations are found in several cancers, including ~1% of papillary thyroid cancers in a mutually exclusive manner with other drivers (BRAF, RAS, and oncogenic fusions). They are enriched in advanced thyroid cancers (11%) where they display a striking co-occurrence with RAS, which we show cooperate to induce tumorigenesis in mouse models and in isogenic cell lines. The C-terminal tail EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer, and private to this disease. We found that EIF1AX-A113spl variants stabilize the PIC and induces ATF4 expression, a sensor of cellular stress, which is co-opted to suppress EIF-2a phosphorylation, thus enabling a general increase in protein synthetic rate. RAS stabilizes c-MYC, an effect augmented by EIF1AX-A113spl. ATF4 and c-MYC induce expression of aminoacid transporters, and enhance sensitivity of mTOR to aminoacid supply. These mutually reinforcing events generate therapeutic vulnerabilities to MEK, BRD4 and mTOR kinase inhibitors. The RNA-Seq and Ribosome Profiling samples provided here were used to support the claim of increased translational efficiency of ATF4. Overall design: Comparison of Ribosome footprints in the context of EIF1AX-splice mutated (C643) and splice reverted isogenic cell line (C643-spl- rev), three replicates of ribosome-protected RNA sequencing and three replicates of RNA-seq were used. Additionally, 3 replicates of RNA-seq comparing KRAS G12R mutant CAL62 vs. CAL62-splice, an isogenic cell line generated with CRISPR-Cas9 mediated knock in of EIF1AX-splice mutation.	Co-expression
SRP143362	CAGE profiling after treatment with JQ1 BET inhibitor in lung cancer cell line.	The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner. Overall design: Lung cancer cell line H23 was treated with JQ1 BET inhibitor. Gene expression profiling by CAGE was performed after 0h, 3h, 6h, 12h and 24h.	Co-expression
SRP143452	Translational control through differential ribosome pausing during amino acid limitation in mammalian cells	Limitation for amino acids is thought to regulate translation in mammalian cells primarily by signaling through the kinases mTORC1 and GCN2. We find that limitation for the amino acid arginine causes a selective loss of tRNA charging, which regulates translation through ribosome pausing at two of six arginine codons. Interestingly, limitation for leucine, an essential and abundant amino acid in protein, results in little or no ribosome pausing. Chemical and genetic perturbation of mTORC1 and GCN2 signaling revealed that their robust response to leucine limitation prevents ribosome pausing, while an insufficient response to arginine limitation led to loss of arginine tRNA charging and ribosome pausing. Codon-specific ribosome pausing decreased protein production and triggered premature ribosome termination without significantly reducing mRNA levels. Together, our results suggest that amino acids which are not optimally sensed by the mTORC1 and GCN2 pathways still regulate translation through an evolutionarily conserved mechanism based on synonymous codon usage. Overall design: Ribosome profiling was performed in HEK293T, HCT116, or HeLa cells during limitation for leucine or arginine for 3 or 6 hours to determine the effect of limiting single amino acid levels of ribosome elongation kinetics at the cognate codons. The same cell lines grown in nutrient-rich conditions were used as a control. These experiments were repeated in HEK293T cells with 250 nM Torin1, in cells stably expressing a flag-tagged wild-type or Q99L mutant RagB-GTPase or hrGFP, and in a GCN2 knockout cell line to determine the role of the mTORC1 and GCN2 pathways.	Co-expression
SRP143514	The Transcriptional Signature of Growth in Human Fetal Aortic Valve Development	Discarded human aortic valve samples from the second trimester, six from early (14, 15, 17 weeks), and six from late timepoints (20, 21, 22 weeks) were collected. RNA was isolated and cDNA libraries were sequenced. Network analysis of RNASeq data identified subnetworks of significantly increasing and decreasing transcripts; subsequent cluster analysis identified patterns of transcription through the time course. Pathway enrichment analysis determined the predominant biological processes at each interval.	Co-expression
SRP143517	RNA sequencing analysis of decidua tissues from unexplained recurrent spontaneous abortion patients and controls with induced abortions	Recurrent spontaneous abortion (RSA), defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation, affects approximately 1% of couples attempting to conceive. However, the underlying mechanisms of 50% of cases are unknown. The decidua plays a crucial role during pregnancy, which can provide a delicate balance between immune tolerance and defense to maintain the pregnancy.We performed RNA-seq to identify gene expression alterations in the deciduas of RSA patients and controls. RNA-seq was done using TruSeq Stranded mRNA Library Preparation. Briefly, intact RNA was fragmented, end repaired, adapter ligation and PCR amplified following illumina protocol. Libraries were sequencing by illumins Hiseq 2000. After quality control, sequence data were processed with STAR to generate read alignments with hg19. Raw read counts for annotated genes were obtained with featureCounts with default settings, normalized and analyzed using DEseq2. Overall design: Intact RNA isolated from 6 human decidua tissues was fragmented, end repaired, adapter ligation and PCR amplified following illumina protocol. Libraries were sequencing by illumins Hiseq 2000.	Co-expression
SRP143521	Trans-differentiation of human adult peripheral blood T cells into neurons	Examining the transcriptomic changes during transdifferentiation of peripheral blood mononuclear cells to induced neuronal cells. Overall design: There are three different populations: PBMC (2 biological replicates, starting population), PSA-NCAM+GFP+ (2 biological replicates, induced neuronal cells) and PSA-NCAM+GFP- (2 biological replicates, induced neuronal cells).	Co-expression
SRP143627	human Distal convoluted tubule with Vpr	human DCT cell line with Vpr	Co-expression
SRP143647	Transcriptome  profiling of mesenchymal stem cells cultured in 3D functionalized hydrogels	Therapeutic applications for mesenchymal stem/stromal cells (MSCs) are growing, including the treatment of chronic wounds ; however, the successful implementation of these therapies requires the development of appropriate MSC delivery systems. Hydrogels are ideally suited to cultivate MSCs in 3D but tuning their properties to match their specific in vivo applications remains a challenge. Herein, we have tethered integrin-binding small molecules to well-defined, cell-degradable hydrogels based on bioinert poly(ethylene glycol) (PEG) tethered with specific integrin-binding peptides and have characterized the resulting effects that these culture systems have on the MSC transcriptome when compared to 2D cultured and untethered 3D hydrogel cultured MSCs. The 3D culture systems resulted in the differential expression of 1,911 genes, many of which were related to the production of extracellular matrix proteins and/or MSC differentiation. In general, genes important for osteogenic differentiation were upregulated in 3D hydrogel cultures; however, the expression of these genes could be partially suppressed by tethering an integrin-binding RGD peptide within the hydrogel.	Co-expression
SRP143700	m6A/m-Seq of human B-lymphocyte cell lines from healthy controls and major depressive disorder patients	N6-Methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed m6A/m, in the human stress response are currently unknown.  Here, we provide m6A/m-Seq of immortalied cell lines derived from B lymphocytes from male healthy donors or male donors diagnosed with major depressive disorder (MDD), harvested 1 h after treatment with 100 nM cortisol or mock treatment. PolyA-RNA-fragments of each sample was processed both as m6A/m-sample (RNA immunoprecipiation RIP with an m6A and m6Am antibody) and RNA-input sample. Overall design: 3 biological replicates of cells from healthy male donors and 3 biological replicates of cells from male donors diagnosed with major depressive disorder each split in two treatment samples: mock treatment (ethanol only) or  100 nM cortisol in ethanol for 1 h creating 4 groups with each 3 biological replicates: healthy-mock: H_x_M, healthy-cortisol: H_x_C, MDD-mock: M_x_M and MDD-cortisol: M_x_C.  Each samples was processed as m6A/m-immunoprecipitation-sample ("m6A") or as input RNA samples ("RNA"). Additionally, 1 RNA sample (equimolar mixed from all samples) was processed as IgG control.	Co-expression
SRP144003	RNA-seq from HNSCC and melanoma populations	Populations were sorted from tumor speciments via flow cytometry using EPCAM, FAP, CD45, and CD31 surface markers Overall design: RNA-seq profiling from sorted populations from head and neck squamous carcinomas and melanomas	Co-expression
SRP144009	Transcriptome sequencing after MAGOHB knockdown in MAGOH-deleted or non-deleted cancer cells	Transcriptome profiling was performed after knocking down MAGOHB in ChagoK1 cells or ChagoK1 cells with ectopic re-expression of MAGOH-V5 Overall design: Knockdown of MAGOHB in either a hemizygous MAGOH-deleted or MAGOH-reconstituted context	Co-expression
SRP144076	Nascent RNA Sequencing after NMYC activation in SH-EP MYCNER cells	In order to distinguish transcription changes from RNA modification and post transcription changed, nascent RNA seq via metabolic labeling of freshly synthesized RNA was carried out using 4sU labeling/biotin purification. Overall design: nascent RNA was extractred post N-MYC activation and compared with untreated cells nascent RNA to gather fold changes of pre-mRNA on gene basis.	Co-expression
SRP144178	TimeSignature: A Universal Method for Robust Detection of Circadian State from Gene Expression	Profiles of circadian gene expression in whole blood from 11 healthy adult subjects. Abstract: Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burden some to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here we introduce TimeSignature, a new algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using Pdistinct microarrays, and further validate it against a new set of samples profiled by RNA-Seq. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique amongst expression–based predictors, and addresses a major challenge in the development of generalizable, clinically–useful tests. Overall design: Whole blood transcriptional profiles of 11 individuals with intermediate circadian phenotype, were generated by RNA sequencing, using Illumina NextGen 500. Whole blood was collected every 2hr over 28hr (15 time points), yelding total of 165 samples, of which 153 passed the QA and underwent further analysis.	Co-expression
SRP144188	RNA Sequencing of Human iPS derived Cardiomyocytes	To investigate transcriptional differences between HCM and WT cells Overall design: Examination of HCM vs WT Cells, with 3 replicates of each sample	Co-expression
SRP144212	CDK12 mediated transcriptional regulation in U2OS cells	While activation of canonical NF-?B signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-?B pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin ß receptor (LTßR)- and FN14-dependent p52 nuclear translocation, but not TNFa receptor (TNFR)-mediated, canonical NF-?B p65 nuclear translocation. Chemoproteomics identified cyclin dependent kinase 12 (CDK12) as the target of 919278. CDK12 inhibition by 919278, THZ1, or siRNA knock down all affect similar global transcriptional changes and prevent LTßR and FN14-dependent MAP3K14 (NIK) mRNA induction and subsequent protein accumulation. In addition, 919278 and THZ1 treatment reduce RNA Pol II CTD phosphorylation. This powerful approach of coupling a phenotypic screen with chemoproteomics revealed a novel regulatory pathway of the non-canonical NF-?B pathway that could serve as a therapeutic target in autoimmunity and cancer. Overall design: There are TWEAK stimulated and unstimulated conditions, 4hr and 24hr time points. 7 treatments (DMSO, BIO0702697, BIO0919278, BIO032202, NTsiRNA, siRNAs523626, siRNAs523629) in duplicates. In total, 56 sample were sequenced and analyzed.	Co-expression
SRP144303	Genome-wide profiling of cervical RNA-binding proteins identified HPV regulation of RNASEH2A expression by viral E7 and E2F1	RNA-binding proteins (RBPs) have been shown to control mRNA processing, stability, transport, editing and translation. Application of large-scale quantitative technologies has facilitated genome-wide identification of RBPs and linked their defects to human diseases and carcinogenesis. We have recently conducted transcriptome analysis comparing normal cervical tissues with HPV-positive cervical cancer tissues by using two different RNA-seq platforms. As the results, 614 differentially expressed protein-coding transcripts were identified, which are enriched in cancer related pathways and consist of 95 known RBPs. TaqMan RT-qPCR was used to verify altered expression of 26 genes with a cohort of 72 cervical samples, including 24 normal cervical, 25 CIN 2-3, and 23 cervical cancer tissues. LY6K, FAM83A, CELSR3, ASF1B, IQGAP3, SEMA3F, CLDN10, MSX1, CXCL5, ASRGL1, ELAVL2, GRB7, KHSRP, NOVA1, PTBP1 and RNASEH2A were identified being novel candidates in association with cervical lesion progression and carcinogenesis. We further demonstrated that HPV16 or HPV18 infection leads to altered expression of 8 RBP genes (CDKN2A, ELAVL2, GRB7, HSPB1, KHSRP, NOVA1, PTBP1, and RNASEH2A) in human vaginal and foreskin keratinocytes.  While both viral E6 and E7 decrease NOVA1 expression, viral E7 was found to increase the expression of both RNASEH2A and PCNA in an E2F1 dependent manner, two key factors closely associated with the progression of cervical neoplasia. By illustration of the first comprehensive cervical genome expression atlas, we have identified the altered expression of many novel genes due to HPV infection, which could be biomarkers for better diagnosis and treatment of cervical cancer. Overall design: Gene expression patterns of seven normal cervical tissues were compared with that of seven cervical cancer tissues by two different RNA-seq platforms. Additional 72 clinical samples and HPV-infected keratinocytes were analyzed by RT-qPCR to verify the HPV-infection altered gene expression.	Co-expression
SRP144316	RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing	RBM20 heterozygous (Het) and homozygous (Homo) R636S and homozygous 8-bp deletion (which causes nonsense-mediated decay) mutations were created by genome editing in an iPS cell line generated from a healthy male patient. Those cells were differentiated into cardiomyocytes by modulating the WNT signaling pathway, and then are subjected to the lactate purification method. Overall design: RNAseq of iPS cell-derived cardiomyocytes with 4 different genotypes as replicates	Co-expression
SRP144363	Sequencing based maternal whole blood expression changes with gestational age and labor in normal pregnancy	Maternal plasama colected longitudinally were profiled using paired-end Illumina RNA-Seq with globin reduction to evaluate changes with gestational age and with labor in normal pregnancy. Overall design: The study included normal pregnancies with (n=8) and without (n=8) spontaneous labor at term.  Half of the women in each group had 3 longitudinal samples taken from 12.1-40.3 weeks of gestation, while the other half of women had only one sample taken at term before delivery, for a total of 32 samples.	Co-expression
SRP144369	Non-coding regions are the main source of tumor-specific antigens [human]	Purpose: Tumor-specific antigens (TSAs) represent ideal targets for cancer immunotherapy, but very few of them have been identified. Therefore, the goal of this study was to develop a novel approach, combining RNA-Sequencing and mass spectrometry, to enlarge the landscape of actionable TSAs in seven human primary samples, namely 4 B-ALL and 3 lung tumor biopsies. Methods: We performed RNA-Sequencing on each primary tumor sample (unreplicated) with the Illumina HiSeq2000. Using those RNA-Sequencing data to build a global cancer database for each sample, we performed a transcriptomic-informed mass spectrometry analysis of their MHC I-associated peptides to identify TSAs. Results: We identified a total of 30 TSAs, 90% of which derived from allegedly non-coding regions and would have been missed by standard approaches. Moreover, most of these TSAs derived from non-mutated yet cancer-restricted transcripts that can be shared by multiple tumors. Conclusions: In conclusion, the strategy reported herein is readily applicable to human tumors and should considerably enlarge the landscape of actionable TSAs. Overall design: Transcriptomic analysis of 7 human primary tumor samples using the Illumina HiSeq 2000.	Co-expression
SRP144382	mRNA-seq Whole Transcriptome Profiling of Fresh Frozen versus Archived Fixed Tissues	Background: The main bottleneck for genomic studies of tumors is the limited availability of fresh frozen (FF) samples collected from patients, coupled with comprehensive long-term clinical follow-up. This shortage could be alleviated by using existing large archives of routinely obtained and stored Formalin-Fixed Paraffin-Embedded (FFPE) tissues. However, since these samples are partially degraded, their RNA sequencing is technically challenging. Results: In an effort to establish a reliable and practical procedure, we compared three protocols for RNA sequencing using pairs of FF and FFPE samples, both taken from the same breast tumor. In contrast to previous studies, we compared the expression profiles obtained from the two matched sample types, using the same protocol for both. Three protocols were tested on low initial amounts of RNA, as little as 100 ng, to represent the possibly limited availability of clinical samples. For two of the three protocols tested, poly(A) selection (mRNA-seq) and ribosomal-depletion, the total gene expression profiles of matched FF and FFPE pairs were highly correlated. For both protocols, differential gene expression between two FFPE samples was in agreement with their matched FF samples. Notably, although expression levels of FFPE samples by mRNA-seq were mainly represented by the 3'-end of the transcript, they yielded very similar results to those obtained by ribosomal-depletion protocol, which produces uniform coverage across the transcript. Further, focusing on clinically relevant genes, we showed that the high correlation between expression levels persists at higher resolutions. Conclusions: Using the poly(A) protocol for FFPE exhibited, unexpectedly, similar efficiency to the ribosomal-depletion protocol, with the latter requiring much higher (2-3 fold) sequencing depth to compensate for the relative low fraction of reads mapped to the transcriptome. The results indicate that standard poly(A)-based RNA sequencing of archived FFPE samples is a reliable and cost-effective alternative for measuring mRNA-seq on FF samples. Expression profiling of FFPE samples by mRNA-seq can facilitate much needed extensive retrospective clinical genomic studies. Overall design: We perform an unbiased evaluation of RNA-seq of archived tumor tissues by comparing the same library preparation methods for both FF and FFPE matched tumor samples and for small amounts of total RNA starting material. We have 3 matched FF/FFPE tumor samples with a moderate archival time of about 4-5 years (T1=T3), and additional 3 FFPE tumor samples archived for more than 10 years (T4-T6). all samples were tested with two protocols: illumina Truseq RNA after poly(A) selection (mRNA-seq); and Truseq after ribosomal depletion (RiboZero). Several initial amounts of starting material was tested for eacg protocol.	Co-expression
SRP144426	Illumina HiSeq Sequencing on Breast cancer PDX samples	RNAseq was done on Breast cancer PDX samples uisng Library protocol =llumina TruSeq Stranded Total RNA Kit with Ribo-Zero Gold , HiSeq 50 Cycle Single-Read Sequencing v4 Overall design: Single Readsequencing of PDX samples	Co-expression
SRP144485	Human 5' UTR design and variant effect prediction from a massively parallel translation assay	Predicting the impact of cis-regulatory sequence on gene expression is a foundational challenge for biology. We combine polysome profiling of hundreds of thousands of randomized 5' UTRs with deep learning to build a predictive model that relates human 5' UTR sequence to translation. Together with a genetic algorithm, we use the model to engineer new 5? UTRs that accurately target specified levels of ribosome loading, providing the ability to tune sequences for optimal protein expression. We show that the same approach can be extended to chemically modified RNA, an important feature for applications in mRNA therapeutics and synthetic biology. We test 35,000 truncated human 5' UTRs and 3,577 naturally-occurring variants and show that the model accurately predicts ribosome loading of these sequences. Finally, we provide evidence of 47 SNVs associated with human diseases that cause a significant change in ribosome loading and thus a plausible molecular basis for disease. Overall design: Polysom profiling and sequencing was performed using a library of 300,000 randomized 5' UTR 50-mers with eGFP used as the CDS. Three RNA chemistries were tested: unmodified, pseudouridine, and 1-methylpseudouridine. These were performed in duplicate (6 samples total). A designed library that includes human 5' UTRs, SNVs, and sequences engineered with a genetic algorithm was used with the eGFP CDS (no duplicate). A second randomized library used mCherry as the CDS, also performed in duplicate.	Co-expression
SRP144491	Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis	Objective:Osteoarthritis (OA) is the most prevalent joint disease. As disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized for their importance in mediating the abnormal phenotype of cells in OA-affected joints. Here, we generated a genome-wide molecular profile of OA to elucidate regulatory mechanisms of OA pathogenesis and to identify possible therapeutic targets using integrative analysis of mRNA-sequencing data obtained from human knee cartilage. Methods:RNA-sequencing (RNA-seq) was performed on 18 normal and 20 OA human knee cartilage tissues. RNA-seq datasets were analysed to identify genes, pathways and regulatory networks that were dysregulated in OA. Results:RNA-seq data analysis revealed 1332 differentially expressed (DE) genes between OA and non-OA samples, including known and novel transcription factors (TFs). Pathway analysis identified 15 significantly perturbed pathways in OA with ECM-related, PI3K-Akt, HIF-1, FoxO and circadian rhythm pathways being the most significantly dysregulated. We selected differentially expressed TFs that are enriched for regulating DE genes in OA and prioritized these transcription factors by creating a cartilage-specific interaction subnetwork. This analysis revealed 8 TFs, including JUN, EGR1, JUND, FOSL2, MYC, KLF4, RELA, and FOS that both target large numbers of dysregulated genes in OA and are themselves suppressed in OA. Conclusion:We identified a novel subnetwork of dysregulated TFs that represent new mediators of abnormal gene expression and promising therapeutic targets in OA. Overall design: RNA-sequencing (RNA-seq) was performed on 18 normal and 20 OA human knee cartilage tissues. RNA-seq datasets were analysed to identify genes, pathways and regulatory networks that were dysregulated in OA.	Co-expression
SRP144495	Identifying dormant cells in colorectal cancer spheroids	Cellular dormancy and heterogeneous cell cycle lengths provide important explanations for treatment failure following adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC) yet the molecular control of the dormant versus cycling state remains unknown.  In CRCs dormant cells are found to be highly clonogenic and resistant to chemotherapies.  We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumour cells. Overall design: Six colorectal cancer cell lines (DLD1, HCT15, HT55, SW948, RKO and SW48) were labelled with the cell permeable dye CFSE and then grown in non-adherent spheroid culture for 6 days to enable identification of dormant cells that retain CFSE (LRC) and cycling cells (BULK).  LRCs and BULK populations were then FACS sorted from each cell line in quadruplicate. As a control experiment, to identify off-target effects of the CFSE dye and culture artefacts, BULK populations from DLD1 cells at d1 and d6 after seeding both with and without CFSE labelling were included in the RNAseq analysis.  RNA was extracted using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific).  RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions.  Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina).  Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.	Co-expression
SRP144496	Identifying the molecular mode of action of itraconazole in colorectal cancer	Two cell lines (HT55 and SW948) were found responsive to itraconazole treatment.  To identify the mode of action cells were treated with itraconazole or control (DMSO) and then subjected to RNAseq analysis once the phenotype had developed Overall design: HT55 and SW948 cells were seeded in adherent culture and treated with 5uM itraconazole or DMSO for 6 days.  Cells then underwent RNA extraction using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific).  RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions.  Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina).  Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.	Co-expression
SRP144499	Gene expression analysis of prostate cancer cells treated with fatty acid synthase (FASN) inhibitor IPI-9119	Alterations in gene expression following fatty acid synthase inhibtion were evaluated in androgen sensitive LNCaP cells and castration resistant 22Rv1 and LNCaP-95 cells.  Cell were exposed to 2 concentrations (0.1 and 0.5 uM) of  FASN inhibitor IPI-9119 or DMSO for 6 days. Overall design: Differential gene expression anlaysis in 3  prostate cancer cell lines treated with FASN inhibitor IPI-9119	Co-expression
SRP144515	m6A mRNA methylation controls the innate immune response to infection by targeting interferon ß	N6-methyladenosine (m6A), the most abundant mRNA modification, was shown to alter the life cycles of diverse DNA and RNA viruses. These effects were proposed to be mediated in a virus-specific manner, through dysregulated methylation of viral RNA. We use RNA-seq to systematically follow differences in gene expression in cells depleted of m6A machinery, compared to control cells, following human cytomegalovirus (HCMV) infection. We show that following viral infection or stimulation of cells with an inactivated virus, depletion of the m6A 'writer' protein METTL3  or 'reader' protein YTHDF2 leads to a dramatic increase in the induction of hundreds of interferon-stimulated genes (ISGs), which constitutes the first line of antiviral defense. Consequently, propagation of different viruses is markedly suppressed in an interferon (IFN)-signaling dependent manner. Furthermore, we used m6A-immunoprecipitation, followed by RNA-seq, to map m6A sites on human and HCMV transcripts, and found that the mRNA of IFNß, the central cytokine that drives the type I IFN response, is m6A modified, and is stabilized upon repression of METTL3 and YTHDF2. Overall design: mRNA-seq of total mRNA and m6A-immunoprecipitated mRNA from METTL3-depleted and control human fibroblasts, following HCMV infection.	Co-expression
SRP144520	The splicing factor RBM25 controls MYC activity in Acute Myeloid Leukemia	Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome. Overall design: Examined transcriptome from U937 cells in biological triplicates.	Co-expression
SRP144523	fixSINC-seq: Electrical lysis and RNA extraction from fixed single cells	No description.	Co-expression
SRP144588	Targeted sequencing based maternal whole blood expression changes with gestational age and labor in normal pregnancy	Maternal plasama colected longitudinally were profiled using targeted sequencing (DriverMapâ„¢) (https://www.cellecta.com) to evaluate changes with gestational age and with labor in normal pregnancy. Overall design: The study included normal pregnancies with (TIL) (n=8) and without (TNL) (n=8) spontaneous labor at term.  Half of the women in each group had 3 longitudinal samples taken from 12.1-40.3 weeks of gestation, while the other half of women had only one sample taken at term before delivery, for a total of 32 samples.  Note that Sample_26 was considered contaminated and hence data for that sample was not included in downstream analyses.	Co-expression
SRP144604	The combination of cantharidin and anti-angiogenic therapeutics presents synergistic antitumor effects against pancreatic cancer	Background: Cantharidin, an active constituent of mylabris, is believed to have anti-tumor activity. Cantharidin selectively inhibit protein phosphatase 2A (PP2A), a repressor of oncogenic kinase pathways (ERK, JNK, NF-?B, and PKC). Cantharidin represses the growth and metastasis of pancreatic cancer cells in vitro. In the present study, we investigated the effects of cantharidin on pancreatic cancer xenografts in vivo.   Methods: Cells stably expressing luciferase were used to establish xenograft models. Xenograft growth was evaluated by living imaging. Gene expression was determined using a microarray, real-time PCR, a RayBiotech antibody array, and the Milliplex assay.   Results: Surprisingly, cantharidin significantly accelerated xenograft growth. Living imaging showed a rapid distribution of D-luciferin in cantharidin-treated xenografts, suggesting a rich blood supply. Immunohistochemistry confirmed increased angiogenesis. Microarray and antibody array identified upregulated pro-angiogenic and downregulated anti-angiogenic factors. The Milliplex assay suggested elevated secretion of IL-6, IL-8, TNF-a, and VEGF. ERK, JNK, NF-?B, and PKC pathway inhibitors attenuated the cantharidin-induced changes to pro-angiogenic gene expression. PKC pathway-inhibiting tamoxifen or antiangiogenic therapeutics, including Ginsenoside Rg3, bevacizumab, Apatinib, and Endostar antagonized the pro-angiogenic effect of cantharidin or its derivatives. These regimens presented remarkable synergistic antitumor effects in vivo.   Conclusion: Although cantharidin presents anti-tumor effects in vitro and has been applied in clinical practice, we revealed an unfavorable pro-angiogenic side effect. We recommend that the clinical application of cantharidin should be performed on the premise of anti-vascularization therapy. Overall design: Examination of gene expression profiles after treatment with Ginsenoside Rg3 or tamoxifen in PANC-1 cells	Co-expression
SRP144623	Discovery of a Drug Candidate for GLIS3-Associated Diabetes	Through development and use of a minimal component protocol for derivation of late stage pancreatic progenitors and beta-like cells, we compared WT and GLIS3-/- pancreatic cells at different stages and discovered that GLIS3-/- cells show an ectopic activation of TGF-beta signaling. Overall design: Comparison of WT and GLIS3-/- cells at various stages of human pancreatic differentiation	Co-expression
SRP144647	Transcriptomes from naïve CD4+ T-cells from infants and children with and without food allergy [RNA-seq]	Here we studied the epigenetic regulation of the naïve CD4+ T-cell activation response among children with IgE-mediated food allergy. Using integrated DNA methylation and transcriptomic profiling, we found that food allergy in infancy is associated with dysregulation of T-cell activation genes. Reduced expression of cell cycle related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) were associated with poorer T-lymphoproliferative responses in infancy after polyclonal activation of the T-cell receptor. Overall design: mRNA sequencing of naïve CD4+ T-cells under two conditions (anti-CD3+CD28 activated, or quiescent) at two ages (baseline (12months) and followup (2 or 4 years)) in allergic and non-allergic children.	Co-expression
SRP144658	Transcriptional Targeting Of Oncogene Addiction In Medullary Thyroid Cancer [RNA-Seq]	Metastatic medullary thyroid cancer (MTC) is a currently incurable disease. FDA approved therapies that target RET, a commonly mutated receptor tyrosine kinase in MTC, and other receptor tyrosine kinases, do not result in complete responses and acquired resistance is universal due to “gatekeeper” mutation in Ret or overactivation of alternative signaling pathways. Based on data from human MTCs and a number of murine models, the CDK/RB cell cycle pathway is a potential alternative target for MTC. The objective of this study was to determine if CDKs represent therapeutic targets for MTC and to define mechanisms of activity. We demonstrate that targeting the CDK/RB pathway with Palbociclib (CDK4/6 inhibitor) is not cytotoxic to MTC cells but that Dinaciclib (CDK1/2/5/9 inhibitor) remarkably reduced cell viability and proliferation at low doses in two MTC cell lines accompanied by loss of CDK9 and RET protein and mRNA levels. In human tumors, CDK9 protein was highly expressed and array CGH demonstrated copy number gain in 11/30 analyzed tumors. RNA sequencing demonstrated that RNA polymerase II-dependent transcription was markedly reduced by Dinaciclib, consistent with transcriptional mode of action. Subsequent studies using the CDK7 inhibitor, THZ1, demonstrated high potency vs. the MTC cell lines and marked loss of RET mRNA and protein. In silico analysis, and CHIP-Sequencing using H3K27Ac antibody confirmed that RET is associated with a super-enhancer in RET-mutated MTC cells. In summary, this study reveals a novel mechanism of RET transcription regulation that represents a potentially translatable finding for new therapeutic approaches for RET-mutated MTC. Overall design: mRNA profiles of TT and MZ-CRC-1 cells treated with Dinaciclib or vehicle control for 12h and 24h were generated	Co-expression
SRP144725	Transcriptomic Analysis of Wild Type and FOXA2-/- ES-derived Pancreatic Progenitors	Transcriptomic Analysis of Wild Type and FOXA2-/- ES-derived Pancreatic Progenitors Overall design: Examination of triplicates per genotypes for each differentiation stage	Co-expression
SRP144750	Stromal Fibroblasts Drive Single Cell Heterogeneity in Pancreatic Cancer	To understand the interplay between cancer and stroma, we performed single cell RNA-sequencing of PDAC cells admixed with stromal fibroblasts and defined different single cell populations with varying levels of proliferative and metastatic transcriptional states. PDAC cell behavior in vitro and in vivo on these phenotypic axes could be tuned with the proportion of stromal fibroblasts. These cell types were identified in human pancreatic tumors, and specific subpopulations were associated with worsened outcomes. Overall design: 92 single PDAC cells and 92 single CAF cells were micromanipulated and prepared for sequencing (23 of each cell type from four culture ratios). The 24th sample from each cell type-culture condition combination is a population control obtained by micromanipulating 100 cells of the given type from the given culture condition and preparing it as if it were a single cell, giving a total of 96 PDAC samples and 96 CAF samples. During the course of library construction, 3 samples were lost, all PDAC cells from the 30:70 condition (two single cells and the population control), leaving 93 total PDAC samples and 96 total CAF samples.	Co-expression
SRP144912	Pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program	Ectopic expression of defined transcription factors can force direct cell fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory towards distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 (AS) encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. Intriguingly, during this transient state key signaling components relevant for neural induction and neural stem cell maintenance are regulated and functionally contribute to iN reprogramming and maturation. Thus, AS-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates. Overall design: Single-cell transcriptomes from multiple time points and conditions during direct conversion of human pericytes into induced pericytes through the overexpression of defined factors. Please note that [1] the *ctrl samples represent mock-transfected cells (analyzed along side of the transfected cells) [2] The cell type (for each sample) is provided as 'pericytes or pericyte-derived induced neuronal cells' (as they are in a differentiation continuum from pericytes to neurons due to the treatment protocol) with the combination of 'genotype/variation' and 'time point' information.	Co-expression
SRP144983	LPS Sensing Mounts an Adaptive MSC Response Enhancing Neutrophil Activation and Wound Healing	We here addressed the question whether the unique capacity of mesenchymal stromal/stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense pathogen associated molecular pattern (PAMP) and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs which had been primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurred, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS treated MSCs as deduced from RNA-seq analysis and its validation.  A network of genes mediating the adaptive response through the TLR-4 pathway responsible for neutrophil activation (GCP- 2, ENA-78, IL-1ß IL-8) and MSC protection (SOX6) profoundly contributes to enhanced wound healing. In fact, silencing of either TRL-4, or IRAK3, a downstream effector of TRL-4, or SOX6 suppressed wound healing most likely due to suppression of neutrophil extracellular trap formation and suppression of the enhanced microbicidal release of reactive oxygen species (ROS), key features of neutrophil activation. This previously unreported results uncover SOX6 which protects MSCs at the wound site from enhanced oxidative stress. This unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds. Overall design: Transcriptome profiling of MSCs	Co-expression
SRP144991	Nuclear transcriptomes of atrial cardiac myocytes	Analysis of nuclear atrial gene expression in purified atrial cardiac myocyte nuclei isolated from right atrial appendages from adult patients undergoing open-heart surgery for coronary bypass or valve correction.	Co-expression
SRP145002	Repurposing of promoters and enhancers during mammalian evolution	The spatiotemporal control of gene expression exerted by promoters and enhancers is central for organismal development, physiology and behaviour. These two types of regulatory elements have long been distinguished from each other based on their function, but recent work highlighted common architectural and functional features. It also suggested that inheritable alterations in the epigenetic and sequence context of regulatory elements might underlie evolutionary changes of their principal activity, which could result in changes in the transcriptional profile of genes under their control or even facilitate the birth of new genes. Here, based on integrated cross-mammalian analyses of DNase hypersensitivity, chromatin modification and transcriptional data, we provide support for this hypothesis by detecting 445 regulatory elements with signatures of activity turnover in sister species from the primate and rodent lineages (termed "P/E" elements). Through the comparison with outgroup species, we defined the directionality of turnover events, which revealed that most instances represent transformations of putative ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5' exons. Notably, P/E elements have distinct GC sequence compositions and stabilizing 5' splicing (U1) regulatory motif patterns, which may predispose them to functional repurposing during evolution. Moreover, we trace changes in the U1 and polyadenylation signal densities and distributions that accompanied and likely drove the evolutionary activity switches. Overall, our work highlights functional repurposing as a notable mechanism that likely facilitated regulatory innovation and the origination of new genes and exons during mammalian evolution. Overall design: 78 single-end strand-specific RNA-seq libraries were generated from polyA-selected RNA from four organs (brain, heart, kidney and liver) from human, macaque, marmoset, mouse, rat and rabbit samples.	Co-expression
SRP145102	Characterization of human mosaic Rett syndrome brain tissue by single-nucleus RNA sequencing (Single-cell or single-nuclei RNA sequencing)	In females with X-linked genetic disorders, wild-type and mutant cells coexist within brain tissue because of random X-chromosome inactivation. This cellular mosaicism leads to phenotypic variability and poses significant challenges for interpreting the effects of X-linked mutant alleles on gene expression. We present a single-nucleus RNA sequencing approach that resolves mosaicism by using single nucleotide polymorphisms in genes that are expressed in cis with the X-linked mutation to determine whether individual nuclei express the wild-type or mutant allele even when the mutant gene is not directly detected. This approach enables genome-wide comparisons of gene expression between mutant and wild-type cells within the same individual and eliminates the variability introduced by comparisons to controls with different genetic backgrounds. We apply this approach to mosaic female mouse models and humans with Rett syndrome, an X-linked neurodevelopmental disorder caused by mutations in the methyl-DNA-binding protein MECP2, and reveal that cell-type-specific DNA methylation patterns largely predict the degree of gene upregulation by MECP2 in specific neuronal subtypes. The approach described here can be broadly applied to the characterization of gene expression in additional mosaic X-linked conditions. Overall design: Single-cell or single-nuclei RNA sequencing was performed on male and female MeCP2 mutant mice or human occipital cortex from Rett syndrome brain donors.	Co-expression
SRP145129	Homo sapiens isolate:iSLK219 Transcriptome or Gene expression	Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. RIG-I also has been shown to sense some DNA viruses, and host RNA polymerase III (RNA Pol III), a cytosolic DNA sensor, converts cytosolic AT-rich DNA into RNA to be sensed by RIG-I. We previously showed that the RIG-I restricts Kaposi Sarcoma-associated herpesvirus (KSHV) reactivation (J Virol. 2014 May;88(10):5778-87). In this study, we report that KSHV stimulates the RIG-I signaling pathway in an RNA Pol III-independent manner and subsequently induces type I IFN responses. Knockdown or inhibition of RNA Pol-III had no effect on IFN-ß induction by KSHV. By using CLIP (Cross-Linking and Immunoprecipitation) and RNA deep sequencing technologies, we identified multiple KSHV regions that give rise to RNA fragments binding to RIG-I, such as ORF810420-10496, ORF6411058-110675, Repeat region (LIR1)119059-119204, and ORF2543561-43650. The sequence dissimilarity between these fragments suggests that RIG-I detects a particular structure rather than a specific sequence motif. Synthesized ORF810420-10496 RNA stimulated RIG-I-dependent but RNA Pol III-independent IFN-ß signaling. In summary, some KSHV viral RNAs are sensed by RIG-I in an RNA Pol III-independent manner.	Co-expression
SRP145257	IRF1 regulates IFN dependent and independent gene expression	We report the RNA sequencig results for the constitutive and IFN inducible gene expression in respiratory epithelial cell line (BEAS-2B). We generated IRF1 KO BEAS-2B cells using CRISPR method.  Parent and IRF1 KO cells were treated with IFNß or IFN?1 for 24h and subjected for RNA isolation and sequencing in Illumina platform. Three independent biological experiments were used for RNA sequenccing. Overall design: Examination of constitutive and interferon inducible transcriptome by Illumina NGS. Tripliate biological experiments were used to compare the differential gene expression between parental cells to that of IRF1 KO cells.	Co-expression
SRP145260	Comprehensive transcriptome anaylsis of psoriasis in a Han Chinese population	Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of  DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes. Overall design: Nine normal skins from healthy volunteers and 18 lesional skins from patients with psoriasis vulgaris  were obtained for RNA sequencing	Co-expression
SRP145267	Decidualization of human endometrial stromal fibroblasts is a multi-phasic process involving distinct transcriptional programs	We sequenced mRNA from endometrial stromal fibroblasts and decidual stromal cells after 3 day and 8 days decidualization treatment Overall design: We sequenced mRNA from endometrial stromal fibroblasts (n=3), and after 3days (n=3) or 8 days (n=2) in vitro decidulization with cAMP and progesterone (MPA)	Co-expression
SRP145274	Pseudotime Ordering of Single Human Beta-Cells Reveals States of Insulin Production and Unfolded Protein Response	We report the pseudotime ordering of single non-diabetic human beta-cells detected by large-scale RNA sequencing. We identified major states with 1) low UPR and low insulin gene expression, 2) low UPR and high insulin gene expression or 3) high UPR and low insulin gene expression. The latter state was enriched for proliferating cells. Stressed human beta-cells do not dedifferentiate and show little propensity for apoptosis. These data suggest that human beta-cells transition between states with high rates of biosynthesis to fulfill the body's insulin requirements to maintain normal blood glucose levels and UPR-mediated recovery from ER stress due to high insulin production. Overall design: Single-cell RNA sequencing of human pancreatic islets	Co-expression
SRP145413	RNA-Seq of Breast and Ovarian Cancer Cell Lines	A panel of 20 commonly used cell lines were used for RNA-Seq in order to measure gene expression. Overall design: RNA-Seq in 20 cell lines	Co-expression
SRP145426	High-resolution comparative analysis of great ape genomes	We couple long-read sequence assembly, full-length cDNA sequencing, and a multi-platform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies where most genes are complete, gaps are closed, and novel gene models are identified. We further analyzed the overlap between structural variants in the human genome and gene expression differences in human and chimpanzee cells, including iPS-derived organoid radial glia cells. Overall design: Single cell mRNA sequencing of iPS-derived neural progenitor cells using the Fluidigm C1 system	Co-expression
SRP145485	RNA transcriptome sequencing analysis of SGC-7901 cells transfected with tcons_00001221 shRNA or control shRNA	An RNA transcriptome sequencing analysis was performed in SGC-7901 cells that were transfected with tcons_00001221 shRNA or control shRNA. Overall design: mRNA profiles of SGC-7901 cells transfected with tcons_00001221 shRNA or control shRNA.	Co-expression
SRP145493	Cell type specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders	Posttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.	Co-expression
SRP145502	AmpliSeq Transcriptome Analysis of Human Alveolar and Monocyte-Derived Macrophages Over Time in Response to Mycobacterium tuberculosis infection	Human alveolar macrophages (HAM) are primary bacterial niche and immune response cells during Mycobacterium tuberculosis (M.tb) infection, and human blood monocyte-derived macrophages (MDM) are a model for investigating M.tb-macrophage interactions. Here, we use a targeted RNA-Seq method to measure transcriptome-wide changes in RNA expression patterns of freshly obtained HAM (used within 6 h) and 6 day cultured MDM upon M.tb infection over time (2, 24 and 72 h), in both uninfected and infected cells from three donors each. The Ion AmpliSeqâ„¢ Transcriptome Human Gene Expression Kit (AmpliSeq) uses primers targeting 18,574 mRNAs and 2,228 non-coding RNAs (ncRNAs) for a total of 20,802 transcripts. AmpliSeqTM yields highly precise and reproducible gene expression profiles (R2 >0.99). Taking advantage of AmpliSeq's reproducibility, we establish well-defined quantitative RNA expression patterns of HAM versus MDM, including significant M.tb-inducible genes, in networks and pathways that differ in part between MDM and HAM. A similar number of expressed genes are detected at all time-points between uninfected MDM and HAM, in common pathways including inflammatory and immune functions, but canonical pathway differences also exist. In particular, at 2 h, multiple genes relevant to the immune response are preferentially expressed in either uninfected HAM or MDM, while the HAM RNA profiles approximate MDM profiles over time in culture, highlighting the unique RNA expression profile of freshly obtained HAM. MDM demonstrate a greater transcriptional response than HAM upon M.tb infection, with 2 to >10 times more genes up- or down-regulated. The results identify key genes involved in cellular responses to M.tb in two different human macrophage types. Follow-up bioinformatics analysis indicates that approximately 30% of response genes have expression quantitative trait loci (eQTLs in GTEx), common DNA variants that can influence host gene expression susceptibility or resistance to M.tb, illustrated with the TREM1 gene cluster and IL-10. Overall design: Assessment of transcriptome profiles from cells infected with Mycobacterium tuberculosis using AmpliSeq.	Co-expression
SRP145507	Estrogen receptor and mTOR signaling rewires cancer metabolism in obesity-associated breast cancer	Obesity is a risk factor for postmenopausal ERa (+) breast cancer. Molecular mechanisms activated by the factors from serum that contribute to this risk and how these mechanisms affect ERa signaling are yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in serum samples, which enabled us to focus on factors that were differentially present in serum from cancer-free vs. breast cancer susceptible and obese vs. non-obese post-menopausal women. These studies combined with in vitro assays identified free fatty acids (FFAs), as serum factors that correlate with increased proliferation and aggressiveness in ERa(+) breast cancer cells by. FFAs activated both ERa and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which target ERa and mTOR signaling, was able to block changes induced by FFAs. In fact, PaPEs were more effective in the presence of FFAs, suggesting a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ERa-(+) breast cancer in postmenopausal women. Our findings provide a basis for preventing or inhibiting obesity-associated breast cancer by using PaPEs that would reverse these newly appreciated metabolic properties of breast tumors in obese postmenopausal women. Overall design: Data set 1 (6 samples): For gene expression analysis, total RNA was extracted from 3 biological replicates for each ligand treatment using Trizol reagent and further cleaned using the RNeasy kit (QIAGEN). MCF-7 cells were treated with Veh (0.1% EtOH), 100 nM oleic acid (OA) in presence or absence of 1 µM PaPE-1 for 24 h. Once the sample quality and replicate reproducibility were verified, 2 samples from each group were subjected to sequencing. Data set 2 (15 samples): For gene expression analysis, total RNA was extracted from 3 biological replicates for each ligand treatment using Trizol reagent and further cleaned using the RNAeasy kit (QIAGEN). MCF-7 cells were treated with Veh (0.1% EtOH) or 100 nM OA, LA, PA or SA  for 24 h. Once the sample quality and replicate reproducibility were verified, 2 samples from each group were subjected to sequencing.	Co-expression
SRP145508	Transcriptome of human primary CD4+ T cells before and after HIV infection, quiescence and reactivation	To define the pattern of gene expression changes in human primary CD4+ T cells during the different stages of HIV life cycle, they were transfected with an HIV construct containing a CD8a-GFP reporter gene which allowed purification of HIV-infected cells. The purified HIV+ population was cultured in step-down media resulting in induction of quiescence. Fully quiescent cells were reactivated through TCR stimulation. Samples were taken for RNA-seq from mock-infected cells and purified HIV+ cells 72 hours after infection, and from fully quiescent cells and 24 hours after TCR stimulation.	Co-expression
SRP145551	Isolation of Heart Field Specific Cardiomyocytes from Differentiating Human Embryonic Stem Cells for Cardiac Regeneration	Analysis of TBX5 and non-TBX5 derived cardiomyocyte populations from differentiating hESCs. Overall design: hESCs from a cardiac differentiation protocol were isolated at different time points of differentiation (Days 0,7,14 and 30) for transcriptomic analysis.	Co-expression
SRP145589	Expression analysis of PC3 cells treated with scramble AON or AON directed against MBNL1	We transfected PC3 cells with 100nM of a scrambled antisense oligonucleotide (AON) and an AON directed against MBNL1 exon 7 (36 basepairs) in order to skip the latter. Cells were harvested at 72h post-transfection and RNAseq was performed with ribozero depletion. Overall design: For RNA-Seq library preparation we followed the Illumina TruSeq RNA Sample Preparation Kit v2 manual. At least 70 million, 75bp long paired end reads were mapped to the GRCh37/hg19 version of the human genome per replicate using STAR 2.4.2a (doi: 10.1093/bioinformatics/bts635) using the default parameters.	Co-expression
SRP145599	Type I and II IFN Conditioning of Human Macrophage Gene Expression Responses	Macrophage responses to pathogen-associated molecules are modulated by prior conditioning with cytokines such as interferons (IFNs). We conducted RNA-seq studies characterizing how conditioning with Type I or II IFN alters the gene expression programs of human macrophages responding to TLR ligands, TNF, and IFN??. Employing a sequential conditioning and stimulation approach, we found that IFN?? and IFN?? have partially overlapping but also remarkably distinct effects.	Co-expression
SRP145663	Gestational diabetes and placental gene expression	Although gestational diabetes affects as great as 9% of all pregnancies, there is ambiguity as to whether it is a distinct disorder or an extended spectrum of normal human pregnancy endocrine physiology. In this study, placental specimens from subjects with rigorously defined pre-gestational diabetes, gestational diabetes, and non-diabetic controls were examined for changes in gene expression to demonstrate differences in molecular profiles by diabetic classification.	Co-expression
SRP145862	Charting in vitro beta cell differentiation by single cell RNA sequencing	In vitro differentiation of human stem cells can produce pancreatic beta cells, the insulin-secreting cell type whose loss underlies Type 1 Diabetes. As a step towards mastery of this process, we report on transcriptional profiling of >100,000 individual cells sampled during in vitro beta cell differentiation and describe the cells that emerge. We resolve populations corresponding to beta cells, alpha-like poly-hormonal cells, non-endocrine cells that resemble pancreatic exocrine cells and a previously unreported population resembling enterochromaffin cells. We show that the beta and alpha-like cells are stable for weeks in culture without exogenous growth factors and that gene expression changes associated with in vivo beta cell maturation are recapitulated in vitro. We demonstrate that stem-cell derived enterochromaffin cells can synthesize and secrete serotonin in vitro. To remove exocrine cells, we characterize a scalable re-aggregation technique that efficiently selects endocrine cells. Finally, we use a high-resolution sequencing time course to characterize gene expression dynamics during human pancreatic endocrine induction from which we develop a lineage model of in vitro beta cell differentiation. This study provides a deeper perspective on the current state of human stem cell differentiation and is a jumping-off point for future endeavors in in vitro differentiation of pancreatic islet cells and their application in regenerative medicine. Overall design: Single-cell mRNA sequencing of pluripotent stem cells differentiating in vitro towards pancreatic beta cells. The data & metadata match the initial submission of the manuscript, not the final version.	Co-expression
SRP146064	OGT knockout S2VP10 cells	Pancreatic Cancer cells were transfected with CRISR based OGT knockouts Overall design: Examination of genes affected by OGT knockout	Co-expression
SRP146070	In-Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example	Cancer stem cell (CSC) identification relies on transplantation assays of cell sub-populations sorted from fresh tumor samples. Herein, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in-vivo propagating patient derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of EMT, invasion/motility, metastasis and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers. Overall design: Tumorigenic fractions from early-passaged PDX	Co-expression
SRP146080	Homo sapiens Transcriptome or Gene expression	Comparing the gene expression level of microRNA-27a-KO U251 ad WT-U251	Co-expression
SRP146249	Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [RNA-Seq; normal samples]	Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube.  Serous tubal intraepithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. RNA sequence and miRNA data did not identify any clear separation between cases with and without STIC lesions.  HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases. Overall design: In this study, 96 previously untreated high-grade serous carcinoma samples were selected to have half with STIC lesions and half without.    Molecular assays were performed that included RNAseq, microRNA expression, and copy number variation.  A total of 10 pools of normal epithelium brushings obtained from ovary (4 pools), peritoneum (3 pools), and fallopian tube (3 pools) for RNA sequencing and molecular barcode analyses.	Co-expression
SRP147277	Modulation of SF3B1 causes global intron retention and downregulation of the B-cell receptor pathway in chronic lymphocytic leukemia	Splicing factor SF3B1 is frequently mutated in chronic lymphocytic leukemia (CLL) patients and has been suggested as a potential therapeutic target. In this study, we performed RNA-seq analysis to evaluate the global impact of SF3B1 modulator sudemycin D6 (SD6) on alternative splicing. Our analysis revealed significant increases in global intron-retention in SD6-treated CLL cells. Pathway analysis of the genes associated with increased intron-retention suggested that B-cell receptor (BCR), protein ubiquitination, and PI3K signaling pathways were among the top canonical pathways being affected by SD6. The increases in intron-retention were inversely correlated with deceases in mRNA and protein levels of the affected BCR/PI3K pathway molecules such as BLNK, BTK, AKT1, PLC?2 and PI3Kd. SD6 also induced a time-dependent exon-skipping event in mRNA of MCL1 and resulted in significant down-regulation of another anti-apoptotic gene TRAF1, which may contribute to the SD6-induced apoptosis. Finally, SD6 can overcome the pro-survival and pro-growth signals and synergize with ibrutinib, idelalisib and venetoclax to induce apoptosis in primary CLL cells co-cultured with bone marrow stromal cells and in the presence of T-cell-derived cytokines. Cumulatively, these results provide a strong rationale for future clinical development of spliceosome modulators and combinatory therapies based on spliceosome modulators in CLL. Overall design: To determine the global impacts of SD6 treaments on transcriptome in CLL cells, we performed RNA-seq analysis in MEC1 and GM12878 cell lines treated with 125nM for three different time points (2, 6, and 24 hours), respectively.	Co-expression
SRP147451	Genetic and transcriptional variation alters cancer cell line drug response [MCF7]	10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells and cultured.	Co-expression
SRP147452	Genetic and transcriptional variation alters cancer cell line drug response [MCF7 strain L]	10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells (strain L) and cultured.	Co-expression
SRP147453	Genetic and transcriptional variation alters cancer cell line drug response [MCF7 strain AA]	10X Genomics single cell RNAseq of MCF7 cells treated with bortezomib. Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: MCF7 cells (strain AA) were treated with bortezomib (500nM) and harvested before treatment, after 12 hours of exposure (t12), after 24 hours of exposure (t48), or after 72 hours of exposure followed by drug wash and 24 hours of recovery (t72+24)	Co-expression
SRP147456	Mitochondrial hypoxic stress induces RNA editing by APOBEC3G in lymphocytes	Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes/macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear. Here we show that the related APOBEC3G cytidine deaminase induces site-specific C-to-U RNA editing in natural killer (NK), CD8+ T cells and lymphoma cell lines upon cellular crowding and hypoxia. RNA seq analysis of hypoxic NK cells reveals C-to-U recoding mRNA editing in dozens of genes including multiple translational and ribosomal genes. APOBEC3G promotes Warburg-like metabolic remodeling and reduces proliferation of HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration, and occurs independently of HIF-1a. Thus, APOBEC3G induces mRNA editing in lymphocytes to promote adaptation to mitochondrial hypoxic stress. Overall design: 6 NK cells. 3 normoxia and 3 hypoxia treatment replicates.	Co-expression
SRP147553	Splicing and epigenetic factors jointly regulate epidermal differentiation	We report the effects of silencing SRSF1 or ZMAT2 in human epidermal stem cells on the transcriptome of epidermal stem cells. We found that silencing ZMAT2 or SRSF1 affects global splicing, however, ZMAT2 seems to regulate splicing of a smaller more specific subset of genes. Overall design: RNA-sequencing data following silencing SRSF1 or ZMAT2	Co-expression
SRP147554	Single cell RNA-sequencing of human fetal kidneys	10X-based scRNA-seq data human fetal kidneys at 5 different ages Overall design: w9, w11, w13, w16 and w18 human fetal kidneys	Co-expression
SRP147746	Transcriptome profiling of microRNA-mediated neuronal reprogramming with REST repression at day 7	Ectopic expression of neuronal microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124) in adult human fibroblasts has been found to evoke extensive reconfigurations of the chromatin and direct the fate conversion to neurons. We found that miR-9/9* and miR-124 led to the repression of REST, a transcriptional repressor of neuronal genes, during microRNA-mediated neuronal conversion and knockdown of REST enhanced the activation of BAF53b, a mature neuronal marker. Furthermore, time series analysis of the transcriptome of cells undergoing the miR-9/9*-124-induced conversion indicated upregulated genetic pathways that were predicted to be targeted by REST although the transcript level of REST remained unchanged (Abernathy et al., 2017). Therefore, we reasoned that knocking down REST in addition to miR-9/9*-124 at an early time point (day 7), in which REST repression is minimally evident during neuronal conversion, would speed up the adoption of neuronal identity. We performed the RNA-seq analysis to compared differentially expressed genes (DEGs) between human adult fibroblasts expressing control shRNA (shCTL) and reprogramming cells expressing shCTL or shREST at day 7. Finally, we found that the repression of REST constitutes an important component of microRNA-mediated neuronal reprogramming of human fibroblasts. Overall design: RNA-seq analysis in 6 samples (2 replicates each) of human adult fibroblasts expressing control shRNA (shCTL) and reprogramming cells expressing shCTL or shREST at day 7.	Co-expression
SRP147915	Aryl hydrocarbon receptor dynamically regulates immunological and secretory gene pathways in decidual endometrial stromal cells	We report mRNA sequencing from decidual stromal cells after 24 hours and 6 days treatment with Aryl Hydrocarbon Receptor (AHR) activators 100 µM L-kynurenine or 10 nM TCDD  (2,3,7,8-Tetrachlorodibenzo-p-dioxin) Overall design: We report mRNA sequencing from samples with 24 hours (n=3) or 6 days (n=2) treatment with Aryl Hydrocarbon Receptor (AHR) activators 100 µM L-kynurenine or 10 nM TCDD  (2,3,7,8-Tetrachlorodibenzo-p-dioxin) that was combined with AHR ChIP-Seq data. Before kynurenine and TCDD treatments endometrial stromal fibroblasts were in vitro decidulization with cAMP and progesterone (MPA) for 2 days. Media and activators were changed every 2 days. The 24 hours control (3 days of decidulization: GSM3138934, GSM3138935 and GSM3138936) and 6 days control (8 days of decidulization: GSM3138937 and GSM3138938) mRNA sequencing samples without AHR activators were submitted previously.	Co-expression
SRP147923	Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profiles: an analysis of every mono and trisomy	Characterization of the transcriptome of normal and abnormal embryos. Overall design: Gene expression profiling of every mono and trisomy.	Co-expression
SRP148096	Comparison of transcriptome responses to isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line	We provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of quizalofop-p-ethyl, isoxaflutole and mesotrione Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the different pesticide active ingredients (quizalofop-p-ethyl, isoxaflutole and mesotrione ) were then tested from day 8 to day 14. In order to ensure coverage of a wide range of potential biological effects, three concentrations of each active principle were tested; a concentration representative of low environmental exposure (0.1 uM), an intermediate concentration (10 uM) and a high concentration (1000 uM).	Co-expression
SRP148097	Quiescent glioblastoma cells shift to an epithelial-mesenchymal transition-like gene program	Quiescent stem cells of glioblastoma (GBM), a malignant primary brain tumor, are potential sources for recurrence after therapy. However, the gene expression program underlying the physiology of GBM stem cells remains unclear. We have isolated quiescent GBM cells by engineering them with a knock-in H2B-GFP proliferation reporter and expanding them in a 3D tumor organoid model that mimics tumor heterogeneity. H2B-GFP label retaining quiescent cells were subjected to stem cell assays and RNA-Seq gene expression analysis. While quiescent GBM cells were similar in clonal culture assays to their proliferative counterparts, they displayed higher therapy resistance. Interestingly, quiescent GBM cells upregulated epithelial-mesenchymal transition (EMT) genes and genes of extracellular matrix components. Our findings connect quiescent GBM cells with an EMT-like shift, possibly explaining how GBM stem cells achieve high therapy resistance and invasiveness, and suggest new targets to abrogate GBM. Overall design: Glioblastoma cancer cells in 3D organoid culture were pulsed for 2 weeks with H2B-GFP, then chased either 2 or 4 weeks. Label-retaining GFP-high cells (quiescent) were separated from bulk population, and both populations were analyzed by RNA-Seq.	Co-expression
SRP148112	RNA-seq profiling of trastuzumab or lapatinib sensitive and resistant SKBR3 breast cancer cells	RNAseq was done using Library protocol =Illumina TruSeq Stranded mRNA Library Preparation Kit with poly(A) selection , HiSeq 101 Cycle Paired-End Sequencing v4 Overall design: Paired-End Sequencing  of breast cancer cell line samples Illumina HiSeq Sequencing	Co-expression
SRP148114	High depth sequencing of BrU-labeled nascent RNA in METTL3 depleted cells.	BrU incorporation into nascent RNA followed by immunoprecipitation with a BrU specific antibody. The nascent RNA was subsequently eluted with BrU competition. Overall design: HEK293T cells, treated with METTL3 siRNA, were incubated with 2 mM bromouridine for 15 min labeling time and chased with 20 mM uridine for 60 min. Nascent RNA was purified during BrU-IP with anti-BrdU.	Co-expression
SRP148163	TRPS1 is a lineage-specific transcriptional dependency in breast cancer [Seq]	We performed an unbiased cell viability-based pooled shRNA screen on 59 cell lines to identify novel epigenetic and transcriptional dependencies of multiple cancer types, including leukemia, neuroblastoma, breast, colorectal, prostate, and rhabdoid tumors. Here, we identified Tricho-Rhino-Phalangeal Syndrome Type I protein (TRPS1) as one of the most significant hits specific for breast cancer cell lines. Downregulation of TRPS1 resulted in cell cycle arrest and apoptosis increase in vitro and impaired tumorigenic capacity in vivo. We characterized TRPS1 genomic targets and protein interactome. We identified GATAD2B as an important partner of TRPS1, uncovering novel epigenetic network crucial for breast cancer cell survival. Overall design: Bulk RNA-Seq: Gene expression analysis of 57 cell lines used in the screen and HCC3153 and SUM159 cell lines with TET-inducible shRNA against TRPS1 with the following variables: Two different shRNA labeled sh1 (sh41) and sh2 (sh43), doxycyclin (plus/treatment) and no doxycyclin (minus/control), 3, 4 and 5 days after doxycyclin treatment. All conditions were sequenced without replicates (24 samples). ChIP-Seq: Examination of H3K27me3, GATAD2A, GATAD2B, H3K27ac, and TRPS1 in three different cell lines, in duplicates. HCC3153 cell line included the following variables: Two different shRNA labeled sh1 (sh41) and sh2 (sh43),  doxycyclin (plus/treatment) and no doxycyclin (minus/control). Please note that  the 'DFCI_EpiCluster_RNA-Seq.reads.gct' processed data file includes 4 re-analyzed samples, which were submitted as a part of series GSE63582 and the data columns correspond to the following samples; SUM149PT - GSM1842497 [SUM149_DMSO_12H_R1] SUM149PT_JQ1R_w_JQ1 - GSM1842493 [SUM149R_DMSO_12H_R1] SUM159PT - GSM1553156 [SUM159_DMSO_3H_1] SUM159PT_JQ1R_w_JQ1 - GSM1553147 [SUM159R_DMSO_3H_2]	Co-expression
SRP148277	Human Organ-Specific Endothelial Cell Heterogeneity	The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. Here, we investigated the properties of endothelial cells (ECs), isolated from four human major organsthe heart, lung, liver, and kidneys in individual fetal tissues at three months'' gestation, at gene expression, and at cellular function levels. We showed that organ-specific ECs have distinct expression patterns of gene clusters, which support their specific organ development and functions. These ECs displayed distinct barrier properties, angiogenic potential, and metabolic rate and support specific organ functions. Our findings showed the link between human EC heterogeneity and organ development and can be exploited therapeutically to contribute in organ regeneration, disease modeling, as well as guiding differentiation of tissue-specific ECs from human pluripotent stem cells. Overall design: We examined the human fetal organ sets from three donors, constituting three biological replicates at 3 months'' gestation (100-125 days). At this stage, all four major organs of interest - the heart, kidney, lung, and liver - have an established microvascular supply and exhibit organ-specific function. The heart beats at 120-160 bpm and is approximately 2 cm, the lungs have developed the entire air-conducting bronchial tree up to 20 generations with respiratory ducts and start to form barriers between alveoli and blood vessels, the liver is the major site of blood cell production and has also started to produce bile, and the kidneys have established nephrons and start to produce urine.	Co-expression
SRP148412	Metabolic reprogramming of Kaposi's sarcoma associated herpes virus infected B-cells in hypoxia	We report differential gene expression in BJAB-KSHV/BJAB cells treated with Cobalt chloride/BJAB-KSHV cells treated with Cobalt Chloride compared to BJAB cells Overall design: Differential gene expression in KSHV positive cells growing under hypoxic conditions	Co-expression
SRP148427	Analysis of copy number alterations from a lncRNA perspective reveals ALAL-1 a mediator of NSCLC immune evasion.	Analysis of the transcriptomic changes after ALAL-1 knockdown in HCC95 cells. Overall design: Inhibition of the lncRNA ALAL-1 in lung cancer cells (HCC95) treated with TNFalpha. Each experimental condition was performed in triplicates.	Co-expression
SRP148436	Small molecule-mediated reprogramming of human hepatocytes into bipotent progenitor cells	Currently, much effort is directed to the development of new cell sources for clinical therapy using cell fate conversion approaches by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes. Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by two small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of human chemically derived hepatic progenitors (hCdHs) were tested by standard in vitro and in vivo assays and transcriptome profiling. We developed a robust culture system for generating hCdHs with therapeutic potential. The use of HGF proved to be an essential determinant of fate conversion process. Based on functional evidence, activation of HGF/MET signal transduction system collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor cells through activation of ERK pathway. hCdHs expressed hepatic progenitor marker genes and proteins, and could self-renew for at least 10 passages while retaining normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. RNASeq gene expression profiling confirmed transcriptional reprogramming of hCdHs toward a progenitor state and suppression of mature hepatocyte transcripts. Upon intrasplenic transplantation into immunocompromised mice with acute liver injury, hCdHs effectively repopulated damaged parenchyma. Our study is a first report of successful reprogramming of human hepatocytes to a population of proliferating bipotent cells with regenerative potential. hCdHs may provide a nove tool that permits expansion and genetic manipulation of patient-specific progenitors to study regeneration and repair of diseased liver. Overall design: Transcriptome analysis for reprogrammed progenitor like cells	Co-expression
SRP148443	Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer	Acquired drug resistance to tyrosine kinase inhibitor (TKI) targeted therapies remains a major clinical challenge. In EGFR mutant non-small cell lung cancer (NSCLC), therapeutic failure of EGFR TKIs can result from both genetic and epigenetic mechanisms of acquired drug resistance. Histologic and gene expression changes consistent with an epithelial-to-mesenchymal transition (EMT) have been associated with resistance to EGFR TKIs in both experimental models and in patients, and may coincide with genetic mechanisms of resistance such as the EGFRT790M gatekeeper mutation. While therapeutic approaches targeting EGFRT790M have been developed, a strategy for overcoming EMT-related resistance remains unclear. We performed whole-genome CRISPR screening on patient-derived, mesenchymal EGFRT790M-positive cell lines and identified FGFR1 as a critical gene promoting resistance to third generation EGFR TKIs. The FGFR1-3 inhibitor, BGJ398 (infigratinib), resensitized resistant mesenchymal-like cell lines to EGFR inhibition in a synergistic manner. Combining EGFR + FGFR inhibitors also inhibited the in vitro survival and expansion of EGFR mutant drug tolerant cells with mesenchymal-like features prior to the development of drug resistance, and delayed the development of in vivo resistance in EGFR mutant NSCLC xenograft tumors. These results suggest that dual EGFR + FGFR blockade may be a promising clinical strategy for preventing and overcoming EMT-associated acquired drug resistance in EGFR mutant NSCLC. Overall design: PC9, HCC4006, HC1975, HCC827, MGH119 treated for two weeks with vehicle or with 300nM Gefitinib (300nM WZ4002 for H1975). Triplicates (duplicate for PC9 and MGH119)	Co-expression
SRP148472	Single cell RNA-seq of the human long-term self-renewing neuroepithelial-like stem cell line  SAI2	The transcriptome of single long-term self-renewing neuroepithelial-like stem cells (LT-NES) was studied in order to establish a baseline for investigations into modules of synergistically active transcription factors that determine developmental cell subpopulations Overall design: RNA-seq of 288 single cells	Co-expression
SRP148477	Single cell RNA sequencing of B cells from allergic individuals	IgE antibodies mediate the symptoms of allergic reactions, yet these antibodies and the cells that produce them remain enigmatic due to their scarcity in humans. To address this, we have isolated single B cells of all isotypes, including rare IgE producing B cells, from the peripheral blood of food allergic individuals. Using single cell RNA sequencing (scRNA-seq) we have characterized the gene expression, splicing, and heavy and light chain antibody sequences of these cells.	Co-expression
SRP148497	Prediction Model of Recurrence in Endometrioid Endometrial Cancer	We have designed an integrated model with clinical and genomic data to estimate recurrence risk for patients diagnosed with endometrioid endometrial adenocarcinoma	Co-expression
SRP148500	Studies of driver genes in prostate cancer	Important gene events in prostate cancer	Co-expression
SRP148514	Disruption of GRIN2B impairs differentiation in human neurons	Mutations in GRIN2B are associated with intellectual disability in humans. We generated iPSC derived mature cortical neurons with mutations in GRIN2B and compared them to isogenic control cells. We found that both loss of function (LOF) and reduced dosage (RD) mutations in GRIN2B lead to reduced expression of NMDAR genes and increased expression of marker of immaturity, including KI67 and MET. Overall design: Examination of transcriptome in iPSC-derved mature neurons with and without the presence of mutations in GRIN2B	Co-expression
SRP148556	Placental transcriptome in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)	Purpose: Identify differentially expressed genes in placental samples from early-onset (EO) IUGR, EO-PE, as well as pregnancies complicated by both EO-PE and EO-IUGR Overall design: Methods: Isolated total RNA from human placenta at birth and used it for RNA-sequencing on the Hiseq2000. Sequences were aligned to the human transcriptome (hg19/genome_build37) . Aligned sequences were then used to obtain abundance measurements and conduct differential expression analysis.	Co-expression
SRP148567	Transcriptomic analysis of acute mitochondrial pyruvate carrier inhibition using UK5099 in ABL prostate cancer cells	ABL cells (derivative of LNCaP) were treated with 100µM UK5099 or vehicle (control) for 72 hours, at which time total RNA was collected and analyzed using RNA-sequencing Overall design: ABL cells, vehicle vs 100µM UK5099, 72 hour treatment in biological triplicate	Co-expression
SRP148569	Impact of Escherichia coli K12 and O18 on human platelets: effects on platelet activation, spliced platelet RNAs and proteins	We report RNA-sequencing data of 12 platelet samples isolated from four healthy individuals and incubated with either E. coli K12, E. coli O18 or no bacteria. This dataset highlights the differential effect of bacteria on spliced platelet RNA profiles. Overall design: Blood platelets were isolated from whole blood in citrate-coated BD Vacutainers by standard centrifugation and multiple washing steps. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the TruSeq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina HiSeq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the human reference genome using STAR, and intron-spanning reads were summarized using HTseq.	Co-expression
SRP148576	RNA-sequencing analysis of CD4 T cells following ipilimumab therapy	We sorted CD4 T cells from patients with metastatic melanoma at baseline and after three doses of ipilimumab. Overall design: We examined the differential expression of epigenetic enzymes	Co-expression
SRP148594	Single-cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment - 5'' RNA sequencing and TCR sequencing	Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells.  Overall design: Single-cell RNA sequencing was performed on three patients using the 10x genomics TCR profiling kits. For each patient, populations of T-cells were assayed for both TCR sequence and trancriptome-wide RNA-sequence. Two donors have a replicate experiment.	Co-expression
SRP148597	Single-cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment 3'' RNA Sequencing	Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells.  Overall design: Single-cell RNA sequencing was performed on eight donors using the InDrop v2 protocol. For each donor populations of CD45+ immune cells were assayed for trancriptome-wide RNA-sequence. At least one replicate was taken for each donor.	Co-expression
SRP148609	Genes regulated by soluble guanylyl cyclase in VCaP prostate cancer cells	The aberrant activation of the ERG oncogenic pathway due to TMPRSS2-ERG gene fusions is the major driver of prostate cancer initiation and progression. We identified the alpha1 and beta1 subunits of soluble guanylyl cyclase (GUCY1A1, GUCY1B1) as major ERG-regulated genes in prostate cancer cells. Soluble guanylyl cyclase (sGC) is the major mediator of nitric oxide signaling in cells that, upon nitric oxide binding, catalyzes the synthesis of cGMP and subsequently activates PKG. We showed in ERG-positive PCa cells (VCaP) that cGMP synthesis was significantly elevated by ERG, leading to increased PKG activity and cell proliferation. To further understand the functions of sGC-cGMP pathway in prostate cancer cells, we performed RNA-seq analyses in VCaP cells to identify genes that are regulated by sGC. Overall design: Firstly, we performed RNA-seq analyses to examine genes differentially regulated by alpha1 or beta1 subunit of sGC in VCaP cells transfected with siRNA against non-target-control (siNTC), GUCY1A1 (siGUCY1A1), or GUCY1B1 (siGUCY1B1). Secondly, we also performed RNA-seq to examine the gene expression profile in VCaP cells treated with vehicle or ODQ, an sGC inhibitor that blocks cGMP synthesis.	Co-expression
SRP148659	Total RNA profiles in response to four tyrosine kinase inhibitors in human induced pluripotent stem cell-derived cardiomyocytes	To define molecular markers of tyrosine kinase inhibitor-induced cardiotoxicity, we measured transcriptome changes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with one of four tyrosine kinase inhibitors (Erlotinib, Lapatinib, Sorafenib, or Sunitinib) displaying a range of mild to severe cardiotoxicity or a vehicle-only control (DMSO). Gene expression changes were assessed at the cell population level using total RNA-seq, which measured levels of both mRNAs and non-coding RNAs. hiPSC-CMs used in this study were the Cor.4U cells purchased from Ncardia. Overall design: hiPSC-CMs were treated with each TKI (Erlotinib, Lapatinib, Sorafenib or Sunitinib) at three doses (1, 3 and 10 µM) for 24 hours and the intermediate dose (3 µM) for an additional three time points (6h, 72h and 168h). hiPSC-CMs were also treated with the DMSO vehicle-only control at four time points (6h, 24h, 72h and 168h). Each treatment condition had three biological replicates, collected from three independent experiments using three different lots of hiPSC-CMs. Total RNA was collected from all these samples.	Co-expression
SRP148695	Regulation of mRNA half-life by an inhibitor of human decapping enzyme Dcp2 following transcription shutoff in HEK293T cells	We report the application of next generation sequencing for measurement of mRNA levels under the effect of a macrocyclic inhibtor of human decapping enzyme 2 (hDcp2). Overall design: Examination of mRNA levels 0 h and 2 h after transcription block by actinomycin D in HEK293T cells treated by either 2 µM macrocyclic inhibitor CP25 or the same volume of vehicle for 18 h in triplicate.	Co-expression
SRP148704	Ovarian Cancer Cell Line Derived Spheroid Gene Expression	The goal of this study was to compare gene expression of ovarian cancer cell lines grown in traditional two-dimensional cultures to multi-cellular tumor spheroids grown using three-dimensional cell culture.	Co-expression
SRP148710	Homo sapiens Raw sequence reads	Triple-negative breast cancer RNA-Seq. Samples from a single patient, but different stages. 1) One healthy tissue sample, 2) One primary tumor, 3)Two different metastatic sites (lymph nodules), and 4) Three circulating tumour cells derived xenografts.	Co-expression
SRP148760	UPA-Seq: Prediction of functional lncRNAs using the sensitivities to UV-crosslinking	Assuming that functional lncRNAs form larger ribonucleoprotein complex and thus are easily crosslinked to proteins upon UV-irradiation, we performed RNA-Seq analyses of RNAs recovered from the aqueous phase after the UV-irradiation and phenol chloroform extraction (UPA-Seq) Overall design: Examination of expression profiles of UV-irradiated and non-irradiated cells (HepG2, HEK293, Neuro2a, HippCulture).	Co-expression
SRP148769	RNA transcriptome sequencing analysis of AGS cells transfected with MFAP2 shRNA or control shRNA	An RNA transcriptome sequencing analysis was performed in AGS cells that were transfected with MFAP2 shRNA or control shRNA. Overall design: mRNA profiles of AGS cells transfected with MFAP2 shRNA or control shRNA.	Co-expression
SRP148773	Single cell RNA-Seq of four human kidney organoids	These files represent single cell RNA-Seq data generated on a 10x Chromium genomics platform from four biological replicates of iPSC-derived human kidney organoids, in two batches, differentiated according to our published protocol (Takasato et al., Nature Protocols 2016). The aggregated human organoid data contains populations representing endothelial cells, podocytes, stroma, nephron, and off-target populations with similarity to neurons. Overall design: Examination of the celular composition of human kidney organoids	Co-expression
SRP148856	Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells (RNA-seq)	The development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.	Co-expression
SRP148892	Transcriptomic profiling of mock-infected primary CD4+ T cells and a model of HIV latency treated with suberoylanilide hydroxamic acid (SAHA) and Romidepsin (RMD)	Purpose: The goal of this study is to identify host genes whose expression is perturbed in primary CD4+ T cells by histone deacetylase (HDAC) inhibitors (HDACi) SAHA and RMD, which have different potencies and specificities for various HDACs. The study aims to evaluate the effects of SAHA and RMD that may promote or inhibit reactivation of HIV provirus out of latency. Methods: Peripheral blood mononuclear cells were collected from 4 HIV-seronegative donors. CD4+ T cells were isolated and utilized to generate an in vitro model of latent HIV infection (model developed in the Spina laboratory and previously described in Spina et al., 2013). Mock-infected cells were cultured in parallel to evaluate effects of SAHA and RMD that may be dependent on the exposure of cells to virus. Following generation of the model, cells were treated with SAHA, RMD or their solvent dimethyl sulfoxide (DMSO) for 24 hours. Mock-infected cells were treated in parallel. The experiment had 4 biological replicates, 6 conditions for each, for a total of 24 samples. ERCC spikes (Thermo Fisher Scientific, Inc.) were added to cell lysates based on cell number in each sample (10 ul of 1:800 dilution per million cells). Mix 1 was used for DMSO- and mix 2 for SAHA- and RMD-treated cells. After all samples were collected, RNA was extracted and subjected to deep sequencing by Expression Analysis, Inc. Sequence reads that passed quality filters were mapped using Tophat (human genome) or Bowtie (ERCC spikes and HIV) and counted using HTSeq. ERCC spikes with the same concentration in mixes 1 and 2 were utilized to remove unwanted technical variation. Any human gene which did not achieve at least 1 count per million reads in at least 4 samples or any ERCC that did not achieve at least 5 reads in at least 4 samples was discarded. Differential gene expression analysis was performed using library EdgeR in Bioconductor R. National Center for Biotechnology Information (NCBI) HIV-1 Human Interaction Database was then searched for genes that have been implicated in controlling HIV latency. EdgeR output was used to extract expression information of the genes of interest from the NCBI database to identify genes implicated in HIV latency that were modulated by SAHA and RMD. The resulting lists were manually curated to verify relevance to HIV latency, using the Description column of the NCBI database, as well as available PubMed references. Results: Using a custom built data analysis pipeline, ~100 million reads per sample were mapped to the human genome (build hg38). After applying filtering criteria, 16058 human transcripts, 19 ERCC spikes transcripts, and HIV NL4-3 transcripts were identified with the Tophat/Bowtie and HTSeq workflow. Differential expression analysis was performed between SAHA or RMD-treated and DMSO-treated cells. In addition, differential modulation of gene expression by SAHA and RMD in the model of HIV latency and mock-infected cells was assessed using EdgeR. In mock-infected cells, SAHA upregulated 3,971 genes and downregulated 2,940 genes; RMD upregulated 5,068 genes and downregulated 4,050 genes. In the model of HIV latency, SAHA upregulated 3,498 genes and downregulated 2,904 genes; RMD upregulated 5,116 genes and downregulated 4,053 genes (FDR < 0.05). SAHA modulated 6, and RMD 11 genes differentially between mock-infected cells and the model of HIV latency. Following search of the NCBI HIV-1 Human Interaction Database, 27 genes upregulated and 29 downregulated in common between SAHA and RMD were found to be relevant to regulation of HIV latency; 31 were up- and 32 downregulated by RMD only; and 6 were up- and 2 were downregulated by SAHA only. Conclusions: This study demonstrates that SAHA and RMD, which have different potencies and specificities for HDACs, modulate a set of overlapping genes implicated in regulation of HIV latency. Some of these genes may be explored as additional host targets for improving the outcomes of “shock and kill” strategies. Overall design: Transcriptomic profiling of the in vitro model of HIV latency and mock-infected cells treated with SAHA, RMD or the solvent DMSO (N=4 donors) by deep sequencing at Expression Analysis, Inc.	Co-expression
SRP148894	Mucin 1 knockdown in EMM myeloma cells	The sialic glycoprotein, Mucin1, is known to be involved in the pathogenesis of various types of cancers. In a fraction of patients with multiple myeloma, their myeloma cells have high Mucin1 expression. We established a myeloma cell line designated EMM1 from a myeloma patient whose myeloma cells have high Mucin1 expression. Then we performed knockdown of Mucin1 to elucidate the role of the high Mucin1 expression. Overall design: we performed knockdown of Mucin1 to elucidate the role of the high Mucin1 expression. Knockdown of MUC1 in EMM1 cells induced cell cycle arrest during S phase and apoptosis in EMM1 cells. To elucidate the role of Mucin1 in EMM1 cells, we generated EMM1 cells lines expressing shMucin1 or control shRNA and performed RNA-seq analysis of the two cell lines and compared the differences in gene expressions.	Co-expression
SRP148895	Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models	We report the expression profiles of 21 T- and NK-cell lymphomas to provide a platform for further investigation of targetable vulnerabilities in diseases represented by these cell lines Overall design: RNA-seq analysis of 21 different cell lines in cuture media	Co-expression
SRP148971	RNA transcriptome analysis of IRF1 and IRF3 knockout in immortalized primary hepatocytes infected with hepatitis A virus	Interferon regulatory factors (IRFs) play key roles in the transactivation of antiviral genes at the step downstream of activated pathogen-associated molecular pattern sensors, such as RIG-I-like receptors or Toll-like receptors. Whereas IRF1 and IRF3 are thought to bind similar DNA elements (ISRE and PRD-III, PRD-I) to activate antiviral gene transcription, genome-wide transcriptome profiling of IRF1 versus IRF3 knockouts in an immortalized primary hepatocyte (PH5CH8) cell line infected with hepatitis A virus (HAV) revealed unexpected disparities in their target genes. IRF1 targets include several anti-HAV effector genes that were not previously recognized to have antiviral functions. Overall design: mRNA transcriptome profiles of the WT, IRF1, and IRF3 knockout cell lines infected with hepatitis A virus HM-175/18f strain, each in triplicate.	Co-expression
SRP149002	Signal sequences in the viral genome regulate the generation of copy-back defective viral genomes	We developed VODKA (Viral Opensource DVG Key Algorithm) to identify cbDVGs from RNA-Seq data from infected samples and used these DVG sequences to identify signals that regulate cbDVG generation. We applied VODKA to datasets from RSV-positive patients. VODKA identified common cbDVGs across multiple samples in both patients, and predicted specific genomic loci that mediate cbDVG formation. Overall design: Total RNA was extracted from 2 RSV positive pediatric samples. RNAs were then used for preparation for the library used in RNA-seq to generate this dataset.	Co-expression
SRP149027	Comparative transcriptome analysis of skeletal muscle in ADSSL1 myopathy	ADSSL1 myopathy was recently identified as the cause of muscular disorders in Korean patients with distal myopathy. We generated transcriptome profiles of muscles from control subjects and patients with ADSSL1 myopathy.	Co-expression
SRP149047	Long Noncoding RNA Expression Profiles in Ovarian Endometriosis	Endometriosis is a common gynecological condition with an unclear pathogenesis. Changes in lncRNA expression profiles may influence this disease, while relevant investigation remains insufficient. To describe the different lncRNA and mRNA expression patterns between endometriosis and a control group, eutopic and normal endometrium in the proliferative phase were analyzed using RNA sequencing.	Co-expression
SRP149071	The NORAD lncRNA assembles a topoisomerase complex critical for genome stability [RNA-seq]	Thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen lncRNAs. One specific lncRNA, Non-coding RNA Activated by DNA Damage (NORAD), has recently been shown by genetic deletion to be required for maintaining genomic stability, but its molecular mechanism is unknown. Here, we combine RNA antisense purification (RAP) and quantitative mass spectrometry to identify proteins that directly interact with NORAD in living cells. We show that NORAD interacts with proteins involved in DNA replication and repair in steady-state cells and localizes to the nucleus upon stimulation with replication stress or DNA damage. In particular, NORAD interacts with RBMX (an emerging component of the DNA-damage response) and encodes the strongest RBMX-binding site in the transcriptome. We demonstrate that NORAD controls the ability of RBMX to assemble a ribonucleoprotein complex, which we term NORAD-Activated Ribonucleoprotein Complex 1 (NARC1), containing known suppressors of genomic instability: topoisomerase I (TOP1), ALYREF and the PRPF19/CDC5L complex. Cells depleted of NORAD or RBMX display an increased frequency of chromosome segregation errors, reduced replication-fork velocity and altered cell cycle progression phenotypes that are mechanistically linked to TOP1 and PRPF19/CDC5L function. Expression of NORAD in trans can rescue defects caused by NORAD depletion, but rescue is significantly impaired when the RBMX-binding site in NORAD is deleted. Our results demonstrate that the interaction between NORAD and RBMX is important for NORAD function and that NORAD is required for the assembly of a previously unknown topoisomerase complex (NARC1) that contributes to maintaining genomic stability. Moreover, we uncover a novel function for lncRNAs in modulating the ability of an RNA-binding protein to assemble a higher-order ribonucleoprotein complex. Overall design: We examined gene expression changes and alternative splicing events in wildtype and NORAD depleted cells using RNA sequencing.	Co-expression
SRP149092	Transcriptional change of THP-1 after HSV-1UL37WT or HSV-1UL37C819S	we reporter the transcritional difference after THP-1 cells were infected with HSV-1UL37WT virus or HSV-1UL37C819S virus. Overall design: RNA sequencing of 3 samples with 2 repeats	Co-expression
SRP149103	Next Generation Sequencing Analysis of Wild Type, ADAR2 over expressing and ADAR2+SRSF9 overexpresssing SH-Sy5y cells Transcriptomes	Purpose: A-to-I RNA editing is critical for many cellular processes. The sites of A-I RNA editing can be identified through RNA-seq and matching the reads to the annotated database like RADAR. The goals of this study is to compare A-I RNA editing profile among wild type, ADAR2 overexpressing and ADAR2+SRSF9 overexpressing 293T cells to evaluate the influence of SRSF9 repressive  action on A-I RNA editing Methods: A-I RNA editing profile and gene expression profiles were generated by deep sequencing from all the samples, using  NEBNext® Ultra™ Directional RNA Library Prep Kit. The sequence reads that passed quality filters were analyzed for identifying the A-I RNA editing sites using RADAR Database Results: Upon overexpression of ADAR2, we found that 18,174 sites were differentially edited compared to control cells, of which 97.0% showed a significant increase in their editing levels as expected (P < 0.05, Fisher's test). Furthermore, when we overexpressed both ADAR2 and SRSF9 together, we found that 6,994 sites were differentially edited compared to overexpression of the deaminase alone (P < 0.05, Fisher's test). Importantly, the editing of 92.5% of these sites was down-regulated, consistent with the function of SRSF9 as a repressor of editing. Conclusions: Our study reports a detailed analysis of the effect of SRSF9 on A-I RNA editing of ADAR2-specific targets. We Conclude that this SRSF9 regulon is significantly enriched for brain-specific editing sites despite our unbiased approach. Overall design: This study illustrates the effect of SRSF9 on A-I RNA editing of ADAR2 specific target sites	Co-expression
SRP149119	Derivation of ventrical and atrial cardiomyocytes and maturation using biowires	Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionise drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line, non-invasive, recording of passive tension, active force, contractile dynamics and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells. Overall design: human embryonic stem cells were cultured under conditions to generate either atrial or ventricle cardiomyocytes. The cardiomyocytes were placed into biowires that simulate normal cardiac sinus rhythm. Cell were harvested and assessed after a period of culture with or without electrical stimulation.	Co-expression
SRP149147	KAP1 regulates ERVs in differentiated human cells and contributes to innate immune control	Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB-zinc finger proteins (KZNFs), but little is known about the regulation of ERVs in differentiated cells. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV-T and HERV-S) and ZNFs, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in primary peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1-regulated loci is necessary to prevent an interferon response, and KAP1-depletion leads to activation of some interferon-stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNFs and an RNA-sensing response mediated through MAVS signaling. These data indicate that the KAP1-KZNF pathway contributes to genome stability and innate immune control in differentiated human cells. Overall design: Dissection of which transposons and genes KAP1 regulates in differentiated human cells	Co-expression
SRP149174	Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures	We report a method for deriving oligodendrocyte lineage cells from human pluripotent stem cells (hPSCs) in three-dimensional (3D) culture called human oligodendrocyte spheroids (hOLS). To characterize oligodendrocyte-lineage cells in hOLS, we isolated O4+ cells by immunopanning and performed deep single cell RNA sequencing. We sequenced 295 cells and compared their profiles to unsorted cells isolated from primary human fetal cortex, primary human adult cortex, and hCS. Clustering of all cells using the t-distributed stochastic neighbor embedding (tSNE) approach revealed a distinct populations of SOX10+ oligodendrocytes, within which the O4+ cells derived from hOLS clustered most closely to oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from the primary human adult cortical tissue. Additionally, subpopulations of OPCs, newly formed oligodendrocytes, and myelinating oligodendrocytes derived were observed in the hOLS-derived cluster. To further assess the state of oligodendrocyte-lineage cells in hOLS, we performed a Monocle analysis which revealed a spectrum of oligodendrocyte-lineage stages in hOLS ranging from dividing cells that closely resembled primary OPCs to mature cells that closely resembled primary oligodendrocytes. Overall design: Examination of gene expression in single oligodendrocyte-lineage cells derived from human pluripotent stem cells in three-dimensional culture	Co-expression
SRP149191	MYC interacts with the G9a histone methyltransferase to drive transcriptional repression and tumorigenesis	MYC is an oncogenic driver that regulates transcriptional activation and repression, yet molecular mechanisms of MYC transformation remain unclear. We demonstrate that MYC interacts with the G9a H3K9-methyltransferase complex to control transcriptional repression. Inhibiting G9a hinders MYC chromatin binding at MYC-repressed genes and de-represses gene expression to antagonize cellular transformation. By identifying the MYC Box II region as essential for MYC-G9a interaction, a long-standing missing link between MYC transformation and gene repression is unveiled. In breast cancer, anti-proliferative sensitivity to G9a pharmacological inhibition associates with MYC sensitivity and the basal subtype. Inhibiting G9a in vivo suppresses MYC-dependent basal breast tumor growth. Our findings reveal G9a as an epigenetic regulator of MYC-mediated transcriptional repression and a therapeutic vulnerability in MYC-driven cancers. Overall design: Transcriptome-wide analysis comparing the effect of G9a knockdown (using two independent shRNAs) versus scramble control (shSCR) in MCF10A breast epithelial cells transformed with ectopic PI3KH1047R and MYC (MCF10A.PM). Three biological replicates for each shRNA condition was performed.	Co-expression
SRP149286	Transcriptomic analysis of the role of the integrin a6b4 in detached cells	Analysis of gene expression profiles of matrix-detached cells with and without expression of ITGB4, in clustering and non-clustering conditions. The experiment tested the hypothesis that the integrin beta 4 (ITGB4) mediates a significant amount of pro-survival signaling in matrix-detached conditions. Expression of ITGB4 in cancer is correlated with poor patient survival and is impliated in increased metastatic spread. Survival in matrix-deprived conditions is essential to metastasis and targeting signaling downstream of the integrin beta 4 may help curtail metasasis. Overall design: Examination of gene expression profile following 3 hours of incubation in matrix-deprived conditions in duplicate	Co-expression
SRP149347	Kidney compartment specific eQTL studies highlight causal genes and pathways for renal disease development	Expression quantitative trait loci (eQTL) analyses were conducted separately on the glomerular and tubular portions of healthy human kidney samples obtained from subjects of European descent. Overall design: We aimed to define genotype driven gene expression changes in the glomerular and tubular compartments of human kidneys, identifying genetic variants (eVariants) that influence the expression of genes (eGenes). Later, we integrated this information with genotype and phenotype association studies (GWAS) to identify genes for which expression in the kidney shows differences in patients with GWAS variants.	Co-expression
SRP149350	Effect of nuclear IL-33 on gene expression	The aim of this study was to examine the transcriptional regulatory activity of nuclear IL-33 independent of its well-described extracellular cytokine activity mediated by its receptor, ST2. Overall design: Single-cell clones of Human TE-7 esophageal epithelial cells, which lack expression of the ST2 receptor, and with lentiviral-mediated, Dox-inducible overexpression of full-length IL-33, a non-chromatin binding form of IL-33 (amino acids 112-270), or empty vector (pINDUCER20) were treated with 100 ng/mL of doxycycline (Clontech) or control media for 48 hours. Expression of wild-type and truncated IL-33 was verified by Western blot. RNA was isolated using Tripure reagent and subjected to genome-wide RNA-sequencing through the Cincinnati Children's Hospital Medical Center Gene Expression Core.	Co-expression
SRP149366	Estrogen responsive transcriptome of estrogen receptor positive normal human breast cells in 3D cultures	Understanding how differentiation, microenvironment, and hormonal milieu influence human breast cell susceptibility to malignant transformation will require the use of physiologically relevant in vitro systems. We developed a 3D culture model that enables the propagation of normal estrogen receptor alpha (ER)+ cells. The purpose of this experiment was to assess ER functionality and compare estrogen-induced transcripts among samples and systems. Overall design: RNA-seq was performed on RNA prepared from replicate 3D cultures from 3 normal 3D breast culture specimens exposed to 10nM estradiol or vehicle alone for 6 or 24 hours.	Co-expression
SRP149371	POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer [RNA-seq]	Transcriptome analysis by high throughput sequencing Overall design: Gene expression profiles in SCLC with gene knockout	Co-expression
SRP149374	RNA sequencing of bone marrow CD34+ hematopoietic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls	SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in MDS. We have performed a comprehensive analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in bone marrow CD34+ cells of a large group of 82 MDS patients. Splicing factor mutations in MDS result in different mechanistic alterations in splicing and largely affect different genes, but these converged in common dysregulated pathways and cellular processes, including RNA splicing, translation and mitochondrial dysfunction, indicating that these mutations operate through common mechanisms in MDS. Many of these dysregulated pathways and cellular processes can be linked to the known disease pathophysiology and to the phenotypes associated with splicing factor mutations in MDS, whilst several others have not been previously associated with MDS, such as sirtuin signalling. Overall design: RNA-sequencing was performed on bone marrow CD34+ hematopoeitic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls to identify differential splicing between samples with mutations in the splicing factor SF3B1, SRSF2 or U2AF1 comparative to samples from myelodysplactic syndrome patients without mutations in these splicing factors and healthy controls. Processed data for the CD34+ hematopoeitic stem and progenitor cells are available in the files: CPM_table.txt.gz, Count_table.txt.gz and TPM_table.txt.gz. RNA-sequencing was also performed on monocytic, granulocytic and erythroid precursors from the bone marrow of patients with myelodysplastic syndrome and healthy controls to identify aberrant splicing in samples with mutations in splicing factors SF3B1 and SRSF2 comparative from healthy controls. Processed data for the monocytic, granulocytic and erythroid precursors are available in the files: CPM_table_fractions.txt, Count_table_fractions.txt and TPM_table_fractions.txt.	Co-expression
SRP149377	ADAR1-editing in HeLa, p150-KO and ADAR1-KO transcriptomes	RNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.	Co-expression
SRP149384	Genes and long non-coding RNAs (lncRNAs) in homocysteine (HCY)-induced vascular endothelial injury	n the present study, human umbilical vein vascular endothelial cells (HUVECs) were treated with HCY to identify the genes and lncRNAs involved in the mechanism underlying the HUVEC response to HCY. HCY-treated and untreated HUVECs were sequenced, and bioinformatics analysis was used to further study the genes and lncRNAs. Our results may offer new insights in understanding the role of lncRNAs in vascular endothelial injury in response to HCY.	Co-expression
SRP149421	A widespread alternate form of cap-dependent mRNA translation initiation	We report the application of polysome profiling sequencing technology for high-throughput transcriptomics and translatomics in mammalian cells. We compare reduction of Dap5 to control in metastatic breast cancer cells in transcription and polysome enriched translation using RNA sequencing. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factor and receptor capped mRNAs and their mRNA targets involved in cell survival, motility, DNA repair and translation initiation, among other mRNAs. Overall design: Examination of transcriptomics and translatomics in breast cancer cells.	Co-expression
SRP149433	PARP-inhibitors applied to BRCA1-null PDX models	Expression changes in BRCA1-deficient breast cancer PDX models treated with PARP-inhibitors.	Co-expression
SRP149446	Regulation of Translation Elongation Revealed by Ribosome Profiling [Dataset_4]	Ribosomes undergo substantial conformational changes during translation elongation to accommodate incoming aminoacyl-tRNAs and translocate along the mRNA template. We used multiple elongation inhibitors and chemical probing to define ribosome conformational states corresponding to different sized ribosome-protected mRNA fragments (RPFs) generated by ribosome profiling. We show using various genetic and environmental perturbations that the previously identified 20-22 nucleotide (nt) RPFs correspond predominantly to ribosomes in a pre-accommodation state with an open 40S ribosomal A site while the classical 27-29 nt fragments correspond to ribosomes in a pre-translocation state with an occupied 40S ribosomal A site. These distinct ribosome conformational states revealed by ribosome profiling are seen in all eukaryotes tested including fungi, worms and mammals. This high-resolution ribosome profiling approach reveals the anticipated Rck2-dependent inhibition of translocation through eEF2 phosphorylation during hyperosmotic stress. These same approaches reveal a strong translation elongation arrest during oxidative stress where the ribosomes are trapped in a pre-translocation state, but in this case the translational arrest is independent of Rck2-driven eEF2 phosphorylation. These results provide new insights and approaches for defining the molecular events that impact translation elongation throughout biology. Overall design: 24 biological samples are included for ribosome footprinting samples. These include HeLa, MB-MDA-231 and yeast cells and C. elegans embryos.	Co-expression
SRP149449	ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin	Here, we present a systematic and quantitative test of the hypothesis that the composition and activities of the endoplasmic reticulum (ER) proteostasis network impact mutational tolerance of secretory pathway client proteins. We focus on influenza hemagluttinin (HA), a viral coat protein that folds in the host's ER via a complex but well-characterized pathway. By integrating chemical methods to modulate the unfolded protein response with deep mutational scanning to assess mutational tolerance, we discover that upregulation of ER chaperones broadly enhances HA mutational tolerance across numerous sites and secondary/tertiary structure elements, including sites targeted by host antibodies. Remarkably, this host chaperone-enhanced mutational tolerance is observed at the same HA sites where mutational tolerance is most reduced by propagation at a fever-like temperature. Thus, host ER proteostasis mechanisms and temperature modulate HA mutational tolerance in opposite directions. This finding has important implications for influenza evolution, because influenza immune escape is contingent on HA possessing sufficient mutational tolerance to acquire antibody resistance while still maintaining the capacity to fold and function. More broadly, this work provides the first experimental evidence that the composition and activities of the ER proteostasis network critically define the mutational tolerance and, therefore, the evolution of secretory pathway client proteins. Overall design: RNA-seq characterizing a clonal HEK293T-Rex cell line, expressing DHFR ATF6f, Tet XBP1s, and the tetracycline repressor. These cell lines were treated with small molecules for 24 hours (in triplicate) to modulate the proteostasis environment in a stress-independent manner, at either 37C or 39C. XBP1s was activated by treatment with 0.1 ug/mL Doxycycline; ATF6f/XBP1s were activated by treatment with 0.1 ug/mL Doxycycline and 1 uM TMP; basal cells were vehicle-treated (0.01% DMSO). These cells were previously characterized in Shoulders et al. Cell Reports, 2013.	Co-expression
SRP149518	Evaluating pre-clinical models for studying NASH driven HCC.	We sequenced liver biopsy tissue from healthy, patients with NAFLD and patients with NASH Overall design: 3 patients either healthy, presenting with NAFLD or NASH	Co-expression
SRP149530	Viral infection enhances NK cell activation via Type I dependent pathways and can be utilized to enhance influenza-specific monoclonal antibody therapies	NK cells are an essential component for the control of influenza infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of the NK cell CD16-receptor by antibody-coated influenza-infected cells results in antibody-dependent cellular cytotoxicity (ADCC). Though NK cell-mediated ADCC is an important mechanism to control influenza, influenza infection itself may act to enhance the potency of NK cell ADCC. To understand if virus-infected cells increase NK cell activation, we co-cultured human PBMCs with influenza-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate ADCC. Pre-incubation of PBMCs with influenza-infected target cells markedly enhanced the functionality of NK cells by ADCC antibodies in response to HA immune-complexes containing intravenous immunoglobulin (IVIG), allogenic target cells, with and without rituximab. Trans-well and supernatant transfer experiments showed that virus released into the supernatant is responsible for the enhanced functionality of NK cells, which is apparent at both the protein and RNA transcriptomic levels.  Furthermore, cytokine multiplex data, RNA sequencing and cytokine blocking/supplementation experiments showed Type I interferons released from PBMCs were the primary mechanism of the influenza-induced increased NK cell functionality and ADCC potency. Importantly, the influenza infection-mediated increase in NK cell mediated anti-influenza ADCC was mimicked by the type I interferon agonist Poly-IC. This suggests a potential mechanism for enhancing monoclonal antibody therapies for influenza. We conclude that influenza-infection induced secretion of type I interferons enhances the ADCC capacity of NK cells and this pathway may potentially be manipulated to improve anti-influenza therapies. Overall design: Three separate donor PBMCs were incubated with either infected A549 cells or uninfected A549 cells for 12 hours. Target cell populations of lymphocytes gated on LIVE/DEAD negative populations or LIVE/DEAD negative CD3-CD56+ NK cells of interest were subsequently sorted from these PBMCs. Transcriptional profiling and differential gene expression was performed using RNA sequencing.	Co-expression
SRP149532	Genome wide analysis of SAHA (vorinostat) treatment in human iPSC-derived neurons from Tau A152T patients and controls	Purpose: The goal of this study was to assess gene expression changes upon SAHA treatment in neurons derived from patients with A152T Tau mutation Overall design: iPSC derived neurons were treated with SAHA at different dosage for several days	Co-expression
SRP149535	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [TF1_clones_scRNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: Individually sorted cells from clonally derived TF1 clones  (C9, D6, and G10) were processed with single cell RNA-seq (Smart-seq2)	Co-expression
SRP149538	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [TF1_clones_RNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: Cells from 3 separate TF1 clones (C9, D6, and G10) were processed with bulk RNA-seq (Smart-seq2)	Co-expression
SRP149541	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [Colonies_scRNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: Single cells from clonally derived hematopoietic colonies were processed with single cell RNA-seq (Smart-seq2)	Co-expression
SRP149545	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [CC100_scRNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing. Overall design: A population of 30 primary hematopoietic cells were expanded and forwarded to a combination of ATAC-seq and single cell RNA-seq. single cell RNA-seq samples are listed here.	Co-expression
SRP149572	FGF2 induces migration of human bone marrow stromal cells by increasing core-fucosylations on N-glycans of integrins	RNAseq analysis of human bone marrow derived stromal cells (MSCs) treated for 24 hours with or wihout 10ng/ml Fibroblast Growth Factor 2 (FGF2) MSCs were derived from 4 different healthy donors. Cells were expanded to passage 3-4. Then cells were treated with FGF-2. 24 hours later, total RNA was extracted (total 8 samples). Overall design: RNA was submitted to BGI Americas for RNAseq. Here, QC was performed  using Agilent 2100. All samples had a RIN above 8.0. For preparation for library, mRNA was enriched by using the oligo (dT) magnetic beads. mRNA was enriched by using the oligo (dT) magnetic beads. mRNA was fragmented into short fragments (about 200bp) using a fragmentation buffer. Then the first strand of cDNA was synthesized by random hexamer-primer using the mRNA fragments as templates. Buffer, dNTSPs, RNase H and DNA polymerase I were added to synthesize the second strand. The double strand cDNA was purified with QiaQuick PCR extraction kit and washed with EB buffer for end repair and base A addition. Finally, sequencing adapters were ligated to the fragments. The fragments are purified by Agarose gel electrophoresis and enriched by PCR amplification. The library products are ready for sequencing analysis via 2 sE50 lanes in Illumina HiSeqâ„¢ 2000.	Co-expression
SRP149625	Viral priming of innate antiviral signaling by the unfolded protein response	The cellular response to a pathogen is critical in determining the outcome of the infection and, as a consequence, viruses deploy a variety of strategies to subdue the antiviral signalling in order to achieve a productive infection. Stress and innate responses are believed to synergise to contain virus replication efficiently. However, the kinetics of the different cellular responses to viral infection and their contribution to innate antiviral signalling has not been clearly established. Tick-borne encephalitis virus, which is a Flavivirus widely diffused in Central Europe, has been shown to efficiently delay the interferon response. Transcriptome analysis of tick-borne encephalitis virus infected cells during the lag phase of interferon activation showed that, in addition to interferon and interferon-stimulated genes (ISG), the genes involved in the unfolded protein response (UPR) were modulated. Intriguingly, this response was induced before interferon transcription. Infection in conditions of UPR priming led to early activation of IRF3, interferon and ISGs transcription, stress granules formation and inhibition of viral replication. This antiviral response in turn was dependent on the IRE1 arm of the UPR and on RIG-I, but was independent of the canonical interferon secondary signalling. Other members of the Flavivirus family such as West Nile virus, Dengue virus and Zika virus were also sensitive to UPR priming. These results demonstrate that the UPR is not only a physiological reaction of the cell to infection, but also favors the induction of the innate antiviral response. For the first time the synergy of the UPR with innate signalling is explained at the molecular level for a viral infection.	Co-expression
SRP149630	RNA sequence analysis of stable versus reversible EMT events and the resultant metastases	The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing. Overall design: The Her2 transformed HMLE cells are referred to as the parental (Par) cell line and serves as the control. These cells were treated with TGF-beta every three days for a period of 4 weeks to induce EMT (TGFB). Alternatively, the parental cells were treated with 1 micromolar of lapatinib every three days also for 4 weeks and a proliferative drug resistant population (LAPR) emerged. The TGF-beta treated cells were engrafted onto the mammary fatpad and resultant long bone metasases (BM) were isolated and subcluted ex-vivo.	Co-expression
SRP149631	Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells	The human pluripotent stem cells cultured on Low-adhesion substrates formed two morphologically different subtypes (Monolayer and Domed).  The dome-like cells showed higher proliferation capacity and KLF4/5 expression than the monolayer cells. A serum response factor based regulatory double loop was proposed to explain how cell-matrix adhesion mediates the interaction between cell morphology and pluripotency genes Overall design: Compare the two type cells with RNA-seq to investigate the different expression	Co-expression
SRP149638	Comprehensive RNA-Seq profiling in PBMCs of ALS patients and healthy controls	Coding and long non-coding RNA metabolism is now revealing its crucial role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed Illumina RNA-seq analysis on Peripheral Blood Mononuclear Cells (PBMCs) from Sporadic and mutated ALS patients (mutations in FUS, TARDBP, SOD1, C9Orf72 and VCP genes) and healthy controls. Our aim is the whole-transcriptome characterization of PBMCs content, both in terms of coding and non coding RNAs, in order to compare the disease state to the healthy controls, both for sporadic patients and for mutated patients. Out dataset is a starting point for the omni-comprehensive analysis of coding and long non coding RNAs, from an easy to withdraw, manage and store tissue that shows to be a suitable model for RNA profiling in ALS. Overall design: whole transcriptome RNA-Seq profiling in PBMCs of ALS and healthy donors	Co-expression
SRP149709	Next Generation Sequencing Facilitates Quantitative Analysis of ALDH+ E-BCSC, CD24-CD44+ M-BCSC and Bulk tumor cell Transcriptomes from MC1 and Vari068 PDX models of TNBC	We report the application of single-molecule-based sequencing technology for high-throughput profiling of genes in E-, M-BCSCs and bulk tumor cells in two PDX models of triple negative breast cancer . Overall design: Examination of global gene expression in  E and M-BCSCs and Bulk tumor cells in 2 PDXs. Total RNA was extracted from E- (H2Kd-ALDH+), M- (H2Kd-CD44+/CD24-) BCSC-enriched and bulk (H2Kd-ALDH-CD44-/CD24+) cell populations freshly sorted from dissociated tumor cells of Vari068 and MC1 PDXs. Total RNA was extracted with RNeasy Mini Kit (Qiagen) according to manufacturer''s instructions, and 500 ng was then taken out from each of them and subjected to mRNA isolation using NEBNext Poly (A) mRNA Magnetic Isolation Module (NEB, Ipswich, MA, USA). The mRNA library was constructed using NEBNext UltraTM RNA Library Prep Kit for Illumina (NEB, Ipswich, MA) according to the instruction manual, which includes sequential RNA fragmentation, reverse transcription using random primers, second strand cDNA synthesis, end repair, dA-tailing, adapter ligation, U excision, and PCR enrichment. mRNA libraries were sequenced on an Illumina HiSeq X Ten platform with 150bp pair-end reads. All reads passed filter were trimmed to remove low-quality bases and adaptor sequences. Reads were then aligned to the mm10 reference genome using tophat2 (v2.0.13), and FPKMs were calculated.	Co-expression
SRP149711	Notch signalling mediates secondary senescence	Oncogene induced senescence (OIS) is a tumour suppressive response to oncogene activation that can be transmitted to neighbouring cells through secreted factors of the senescence associated secretory phenotype (SASP). Using single-cell transcriptomics we observed two distinct endpoints, a primary marked by Ras and a secondary by Notch. We find that secondary senescence in vitro and in vivo requires Notch, rather than SASP alone as previously thought. Currently, primary and secondary senescent cells are not thought of as functionally distinct endpoints. A blunted SASP response and the induction of fibrillar collagens in secondary senescence compared to OIS point towards a functional diversification. Overall design: (Smart-seq2 Time course experiment): ER:RasG12V -expressing cells were induced into senescence for 7 days with 4-hydroxytamoxifen (4-OHT) and were isolated as single cells using FACS. Single cells that were not induced with 4-OHT were used as control. Single cells were also collected at another two time points, day 2 and day 4, before they became fully senescent on day 7. (10x Co-culture experiment): GFP cells are co-cultured with ER:Ras expressing cells and were induced into senescence with 4-OHT. Single cell 3' gene expression data was generated using 10x Genomics Chromium.  (Smart-seq2 Hepatocyte experiment): Ex vivo primary hepatocytes were isolated using a modified retrograde perfusion technique as previously described[27]. Briefly, following perfusion with Perfusion Medium (Gibco) for 5 min, and Liver Digest Medium (Gibco) for 10 min, the liver was excised and the capsule disrupted to yield a cell suspension that was collected in Williams' E Medium supplemented with 2% FCS. Hepatocytes were purified by pelleting through a 40% (v:v) percoll gradient prior to FACS analysis.  (10x dnMAML1 experiment): We used normal diploid human female lung fibroblasts IMR90 isolated at 16 weeks of gestation for all in vitro assays (ATCC® CCL-186™). pLNCX2 ER:rasG12V-expressing IMR90 were maintained and senescence induced as described under 5% O2 conditions. ER:IMR90 cells were co-cultured with IMR90:GFP (an empty vector fused with mVenus  or with a dominant negative form of MAML1 fused with mVenus  cells at 1:10 ratio. (Transwell bulk-RNA-seq): ER:RasG12V-expressing cells were co-cultured with IMR90:GFP. The co-cultured cells were placed into the lower chamber of a transwell system (density 5x103 cells/well). Another pure population of IMR90:GFP cells were cultured in the upper chamber of the transwell system. All cells were maintained in 4-hydroxytamoxifen (Sigma) for 7 days. All experiments were performed in triplicate.	Co-expression
SRP149729	Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk [RNA-seq]	Although numerous genetic loci have been associated with coronary artery disease (CAD) with genome wide association studies (GWAS), efforts are needed to identify the causal genes in these loci and link them into fundamental signaling pathways. Toward that end, experiments reported here extend our investigation of the disease mechanism of CAD associated gene SMAD3, a central transcriptional intermediate in the TGFb pathway, investigating its role in smooth muscle biology. In vitro studies in human coronary artery smooth muscle cells (HCASMC) revealed that SMAD3 modulates cell state decisions in this cell type, promoting expression of differentiation marker genes and migration while inhibiting proliferation. RNA and chromatin immunoprecipitation sequencing (ChIPseq) studies in HCASMC identified downstream genes that reside in pathways which mediate vascular development and disease processes, including those related to atherosclerosis pathophysiology, expanding understanding of the TGFb canonical pathway in this cell type. ChIPseq studies also found colocalization of SMAD3 binding in loci targeted by TCF21, a CAD associated transcription factor that has been shown to produce a CAD protective de-differentiation program in HCASMC. In loci where these factors are juxtaposed on DNA, SMAD3 binding was anti-correlated with TCF21, and increased in cells depleted of TCF21, as shown by ChIPseq and ChIP experiments. Further, reporter gene studies revealed that while SMAD3 increased transcription at a SERPINE1 enhancer, and this effect was blocked by TCF21. Together, these data suggest that SMAD3 regulation of gene expression is modulated by TCF21, through independent regulation of jointly occupied genes and through epigenetic and possibly direct protein-protein interactions. Finally, eQTL studies in HCASMC indicated that SMAD3 expression is directly associated with increased disease risk, opposing the known protective effect of TCF21. We propose that the pro-differentiation function of SMAD3 inhibits HCASMC dedifferentiation of these cells as they respond to vascular stresses and expand and migrate to stabilize the plaque, and that SMAD3 function is directly opposed at the transcriptional level by the disease protective expression of TCF21, which promotes dedifferentiation and phenotypic modulation. Methods: Primary human coronary artery smooth muscle cells (HCASMCs) were purchased from three different manufacturers, PromoCell, Lonza and Cell Applications at passage 2 and were cultured in smooth muscle cell basal media along with hEGF, insulin, hFGF-B and fetal bovine serum (FBS) (Lonza # CC-3182) according to the manufacturer's instructions. HCASMCs between passages 5-8 were used for all the experiments. SMAD3 (s8401 and s8402) silencer select siRNAs were purchased from Life Technologies. siRNA transfection was performed using Lipofectamine RNAiMAX (Life Technologies). For each well treated with the SMAD3 siRNA or scrambled control (Life technologies, #4390843), the final concentration was 20 nM. HCASMCs were seeded in 6 well plates and grown to 75% confluence before siRNA transfection. HCASMCs were transfected with the SMAD3 siRNA or scrambled control for 12 hours and subsequently collected and processed for RNA isolation after 48 hrs of transfection using the RNeasy kit (Qiagen). Three experimental and three control samples were generated and sequenced on a HiSeq 4000 machine, 125 bp paired end reads. Reads were processed using rnaSeqFPro, a workflow for full processing of RNASeq data starting from fastq files. In brief, the quality control was performed using FastQC, mapping to the human genome hg19 was performed using STAR second pass mapping to increase the percentage of mapped reads, and counting was done with featureCounts using GENCODE gtf annotation. Next, rnaSeqFPro performed differential analysis using DESeq2, conducted principal component analysis and hierarchical clustering using standard R functions, plotPCA and heatmap.2 and generated graphs using gglot2. DESeq2 gave 493 differentially expressed (DE) genes (FDR < 0.05). Overall design: Human coronary artery smooth muscle cells were grown in culture in the presence of serum. Three control replicates and three SMAD3 siRNA knockdown replicates were studies, RNA was extracted, libraires prepared, and sequenced on a HiSeq 4000 machine.	Co-expression
SRP149781	Human dorsal root ganglia from patient treated with intrathecal resiniferatoxin	Transient vanilloid potential 1 (TRPV1) agonists are emerging as highly efficacious non-opioid analgesics in preclinical studies. These drugs selectively lesion TRPV1+ primary sensory afferents, which are responsible for the transmission of many noxious stimulus modalities. Resiniferatoxin (RTX) is a very potent and selective TRPV1 agonist and is a promising candidate for treating many types of pain. Recent work establishing intrathecal application of RTX for the treatment of pain resulting from advanced cancer has demonstrated profound analgesia in client-owned dogs with osteosarcoma. The present study uses transcriptomics and histochemistry to examine the molecular mechanism of RTX action in rats, in clinical canine subjects, and in one human subject with advanced cancer treated for pain using intrathecal RTX. In all three species, we observe a strong analgesic action, yet this was accompanied by limited transcriptional alterations at the level of the DRG. Functional and neuroanatomical studies demonstrated that intrathecal RTX largely spares susceptible neuronal perikarya, which remain active peripherally but unable to transmit signals to the spinal cord. The results demonstrate that central chemo-axotomy of the TRPV1+ afferents underlies RTX analgesia and refine the neurobiology underlying effective clinical use of TRPV1 agonists for pain control.	Co-expression
SRP149794	Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline [cell populations]	Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms leading to ageing remain elusive. We present a proteome-wide atlas of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) along with five other cell types that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified was assessed in a cohort of healthy human subjects from different age. As the HPCs became older, pathways in central carbon metabolism exhibited features reminiscent of the Warburg effect where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation revealed a reduced functionality and a bias towards myeloid differentiation at the expense of lymphoid development. Ageing caused significant alterations in the bone marrow niche too, such as functionality of the pathways involved in HPC homing and lineage differentiation. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models. Overall design: RNA-seq samples extracted from human bone marrow, from 6 cell populations (HPC, LYM, MON, ERP, GRA, MSC). Technical replicates are included for each donor and cell type. Technical replicates were produced by making independent libraries from the same RNA.	Co-expression
SRP149809	Expression data from miR340 overexpressing human A549 cells	To characterize the differentially expressed genes of miR340, we compared the gene expression profiles of miR-340 overexpressing human A549 cells with that of  empty vector transfected A549 cells Overall design: The precursor form of miR-340 was overexpressed in A549 cells using pcDNA3.1 plasmid, and empty vector transfection was used as control. The miR340 or empty vector transfected cells were incubated at 37°C for 24 hr. Total RNA was extracted for RNA sequencing.	Co-expression
SRP149845	The effects of microRNA-22 loss in the megakaryocytic and erythrocytic lineages	The goal of this study was to identify genes dysregulated upon modulation of microRNA-22 expression in the megakaryocytic and erythrocytic hematopoietic lineages. These goals were achieved through RNA-sequencing analysis of multiple samples: megakaryocyte-erythroid progenitors (MEP) isolated from microRNA-22 knockout mice, the K562 human erythroleukemia cell line knocked-out for microRNA-22 by CRISPR/cas9 genome editing, and K562 cells overexpressing miR-22 through transient transfection.	Co-expression
SRP149846	RNA-Seq analysis of HIF-2a-responsive genes in clear-cell renal cell carcinoma	We performed RNA-Seq analysis of wildtype and three EPAS1-/- 786-O single cell clones generated by CRISPR/Cas9 to identify the HIF-2a-responsive genes in this cell line. Samples from wildtype 786-O cells treated with DMSO or HIF-2a antagonist compound C2 were also included in this analysis. Overall design: In this experiment, we analyzed the transcriptomic profiles of 2 replicates of wildtype (WT) EPAS1+/+ 786-O cells, 1 replicate for each of the three independent EPAS1-/- 786-O single cell clones, 1 replicate of WT-786-O cells treated with DMSO and 1 replicate of WT-786-O cells treated with 10uM HIF-2a antagonist C2.	Co-expression
SRP149847	Differences in tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients	Treatment of severely refractory Crohn's disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT. Overall design: Biopsy mRNA profiles of 14 CD patients undergoing HSCT were generated by deep sequencing, using HiSeq-4000 platform (Illumina, San Diego, CA).	Co-expression
SRP149865	Knockout of ER membrane protein complex subunits	The ER-membrane protein complex (EMC) functions as a transmembrane domain insertase with a broad client range, among which are proteins critical for maintaining cholesterol homeostasis. RNAseq was performed to determine whether the EMC-deficient cell lines elicited a transcriptional response to restore cholesterol homeostasis through the SREBP2 transcription factor. These data provide insight into the transcriptional programs that are activated when the insertase activity provided by the EMC is absent, from which key client proteins may be determined.	Co-expression
SRP149882	RNA-Seq analysis of prostate cancer cell line LNCaP treated with vehicle, androgen, androgen and IMTPPE, androgen and JJ-(+)-450, androgen and JJ-(-)450, androgen and enzalutamide	RNA-Seq analysis of prostate cancer cell line LNCaP treated with vehicle (C), androgen (R), androgen and IMTPPE (R + IMTPPE), androgen and JJ-(+)-450 (androgen + (-)450), androgen and JJ-(-)450 (androgen + (-)450), androgen and enzalutamide (androgen +Enz). To evaluate if our compounds can inhibit AR function specifically and completely, LNCaP mRNA profiles of cells treated with IMTPPE, (+)-JJ-450 and (-)-JJ-450, comparing to enzalutamide. RNA isolation was performed using RNeasy Mini kit (Qiagen), RNA Sequencing was carried out by Genomics Research Core of University of Pittsburgh using Illumina NextSeq 500 system. The sequence reads that passed FASTQC were analyzed at the transcript level. Each sample was mapped to the Human Ensembl reference genome GRCh38. We definied different expression genes with a fold change =2.0 and FDR <0.05. Both (-)-JJ-450 and enzalutamide are very specific to AR, with 56 and 186 DE genes comparing to control samples respectively. IMTPPE and (+)-JJ-450 can inhibit most of the androgen responsive genes, but also some other genes were affected. (-)-JJ-450 is a novel compound inhibts AR function specifically and completely, and it is a potential lead compound for the treatment of CRPC, including those resistant to enzalutamide. Overall design: LNCaP prostate cancer cells treated with androgen and vehicle/IMTPPE/JJ-(+)-450/JJ-(-)-450/enzalutamide mRNA profiles were generated by deep sequencing, using Illumina NextSeq 500 system.	Co-expression
SRP149884	Non-inflammatory tumor microenvironment of Diffuse Intrinsic Pontine Glioma (DIPG)	Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult glioblastomas (GBM). Thus, we directly compared inflammatory characteristics of DIPG and adult GBM. We found that the leukocyte (CD45+) compartment in primary DIPG tissue samples is predominantly composed of CD11b+ macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant in adult GBM tissue samples. RNA sequencing of macrophages isolated from primary tumor samples revealed that DIPG- and adult GBM-associated macrophages both express gene programs related to ECM remodeling and angiogenesis, but DIPG-associated macrophages express substantially fewer inflammatory factors than their adult GBM counterparts. Examining the secretome of glioma cells, we found that patient-derived DIPG cell cultures secrete markedly fewer cytokines and chemokines than patient-derived adult GBM cultures. Concordantly, bulk and single-cell RNA sequencing data indicates low to absent expression of chemokines and cytokines in DIPG. Together, these observations suggest that the inflammatory milieu of the DIPG tumor microenvironment is fundamentally different than adult GBM. The low intrinsic inflammatory signature of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory phenotype of DIPG-associated microglia/macrophages. Understanding the glioma subtype-specific inflammatory milieu may inform the design and application of immunotherapy-based treatments. Overall design: RNA-seq of primary isolated microglia/macrophages from early post-mortem DIPG tissue samples, pediatric normal cortex, and adult GBM tissue samples. Libraries were sequenced on Illumina NextSeq 500, 1x75.	Co-expression
SRP149899	Analysis of single-cell RNA-seq data from human PBMCs and from in vitro cultures of human cord blood CD34+ progenitors encompassing different DC types	For both PBMC and cells from the in vitro cultures, RNA purification and library generation was performed using the Chromium Single Cell Controller apparatus and associated protocols (10X Genomics). Libraries were sequenced by 75-bp single-end reading on a NextSeq500 sequencer (Illumina). Reads were aligned on the GRCh38 human genome assembly. Data analysis was performed using the R software package Seurat (https://github.com/satijalab/seurat) Overall design: Single cell RNA-seq data were generated on the 10X emulsion platform (10X Genomics, Pleasanton, CA) according to the manufacturer's instructions. NextSeq data from the Chromium platform were processed using CellRanger v1.3.1, and subsequent normalization, QC, filtering, and differential gene expression analysis was performed in R using Seurat v1.4.0.16.	Co-expression
SRP149913	Origin and Evolution of Neural Microexons	Our study focuses on the origin of the neural microexon program.We discover that neural microexon programs are present in non-vertebrate speciesand trace their origin to bilaterian ancestors through the emergenceof a previously uncharacterized "enhancer of microexon" (eMIC) protein domain	Co-expression
SRP149923	Single-cell analysis reveals stochastic regulation of type I IFN production by plasmacytoid dendritic cells and identifies host-derived environmental cues as amplifier of type I IFN production	Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mech-anisms that control this process are poorly understood. Here, we developed a droplet-based microfluidic platform and investigated type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNF alpha production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. Intriguingly, by modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level. Overall design: Examination of the transcriptional profiles from single human plasmacytoid dendritic cells that were stimulated with CpG-C	Co-expression
SRP149965	Understanding the role of PCAT92 in prostate cancer	Many lncRNA are known to be differential expressed in prostate cancer. One such lncRNA is PCAT92, which by has been shown to be over-expressed in prostate cancer samples when compared to adjacent normal tissue. PCAT92 shares its chromosomal locus with ABCC4, a genes already reported to be implicated in prostate cancer. Here we have explored the possible mechanism by which PCAT92 is playing a role in prostate cancer. Here we made LNCaP which were knockdown PCAT92 and ABCC4 independently and performed a RNA-sequencing to see the change in gene expression under both the knockdown condition.	Co-expression
SRP149978	RNA-seq of HIV bnAb and control individuals PBMC	We sought to determine differences in transcript expression between a cohort of HIV-infected individuals that either developed broadly neutralizing antibodies (bnAb) or did not develop them (control). With the ultimate goal to identify transcripts that are associated with the development of bnAbs that would identify novel pathways that could be targeted in future vaccine strategies to increase the frequency of individuals that develop bnAbs against HIV. Using this approach we identified that Rab11 recycling endosomes, particularly in dysfunctional natural killer cells are associated with the development of HIV-1 bnAbs. Overall design: RNA extracted from peripheral blood mononuclear cells of 95 subjects was subject to RNA-seq for transcriptome analysis comparing individuals that developed HIV-1 broadly neutralizing antibodies to those that did not develop them (control).	Co-expression
SRP150013	ERa-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity [RNA-seq]	Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers. Epithelial ovarian cancer (EOC) is a typical hormone-related tumor, with defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown. Here we report an inverse correlation between estrogen signaling and HRR activity in EOC. Genome-wide mapping of ERa reveals ERa co-bindings with co-repressor CtBP, especially on many HRR gene loci, in EOC cells but not in breast cancer cells. Consistently, depleting ERa in EOC cells up-regulates HRR activity and HRR gene expression. Importantly, estrogen signaling enhances the sensitivity of ovarian cancer cells to chemotherapy agents in vitro and in vivo. Large-scale analyses further indicate that estrogen replacement and ERa expression are associated with favorable survival of EOC patients. These findings characterize a novel role of ERa in mediating the molecular connection between hormone and HRR in EOC, and suggest that estrogen signaling may improve the treatment outcome of EOC patients. Overall design: RNAseq of SKOV3 cells (Control, ERa overexpression and CtBP overexpression)	Co-expression
SRP150014	Cytokine sensitivity screening highlights BMP4 signaling as a therapeutic opportunity in ER+ breast cancer	Microenvironmental secreted factor screening revealed cytokines that modulate drug sensitivity in ER+ breast cancer cells. BMP4 was a top hit that is not normally expressed in ER+ breast cancer, and was found to enhance efficacy of anti-estrogens and CDK4/6i in anti-estrogen-sensitive and -resistant ER+ breast cancer cells. The anti-cancer effects of BMP4 were mediated by ALK3 and canonical BMP pathway signaling, leading to downstream p21 induction and cell cycle arrest. The clinical relevance of this phenotype was confirmed in analyses of 3 cohorts of patients with ER+ breast cancer, highlighting BMP4 pathway activation as a potential therapeutic opportunity in ER+ breast cancer.	Co-expression
SRP150019	Homo sapiens Raw sequence reads	Expression profile of messenger RNA in MDA-MB-231 cells with GDF15/GDF15(nonSIG) overexpression or not	Co-expression
SRP150042	ZBTB38  gene knockdown Human neuroblastoma cells Raw sequence reads	Transcription factor ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. Only several predicted BTB domain-containing proteins encoded in the human genome have been functionally characterized. No relevant studies have been reported concerning the effect of down-regulated ZBTB38 gene expression on tumor cells through transcriptome analysis. In the present study, 2,438 differentially expressed genes in ZBTB38-/- SH-SY5Y cells were obtained via high-throughput transcriptome sequencing analysis, 83.5% of which was down-regulated. Furthermore, GO functional clustering and KEGG pathway enrichment analysis of these differentially expressed genes (DEGs) revealed that the knocked-down transcription factor ZBTB38 interacted with p53 and arrested cell cycles to inhibit the proliferation of the tumor cells. Besides, it also significantly down-regulated the expressions of PTEN, a "molecular switch" of the PI3K/Akt signaling pathway, and RB1CC1, the key gene for autophagy initiation, and blocked autophagy to accelerate the apoptosis of tumor cells. ZBTB38-/- SH-SY5Y cells were investigated at the whole transcriptome level and key DEGs were screened in the present study, providing a theoretical foundation for exploring the molecular mechanism of inhibition of tumor cell proliferation and targeted anti-tumor therapies.	Co-expression
SRP150074	Transcriptome landscape of human primary monocytes response upon different ligand glucocorticoids	Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties. Overall design: Monocytes from healthy donors were cultured in the presence of 100 nM triamcinolone acetonide (TA), 100 nM Dexamethasone (Dex) or 100 nM Prednisolone (Pred) for 4 hours. Cells were then collected for RNA-seq.	Co-expression
SRP150101	Transcriptome analysis of Group 3 and 4 medulloblastoma orthotopic xenograft mice with digoxin treatment	RNA-seq data of Group 3 and 4 medulloblastoma with digoxin treatment. Overall design: Investigate the differential expressed genes in Group 3 and 4 Medulloblastoma under digoxin treatment	Co-expression
SRP150151	Determination of branch point (BP) usage by wild-type and mutant SF3B1 using a minigene library	We address define differential usage of branchpoint (BP) in by wild-type SF3B1  SF3B1-K700E using a synthetic mini-gene synthetic library with variable 3' spice sites (3'SS).  Minigene-specific libraries were prepared and sequenced on the illumina platform to determine differnces in splice-site usage. Overall design: Minigene-based analysis of differential splicing	Co-expression
SRP150159	Spatially Constrained Tandem Bromodomain Inhibition Bolsters Sustained Repression of BRD4 Transcriptional Activity for TNBC Cell Growth	We performed RNA-seq of MDA-MB-231 cells that were treated with MS645 or JQ1 at 50 nM and 500 nM in an effort to understand how MS645 exerts such a profound cell growth inhibition on cancer cells. Overall design: MDA-MB-231 cells were treated with DMSO and different concentrations of JQ1 and MS645 for 18 hrs to compare the compounds' effect in transcriptional regulation.	Co-expression
SRP150178	Homo sapiens Transcriptome or Gene expression	Two tumor patients (two-control tumor periphery tissues, C1 &amp; C2), two cadavers (two autopsy tissues A4 &amp; A10) AND five FCD patients (F1-F5) . We have only one tissue sample (E8) from F3 patient and two tissue samples from rest of the four FCD patients	Co-expression
SRP150209	yylncT acts as a gatekeeper of the mesodermal transcriptional program by local modulation of DNMT3B [human_1]	Bidirectional transcription is a prevalent feature of eukaryotic promoters. The goal of this study is to identify novel divergent long-coding RNAs during differentiation of human ES to cardiomyocytes. Methods: Paired end RNA-Seq was performed on key time-points of human ES cell differentiation to cardiomyocytes. The time-points include day 0, day 1, day 2, day 4,day 6, day 8 and day 14. Results: Using an optimized data analysis workflow, we mapped about ~70 million sequence reads per sample to the human genome (build hg38) and identified 781 novel yylncRNAs during ES cell differentiation to cardiomyocytes. Expression kinetics of a subset of  yylncRNAs identified from RNA-Seq  had a linear relationship with qRT–PCR . Conclusions: Our study represents the detailed analysis of the genome wide identification of divergent long-coding RNA generated by paired end RNA-seq technology. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of long-non coding RNA content in the process of cardiac differentitation. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biological functions. Overall design: We have used 7 different time-point (all in triplicates), covering key stages of human  ES cell differentiation to cardiomyocytes. It includes day 0 (ES cells), day 1(   early mesoderm), day 2 (late mesoderm), day 4 (cardiac mesoderm), day 6 (cardiac progenitors), day 8 (early cardiomyocytes) and day 14 (cardiomyocytes).	Co-expression
SRP150212	RNA-seq of Hs578T cells with TET1 knockout	Both gains and losses of DNA methylation are common in cancer but the factors controlling this methylation balance remain unclear. Triple negative breast cancer (TNBC), a subtype that does not overexpress hormone receptors or HER2/NEU is one of the most hypomethylated cancers observed. In search for an explanation for this, we discovered that the TET1 DNA demethylase is specifically overexpressed in about 40% of patients with TNBC, where it is associated with hypomethylation of up to 10% of queried CpG sites and a worse overall survival. Through bioinformatic analyses in both breast and ovarian cancer cell line panels, we uncovered an intricate network connecting TET1 to hypomethylation and activation of cancer specific oncogenic pathways including PI3K, EGFR and PDGF. TET1 expression correlated with sensitivity to drugs targeting the PI3K-mTOR pathway. CRISPR mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression. Our work establishes TET1 as a potential oncogene that contributes to aberrant hypomethylation in cancer and suggests that TET1 could serve as a novel druggable target for therapeutic intervention. Overall design: Three biological replicates of empty vector single clones and TET1 KO single clone (in triplicate) were used to make RNA-seq libraries.  Fold change of each gene was calculated by comparing changes in expression in KO compared to the empty vector control samples	Co-expression
SRP150227	Regulatory network controlling tumor-promoting inflammation in human cancers [RNA-seq]	Using an inducible, inflammatory model of breast cellular transformation, we describe the transcriptional regulatory network mediated by STAT3, NF-kB, and AP-1 factors on a genomic scale.  These regulators form transcriptional complexes that directly regulate the expression of hundreds of genes in oncogenic pathways, such as cell proliferation, metastasis, angiogenesis, apoptosis and metabolism, via a positive feedback loop.  This inflammatory feedback loop and associated network, which function to various extents in many types of cancer cells and patient tumors, is the basis for an “inflammation” index that defines cancer types by functional criteria.  The inflammation index is negatively correlated with expression of genes involved in DNA metabolism, and transformation is associated with genome instability.  Inflammatory tumors are preferentially associated with infiltration immune cells that might be recruited to the site of the tumor via inflammatory molecules produced by the cancer cells. Overall design: RNA-seq during MCF10A-ER-Src cell transformation and after STAT3, NF-kb, JUN, JUNB and FOS knockouts	Co-expression
SRP150229	ML29755 RNA-seq data	Programmed death-ligand 1 (PD-L1) expression has been associated with response to PD-1/PD-L1 inhibition, but responses are also seen in patients with PD-L1 negative tumors when assessed immunohistochemically (IHC) with various antibodies. To help elucidate these findings, we performed a positron emission tomography (PET) imaging study in human with the anti-PD-L1 antibody atezolizumab labeled with Zirconium-89 (89Zr) prior to treatment with atezolizumab to assess normal tissue distribution and evaluate tumor tracer uptake. Additionally, to help explain why some patients respond to checkpoint inhibitors despite low or absent PD-L1 expression, we compared PD-L1 expression and immune phenotypes based on both CD8 IHC and RNA sequencing of post-tracer biopsies to tumor tracer uptake (SUVmax). Overall design: In this trial, 22 patients completed the full imaging series of up to 4 PET scans and were subsequently treated with atezolizumab monotherapy until progressive disease (PD) from which 11 post-tracer tumor biopsies were available for RNA sequencing, which are available here.	Co-expression
SRP150234	RNA seq in human gastroparesis	Both diabetic and idiopathic gastroparesis have unique and overlapping changes in the transcriptome.  Immune signaling predominately plays a role in the pathogenesis of gastroparesis. Overall design: RNA sequencing was completed on full thickness gastric body samples from diabetic gastroparetics, diabetic non-gastroparetics controls, idiopathic gastroparetics and non-diabetic non-gastroparetic patients.	Co-expression
SRP150240	Transcriptional profiling of MCF7 cells treated with H3B05942, E2, or standard of care compounds	The objective of this experiment was to compare the affect of H3B-5942 treatment on global  gene expression and to compare to treatment with standard of care agents tamoxifen and fulvestrant. Overall design: 4 conditions were assessed (H3B-5042, tamoxifen, fulvestrant, and DMSO as control). Three samples of each condition were collected.	Co-expression
SRP150241	Transcriptional profiling of Ishikawa cells treated with H3B-5942, E2, or standard of care compounds	The objective of this experiment was to determine the affect of H3B-5942 treatment on global  gene expression in an estrogen-deprived setting (agonist mode) and to compare to treatment with a saturated analog of H3B-5942, GDC-0810, and standard of care agents tamoxifen and fulvestrant. Overall design: 7 conditions were assessed  (H3B-5924, H3B-9224, E2, fulvestrant, tamoxifen,  GDC-810, and DMSO as negative control). Compounds were added at 2 concentrations (3nM and 30nM). Two samples of each condition were collected.	Co-expression
SRP150287	EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains transcriptional modulation and self-renewal via enhanced CtBP1 association	The transcriptional regulator EVI1 has an essential role in early hematopoiesis and development. However, aberrantly high expression of EVI1 has potent oncogenic properties and confers poor prognosis and chemo-resistance in leukemia and solid tumors. To investigate to what extent EVI1 function might be regulated by posttranslational modifications, we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. In the presence of genotoxic stress, EVI1-WT (SQS), but not site mutated EVI1-AQA was able to maintain transcriptional patterns and transformation potency, while under standard conditions carboxy-terminal mutation had no effect. Maintenance of hematopoietic progenitor cell clonogenic potential was profoundly impaired with EVI1-AQA compared with EVI1-WT, in particular in the presence of genotoxic stress. Exploring mechanistic events underlying these observations, we showed that after genotoxic stress EVI1-WT, but not EVI1-AQA increased its level of association with its functionally essential interaction partner CtBP1, implying a role for ATM in regulating EVI1 protein interactions via phosphorylation. This aspect of EVI1 regulation is therapeutically relevant, as chemotherapy-induced genotoxicity might detrimentally sustain EVI1 function via stress response mediated phosphorylation, and ATM-inhibition might be of specific targeted benefit in EVI1-overexpressing malignancies. Overall design: Poly-A RNA sequencing (RNAseq) analysis of EVI1-mediated modulation of gene expression RNA was extracted from HEK293 cells, which were subjected to transient transfection using half confluent cultures with pCMV-flag, pCMV-EVI1-WT-flag or pCMV-EVI1-AQA-flag, exposed to 150 µM H2O2 or left untreated for 8 h.	Co-expression
SRP150313	Aberrant splicing in B-cell acute lymphoblastic leukemia [B-ALL]	Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3'UTR was most pervasively misspliced, yielding the transcript  subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs involved the 5' UTR, suggestive of splicing as a mechanism of translational deregulation. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis. Overall design: We profiled 18 pediatric B-cell acute lymphoblastic leukemias	Co-expression
SRP150314	Aberrant splicing in B-cell acute lymphoblastic leukemia [cell line]	Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3'UTR was most pervasively misspliced, yielding the transcript  subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs involved the 5' UTR, suggestive of splicing as a mechanism of translational deregulation. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis. Overall design: We profiled hnRNPA1 Ctrl and hnRNPA1 knockdown with 2 replicates each.	Co-expression
SRP150315	Bone marrow derived human B cells [normal proB]	Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3'UTR was most pervasively misspliced, yielding the transcript  subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs involved the 5' UTR, suggestive of splicing as a mechanism of translational deregulation. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis. Overall design: We profiled adult and pediatric early B pro B, pre B and immature B cells	Co-expression
SRP150320	Next generation sequencing on knockdown of AC093323.3 in lung cancer cells	In this study we predict functionally important long intergenic non-coding RNAs (lincRNAs) with a role in core essential processes in human. One of the candidate lincRNA, AC093323.3, was experimentally verified to affect cell viability. We performed RNASeq on knockdown of AC093323.3 to further investigate the functional role of this lincRNA. Overall design: RNA profiles of NCI-H460 lung cancer cells after treatment with scrambled siRNAs and AC093323.3-siRNA.	Co-expression
SRP150323	yylncT acts as a gatekeeper of the mesodermal transcriptional program by local modulation of DNMT3B [human_2]	Bidirectional transcription is a prevalent feature of eukaryotic promoters. The goal of this study is to identify novel divergent long-coding RNAs during differentiation of human ES to cardiomyocytes. Methods: Paired end RNA-Seq was performed on key time-points of human ES cell differentiation to cardiomyocytes. The time-points include  day2, day4, day6 and day8. Results: Using an optimized data analysis workflow, we mapped about ~70 million sequence reads per sample to the human genome (build hg38) and identified 781 novel yylncRNAs during ES cell differentiation to cardiomyocytes. Expression kinetics of a subset of  yylncRNAs identified from RNA-Seq  had a linear relationship with qRT–PCR . Conclusions: Our study represents the detailed analysis of the genome wide identification of divergent long-coding RNA generated by paired end RNA-seq technology. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of long-non coding RNA content within a cell. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biological functions. Overall design: We have used 4 different time-point (all in duplicates), covering key stages of human  ES cell differentiation to cardiomyocytes. It includes day 2 (late mesoderm), day 4 (cardiac mesoderm), day 6 (cardiac progenitors) and day 8 (early cardiomyocytes).	Co-expression
SRP150331	Transcriptome landscape of HeLa response upon triamcinolone acetonide	Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties. Overall design: HeLa cells were cultured with DMEM plus 10% charcoal-stripped FBS. HeLa cells were treated in the presence of 100 nM triamcinolone acetonide (TA) for 4 hours. Cells were then collected for RNA-seq.	Co-expression
SRP150348	Leiomyosarcoma RNA-Seq	RNA-Seq performed on 20 samples of leiomyosarcoma.	Co-expression
SRP150349	Integrated epigenomic and transcriptomic profiling of terminal human erythropoiesis [RNA-seq]	In vitro cultured CD34+ derived erythroblasts were sorted using surface markers and processed using RNA-seq Overall design: Biological replicates (3 or 4 per population) were processed across 2-3 biological donors for 8 sorted populations for RNA-seq	Co-expression
SRP150355	Domain-focused CRISPR-screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells	Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of beta-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase-domain focused CRISPR/Cas9-based genetic screen with a newly optimized sgRNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies. Overall design: A CRISPR-screen reveals HRI kinase as a fetal hemoglobin repressor and further validated in HUDEP2 and CD34+ derived primary erythroid cultures.	Co-expression
SRP150362	Histone deacetylase inhibitors in alveolar rhabdomyosarcoma	Multiple histone deacetylase inhibitors were tested on multiple alveolar rhabdomyosarcoma cell lines and multiple patient-derived xenograft models of alveolar rhabdomyosarcoma Overall design: Alveolar rhabdomyosarcoma cell lines were treated with various histone deacetylase inhibitors or with vehicle. Post experiment cells were snap frozen and had RNA isolated from cell pellets. Isolated RNA was sequenced and quantified	Co-expression
SRP150363	Transcriptomic hallmarks of tumor plasticity and stromal interactions in brain metastasis [BrainMet_Othotopic]	We find that malignant LUAD tumor cells grown in the brain microenvironment display significantly altered transcriptomic profiles when compared to tumor cells grown in monolayer or subcutaneously. Additionally, we characterize the reciprocal neuroinflammatory response of the surrounding brain stroma to metastatic LUAD. This dataset can be utilized to explore the mechanisms of LUAD cell plasticity as well as the co-adaptation of the brain microenvironment to metastatic disease. Overall design: Examination of the transcriptomic profiles of LUAD cells grown in different microenvironments (i.e., brain or lung) and the corresponding gene expression changes of the stroma in the tumor-bearing brain.	Co-expression
SRP150366	Transcriptomic hallmarks of tumor plasticity and stromal interactions in brain metastasis [BrainMet_SQ_2D]	We find that malignant LUAD tumor cells grown in the brain microenvironment display significantly altered transcriptomic profiles when compared to tumor cells grown in monolayer or subcutaneously. Additionally, we characterize the reciprocal neuroinflammatory response of the surrounding brain stroma to metastatic LUAD. This dataset can be utilized to explore the mechanisms of LUAD cell plasticity as well as the co-adaptation of the brain microenvironment to metastatic disease. Overall design: Examination of the transcriptomic profiles of LUAD cells grown in different microenvironments (i.e., Brain, subcutaneous, monolayer culture) and the corresponding gene expression alterations of the stroma in the tumor-bearing brain.	Co-expression
SRP150367	Transcriptomic hallmarks of tumor plasticity and stromal interactions in brain metastasis [MultiDisease]	We report that well-defined xenograft models of leading sources of CNS metastasis (melanoma, breast cancer, lung cancer) undergo specific transcriptomic alterations upon entering the brain microenvironment. This dataset can be utilized to explore the mechanisms of tumor cell plasticity as well as the co-adaptation of the brain microenvironment to metastatic disease. Overall design: Examination of the transcriptomic profiles of lung cancer, breast cancer, and melanoma models of brain metastatic disease and the resulting gene expression changes of the stroma in the tumor-bearing brain.	Co-expression
SRP150416	Differentiation of human embryonic stem cells into cardiomyocytes	Regulation of gene expression acts at numerous complementary levels to control and refine the protein abundance. The analysis of mRNAs associated to polysomes, called polysome profiling, has been used to investigate post-transcriptional mechanisms involved in different biological processes. Pluripotent stem cells, as human embryonic stem cells (hESCs), are able to differentiate into a variety of cell lineages and the cell commitment progression is carefully orchestrated. Genome-wide expression profiling had provided the possibility to investigate transcriptional changes during cardiomyogenic differentiation, however, a more accurate study regarding post-transcription regulation is required. In the present work, we isolated and high-throughput sequenced ribosome-free and polysome-bound RNAs from undifferentiated pluripotent stem cells and the subsequent differentiation stages of cardiomyogenesis: embryoid body aggregation, mesoderm, cardiac progenitor and cardiomyocytes. Expression of developmental markers were followed by flow cytometry and quality analysis were performed as technical controls to ensure high quality data. Our dataset provides valuable information about hESC cardiac differentiation and can be used to investigate genes potentially controlled by post-transcriptional mechanisms.	Co-expression
SRP150418	Tamoxifen-induced apoptosis of MCF-7 cells via GPR30/PI3K/MAPKs interactions: Verification by ODE modeling and RNA sequencing	Tamoxifen (Nolvadex) is one of the most widely used and effective therapeutic agent for breast cancer. It benefits nearly 75% of patients with ER-positive breast cancer that receive this drug. Its effectiveness is mainly attributed to its capacity to function as an estrogen receptor (ER) antagonist, blocking estrogen binding sites on the receptor, and inhibiting the proliferative action of the receptor-hormone complex. Although, tamoxifen can induce apoptosis in breast cancer cells via upregulation of pro-apoptotic factors, it can also promote uterine hyperplasia in some women. Thus, tamoxifen as a multi-functional drug could have different effects on cells based on the utilization of effective concentrations or availability of specific co-factors. Evidence that tamoxifen functions as a GPR30 (G-Protein Coupled Receptor 30) agonist activating adenylyl cyclase and EGFR (Epidermal Growth Factor Receptor) intracellular signaling networks, provides yet another means of explaining the multi-functionality of tamoxifen. Here ordinary differential equation (ODE) modeling, RNA sequencing and real time qPCR analysis were utilized to establish the necessary data for gene network mapping of tamoxifen-stimulated MCF-7 cells, which express the endogenous ER and GPR30. The gene set enrichment analysis and pathway analysis approaches were used to categorize transcriptionally upregulated genes in biological processes. Of the 2,713 genes that were significantly upregulated following a 48 h incubation with 250 µM tamoxifen, most were categorized as either growth-related or pro-apoptotic intermediates that fit into the Tp53 and/or MAPK signaling pathways.  Collectively, our results display that the effects of tamoxifen on the breast cancer MCF-7 cell line are mediated by the activation of important signaling pathways including Tp53 and MAPKs to induce apoptosis. Overall design: Gene expression analysis between tamoxifen-treated MCF-7 cells and untreated MCF-7 cells.	Co-expression
SRP150419	Haemopedia: Human Haematopoietic Gene Expression	Database of gene expression in different haematopoietic cell types at haemosphere.org Overall design: Comparison of gene expression in different haematopoietic cell types	Co-expression
SRP150441	Heat shock-induced ribosomal intergenic spacer RNA	Cells adapt to environmental stressors such as heat shock and extracellular acidosis through formation of nuclear membrane-less compartments called Amyloid bodies (A-bodies). Stressors activate formation of Amyloid bodies (A-bodies) via induction of ribosomal intergenic spacer RNA (rIGSRNA). RNA-seq on non-ribosome depleted RNA from human MCF7 cells exposed to heat shock (43C, 30 minutes) revealed the heat shock-specific expression profile of rIGSRNA. Overall design: Expression profile of the ribosomal intergenic spacer (i.e. rIGSRNA) in cells exposed to heat shock	Co-expression
SRP150447	RNA-seq data sets of human brain and Hela cell line	Generation of HeLa cell RNA-seq data Total RNA was isolated using TRIZOL (Invitrogen) from HeLa cells grown in standard medium under standard conditions. The RNA was divided into three samples containing equal amounts of RNA. The quality of these samples was manually controlled to produce different RIN values. Specifically, the RIN value of the low-quality RNA sample was 5 and that of the two high-quality samples was 10. Next, a RiboMinus kit (Invitrogen, Carlsbad, CA, USA) was utilized to deplete ribosomal RNA in these samples. The resulting RNA was incubated at 37 ? and treated with 10 U µg-1 RNase R (Epicentre, Madison, WI, USA). One of the high-RIN samples and the low-RIN sample were used separately as templates for cDNA libraries following the TruSeq protocol (Illumina, San Diego, CA, USA); the other high-RIN sample was used to construct a sequencing library using the same protocol but without the fragmentation step. Fragments with a broad range of fragment size (300-800 bp) were selected for library construction. The three libraries (Low RIN/Fragmented, High RIN/Fragmented High RIN/Unfragmented) were sequenced on the Illumina HiSeq 2500 platform of the Research Facility Center at the Beijing Institutes of Life Science, CAS, with a read length of 250 bp.   Generation of whole brain RNA-seq data Human, macaque, and rabbit whole brain RNA samples were purchased from Zyagen (San Diego, CA, USA). Mouse, rat and chicken whole brain tissues were obtained from the Research Facility Center at the Beijing Institutes of Life Science, CAS. RNA samples were isolated using TRIZOL (Invitrogen). For each species, three types of cDNA library were prepared. Specifically, a Ribo-/RNase R library was constructed using RNA samples that had been treated with the RiboMinus kit (Invitrogen) and then incubated at 37 ? with 10 U µg-1 RNase R; a Ribo-/cDNA library was constructed using RNA samples that were only treated with the RiboMinus kit; and a poly-A library was prepared according to the TruSeq v2 guide. Poly-A and Ribo- RNA samples were used as templates for cDNA libraries according to the TruSeq protocol (Illumina); Ribo-/RNase R-treated samples used the same protocol but without fragmentation. These libraries were sequenced on the Illumina HiSeq 2500 platform of the Research Facility Center at Beijing Institutes of Life Science, CAS. PolyA+ and Ribo-/RNase R libraries were sequenced with paired-end 250-bp reads, and Ribo-libraries were sequenced with paired-end 150-bp reads.	Co-expression
SRP150534	Metabolic labeling of Hek293 cells using 4-thiouracil	Hek293 cells were metabolically labelled using 4-thiouracil as described in (Schwalb et al, Science. 2016 Jun 3;352(6290):1225-8) but without fragmentation, and then bulk RNA was prepared for sequencing using the STRT method (Islam et al, Genome Res. 2011 Jul;21(7):1160-7). Samples were incubated in duplicate for 5, 15 and 30 minutes and included an unlabeled control representing the steady-state expression state. Overall design: 2 samples each of 4 incubation times, 2 cDNA preparations, 2 tagmentation replicates, and 2 biological replicates	Co-expression
SRP150548	Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma	Immune checkpoint blockade (ICB) therapy provides remarkable clinical gains, where melanoma is at the forefront of its success. However, only a subset of patients with advanced tumors currently benefit from these therapies, which at times incur considerable side-effects and costs. Constructing such predictors of patient's response has remained a serious challenge due to the complexity of the immune response and the shortage of large ICB-treated patient cohorts including both omics and response data. Here we build IMPRES, a predictor of ICB-response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes. It is based on two key conjectures: (a) immune mechanisms underlining spontaneous regression in neuroblastoma can predict ICB response in melanoma, and (b) key immune interactions can be captured via specific pairwise relations of immune checkpoint genes' expression. IMPRES is validated on 9 published datasets1–6 and on a newly generated dataset of 31 tumor samples treated with anti-PD-1 and 10 tumor samples treated with anti-CTLA-4 (some of these are treated with both antibodies), spanning 297 samples in total. It achieves an overall accuracy of AUC=0.83, outperforming existing predictors, capturing almost all true responders while misclassifying less than half of the non-responders.  Future studies are warranted to determine the value of the approach presented here in other cancer types. Overall design: RNA was purified from patients'' frozen or formalin-fixed tumor specimens and subject to quality control.  RNA samples of good quality were sequenced. For some patients, samples were taken at multiple time points or different biopsies from the same time point.	Co-expression
SRP150555	RNA-seq data from human SGBS adipocytes differentiated with marine oxohexadecenoic acids	We recently isolated and identified (7E)-9-oxohexadec-7-enoic acid (1) and (10E)-9-oxohexadec-10-enoic acid (2) from the marine algae Chaetoceros karianus. Synthesis and biological characterization show that these are PPARa/? dual agonists. Herein we report the gene expression data from human SGBS pre-adipocytes, stimulated to differentiate with 1, 2 or the classical PPAR? agonist rosiglitazone. The transcriptome analysis shows that both compounds induce anti-diabetic gene programs in adipocytes by upregulating insulin-sensitizing adipokines and repressing pro-inflammatory cytokines. Overall design: Human SGBS pre-adipocytes were stimulated with adipogenic media supplemented with either (7E)-9-oxohexadec-7-enoic acid, (10E)-9-oxohexadec-10-enoic acid, or rosiglitazone from day 0 to day 4. On day 4, agonists were withdrawn, and the cells were allowed to differentiate following standard protocol. On day 8, RNA was isolated and sent to sequencing.	Co-expression
SRP150561	RNA-seq of human gastric cancer cell line (AGS)	Transcriptomic sequencing of human gastric cancer cell line (AGS) upon citral treatment	Co-expression
SRP150582	Identification and comparison of the effects of radon, tobacco smoke and cannabis smoke exposure on the transcriptome of human lung epithelial cells	We exposed lung epithelial cells to low dose radon, tobacco smoke or cannabis smoke for a period of up to four months. Using RNA-Seq, we identified the impact that exposure to these factors had on the transcriptome of cultured lung cells at various time points during the exposure regimens. The goal of this project was to determine if low dose radon impacts the gene expression of lung epithelial cells and to be able to compare any observed effects to those induced by tobacco smoke exposure (established carcinogen) and cannabis smoke exposure (smoke exposure control).	Co-expression
SRP150586	Transcriptome of human decidual cells treated by siRNA targeting FOXO1	Here we report the gene expression profile of in vitro cultured human endometrial stromal cells treated with siRNA targeting FOXO1 piror to eutherian differentiation media exposure. The eutherian differentiation media contains cyclic AMP (cAMP) analogue 8-Br-cAMP and the progesterone (P4) analogue medroxyprogesterone acetate (MPA). Overall design: RNA-seq on decidualizing human endometrial stromal cells treated with siRNA targeting FOXO1.	Co-expression
SRP150595	Homo sapiens Transcriptome or Gene expression	In the current study we sought to investigate systemic effects of aneurysmal subarachnoid hemorrhage (SAH) through analysis of gene expression profiles in peripheral blood cells by means of deep transcriptome sequencing. We included 19 patients in the acute phase of IA rupture (RAA, first 72 hours), 20 patients in the chronic phase (RAC, 3-15 months), and 20 controls. We performed a global analysis of protein coding and non-coding gene variants regulated by SAH. We investigated expression of specific gene variants that may lead to production of functionally distinct protein isoforms and influence systemic response to IA rupture.	Co-expression
SRP150612	Rapid and efficient conversion of human fibroblasts into functional neurons by small molecules	Recent studies have demonstrated that human astrocytes and fibroblasts can be directly converted into functional neurons by small molecules. However, the reported reprogramming efficiency of human fibroblasts is extremely low, resulting in limited clinical application for the treatment of neurological disorders. Here, we report that human fibroblasts can be efficiently and directly reprogrammed into functional neuron-like cells (with a yield up to 82% TUJ1-positive neuron-like cells) by serially exposing cells to a combination of small molecules. These chemically induced neurons (iNs) displayed typical neuronal morphologies and showed neuronal transcriptional networks resembling human primary embryonic brain neurons. The iNs also exhibited mature firing patterns and formed functional synapse when cultured on mouse astrocytes. Importantly, the iNs can survive, mature and integrate into local circuits after transplantation into the postnatal mouse brains. Our study provides a rapid and efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts. Further, our approach offers strategies for disease modeling and drug discovery in central nervous system disorders.	Co-expression
SRP150616	RNA seq comparison between scrambled and shGRP78 cells	Pancreatic cancer cells transduced with sh knockdown of GRP78 Overall design: Pancreatic cancer mRNA profiles of scrambled control versus shGRP78 cell line, in triplicate, using Illumina Truseq Stranded Total-RNA library	Co-expression
SRP150617	RNA deep sequencing analysis of human brain microvascular endothelial cells (ECs) treated with glioma-conditioned medium (glioma-CM)	To determine the effects of glioma-conditioned medium on global gene expression in ECs. Overall design: Three lines of human microvascular ECs were treated with or without glioma-CM, followed by RNA extraction and RNA-seq.	Co-expression
SRP150624	Comparison of single-cell transcriptomics quality between unfixed cells and cells that were fixed and mock stained according to the RAID procedure	Cell fixation, permeabilization and antibody staining of could have adverse effects on the quality of single cell transcriptomics data. To assess the effects of the RAID procedure, which includes such steps, we performed a direct comparison of single cell transcriptomics by CELseq2 using unfixed and RAID-processed cells.  Quality measures (gene complexity, gene detection rate, average gene expression) were performed using 40000 samples UMI counts per cell. Overall design: Single cells were sorted in 96, wells plates. Per condition (unfixed or RAID) three sets (A,B,C) of 48 cells were processed with the CELseq2 protocol.	Co-expression
SRP150634	The ESCRT-III protein CHMP1A mediates secretion of sonic hedgehog on a novel class of extracellular vesicles	Extracellular vesicles (EVs) enable cell-to-cell communication in the nervous system essential for development and adult function. Endosomal Sorting Complex Required for Transport (ESCRT) complex proteins regulate EV formation and release. Recent work shows loss of function (LOF) mutations in, CHMP1A, which encodes one ESCRT-III member, cause autosomal recessive microcephaly with pontocerebellar hypoplasia in humans (Mochida et al., 2012). Here we show CHMP1A is required for maintenance of progenitors in human cerebral organoids and that mouse Chmp1a is required for progenitor proliferation in cortex and cerebellum and specifically for sonic hedgehog (SHH) mediated proliferation through SHH secretion. CHMP1A mutation reduces intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs), and EV release. SHH protein is present on a subset of EVs marked by a unique set of proteins we call ART-EVs. CHMP1A's requirement in formation of ART-EVs and other EVs provides a model to elucidate EV functions in multiple brain processes. Overall design: Gene expression profiling in a hiPSC WT line and a hiPSC CHMP1A null line. Comparative analysis by RNA-seq in hIPSCs and directed differentiation to cerebral organoids. Treatment with smoothened agonist (SAG) was used for examination of SHH dependent response in WT and CHMP1A null organoids.	Co-expression
SRP150657	Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin	Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, CD4+ Treg cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types. Overall design: Transcriptomic profiles from keratinocyte, dendritic cell, CD4+ T cell, CD4+ Treg cells, and CD8+ T cell populations were obtained from surgical skin discards from 11 healthy adults. Cell populations from whole skin were sorted via FACS and transcripts generated using an Illumina HiSeq 2500 platform. RNA-seq data for the bulk control samples were originally deposited in GEO study GSE74697.	Co-expression
SRP150723	Effect of BMP inhibition or stimulation of primary human keratinocytes	BMP treatment induces expression of late differenitation genes in primary human keratinocytes. Overall design: RNA-seq analysis after treatment with EGFR inhibitor AG1478 with or without BMP27 or BMP inhibitor DMH1. each treatment and control was performed in triplicate	Co-expression
SRP150742	Profiling  Cas13a activity targeting influenza virus	A549 cell lines transfected with Cas13a mRNA and crRNA targeting influenza virus. RNA was extracted using RNeasy mini kit and depleted for rRNA using NEB Next rRNA depletion kit. Library prepared using NEB Ultra II RNA library prep kit for Illumina.	Co-expression
SRP150758	Simultaneous quantification of antibody-RNA conjugates and the transcriptome by single cell RNA-sequencing	Undifferentiated and differentiated Keratinocytes (AG1478 treated) were stained with antibody-RNA conjugates (targeting EGFR and ITGA6) to measure protein-based differentiation changes in conjunction with single-cell transcriptomics. Overall design: Two 384 wells plates for untreated and two 384 wells plates for AG1478 treated cells were processed for single cell transcriptomics.	Co-expression
SRP150759	Simultaneous quantification of antibody-RNA conjugates and the transcriptome from fixed cells by RAID	Undifferentiated and differentiated Keratinocytes (AG1478 treated) were stained with antibody-RNA conjugates to measure protein-based diffrentiation changes in conjunction with single-cell transcriptomics. The cells were crosslinked and stained according to the RAID procedure to allow intracellular immunostaining. Antibodies used in this experiment are (TGM1, NOTCH1, KLK6, JAG1, phospho-RPS6, phospho-FAK). Overall design: Three 384 wells plates for untreated and Three 384 wells plates for AG1478 treated cells were processed for single cell transcriptomics	Co-expression
SRP150761	Expression Profiling of Cisplatin Resistant IGROV1 Cell Lines vs. Wild Type IGROV1 Cell Lines	Ovarian cancer IGROV1 cells were studied to profile the expression of wild type (WT, Cisplatin Susceptible) cells and Cisplatin Resistant (CR) cells. The goal was to gain insights or to build hypotheses into the mechanisms of Cisplatin resistance in this cell-based model. Overall design: The study included two experimental groups, IGROV1 wild-type cells and IGROV1 Cisplatin resistant (CR) cells.  Each group had two biological replciate samples.	Co-expression
SRP150779	Genome-wide gene expression profiling of primary human glomerular and kidney cortex tubular outgrowth cultures (RNA-seq)	We generated primary cultures from mechanically isolated kidney glomeruli (filtration unit of the nephron) which are composed of podocytes and mesangial cells. In parallel, we generated primary kidney cortex tubule cell cultures, which are composed primarily of proximal tubule cells. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). We found thousands of dynamically regulated enhancers in both cell types that potentially regulate nearby and distal target genes that are differentially expressed. These data will be useful for understanding the epigenomic regulation of gene transcription in key kidney cell types. Overall design: Paired DNase-seq and RNA-seq data sets from 2 different primary human kidney cell types ------------------------------------- For HIM23 and HIM26, authors state "we will be submitting the raw data to dbGaP".	Co-expression
SRP150784	RNA sequencing and pathway analysis identify important pathways involved in hypertrichosis and intellectual disability in patients with Wiedemann-Steiner syndrome	RNAseq in Wiedemann Steiner syndrome Overall design: examination of two cohorts of patients with or without KMT2A mutation	Co-expression
SRP150831	Single-cell analysis of human kidney organoids	We have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories in organoid cell differentiation Overall design: We have used DropSeq to perform single cell sequencing of 8 organoid samples that were harvested between 19-21 days.	Co-expression
SRP150833	Novel potential causative genes in carotid paragangliomas	Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from the paraganglion at the bifurcation of the carotid artery and are responsible for approximately 65% of all head and neck paragangliomas. CPGLs can occur sporadically or along with different hereditary tumor syndromes. Approximately 30 genes are known to be associated with CPGLs. However, the genetic basis behind the development these tumors is not fully elucidated, and the molecular mechanisms underlying CPGL pathogenesis remain unclear. We analyzed exome and transcriptome data derived from high-throughput sequencing of carotid paraganglioma samples. Using the xseq model, we evaluated the effects of potential somatic mutations on gene expression profiles. Novel potentially causative genes, were identified in carotid paragangliomas.	Co-expression
SRP150835	Specific inhibition of DPY30 activity by peptides suppresses blood cancer cell growth	Epigenetic modulators are being recognized as attractive targets for potential cancer treatment. SET1/MLL complexes are the major H3K4 methyltransferase complexes in mammals. The DPY30 subunit is associated with these complexes by forming a dimer that directly binds to the ASH2L subunit in the complexes and facilitates methylation. We have previously established an important role of DPY30 in certain hematologic malignancies including MLL-rearranged leukemia and Burkitt's lymphoma, but the domain on DPY30 that regulates cancer growth is not evident. Moreover, the potential of pharmacologically targeting this chromatin modulator to inhibit cancer has not been explored. Here we have developed a peptide-based strategy to specifically target DPY30 activity. We have designed cell-penetrating peptides that can either bind to DPY30 or show defective or enhanced binding to DPY30. The DPY30-binding peptides, but not the non-binding peptide, inhibit DPY30's activity in interacting with ASH2L and in enhancing H3K4 methylation. Treatment with the DPY30-binding, but not the non-binding, peptide significantly inhibited the growth of MLL-rearranged leukemia and other MYC-dependent hematologic cancer cells including Burkitt's lymphoma cells. These results strongly support a critical role of the ASH2L-binding groove of DPY30 in promoting the growth of certain blood cancers, and also demonstrate a proof-of-principle for the feasibility of pharmacologically targeting the ASH2L-binding groove of DPY30 for potential cancer inhibition. Overall design: Samples are RNA-seq from peptide treated cancer cell lines. Y518R peptide binds DPY30 while 3R peptide does not bind DPY30.	Co-expression
SRP150872	Discovering in vivo cytokine eQTL interactions from a lupus clinical trial	Background: Cytokines are critical to human disease and are attractive therapeutic targets given their widespread influence on gene regulation and transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central to defining drug and disease mechanisms. One promising strategy is to use interactions between expression quantitative trait loci (eQTLs) and cytokine levels to define target genes and mechanisms.   Results: In a clinical trial for anti-IL-6 in patients with systemic lupus erythematosus we measured interferon (IFN) status, anti-IL-6 drug exposure and whole blood genome-wide gene expression at three time points (379 samples from 157 individuals). First, we show that repeat transcriptomic measurements increases the number of cis eQTLs identified compared to using a single time point by 64%. Then, after identifying 4,818 cis-eQTLs, we observed a statistically significant enrichment of in vivo eQTL interactions with IFN status (p<0.001 by permutation) and anti-IL-6 drug exposure (p<0.001). We observed 210 and 72 interactions for IFN and anti-IL-6 respectively (FDR<20%). Anti-IL-6 interactions have not yet been described while 99 of the IFN interactions are novel. Finally, we found transcription factor binding motifs interrupted by eQTL interaction SNPs, pointing to key regulatory mediators of these environmental stimuli and therefore potential therapeutic targets for autoimmune diseases. In particular, genes with IFN interactions are enriched for ISRE binding site motifs, while those with anti-IL-6 interactions are enriched for IRF4 motifs.   Conclusion: This study highlights the potential to exploit clinical trial data to discover in vivo eQTL interactions with therapeutically relevant environmental variables. Overall design: Whole blood RNA-seq of 379 samples (across 3 time points) from 157 individuals with systemic lupus erythematosus	Co-expression
SRP150876	An Optically Decodable Bead Array for Linking Imaging and Sequencing with Single-Cell Resolution	Optically decodable beads link the identity of an analyte or sample to a measurement through an optical barcode, enabling libraries of biomolecules to be captured on beads in solution and decoded by fluorescence. This approach has been foundational to microarray, sequencing, and flow-based expression profiling technologies. We have combined microfluidics with optically decodable beads to link phenotypic analysis of living cells to sequencing. As a proof-of-concept, we applied this to demonstrate an accurate and scalable tool for connecting live cell imaging to single-cell RNA-Seq called Single Cell Optical Phenotyping and Expression (SCOPE-Seq). Overall design: Performed SCOPE-Seq on thousands of cells from two cell lines.	Co-expression
SRP150954	Identification of YY1 target gene in resting CD4 naive T cell	Naïve CD4 T cells from healthy adult individuals were isolated using EasySep Human Naive CD4 T cell Enrichment Kit (StemCell Technologies). Cells were transfected with control siRNA (Dharmacon: D-001910-01) or YY1 siRNA (Dharmacon A-011796-16) using the P3 Primary cell 4D-Nucleofector kit and the Lonza 4D-Nucleofector system. Transfected cells were cultured without stimulation for 48 hours, when YY1 protein expression had declined by >50%. Libraries were prepared using the Ovation RNA-seq whole blood kit (NuGen) and sequenced on an Illumina HiSeq 2500.	Co-expression
SRP150955	Comprehensive Off-target Analysis of dCas9-SAM-mediated HIV Reactivation via Long Noncoding RNA and mRNA Profiling	CRISPR/CAS9 (epi)genome editing brought revolutionary changes to the field of gene and cell therapy. However, a major concern is the potential off-target effects. A comprehensive analysis of the host transcriptome including mRNA, lncRNA, and alternative splicing was done using human cell line expressing the dead Cas9-mediated synergistic activation mediator (dCas9-SAM) plus HIV long terminal repeat (LTR)-specific MS2-mediated single guide RNA (msgRNA). The control scrambled msgRNA (LTR-Zero), and two LTR-specific msgRNAs (LTR_L and LTR_O) groups show very similar expression profiles of the whole transcriptome. Among 839 identified lncRNAs, none exhibited significantly different expression in LTR_L vs. LTR-Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were significantly decreased. Among 142,791 mRNAs, four genes were differentially expressed in LTR_L vs. LTR-Zero group. There were 21 genes significantly downregulated in LTR_O vs. either LTR-Zero or LTR_L group and one third of them are histone related. The distributions of different types of alternative splicing were very similar either within or between groups. There were no apparent changes in all the lncRNA and mRNA transcripts between LTR_L and LTR-Zero groups. This is the most comprehensive study of its kind to date demonstrating the rare off-target effects of the HIV-specific dCas9-SAM system in human cells.	Co-expression
SRP151000	Specific modulation of HIV RNA splicing and upregulation of anti-inflammatory miR-124 by the new drug candidate ABX464	Purpose: To ensure that ABX464 acted specifically on HIV splicing and did not significantly or globally affect the splicing events of human genes, we used a high-throughput RNAseq approach. Many genome-wide expression studies of HIV infection are based on analyses of total peripheral blood mononuclear cells (PBMCs), which consist of over a dozen cell subsets, including T cells, B cells, NK cells and monocytes Methods: The CD4 T cells were uninfected or infected with the YU2 strain and were untreated or treated for 6 days with ABX464, followed by high-throughput RNAseq. Each raw dataset of the samples contained between 44 and 105 million single-end reads (50 bp), with an average of approximately 60 million raw reads per sample Results: Approximately 98% of the total raw reads were mapped to the human genome sequence (GRCh38), giving an average of 60 million human reads per sample for further analyses. The reads that were correctly mapped (approximately 98% of total input reads) to the gene and transcript locations (GTF annotation file) Conclusions: The MDS of our gene expression data showed, without any outliers, that the different donors segregated well and distributed into the DMSO (untreated) and ABX464 treatments that were infected or uninfected. The displayed variance was donor-dependent (clustered by donor) but treatment-independent (no data structure related to the different treatments), which suggests that the ABX464 molecule did not induce a major difference in CD4 T cell gene expression. Overall design: We used purified CD4 T cells from the PBMCs of 4 donors. The CD4 T cells were uninfected or infected with the YU2 strain and were untreated or treated for 6 days, followed by high-throughput RNAseq to generate 32 mRNA profiles.	Co-expression
SRP151009	A role for p53 in the adaptation to glutamine starvation through the expression of Slc1a3	Numerous mechanisms to support cells under conditions of transient nutrient starvation have been described. The tumor suppressor protein p53 can contribute to the adaptation of cells to metabolic stress through various mechanisms that may help cancer cell survival in nutrient limiting conditions. We show here that p53 helps cancer cells to survive glutamine starvation by promoting the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition. Overall design: We quantify transcription via high throughput RNA sequencing in HCT116 cells (WT1 and WT2 clones) grown in complete medium (CM) or in glutamine-free medium (GD) for 48 hours.	Co-expression
SRP151036	Pro-angiogenic Ginsenoside F1 and Rh1 Inhibit Vascular Leakage by Modulating NR4A1	Angiogenesis is an essential process in human physiology and disease pathology. Particularly, in ischemic disease condition, the proper induction of angiogenesis without vascular leakage will be crucial for its effective therapy. Ginsenosides, triterpenoid saponins from a well-known medicinal plant ginseng, have been considered as a strong candidate for modulating angiogenesis. However, the biologic activity of individual gensenoside compounds and their target pathway have not been elucidated systematically. To find the candidates of vascular-related therapeutic agents, we evaluated in vitro angiogenic efficacy of 10 ginsenosides using tube formation assay with human umbilical vein endothelial cells (HUVECs). Among them, F1 and Rh1 showed strong in vitro angiogenic properties including EC tube formation, proliferation, and migration similar to vascular endothelial growth factor (VEGF). However, RNA transcriptome analysis showed that F1 and Rh1 differentially regulate gene expressions in HUVECs compared to VEGF. Not only that, F1 and Rh1 significantly inhibited vascular endothelial growth factor (VEGF)-induced vascular leakage both in vitro and in vivo. From RNA transcriptome analysis, we identified that nuclear receptor subfamily 4 group A member 1 (NR4A1) is regulated by F1 and Rh1 for suppression of VEGF-induced vascular leakage. By suppressing the expression and transcriptional activity of NR4A1, F1 and Rh1 could stabilize the expression and localization of junctional vascular endothelial (VE)-cadherin. These findings demonstrate that F1 and Rh1 could be potential compounds in the development of vascular pharmaceuticals. Overall design: mRNA profiles of VEGF- and ginsenoside F1/Rh1-treated HUVEC were generated by deep sequencing, in duplicate, using Hiseq-2500.	Co-expression
SRP151040	RNA-sequencing (RNA-seq) of induced pluripotent stem cells (iPSC) and iPSC-derived astrocytes from control and Parkinson's disease patients carrying LRRK2 G2019S point mutation	Purpose: The goal of this study is to compare the NGS-derived from transcriptome profiling (RNA-seq) of human iPSC, human iPSC-derived astrocytes from control and Parkinson's disease LRRK2 G2019S, and human commercial astrocytes to gain insight into the identity of human iPSC-derived astrocytes in vitro during the differentiation process. Total RNA was assayed for quantity and quality using Qubit® RNA HS Assay (Life Technologies) and RNA 6000 Nano Assay on a Bioanalyzer 2100.  The RNASeq libraries were prepared from total RNA using the TruSeq®Stranded mRNA LT Sample Prep Kit (Illumina Inc., Rev.E, October 2013). Briefly, 500ng of total RNA was used as the input material and was enriched for the mRNA fraction using oligo-dT magnetic beads. The mRNA was fragmented in the presence of divalent metal cations and at high temperature (resulting RNA fragment size was 80-250nt, with the major peak at 130nt). The second strand cDNA synthesis was performed in the presence of dUTP instead of dTTP, this allowed to achieve the strand specificity. The blunt-ended double stranded cDNA was 3´adenylated and Illumina indexed adapters were ligated. The ligation product was enriched with 15 PCR cycles and the final library was validated on an Agilent 2100 Bioanalyzer with the DNA 7500 assay.  The libraries were sequenced on HiSeq2000 (Illumina, Inc) in paired-end mode with a read length of 2x76bp using TruSeq SBS Kit v4. We generated over 30 million paired-end reads for each sample in a fraction of a sequencing v4 flow cell lane, following the manufacturer's protocol. Image analysis, base calling and quality scoring of the run were processed using the manufacturer's software Real Time Analysis (RTA 1.18.66.3) and followed by generation of fastq.gz sequence files by CASAVA. Results: We found that transcriptome of human iPSC-derived astrocytes is similar to human commercial astrocytes than human iPSC. Conclusion: These results suggest that iPSC-derived astrocytes resemble human commercial astrocytes validating the differentiating protocol used. Overall design: Human iPSC-derived astrocyte identity was obtained by comparing human iPSC from the same control and Parkinson's disease LRRK2 G2019S patients and human commercial astrocytes. mRNA profiles were generated by deep sequencing using Illumina HiSeq2000.	Co-expression
SRP151048	RNA-seq of synchronized S phase or G2 phase cells treated with an ATR inhibitor	We performed RNA-seq in cells synchronized to S or G2 phase to identify genes that were transcriptionally regulated by ATR activity. Overall design: RPE-1 cells were synchronized to late S (4 hours post-release from thymidine block), or to G2 phase (6 hours post-released from thymidine block) and either mock-treated or ATR-inhibited to identify genes that were transcriptionally controlled by ATR. An asynchronous control and an un-released from the thymidine block control were included. These 6 conditions were repeated in 3 independent experiments (total of 18 samples) and analyzed by RNA-seq.	Co-expression
SRP151055	A human TH17 population with a tissue-resident signature in healthy and inflamed oral mucosal tissues [10x]	T cells in mucosal tissues fulfill a complex array of duties to ensure maintenance of barrier immunity. In oral mucosa tissue, we found that increased inflammation altered CD4 T cell subsets in a spatially-dependent manner, although it had a modest effect on the frequency of tissue-resident memory T cells (TRM) and the CD4 T cell transcriptome. In contrast, localization to the tissue profoundly altered the transcriptional profile, emphasizing the importance of studying healthy tissue to understand disease-specific changes. Our data revealed the existence of a TH17 cell population that is predominantly found in the tissue-resident, but not transient, CD4 T cell compartment in mucosal tissue. Overall design: This project contains bulk RNA-seq data from paired oral mucosa tissue and blood CD4 T cell subsets from 10 subjects and 10X genomics sequencing of CD4 T cell subsets from one individual	Co-expression
SRP151057	IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [Huh-7]	The oncofetal mRNA-binding protein IGF2BP1 and the transcriptional regulator SRF modulate gene expression in cancer. In cancer cells, we demonstrate that IGF2BP1 promotes the expression of SRF in a conserved and N6-methyladenosine (m6A) dependent manner by impairing the miRNA-directed decay of the SRF mRNA. This results in enhanced SRF-dependent transcriptional activity and promotes tumor cell growth and invasion. At the post-transcriptional level, IGF2BP1 sustains the expression of various SRF-target genes. The majority of these SRF/IGF2BP1-enhanced genes, including PDLIM7 and FOXK1, shows conserved upregulation with SRF and IGF2BP1 synthesis in cancer. PDLIM7 and FOXK1 promote tumor cell growth and were reported to enhance cell invasion. Consistently, 35 SRF/IGF2BP1-dependent genes showing conserved association with SRF and IGF2BP1 expression indicate a poor overall survival probability in ovarian, liver and lung cancer. In conclusion, these findings identify the SRF/IGF2BP1-, miRNome- and m6A-dependent control of gene expression as a conserved oncogenic driver network in cancer. Overall design: total RNA-Seq of Huh-7 cells transfected with either control siRNAs (siC) or siRNAs directed against IGF2BP1.	Co-expression
SRP151069	Fibroblasts in cholesteatoma activate osteoclasts.	Cholesteatoma arises from a tympanic membrane and expands in the middle ear. It erodes the surrounding bone and leads to hearing loss or brain abscess which is lethal complication. Currently, the only effective treatment is the complete surgical removal of cholesteatoma. However, possibility of recurrence is not satisfactory, other clinical treatment is desired. A mechanism of bone erosion in rheumatoid arthritis, which is one of the bone destructive disease, is progressing to be clarified. Receptor activator of NF-?B ligand (RANKL) secreted by synovial fibroblasts, T cells, and B cells lead to differentiation and activation of osteoclast precursor in rheumatoid arthritis. In contrast it has been still unclear why cholesteatoma erodes bone. In the current study we studied that osteoclasts statistically increased in cholesteatoma, and that fibroblasts in the prematrix of cholesteatoma express RANKL. In this study we studied that osteoclasts statistically increased in cholesteatoma, and that fibroblasts in the prematrix of cholesteatoma express RANKL. We investigated upstream of RANKL from RNA sequence results by Ingenuity Pathways Analysis, which is data base of abundance information about molecular biology. Overall design: To generate the transcriptome profiles of the permatrix of cholesteatoma and dermis cut by laser micro dissection from cholesteatoma, three pairs of both sample from the same patients were adapted to RNA sequencing.	Co-expression
SRP151120	RNA-seq profiling of patient-derived xenograft models in Urothelial Cancer	To probe the tissue source (cancer cell VS stromal cell) of gene expression in the mixed tumor samples, we took advantage of a set of Urothelial Cancer patient-derived xenograft (PDX) models given that the transcriptome in these models is a mixture of human RNA (derived from cancer cells) and mouse RNA (derived from stromal cells). Overall design: The cohort includes 5 different patient-derived PDX models, 3 replicates for each model, and thus a total of 15 samples	Co-expression
SRP151142	An atlas of genetic variation for linking pathogen-induced cellular traits to human disease	Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with disease. To facilitate moving from associations to disease mechanisms, we leveraged the role of pathogens in shaping human evolution with the Hi-HOST Phenome Project (H2P2): a catalog of cellular GWAS comprised of 79 phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance (p<5x10-8) for phenotypes ranging from pathogen replication to cytokine production. Combining H2P2 with clinical association data on 83,717 patients from the eMERGE Network and experimental validation revealed evidence for mechanisms and connections with diseases. We identified a SNP near CXCL10 as a cis-cytokine-QTL and risk factor for inflammatory bowel disease. A SNP in ZBTB20 demonstrated pleiotropy, likely through suppression of multiple target genes, and was associated with viral hepatitis. Data are in an H2P2 web portal to facilitate interpreting human genome variation through the lens of cell biology. Overall design: Three human Huh7s'' mRNA profiles from non-target, ZBTB20 siRNA Chlamydia infection were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000/2500 platform.	Co-expression
SRP151147	Human bone marrow resident natural killer cells have a unique transcriptional profile and resemble resident memory CD8+ T cells	Human lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study we performed RNA sequencing on the CD56bright and CD56dim NK cells (from bone marrow and blood), and the ltNK cells (from bone marrow). In addition, the blood derived CD56dim, and bone marrow derived ltNK cells were further subdivided into a NKG2A+ and NKG2A- fraction. Paired blood and bone marrow samples of 4 healthy donors were included. When comparing the NKG2A fractions, only 3 genes (of 9382 genes included) had a significantly differential expression. Therefore, we pooled the expression data proportionally from the NKG2A+ and NKG2A- fractions in subsequent analyses. In ltNK cells, 1353 genes were differentially expressed compared to circulating NK cells. Several molecules involved in migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow cytometry we confirmed that the expression profile of adhesion molecules (CD49e-, CD29low, CD81high, CD62L-, CD11c-) and transcription factors (Eomeshigh, Tbetlow) of ltNK cells differed from their circulating counterparts. LtNK cells were characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their proliferative capacity was reduced compared to the circulating NK cells. By performing gene set enrichment analysis we identified DUSP6 and EGR2 as potential regulators of the ltNK cell transcriptome. Remarkably, comparison of the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in bone marrow. Together, we provide a comprehensive molecular framework of the conventional CD56bright and CD56dim NK cells as well as the tissue-resident ltNK cells and provide a core gene signature which might be involved in promoting tissue-residency. Overall design: mRNA sequencing of NK cell populations isolated from blood: CD56bright, NKG2A+ CD56dim and NKG2A- CD56dim, and bone marrow: CD56bright, CD56dim, NKG2A+ ltNK, and NKG2A- ltNK. Each sample has 4 biological replicates.	Co-expression
SRP151196	Homolog-selective degradation as a strategy to probe the function of CDK6 in AML	The design of selective small-molecules is often stymied by similar ligand binding pockets. Here we report the first cyclin-dependent kinase 6 (CDK6) degrader, BSJ-03-123, that uses phthalimide-conjugation to exploit protein-interface determinants to achieve proteome-wide degradation selectivity.  Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and coupling acute degradation with transcriptomics and phosphoproteomics enabled dynamic mapping of the immediate role of CDK6 in coordinating signaling and transcription. Overall design: RNA-seq of MV4-11 cells treated for 6h with the CDK4/6 inhibitor palbociclib or the CDK6-specific phthalimide conjugates BSJ-03-123 and YKL-06-102	Co-expression
SRP151199	Transcriptional profiling of WM1976 cells with siRNA knockdown of the long non-coding RNA SLNCR	RNA-Seq was used to profile transcriptional changes induced by siRNA knockdown of the long non-coding RNA SLNCR (all isoforms). Overall design: The WM1976 melanoma short-term culture transfected with either scrambled or SLNCR-targeting siRNAs	Co-expression
SRP151208	Identification of a cancer driver lncRNA in DNA damage response	We report that the lncRNA SCAT7 (ELF3-AS1) is involved in the activation of the DNA damage response in cisplatin resistant LUAD cells, akin cisplatin in sensitive cells. Therefore SCAT7 is a potential therapeutic target for drug resistant cancers Overall design: Effects of cisplatin treatment were assessed for cisplatin resistant (A549/cDDP) cells and their parental cell line by RNA-Seq. Evaluation of the role of lncRNA SCAT7 in a therapeutic approach alternative to cisplatin in A549/cDDP cells was assessed by RNA-Seq following lncRNA knockdown, in presence or absence of drug treatment.	Co-expression
SRP151274	BCL-XL strikingly increases survival of human iPSCs after electroporation leading to highly efficient genome editing	Our study reports that transient delivery of BCL-XL increases survival of human induced pluripotent stem cells (iPSCs) by ~10-fold after plasmid transfection, leading to a 20- to 100-fold increase in HDR (homology directed repair) mediated knockin efficiency and a 5-fold increase in knockout efficiency. We examined the transcriptomes of survived iPSCs at 2 hour, 4 hour and 8 hour after electroporation with or without BCL-XL overexpression by RNA-seq.	Co-expression
SRP151313	Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-Seq of LMNA KD)	Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: shRNA-mediated knockdown of LMNA was performed in human peripheral blood CD34+ cells (n=8 biological replicates). RNA-seq was utilized to determine the effect of LMNA knockdown compared to empty vector control.	Co-expression
SRP151416	Transcriptomics of FGF16-treated cells	Cellular antiviral programs can efficiently inhibit viral infection. These programs are often initiated through signaling cascades induced by secreted proteins such as type I interferons, IL-6 or TNF-a. Here, we generated an arrayed library of 756 human secreted proteins to perform a secretome screen focused on the discovery of novel modulators of viral entry and/or replication. The individual secreted proteins were tested for their capacity to inhibit infection by two replication-competent recombinant vesicular stomatitis viruses (VSV) with distinct glycoproteins utilizing different entry pathways. Fibroblast growth factor 16 (FGF16) was identified and confirmed as the most prominent novel inhibitor of both VSVs and therefore of viral replication and not entry. Importantly, an antiviral interferon signature was completely absent in FGF16-treated cells.	Co-expression
SRP151417	Bulk RNA-seq analysis of HUVEC cell cultures with Cerebral Cavernous Malformation (CCM) protein knockdown	Gene expression profiles of WT (wild type) and CCM-1, -2, and -3 KD (knockdown of krit1, ccm2 and pdcd10 genes) cells under 2D (Matrigel-coated plastic) and 3D (Matrigel) conditions. Deep sequencing of RNA was performed for cells at the initial (2hrs) and later (6hrs) stages of EC tubule formation. Overall design: Comparative analysis of gene expression of healthy and diseased cells in the tube formation assay	Co-expression
SRP151425	RNA-Seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature	Improving outcomes in multiple myeloma will not only involve development of new therapies, but better use of existing treatments. We performed RNA sequencing (RNA-Seq) on samples from newly diagnosed patients enrolled into the phase II PADIMAC study. Using an empirical Bayes approach and synthetic annealing, we developed and trained a seven-gene signature to predict treatment outcome. We tested the signature on independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass dataset, patients who were treated correctly according to the signature had a better progression-free and overall survival than those who were not. Indeed, the outcome for these correctly treated patients was non-inferior to those treated with combined bortezomib, lenalidomide, and dexamethasone (VRD). PADIMAC: Bortezomib, Adriamycin and Dexamethasone (PAD) therapy for previously untreated patients with multiple myeloma: Impact of minimal residual disease (MRD) in patients with deferred ASCT (autologous stem cell transplant) Overall design: RNA-Seq data from 44 patients enrolled into the PADIMAC study who provided RNA with an RNA Integrity score of 6 or greater. Thirteen out of forty-four patients had at least a very good partial remission sustained for at least a year without progression and were labelled as "bortezomib-good".	Co-expression
SRP151460	Human Treg IFNg/IL-10 subpopulations	Human Tregs isolated from PBMCs were sorted into 4 different subpopulations based on IFNg and IL-10 production and were performed mRNA-seq. Overall design: mRNA profiles of human Treg subpopulations	Co-expression
SRP151471	Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types.	We reported transcriptional characterization of tumor-infiltrating T regulatory cells (TITRs) that is shared between species and among different tumor types and stages. We genomically profiled immunocytes from 2 species: 1. Mouse: CD4+ Treg and Tconv, and CD8+ T cells from tumor and spleen of B16, MC38 or CT26 tumor bearing mice, as well as from spleens of non-tumor bearing mice. 2. Human: CD4+ Treg cells from surgically resected and cryopreserved human colorectal carcinomas or normal colon tissue. Overall design: Gene expression profiles of CD4+ Treg and Tconv, and CD8+ T cells from tumor and spleen of B16, MC38 or CT26 tumor bearing mice (biological triplicates), as well as from spleens of non-tumor bearing mice, and CD4+ Treg cells from 12 surgically resected and cryopreserved human colorectal carcinomas or normal colon tissue.	Co-expression
SRP151475	A code of mono-phosphorylation modulates the function of RB.	Hyper-phosphorylation of RB controls its interaction with E2F and inhibits its tumor suppressor properties. However, during G1 active RB can be mono-phosphorylated on any one of 14 CDK phosphorylation sites. Here we used quantitative proteomics to profile protein complexes formed by each mono-phosphorylated RB isoform (mP-RB) and identified the associated transcriptional outputs. The results show that the 14 sites of mono-phosphorylation co-ordinate RB's interactions and confer functional specificity. All 14 mP-RBs interact with E2F/DP proteins but they provide different shades of E2F regulation. RB mono-phosphorylation at S811, for example, alters RB transcriptional activity by promoting its association with NuRD complexes. The greatest functional differences between mP-RBs are evident beyond the cell cycle machinery. RB mono-phosphorylation at S811 or T826 stimulates the expression of oxidative phosphorylation genes, increasing cellular oxygen consumption. These results indicate that RB activation signals are integrated in a phosphorylation code that determines the diversity of RB activity. Overall design: Transcriptional changes caused by replacing endogenous RB with exogenous wild-type RB, constitutive active RB?cdk or any of the 14 mono-phosphorylation RB isoforms in human RPE1 cells.	Co-expression
SRP151482	Mixed tailing by TUT3 and TUT5 shields mRNA from rapid deadenylation [TAIL-Seq]	RNA tails play integral roles in the control of mRNA translation and decay. Guanylation of poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TUT3 (PAPD5) and TUT5 (PAPD7) (TUT3/5) as the enzymes responsible for mRNA guanylation. Purified TUT3/5 predominantly incorporate GTPs to generate a mixed poly(A) tail with intermittent non-adenosine residues. A single guanosine is sufficient to impede the deadenylation complex (CCR4-NOT) which trims the tail and exposes guanosine at the 3' end. Consistently, the depletion of TUT3/5 leads to a decrease in mRNA half-­life and abundance in cells. Thus, TUT3/5 produce a mixed tail which shields the mRNA from rapid deadenylation. Our study unveils the role of mixed tailing, and expands the complexity of post-transcriptional gene regulation. Overall design: HeLa cells and HFF cells were knocked down of control or TUT3/5 with two different siRNAs.	Co-expression
SRP151496	Generation of FOXO3 engineered human stem cells with enhanced efficacy and safety	FOXO3 is an evolutionally conserved transcription factor that has been linked to longevity. Here we asked whether human stem cells could be functionally enhanced by engineering them to express an activated form of FOXO3. This was accomplished via HDAdV-mediated gene editing of human embryonic stem cells. These cells were then differentiated into a range of vascular cell types, as FOXO3 has been shown to play a protective role in the cardiovascular system. FOXO3-enhanced vascular cells exhibited delayed senescence and increased resistance to oxidative injuries, compared with wild type cells. When tested in a therapeutic context, FOXO3-enhanced human mesenchymal stem cells promoted vasculature regeneration in a mouse model of ischemic injury, and were resistant to tumorigenic transformation, both in vitro and in vivo. Mechanistically, constitutively active FOXO3 conferred cytoprotection by transcriptionally downregulating CSRP1. Taken together, our findings provide mechanistic insights into FOXO3-mediated vascular protection, and indicate that FOXO3 activation may provide a means for generating more effective and safe biomaterials for cell replacement therapies. Overall design: In this study, we investigated the functions of FOXO3-enhanced human embryonic stem cells (hESCs), vascular endothelial cells (hVECs), vascular smooth muscle cell (hVSMCs), mesenchymal stem cells (hMSCs) and transformed mesenchymal stem cells (transMSCs) through multi-omics analysis.	Co-expression
SRP151530	Discovering human diabetes-risk gene function with genetics and physiological assays	To delineate the effects of BCL11A (a type 2 diabetes risk gene) in human beta cell function we knockdown BCL11A in primary human beta cells and generated and sequenced RNA-seq libraries from 4 human donors Overall design: Examination of the effects of BCL11A knockdown in primary human beta cells	Co-expression
SRP151602	A proteomics approach to profiling the temporal translational response to stress and growth	The goal of this project is to develop a high throughput proteomics approach to directly measure and quantify protein synthesis. Here, HeLa cells were stimulated with EGF, and ribosome profiling and mRNA sequencing was performed at various time points following stimulation to quantify changes in transcript abundance and translation. These data are compared to proteomics data to support the accuracy of the method as well as to gain insights into features captured in the proteomics data that may not be observed through traditional sequencing methods.	Co-expression
SRP151657	Breast cancer heterogeneity	Tumor heterogeneity is generated through a combination of genetic and epigenetic mechanisms, the later of which generate stem like cells responsible for tumor formation and metastasis. Although the development of single cell transcriptomic technologies hold promise to deconvolute this complexity, a number of these techniques have limitations of depth and potential bias. We adopted deep and full-length single-cell RNA sequencing to study the cellular and transcriptomic heterogeneity of SUM149, an ER-/PR-/HER2- triple negative breast cancer (TNBC) cell line.	Co-expression
SRP151738	Effects of anti-integrin treatment with vedolizumab on immune pathways and cytokines in inflammatory bowel diseases	Background and aims: Despite proven clinical efficacy of vedolizumab (VDZ) for inducing and maintaining remission in patients with Crohn's disease (CD) and ulcerative colitis (UC), subgroups of patients have no therapeutic benefit from anti-a4ß7 integrin therapy with VDZ. Within this study, we aimed to identify genetic, cellular and immunological mechanisms that define response and failure to VDZ treatment.Methods: Intestinal RNA Sequencing was performed in UC and CD patients before and at week 14 of VDZ therapy. a4ß7 expression on peripheral and mucosal immune cells was assessed by flow cytometry and immunohistochemistry. Cellular modes of VDZ mediated action were analysed ex vivo and in VDZ treated IBD patients.Results: Transcriptome analysis showed an impairment of signaling cascades associated with adhesion, diapedesis and migration of granulocytes and agranulocytes upon VDZ therapy. In non-remitters to VDZ therapy, a tissue destructive and leucocyte mediated inflammatory activity with activation of TNF dependent pathways was present, all of which were inhibited in remitters to VDZ. Clinical remission was associated with a significant reduction of a4ß7 expression on Th2 and Th17 polarized mucosal CD4+ T cells at week 14 of VDZ therapy and with significantly higher numbers of a4ß7 expressing mucosal cells prior to the initiation of VDZ therapy compared to non-remitters.Conclusions: Intestinal a4ß7 expression prior to VDZ therapy might represent a biomarker that predicts therapeutic response to subsequent VDZ treatment. Due to high activation of TNF signaling in VDZ non-remitters, anti-TNF treatment might represent a promising therapeutic strategy in VDZ refractory patients.	Co-expression
SRP151752	mRNA profiles of JMJD3 overexpression NB4 cells	Next Generation Sequencing Facilitates Quantitative Analysis of NB4 cells transduced with control or JMJD3-expression vector. JMJD3, a stress-inducible H3K27 demethylase, plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. However, how this histone modifier effects in a cell type-dependent manner remains unclear. Here, we show that in contrast to its oncogenic effect in preleukemia state and lymphoid malignancies, JMJD3 relieves the differentiation-arrest of certain subtypes (such as M2 and M3) of acute myeloid leukemia (AML) cells. RNA-sequencing and ChIP-PCR analyses revealed that JMJD3 exerts anti-AML effect by directly modulating H3K4 and H3K27 methylation levels to activate the expression of a number of key myelopoietic regulatory genes. Mechanistic exploration identified a physical and functional association of JMJD3 with C/EBPb that presides the regulatory network of JMJD3. Thus, the leukemia regulatory role of JMJD3 varies in a disease phase- and lineage-dependent manner, and acts as a potential oncorepressor in certain subsets of AML largely by coupling to C/EBPb-centered myelopoietic program. Overall design: mRNA profiles of NB4 cells were generated by deep sequencing, using  Illumina HiSeq 4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using  SYBR Green assays.	Co-expression
SRP151759	Temporal activation of NR5A2 and RAR? induce functional human naïve pluripotent state via modulating TGFß pathway	Rejuvenated primed human pluripotent stem cells, naïve cells, are accessible through the manipulating transcription factors, singaling pathways or a combination of both. However, there is a notable challenge in the functions of naïve hPSCs. Here, we show that the brief treatment with two chemical agonists (2a) of nuclear receptors NR5A2 and RAR? along with 2i and lif (2a2iL) is sufficient to induce naive pluripotency during the reprogramming of fibroblasts and pre-established hPSCs as well as the generation of new cell lines from preimplantation embryos. These cells manifested global naive-specific critera especially the contribution into the human-mouse chimeras. We demonstrated that TGF-ß pathway activity is potentially critical for induction and maintenance of 2a2iL naive hPSCs. Consequently, transient activation of TGF-ß resulted in generation of naive hPSCs in 2iL condition. These results represent a naive pluripotent state which is in a top point of developmental potential equivalent with preimplantation human embryo. Overall design: Primed and naïve hESCs mRNA profiling in two cell lines.	Co-expression
SRP151763	Integrated analysis of genetic variants regulating retinal transcriptome (GREx) identifies genes underlying age-related macular degeneration	Age-related macular degeneration (AMD) is a complex multifactorial disease with at least 34 loci contributing to genetic susceptibility.  To gain functional understanding of AMD genetics, we generated transcriptional profiles of retina from 453 individuals including both controls and cases at distinct stages of AMD.  We integrated retinal transcriptomes, covering 13,662 protein-coding and 1,462 noncoding genes, with genotypes at over 9 million common single nucleotide polymorphisms (SNPs) for expression quantitative trait loci (eQTL) analysis of a tissue not included in Genotype-Tissue Expression (GTEx) and other large datasets.  Cis-eQTL analysis revealed 10,474 genes under genetic regulation, including 4,541 eQTLs detected only in the retina.  We then integrated the AMD-genome-wide association studies (GWAS) data with eQTLs and ascertained target genes at six loci.  Furthermore, using transcriptome wide association analysis (TWAS), we identified 23 additional AMD-associated genes, including RLBP1, HIC1 and PARP12.  Our studies expand the genetic landscape of AMD leading to direct targets for biological evaluation and establish the Genotype-Retina Expression (GREx) database as a resource for post-GWAS interpretation of retina-associated traits including glaucoma and diabetic retinopathy. Overall design: Retinal samples from 523 aged post-mortem human subjects from a spectrum of age-related macular degeneration (AMD) were RNA-seq profiled.	Co-expression
SRP151780	RNA-sequencing analysis of differentially expressed genes (DEGs) induced by STC2 overexpression in colorectal cancer cells	To identify STC2-regulated downstream target genes, we compared the results of RNA-seq analysis between colorectal cancer cells without STC2 (SW480-NC) and cells with STC2 (SW480-STC2). Overall design: Colorectal cancer cells SW480 were transfected with negative control (named SW480-NC) or STC2 overexpression vectors (named SW480-STC2). Then cells were harvested for RNA isolation for RNA-seq analysis.	Co-expression
SRP151808	Therapeutic targeting of CD146/MCAM highlights its supportive function in prostate cancer bone metastasis	To identify the putative mechanisms of action of MCAM, we performed RNA-sequencing to define the transcriptional changes induced by MCAM knockdown. A biological triplicate for MCAM knockdown cells and control samples (shRNA-NT) was generated and total RNA extracted for RNA sequencing.	Co-expression
SRP151827	NTPDase3 antibody targets adult human pancreatic ß-cells for in vitro and in vivo analysis	Identification of cell surface markers specific to human pancreatic ß-cells would allow in vivo analysis and imaging. Here we introduce a biomarker – ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3) – that is expressed on the cell surface of essentially all adult human ß-cells, including those from individuals with type 1 or type 2 diabetes (T1D, T2D). NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerges in islet ß-cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human ß-cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human ß-cells. Thus, NTPDase3 is a cell surface biomarker of adult human ß-cells and the antibody directed to this protein should be a useful new reagent for ß-cell sorting, in vivo imaging, and targeting. Overall design: Total of 5 non-diabetic control donors were analyzed. ß-cells were FACS-sorted and RNA was extracted from each of these samples. RNAseq was performed on all 5 samples.	Co-expression
SRP151859	Transcriptomic analysis of cardiomyocyte differentiation from human induced pluripotent stem cells (hiPSCs) in 2D and 3D culture	Tridimensional cardiac differentiation from hiPSCs has been largely described in the literature. However, the exact impact that 3D culture has throughout the entire process of cardiac differentiation remains poorly defined. We developed a robust and efficient 3D platform for cardiomyocyte differentiation from hiPSCs, based on the temporal modulation of WNT signalling using small molecules. 3D aggregates of hiPSCs were generated by forced aggregation in microwells and subsequently differentiated. In order to determine the differences in gene expression profile due to 3D culture throughout the different stages of cardiac differentiation, we compared transcriptional changes between cells in 3D aggregates and standard 2D monolayer cardiac differentiation. Analysis of these data suggests a faster commitment of hiPSCs toward the cardiac lineage and also higher degree of cardiomyocyte functional maturation after 20 days of culture in the 3D aggregates when compared with the 2D monolayer. Overall design: Cells from different time points of cardiac differentiation (day 0, 1, 3, 5, 7, 9, 12, 15, 18 and 20), from 3D and 2D culture conditions were collected for RNA-seq. Three biological replicates were obtained for each time point. Deep sequencing was performed in the Illumina platform.	Co-expression
SRP151911	Identification and validation of circHIPK3 is upregulated in colorectal cancer and characterization of its role in promoting carcinogenesis	In order to confirm that circHIPK3  in colorectal cancerand characterization of its role in carcinogenesis, verified the expression level of circHIPK3 in additon 18 samples, and further collected 30 health controls and 30 colorectal cancer patients for exosome detection. The present study identified circHIPK3 is higher expression in CRC tissues and exosome of CRC patients. Overall design: Total circRNAs were detected in two colorectal cancer biopsies and corresponding para-cancer tissues	Co-expression
SRP151960	Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism	Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of a disease spectrum with shared clinical, genetic and pathological features. These include near ubiquitous pathological inclusions of the RNA binding protein (RBP) TDP-43, and often the presence of a GGGGCC expansion in the C9ORF72 (C9) gene. Here we show unexpectedly that the signature of hnRNP H sequestration and altered splicing of target transcripts we identified in C9ALS patients (Conlon et al. 2016) also occurs in fully half of 50 post-mortem sporadic, non-C9 ALS/FTD post-mortem brains. Furthermore, and equally surprisingly, these “like-C9” brains also contained correspondingly high amounts of insoluble TDP-43, as well as several other disease-related RBPs, and this correlates with widespread global splicing defects. Finally, we show that the like-C9 sporadic patients, like actual C9ALS patients, were much more likely to have developed FTD. We propose that these unexpected links between C9 and sporadic ALS/FTD define a common mechanism in this disease spectrum. Overall design: Differential splicing analysis of Amyotrophic Lateral Sclerosis  (ALS) and Control samples contributor: NYGC ALS Consortium contributor:  The Target ALS Human Postmortem Tissue Core	Co-expression
SRP152203	RNA-seq of eight lymphoblastoid cell lines after AHR ligand treatments	RNA-seq was done on eight different lymphoblastoid cell lines for vehicle control, 3-MC agonist treatment and GNF-351 antagonist treatment for AHR to look at AHR regulated genes with different genetic backgrounds.  We identified 69 genes that were highly differentially expressed after 3-MC or GNF-351 antagonist treatment with variation in the degree fo differential expression between the eight cell lines. Overall design: Eight lymphoblastoid cells lines were treated in duplicate with vehicle control, 3-MC or GNF-351 for 24 hours before RNA collection.  Libraries were prepared on the TruSeq RNA Library Prep Kit v2 and paired end sequencing was carried out on Illumina HiSeq 4000	Co-expression
SRP152218	RIG-I and MDA5 fRIP during KSHV lytic reactivation	The RIG-I like receptors (RLRs) RIG-I and MDA5 are cytosolic RNA helicases best characterized as restriction factors for RNA viruses. However, evidence suggests RLRs participate in innate immune recognition of other pathogens, including DNA viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). We demonstrate that RIG-I and MDA5 restrict KSHV lytic reactivation in PEL. By performing fRIP-Seq, we define the in vivo RLR substrates and demonstrate that RIG-I and MDA5-mediated restriction is facilitated exclusively by the recognition of host-derived RNAs. Overall design: Inducible F-RIG-I and F-MDA5 BC-3 cells, as well as control BC-3 cells were treated with 1 µg/ml of doxycycline, 20ng/ml tetradecanoyl phorbol acetate and 0.1 mM sodium butyrate for 48 h. Flag fRIP was performed and RNA was submitted for high throughput sequencing.	Co-expression
SRP152310	The Epstein Barr virus circleRNAome	Our appreciation for the extent of Epstein Barr virus (EBV) transcriptome complexity continues to grow through findings of EBV encoded microRNAs, new long non-coding RNAs, and hundreds of new polyadenylated lytic transcripts. Here we report an additional layer to the EBV transcriptome through the identification of a repertoire of latent and lytic viral circRNAs. Utilizing RNase R-sequencing with cell models representing latency types I, II, and III, we identified circRNAs expressed from the latency Cp promoter involving backsplicing from the W1 and W2 exons to the C1 exon, from the EBNA BamHI U exon, and from the latency long-non-coding RPMS1 locus. We also identified circRNAs expressed during reactivation including an exon 8-to-2 backspliced LMP2 transcript and a highly expressed circRNA derived from the BHLF1 gene. Altogether we identified over 30 EBV circRNA candidates and validated and determined the structural features, expression profiles and nuclear-cytoplasmic distributions of several prominent viral circRNAs. Further, we show that two RPMS1 circRNAs are expressed in stomach cancer specimens. This study increases the known EBV latency and lytic transcriptome repertoires to include viral circRNAs and provides an essential foundation for investigations into the functions of this new class of EBV transcripts in EBV biology and disease. Overall design: RNase R treated, Ribodepletion, and Poly-A selection libraries of EBV+ B-cell lymphoma and gastric carcinoma cell lines were generated and RNA-sequencing was done.	Co-expression
SRP152523	Contribution of SRF and Nkx2-5 to androgen-dependent gene expression in prostate cancer	To study and compare the effect of siRNA-mediated SRF or Nkx2-5 silencing on androgen-responsive genes in LNCaP cells. Overall design: Human LNCaP prostate cancer cells were transfected with siRNA SmartPools targeting SRF or Nkx2-5 or a non-targeting siRNA SmartPool.  Forty-two hours after transfection, cells were treated with synthetic androgen R1881 (5nM) or vehicle.  Three biological replicates were generated per treatment group.  Forty-eight hours later, total RNA was isolated and processed for RNA-Seq analysis.	Co-expression
SRP152557	RNA-Seq analysis of long-term estrogen-deprived (LTED) MDA-MB-134VI (MM134) and SUM44PE (SUM44) ILC cell lines	Background: Invasive lobular breast carcinoma (ILC) is a histological subtype of breast cancer that is characterized by loss of E-cadherin, and high expression of estrogen receptor alpha (ER). Many patients with ILC are effectively treated with adjuvant aromatase inhibitors (AIs), however, acquired AI resistance remains a significant problem. Methods: To identify underlying mechanisms of acquired antiestrogen resistance in ILC, we developed a total of 6 long-term estrogen-deprived (LTED) variant cell lines of the human ILC cell lines SUM44PE (SUM44; 2 lines) and MDA-MB-134VI (MM134; 4 lines). To better understand mechanisms of AI resistance in these models, we performed transcriptional profiling analysis by RNA-sequencing. Results: MM134 LTED cells expressed ER at decreased level and lost growth response to estradiol, while SUM44 LTED cells retained partial ER activity. Our transcriptional profiling analysis identified shared activation of lipid metabolism across all 6 independent models. However, the underlying basis of this signature was distinct between models. Oxysterols were able to promote the proliferation of SUM44 LTED cells, but not MM134 LTED. In contrast, MM134 LTED cells displayed high expression of the Sterol regulatory element-binding protein 1 (SREBP1), a regulator of fatty acid and cholesterol synthesis, and were hypersensitive to genetic or pharmacological inhibition of SREBPs. Several SREBP1 downstream targets involved in fatty acid synthesis, including FASN, were induced, and MM134 LTED cells were more sensitive to etomoxir, an inhibitor of the rate-limiting enzyme in ß-oxidation, than their respective parental control cells. Conclusions: Our characterization of a unique series of AI-resistant ILC models identifies a lipogenic phenotype, including overexpression of SREBP1. This novel metabolic target deserves further study for the prevention and treatment of AI-resistance for patients with ILC. Overall design: Parental and LTED MM134 and SUM44 cells were seeded in triplicates in 6-well plates. Parental cells were hormone deprived for three days before cell collection. RNA-Seq was carried out by Illumina HiSeq 2000. Raw sequence data were mapped to hg38 genome (ensembl release version 82) and gene counts were quantified with Salmon (version 0.6.0)	Co-expression
SRP152577	PyMINEr Finds Gene and Autocrine/Paracrine Networks from Human Islet scRNAseq	Toolsets available for in-depth analysis of scRNAseq datasets by biologists with little informatics experience is limited. Here we describe an informatics tool (PyMINEr) that fully automates cell type identification, cell type-specific pathway analyses, graph theory-based analysis of gene regulation, and detection of autocrine/paracrine signaling networks in silico. We applied PyMINEr to interrogate human pancreatic islet scRNAseq datasets and discovered several features of co-expression graphs including: concordance of scRNAseq-graph structure with both protein-protein interactions and 3D-genomic architecture; association of high connectivity and low expression genes with cell type-enrichment; and potential for graph-structure to clarify potential etiologies of enigmatic disease-associated variants. We further created a consensus co-expression network and autocrine/paracrine signaling networks within and across islet cell types from 7-datasets. PyMINEr correctly identified changes in BMP/WNT signaling associated with cystic fibrosis pancreatic acinar-cell loss. This proof-of-principle study demonstrates that the PyMINEr framework will be a valuable resource for scRNAseq analyses. Overall design: Human islets were obtained from the integrated islet distribution program (IIDP), cultured overnight, then prepared for scRNAseq via the Fluidigm C1 platform. RNAseq was perfromed on Illumina HiSeq 2500.	Co-expression
SRP152744	Homo sapiens Transcriptome or Gene expression	RNA-sequencings of TSPY1-overexpressed A549 and HepG2 cells were performed to systematically explore the signaling pathways in which TSPY1 is involved during tumor progression.	Co-expression
SRP152858	XPO1 inhibition antagonizes MCL via nuclear retention of IkB: Selinexor demonstrates antitumor activities in both ibr-sensitive and ibr-resistant tumor cells	Inhibition of BCR signaling through BTK inhibitor, ibrutinib, has generated a remarkable response in mantle cell lymphoma (MCL).  However, approximately one-third of the patients do not respond well to the drug and disease relapse on ibrutinib is nearly universal.  Alternative therapeutic strategies aimed to prevent and overcome ibrutinib resistance are needed.  We compared and contrasted the effects of selinexor, a selective inhibitor of nuclear export, with ibrutinib in six MCL cell lines that display differential intrinsic sensitivity to ibrutinib.  We found that selinexor had a broader anti-tumor activity in MCL than ibrutinib.  MCL cell lines resistant to ibrutinib remained sensitive to selinexor.  We showed that selinexor induced apoptosis/cell cycle arrest and XPO-1 knockdown also retarded cell growth.  Further, down-regulation of the NF-?B gene signature, as opposed to BCR signature, was a common feature that underlies the response of MCL to both selinexor and ibrutinib. Meanwhile, unaltered NF-?B was associated with ibrutinib resistance.  Mechnistically, selinexor induced nuclear retention of I?B that was accompanied by the reduction of DNA binding activity of NF-?B suggesting that NF-?B is trapped in an inhibitory complex. Co-immunoprecipitation confirmed that p65 of NF-?B and I?B were physically associated.  In primary MCL tumors, we further demonstrated that the number of cells with I?B nuclear retention was linearly correlated with the degree of apoptosis.  Our data highlight the role of NF-?B pathway in drug response to ibrutinib and selinexor and show the potential of using selinexor to prevent and overcome intrinsic ibrutinib resistance through NF-?B inhibition. Overall design: To capture early changes in RNA transcription, JEKO1 and MAVER were treated for 6 hr with or without the inhibitors (0.4 uM for ibrutinib and 1.5 uM for selinexor) with three biological triplicates. Cells were harvested and subjected to RNA sequencing and diffrences in biological pathway perturvation were analyzed using GSEA.	Co-expression
SRP152865	Generation of trichogenic adipose-derived stem cells by expression of three factors	Background: Previous studies demonstrated that adipose-derived stem cells (ASCs) can promote hair growth, but unmet needs exist for enhancing ASC hair inductivity. Objective: Therefore, we introduced three trichogenic factors platelet-derived growth factor-A, SOX2, and ß-catenin to ASCs (tfASCs) and evaluated whether tfASCs have similar characteristics as dermal papilla (DP) cells. Method: Global gene expression was examined using NGS analysis. Telogen-to-anagen induction, vibrissae hair follicle organ culture and patch assay were used. Results: tfASC cell size is smaller than that of ASCs, and they exhibit short doubling time. tfASCs also resist aging and can be expanded until passage 12. Cell proportion in S and G2/M increases in tfASCs, and tfASCs express high mRNA levels of cell cycle related genes. The mRNA expression of DP markers was notably higher in tfASCs. Moreover, NGS analysis revealed that the global gene expression of tfASCs is similar to that of DP cells. The  injection of tfASCs accelerated the telogen-to-anagen transition and conditioned medium of tfASCs increased the anagen phase of vibrissal hair follicles. Finally, we found that the injection of 3D-cultured tfASCs at p 9 generated new hair follicles in nude mice. Conclusion: Collectively, these results indicate that 1) tfASCs have similar characteristics as DP cells, 2) tfASCs have enhanced hair-regenerative potential compared with ASCs, and 3) tfASCs even at late passage can make new hair follicles in a hair reconstitution assay. Because DP cells are difficult to isolate/expand and ASCs have low hair inductivity, tfASCs and tfASC-CM are clinically good candidates for hair regeneration. Overall design: NGS analysis was carried out using RNA from ASCs, tfASCs and DP cells. ---------------------- contributor: MACROGEN	Co-expression
SRP152870	LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state [human]	Deregulated activity of the LATS tumor suppressors has broad implications on cellular and tissue homeostasis. We examined the consequences of downregulation of either LATS1 or LATS2 in breast cancer. Consistent with their proposed tumor suppressive roles, expression of both paralogs is significantly downregulated in human breast cancer, and loss of either paralog accelerated mammary tumorigenesis in mice. However, each paralog had a distinct impact on breast cancer. Thus, LATS2 depletion in luminal B tumors resulted in metabolic rewiring, with increased glycolysis and reduced PPARg signaling. Furthermore, pharmacological activation of PPARg elicited LATS2-dependent death in luminal B-derived cells. In contrast, LATS1 depletion augmented cancer cell plasticity, skewing luminal B tumors towards increased expression of basal-like features, in association with increased resistance to hormone therapy. Hence, these two closely related paralogs play distinct roles in protection against breast cancer; tumors with reduced expression of either LATS1 or LATS2 may rewire signaling networks differently and thus respond differently to anti-cancer treatments. Overall design: RNA from ZR75-1 and MCF7 transfected with siControl, siLATS1 or siLATS2 oligonucleotides was isolated and subjected to RNA-seq as above. For ZR75-1, three independent biological replicates were used. For MCF7, two independent biological replicates were used. ZR75-1 were transfected with either GFP only, GFP-LATS1 or GFP-LATS2. GFP-positive cells were sorted by FACS 24h following transfection (~80000 cells per sample). Two independent replicates were used.	Co-expression
SRP152878	LHX9 rescues KRAS suppression through transcriptional regulation of YAP1 [RNA-Seq]	Oncogenic KRAS signaling is required for tumor survival in cancers that harbor KRAS mutations. We recently performed a genome-scale expression screen to identify genes that bypass KRAS dependency. Here we demonstrate that the developmental transcription factor LHX9 rescues KRAS suppression in vitro and xenograft models. Furthermore, LHX9 decreases cell sensitivity to KRASG12C and MEK1/2 inhibitors. LHX9 promotes transcriptional changes associated with KRAS. Importantly, YAP1 upregulation by LHX9 is required for the rescue of KRAS suppression. Together we identify LHX9 as a YAP1 transcriptional regulator that permits KRAS-dependent cells to proliferate without KRAS expression. Overall design: mRNA profiles of HCT116 cells expressing different open reading frames and tet-inducible shKRAS were generated by sequencing, in duplicates, using Illumina Hiseq-2500	Co-expression
SRP152951	RNAseq of (Dimethylfumarate)DMF-induced changes in human CD8+ memory cells	IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: CD8+ memory cells from human blood	Co-expression
SRP152983	Synovial fluid and blood neutrophils from rheumatoid arthritis patients and matched healthy controls	Synovial fluid and blood neutrophils from 7 rheumatoid arthritis patients and 5 matched healthy controls Overall design: Experiment designed to compare gene signatures of neutrophils isolated from site of pathiology (synovial fluid (SF)) and from peripheral blood (PB) of RA patients.  Neutrophils were isolated from SF and PB from the same individuals (n = 3) to provide paired sample analysis.  Neutrophils were also isolated from PB from healthy donors as controls. There are two technical replicates for each donor and tissue.  The technical replicates were made by running the same library in two lanes.	Co-expression
SRP153016	markers of glioblastoma TMZ resistance	We study the expression pattern during the expression of drug resistance in cancer. We use, as model, the human glioma cell line, U251, cultured in the presence of Temozolomide (TMZ), the chemotherapy standard of care for patients with glioblastoma (GBM), to identify new therapeutic targets. We found that U251 cells become resistant to TMZ along with the induction expression of the DNA repair protein O6-methylguanine-DNA methyl-transferase (MGMT). However, prior to MGMT expression, TMZ induced a transient state wherein cells adopted a distinct morphology and expressed a specific set of genes.	Co-expression
SRP153037	Response of triple negative breast cancer to BAZ2A/B inhibition and BET bromodomain inhibition alone and in combination (RNAseq)	Three triple negative breast cancer cell lines (MDAMB231, SUM159, and HCC1806) were treated with small molecule inhibitors (JQ1, BET bromodomain inhibitor; GSK2801, BAZ2A/B bromodomain inhibitor) alone and in combination for 72 hours Overall design: 12 experimental samples	Co-expression
SRP153049	Transcriptome profiling of intestinal organoids stimulated with TNF and PGE2	To address the effect of inflammatory stimulation on intestinal epithelial cells, we performed RNA-seq analysis on human colonic epithelial organoids treated with TNF and/or PGE2. Overall design: Intestinal organoids were cultured for 4 days and treated with TNF (10 ng/ml) with or without PGE2 (1 µM), or treated with PGE2 alone for 48 h. RNA was isolated (n = 3/group), and RNA-seq analysis was performed for the four different groups (Control/TNF/TNF+PGE2/PGE2).	Co-expression
SRP153060	Effects of HSP90 inhibitors on airway goblet cell metaplasia	Goblet cell metaplasia and mucus hypersecretion are disabling hallmarks of chronic lung diseases for which no curative treatments are available. Therapies targeting specific upstream drivers of asthma have had variable results. We hypothesized that an a priori-knowledge independent approach would point to new therapies for airway goblet cell metaplasia. We analyzed the transcriptome of an organotypic model of human goblet cell metaplasia. We combined our data with previously published datasets from IL13-exposed in vitro and asthmatic in vivo human airway epithelial cells. The drug perturbation-response connectivity approach identified the heat shock protein 90 (HSP90) inhibitor geldanamycin as a candidate for reverting airway goblet cell metaplasia. We found that geldanamycin not only prevented but reverted IL13-induced goblet cell metaplasia. Geldanamycin did not induce goblet cell death, did not solely block mucin synthesis, and did not block IL13 receptor-proximal signaling. Moreover, the transcriptional effects of geldanamycin were absent in unstimulated cells and became evident only after stimulation with IL13. The predicted mechanism of action suggested that geldanamycin should also revert IL17-induced goblet cell metaplasia, a prediction confirmed by our data. Our findings suggest HSP90 activity may be required for persistence of goblet cell metaplasia driven by various mechanisms in chronic lung diseases. Overall design: For both batches, airway epithelia cultures from the lungs of eight different humans were studied, therefore, there are eight biological replicates. Comparisons should be made within batches. In batch 1 (XAM1), epithelia were exposed to vehicle (DMSO 0.5%),   geldanamycin 25 uM, or the HDAC6 inhibitor ISOX 10 uM for 48 hours. In batch 2 (XAM3), the epithelia were exposed to vehicle (DMSO 0.5%), IL13 (20 ng/mL) or IL13 plus geldanamycin (10 uM) for 48 hours.	Co-expression
SRP153104	PRMT5 Interacts with the BCL6 Oncoprotein and is Required for Germinal Center Formation and Lymphoma Cell Survival	We have found that PRMT5 methylates BCL6 and is needed for its full transcriptional repressor activity. Concomitant inhibition of both BCL6 and PRMT5 exhibits synergistic killing of BCL6-expressing lymphoma cells. Overall design: SUDHL6 cells were treated with DMSO or the PRMT5 inhibitor, GSK591, for 24 and 96 h. Total RNA was harvested from cells after vehicle or GSK591 treatment and used for expression profiling via mRNA-seq.	Co-expression
SRP153114	Whole Transcriptome RNASeq Data for Cell-Sorted Antibody Secreting Cells (ASC)	We report whole transcriptome RNASeq data for cell-sorted pop2, pop3, and pop5 which are antibody-secreting cells from human peripheral blood Overall design: 17 ASC samples, including 6 pop2 samples, 6 pop3 samples, and 5 pop5 samples across 6 individuals.	Co-expression
SRP153139	Trans-chalcone increases p53 activity	Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition	Co-expression
SRP153154	Genome-wide maps in MCF-7 cells with six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR overexpression or not	Analysis of MCF-7 cells following  six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR overexpression. Overexpression of six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR positively regulates the abundance of embryonic stem cell function. Results provide insight into the role of six2 mediated-regulation on the ceRNA network between CYP4Z1 and pseudogene CYP4Z2P in breast cancer stemness. Overall design: mRNA profiles of MCF-7 cells with six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR overexpression or not were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.	Co-expression
SRP153205	Genome wide mapping of polyadenylation sites in proliferating and contact-inhibited cells and cells with knockdown of cleavage and polyadenylation factors	Purpose: Quiescence is a state of reversible cell cycle exit. Levels of polyadenylation factors decreases when proliferating cells become quiescent.  The goals of this study are to determine the differential use of polyadenylation sites (changes in alternative polyadenylation) in quiescent vs. proliferating cells and also upon knockdown of polyadenylation factors. Methods: Two biological replicates of human dermal fibroblasts (12-1 and 12-3) were used for polyadeylation-site enriched RNA-seq on an Illumina HiSeq 2500 to compare quiescent vs. proliferating cells and polyadenylation factor knockdown vs. control cells. The reads were aligned to the human genome (hg19) uisng Tophat (2.0.14). The resulting bam files were used as an input to a python script provided by Gruber et al. (PMID: 27382025) to determine the counts for each polyadenylation site. Results: We observed a shift toward greater use of distal polyadenylation sites when the fibroblasts entered quiescence. We observed significant overlap between the genes that shift to greater distal site use with quiescence and CstF-64 or CPSF73 knockdown. Conclusions: The shift to greater distal site use with quiescence may reflect in part the reduced levels of cleavage and polyadenylation factors. Overall design: Perform polyadenylation site-enriched RNA-Seq on: (1) two biological replicates of proliferating and quiescent (contact-inhibited) cells, and (2) two biological replicates of control and polyadenylation factor (CstF64, CPSF73 or CFIm25) knockdown cells.	Co-expression
SRP153228	lncRNA expression analysis in patients with eosinophilic and neutrophilic asthma	Long non-coding RNA (lncRNA) are known to be important in many diseases. There has been some reports that lncRNA take part in the pathogenesis of systemic inflammation of asthma. lncRNA regulates gene transcription, protein expression and epigenetic regulation. However, the lncRNAs associated with differently airway phenotype such as eosinophilic and neutrophilic asthma remains unknown.  We aimed at identifying the differences in circulating lncRNA signature in Eos and Neu samples. lncRNA expression were studied between blood samples from Eos patients, Neu patients and healthy individuals (Control). Bioinformatic analysis was used to describe relevant biological pathways. Using quantitative real-time PCR, lncRNA expression was measured.   Comparing with Control samples, Eos sample has 190 own lncRNA and Neu sample has 166 own lncRNA(difference = 2-fold).  KEGG pathway annotation data and GO terms revealed that several lncRNAs are possibly associated with respective phenotype. lncRNA was identifying  to differ significantly between Eos and Neu samples by using qRT-PCR.  The results show us that lncRNA may be involved in different phenotypes of asthma. Whether we can recognize different phenotypes of asthma through these lncRNA (as biomarkers) needs further study. Overall design: Patients with eosinophilic asthma  (Eos, n = 12) and neutrophilic asthma  (Neu, n = 6) were selected in the study according the accepted standard (Eos: induced sputum eosinophil count >3% and neutrophils <63%; Neu: induced sputum eosinophil count <3% and neutrophils>63% )1. Exclusion criteria contained recent (within the past weeks) respiratory tract infection, recent unstable asthma, recent asthma exacerbation, current smoking (or a history of smoking, within 6 months of cessation), and changes in maintenance therapy. All participants were selected from the People's Liberation Army General Hospital, and all participants have been given informed consent before their inclusion. Healthy individuals were selected as Control samples (n = 6). The results show us that lncRNA may be involved in different phenotypes of asthma. Whether we can recognize different phenotypes of asthma through these lncRNA (as biomarkers) needs further study. This dataset is related to GSE106230	Co-expression
SRP153231	Transcriptional Profiling Identifies Novel Regulators of Macrophage Polarization [RNA-Seq]	Identification of novel differentially expressed genes in human M1 and M2 macrophages using RNA-Seq Overall design: RNA-Seq was performed using RNA from M1 and M2-polarized macrophages from 4 biological replicates	Co-expression
SRP153334	The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells	The translocation t(7;12)(q36;p13) occurs in infants and very young children with AML and usually has a fatal prognosis. Whereas the transcription factor ETV6, located at chromosome 12p13, has largely been studied in different leukemia types, the influence of the translocation partner HB9 (chr. 7q36), is still unknown. This is particularly surprising as ectopic expression of HB9 is the only recurrent molecular hallmark of translocation t(7;12) AML. We investigated the influence of HB9 as a potential oncogene on cell proliferation and cell cycle in vitro, as well as on hematopoietic stem cell differentiation in vivo using murine and human model systems.   We show, that HB9 induces premature senescence in human HT1080 and murine NIH3T3 cells, providing for the first time evidence for an oncogenic potential of HB9. Furthermore, HB9-transduced primary murine hematopoietic stem and progenitor cells underwent a profound differentiation arrest and accumulated at the megakaryocyte/erythrocyte progenitor stage, resulting in a premalignant myeloid cell population in vivo. Concomitantly, HB9 expression upregulates erythropoiesis-related genes in primary human hematopoietic stem and progenitor cells, and enriches gene expression profiles for cell cycle and mitosis-related biological processes.   In summary, the novel findings of HB9 dependent premature senescence and perturbed hematopoietic differentiation shed light on the oncogenic properties of HB9 in translocation t(7;12) AML and offer novel targets for therapeutic intervention. Overall design: CD34+ cells were transduced with either GFP or HB9	Co-expression
SRP153396	Joint profiling of chromatin accessibility and gene expression in thousands of single cells	Here we describe sci-CAR, a combinatorial indexing strategy to jointly profile chromatin accessibility and mRNA in each of thousands of single cells. As a proof-of-concept, we apply sci-CAR to 4,825 cells comprising a time-series of dexamethasone treatment, as well as to 11,233 cells from the mouse kidney. Overall design: single cell RNA-seq and ATAC-seq co-profiling for HEK293T cells, NIH/3T3 cells, A549 cells across three treatment conditions (DEX 0 hour, 1 hour and 3 hour treatment), and wild type mouse kidney.	Co-expression
SRP153410	Generation of human oogonia from induced pluripotent stem cells in vitro	Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis. Overall design: RNA-seq analysis of human iPSC, iMeLC, PGCLC and aggregate cultured cells oogonia-like cells.	Co-expression
SRP153417	Gene expression changes in THP1 cells at day 2 and 4 following shRNA knock-down of RUVBL2	We used an inducible shRNA system and RNA-Seq to examine gene expression changes in acute myeloid leukemia THP1 cells following silencing of RUVBL2. RUVBL2 is a AAA+ ATPase that functions in a number of cellular processes, including chromatin remodeling and transcriptional control, and is critical for survival of acute myeloid leukemia cells and in vivo disease progression. Overall design: Total cellular RNA was extracted using the RNeasy Plus Mini Kit from THP1 cells transduced with RUVBL2-specific inducible shRNA, following 2 and 4 days exposure to doxycycline or medium controls. In total, 6 pairs of control and doxycycline-treated samples were analysed (3 control and 3 doxycycline-treated for each time-point).	Co-expression
SRP153423	The miR-96 and RARG signaling axis governs androgen signaling and prostate cancer progression V	Expression levels of retinoic acid receptor gamma (NR1B3/RARG, encodes RARG), are commonly reduced in prostate cancer (PCa). Therefore we sought to establish the cellular and gene regulatory consequences of reduced RARG expression, and determine RARG regulatory mechanisms. RARG shRNA approaches in non-malignant (RWPE-1 and HPr1-AR) and malignant (LNCaP) prostate models revealed that reducing RARG levels, rather than adding exogenous retinoid ligand, had the greatest impact on prostate cell viability and gene expression. ChIP-Seq defined the RARG cistrome which was significantly enriched at active enhancers associated with AR binding sites. Reflecting a significant genomic role for RARG to regulate androgen signaling, RARG knockdown in HPr1-AR cells significantly regulated the magnitude of the AR transcriptome. RARG down-regulation was explained by increased miR-96 in PCa cell and mouse models, and TCGA PCa cohorts. Biochemical approaches confirmed that miR-96 directly regulated RARG expression and function. Capture of the miR-96 targetome by biotin-miR96 identified that RARG and a number of RARG  interacting co-factors including TACC1 were all targeted by miR-96, and expression of these genes were prominently altered, positively and negatively, in the TCGA-PRAD cohort. Differential gene expression analyses between tumors in the TCGA-PRAD cohort with lower quartile expression levels of RARG and TACC1 and upper quartile miR-96, compared to the reverse, identified a gene network including several RARG  target genes (e.g. SOX15) that significantly associated with worse disease free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p=0.015). In summary, miR-96 targets a RARG network to govern AR signaling, PCa progression and disease outcome. RNA-seq: HPr1-AR non-malignant, immortalized cell line +/- shRARG, +/- 10nM DHT for 0,24,96 hours Overall design: 18 samples total, 6 experimental conditions (each in triplicate); shCTL-0hr, shCTL_24hr, shCTL_96hr, shRARG-0hr, shRARG-24hr, shRARG-96hr	Co-expression
SRP153724	To investigate the decay constants (half-lives) of transcript isoforms generated by alternative polyadenylation in proliferating and quiescent cells	Purpose: Alternative polyadenylation (APA) can result in the generation of transcripts that terminate at different locations within the gene, which can result in different 3'' UTRs.   3´ UTRs are known to contain RNA stabilizing and destabilizing motifs that provide a platform for binding of  RNA binding proteins. Changes in 3´ UTRs for the different APA-generated isoforms of a gene could allow for inclusion or exclusion of these RNA stability elements. The goal of this study is determine the stability (half-lives based on transcript decay) of APA isoforms in proliferating and quiescent cells. Methods: The proliferating and quiescent (7-day contact inhibited) cells were treated with actinomycin D to stop transcription and the cells were harvested at different time points (0. 2, 4, 8 hours) for RNA isolation and global sequencing of 3´ ends. The adaptors and polyA sequenced were trimmed from each read.  The reads were aligned to the human genome (hg19) using TopHat (v2.0.14). The aligned read files were used to determine the counts of APA isoforms of each gene using the code provided by Gruber et al. (PMID: 27382025). The counts of the APA isoforms were fit to an exponential decay model to obtain half-lives. The entire workflow was performed for two biological replicates: 12-1 and 12-3 strains of human dermal fibroblasts. Results:  In two different fibroblast strains (12-1 and 12-3), we found that isoforms terminating at distal polyadenylation sites were more stable than isoforms terminating at proximal polyadenylation sites in quiescent, but not proliferating, fibroblasts. Conclusions: The transition from shorter to longer isoforms in quiescent cells is associated with stabilization of the transcripts. Overall design: The proliferating and quiescent (7-day contact inhibited) cells were treated with actinomycin D to stop transcription and the cells were harvested at different time points (0. 2, 4, 8 hours) for RNA isolation and global sequencing of 3´ ends.	Co-expression
SRP153743	BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors	To understand epileptogenesis mechanism using transcriptome of epilepsy associated tumor	Co-expression
SRP153809	Long noncoding RNA signatures induced by TLR7 and type I IFN signaling in activated human plasmacytoid dendritic cells	Using genome-wide sequencing approaches we viewed the contributions of Toll-like receptor 7 (TLR7) and type I interferon (IFN-I) in the regulation of coding and noncoding RNA expression in CAL-1 pDC treated with R848 or IFNß. Functional enrichment analysis revealed both the unique and synergistic roles of TLR7 and IFN-I signaling in the orchestration of pDC function. Overall design: Total RNA-seq profiling was performed on CAL-1 cells (1 million cells/mL) were cultured in 0.1% FBS CAL-1 media in triplicate in a 12-  well tissue culture plate for 6 hours prior to stimulation with 1,000 U/mL recombinant human  IFN-ß (PBL Interferon Source) or 1ug/mL R848 (Invitrogen) or 1ug/mL R848 (Invitrogen) +  1ug/mL recombinant vaccinia virus B18R protein (Thermo Fisher Scientific) or mock  stimulation. Total RNA was harvested 12 hours post stimulation	Co-expression
SRP153810	Discovery of a Pro-Tumoral Clonogenic Unipotent Neutrophil Progenitor in Mouse and Human Bone Marrow	Neutrophils are short-lived immune cells that play important roles in a variety of diseases. The oligopotent Granulocyte Monocyte Progenitors (GMP) in the bone marrow give rise to monocytes and all granulocytes. Although several monocyte progenitors have been identified in mouse bone marrow, the unipotent neutrophil progenitors are still not well-defined. Here, we use Cytometry by Time-of-Flight (CyTOF) and Single-cell RNA-Sequencing (scRNA-Seq) methodologies to identify a committed unipotent early-stage neutrophil progenitor in adult mouse bone marrow. Importantly, we also discovered a similar unipotent, committed neutrophil progenitor (hNeP) that is present in healthy human bone marrow. Both mouse and human progenitors demonstrate unipotent neutrophil potency in vivo. Study of the identified mouse (NeP) and human (hNeP) neutrophil progenitors in cancer revealed that both NeP and hNeP significantly increased tumor growth when transferred into murine cancer models, including a humanized model.  Further, we discovered that the hNeP was present in the blood of human patients recently diagnosed with melanoma, and could be readily identified by flow cytometry, suggesting that this human neutrophil progenitor could be used as a biomarker for early cancer discovery.  The discovery of this early committed unipotent neutrophil progenitor in humans will allow for development of important new therapeutic targets for regulation of neutrophil levels and function in disease, particularly in cancers, where neutrophils play a significant role. Overall design: Neutrophil progenitor isolated from mouse and human fresh bone marrow without treatment were sequeced to explore heterogeneities; 3'' Transcriptome sequencing (10X genomics)	Co-expression
SRP153815	RNA-seq after siRNA targeting DDX24 applied to iHUVECs cell lines	DDX24 Mutations Associated with Vascular Malformations Overall design: To detect the vascular-related functions of the causative gene, two short interfering (si)RNAs targeting DDX24 were designed by GenScript bioinformatics tools (https://www.genscript.com/tools/sirna-target-finder) and transfected into immortal human umbilical vein endothelial cells (iHUVECs). A vehicle comprising scrambled siRNA (RIBOBIO) was used as a control. The knockdown efficiency was determined by real-time quantitative PCR and western blotting. RNA sequencing analysis was performed using the siRNA-targeted HUVEC cells to evaluate the effects of the causative gene knockdown on gene expression. Genes involved in cell migration were validated by real-time quantitative PCR.	Co-expression
SRP153913	RNA-seq analysis of PMA treament with or without LPS on human monocytic cell line THP1	Transcriptome analysis of the human monocytic cell line THP1 (ATCC TIB-202) treated or not with phorbol myristate acetate (PMA) +/- lipopolysaccharides-lipopolysaccharides binding protein (LPS-LBP) Overall design: THP1 were treated or not with PMA +/- LPS-LBP	Co-expression
SRP153919	Hyperactivation of MAPK signaling is deleterious to RAS/RAF mutant melanoma	The most frequent genetic alterations in melanoma are gain-of-function mutations in BRAF, which result in addiction to the RAF-MEK-ERK signaling pathway. Despite success of RAF and MEK inhibitors in treating BRAFV600 mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, we generated isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells by overexpression of ERK2. Using this model system, we demonstrated that supra-physiological levels of MAPK signaling led to cell death, which was reversed by MAPK inhibitors. Whereas MAPK pathway inhibition led to cell stasis in BRAFV600E melanoma cells, MAPK hyperactivation induced cytotoxicity. Furthermore, complete tumor regression was observed in an ERK2 overexpressing xenograft model. To identify mediators of MAPK hyperactivation- induced cell death, we conducted a large-scale pooled screen which showed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wildtype melanoma were sensitive to this perturbation. This vulnerability to MAPK hyperactivation raises the possibility of a novel therapeutic approach for RAS/RAF mutant cancers.	Co-expression
SRP153936	Gene expression profiling of LNCaP cells following shRNA-mediated knockdown of TMEFF2 and growth in presence and absence of dihydrotestosterone	TMEFF2 is an androgen regulated transmembrane protein mainly restricted to brain and prostate, that functions as a tumor suppressor in prostate cancer (PCa). Studies using publically available prostate cancer (PCa) datasets, reveal changes in the expression of TMEFF2 with disease stage, supporting an important role of TMEFF2 in this disease. However, the role of TMEFF2 in the biology and pathogenesis of PCa is still unknown.  Using a transgenic TMEFF2 mouse, we have demonstrated that TMEFF2 overexpression modulates prostate branching morphogenesis, and androgen regulated process, during prostate regeneration. We hypothesized that TMEFF2 may have a regulatory function within androgen signaling that could explain its role in PCa. To better understand its function in androgen signaling and PCa, we compared the transcriptome of LNCaP prostate cancer cells transduced with control shRNA and shRNA targeting TMEFF2 in the presence and absence of dihydrotestosterone (DHT). The results indicated that globally, there is a significant interaction between the effects of DHT and shTMEFF2. Of the 519 genes with significant gene expression changes after DHT treatment of Scramble control cells, 208 (40%) had significant differential expression when the shTMEFF2 +DHT group was compared to Scramble +DHT group, including numerous androgen activated and androgen repressed genes. Overall design: Transcriptome profiles of LNCaP tissue under 4 conditions investigating effects of long term (17 days) shRNA targeting TMEFF2 or scrambled sequence in the presence or absence of dihydrotestosterone (DHT). Each sample was run in triplicate.	Co-expression
SRP154005	The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance	Clinical expression of core pluripotent stem cell master regulators OCT4, SOX2 and NANOG is associated with treatment resistance and lethal cancers. We have described a novel model to induce the expression of these factors in vitro. We term this culture environment 'Acquired Pluripotent Stem Cell Environment (APSCE)' and RNA-seq comparisons were made to culture in conventional serum supplemented 'Full Media' (FM) in human prostate (LNCaP, CWR22Rv1) and bladder (RT112) cancer cell lines. Depletion of the androgen receptor (AR) with siRNA targeting exon1(siEX1) was additionally performed in the CWR22Rv1 cell line alongside a scrambled control (siCTRL).  Overall design: mRNA profiles of LNCaP, CWR22Rv1 and RT112 cell lines cultured in APSCE and FM were generated in triplicate via RNA-Seq. CWR22Rv1 mRNA profiles of Scrambled and AR Exon1 siRNA knockdown cultured in the APSCE and FM were additionally generated in triplicate.	Co-expression
SRP154013	Inhibition of the Aryl Hydrocarbon Receptor - Polyamine Biosynthesis Axis Suppresses Multiple Myeloma and prostate cancer progression	Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of xenobiotic response. Our study revealed that AHR also positively regulated intracellular polyamine production via direct transcriptional activation of two genes (ODC1 and AZIN1) involved in polyamine biosynthesis and control, respectively. In multiple myeloma patients, AHR levels inversely correlated with survival, suggesting that AHR inhibition may be beneficial for treatment of this disease .We identified clofazimine, an FDA-approved anti-leprosy drug, as a potent AHR antagonist and a suppressor of polyamine biosynthesis. Experiments in a transgenic model of multiple myeloma (Vk*Myc mice) and in immunocompromised mice bearing multiple myeloma cell xenografts, revealed high efficacy of clofazimine comparable to that of bortezomib, a first-in-class proteasome inhibitor used for treatment of multiple myeloma. This study identified a previously unrecognized regulatory axis between AHR and polyamine metabolism and discovered clofazimine as an inhibitor of AHR and a potentially clinically-relevant anti-multiple myeloma agent. RNA-seq: human multiple myeloma MM1S and human normal fibroblasts WI38 cells -/+ CLF 2-4uM for 24hrs; -/+ shAHR Overall design: 18 samples total, 9 experimental conditions (each in duplicate): MM1S_pLKO_NT_2hrs ; MM1S_pLKO_NT_24hrs; MM1S_pLKO_CLF_2uM_24hrs; MM1S_shAHR2; MM1S_shAHR_3; WI38_pLKO_NT; WI38_pLKO_CLF_4uM; WI38_shAHR1; WI38_shAHR4	Co-expression
SRP154111	Alternative splicing controls Leucine-rich repeat domain modularity in NOD-like receptors	Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Somatic recombination of LRR sequences evolved to create diversity in jawless vertebrate adaptive immunity, yet the role repetitive LRR-encoding exons in humans remains unknown.  We performed this RNA Seq study to understand how alternative splicing of NOD-like receptors (NLRs) at the locus encoding a LRR domain can regulate NLRs function, with a focus on NLRP3. Overall design: RNA Seq of GM-CSF differentiated human monocyte derived macrophages from 5 individuals	Co-expression
SRP154189	Transcriptome profiling identified a 3-lncRNA regulatory network in transthyretin against glucose induced hRECs dysfunction	Transcriptome of human retinal endothelial cells (hRECs) treated with low glucose (LG), high glucose (HG) or high glucose with 4 uM TTR (HG+TTR) were conducted. Differentially expressed lncRNAs, mRNAs and TTR related lncRNAs and mRNA were acquired for further analysis. Functional annotation and enrichment including KEGG pathway, GO and GSEA were applied to analyze TTR regulated pathway and process. WGCNA analysis was implemented to obtain hub modules and genes. LncRNA-mRNA regulatory network were constructed based on cis, trans and ceRNA acting mode. Overall design: Examination of Human retinal endothelial cells (hRECs) treated with low glucose (LG), high glucose (HG), or high glucose with 4 uM TTR (HG+TTR)	Co-expression
SRP154234	SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival	T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with complicated heterogeneity. Although expression profiling reveals common elevated genes in distinct T-ALL subtypes, little is known about their functional role(s) and regulatory mechanism(s). We here show the expression of SHQ1, an H/ACA snoRNPs assembly factor involved in snRNA pseudouridylation, is specifically and highly expressed in T-ALL. Mechanistically, oncogenic NOTCH1 directly binds to the SHQ1 promoter and activates its transcription. SHQ1 depletion induces massive leukemia cell death in vitro and in vivo, and prolongs animal survival in murine T-ALL models. RNA-Seq reveals that SHQ1 depletion impairs widespread RNA splicing, and MYC is one of the most prominently downregulated genes due to inefficient splicing. Ectopically expressed MYC significantly rescues T-ALL cell death resulted from SHQ1 inactivation. We herein report a previously unsuspected mechanism of NOTCH1-SHQ1-MYC axis in T cell leukemogenesis. Our findings not only shed light on the role of SHQ1 in promoting RNA splicing and tumorigenesis, but also provide a new mechanism of MYC regulation. Overall design: Examination of intron rentention in SHQ1-depleted KOPTK1 and HPB-ALL cells	Co-expression
SRP154276	RNA-sequencing of Korean hereditary gingival fibromatosis patients	Hereditary gingival fibromatosis (HGF) is a rare oral disease characterized by either localized or generalized gradual, benign, non-hemorrhagic enlargement of gingivae. Although several genetic causes of HGF are known, the genetic etiology of HGF as a non-syndromic and idiopathic entity remains uncertain. Here, we analyzed transcriptomic alterations between idiopathic HGF patients and controls.	Co-expression
SRP154280	Alternative Splicing regulation protein subcellular localization	The impact of the transcriptome-wide alternative splicing on proteomic-wide protein subcellular localization was investigated by analyzing RNA-Seq data.	Co-expression
SRP154351	mRNA expression profiles of MDA231 Cells overexpressing lncRNA MACC1-AS1	LncRNA MACC1-AS1 is the antisense RNA of Metastasis-associated in colon cancer-1 (MACC-1), which is located on the sixth intron of MACC-1. To determine gene expression changes associated with overexpression of MACC1-AS1, we performed RNA-seq analysis on MDA231-Con and MDA231-MACC1-AS1 cells.	Co-expression
SRP154360	Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [RNA-Seq]	We generated primary cultures from renal cell carcinoma and matched normal primary kidney cortex tubule cell cultures from 3 patients. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). Studying these paired and patient-matched controlled data sets will shed light on the epigenomic changes that underlie transformation of kidney tubules into malignant cancers. Overall design: Paired DNase-seq and RNA-seq data sets from 2 different primary human kidney cell types (normal and cancer) Note from submitter: The HIM23 samples have a more narrow consent and their raw data will be submitted to dbGaP.	Co-expression
SRP154380	Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma	Multiple myeloma (MM), a plasma cell (PC) malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity within and between patients is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA-seq to study the heterogeneity of 40 individuals along the MM progression spectrum. We define malignant PC at single cell resolution, demonstrating high inter-patient variability that can be explained by expression of known MM drivers and additional putative factors. Within newly diagnosed patients, we identify extensive sub-clonal structures for 10/29 patients. In asymptomatic patients with early disease and in minimal residual disease post-treatment, we detect tumor PC for a subset of the patients, with the same drivers of active myeloma. Single cell analysis of rare circulating tumor cells (CTC) allows detection of malignant PC, which reflect the BM disease. Our work establishes scRNA-seq for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients. Overall design: The study includes 29 newly diagnosed patients with plasma cell neoplasms and 11 control donors, for which bone marrow plasma cells were single cell sorted by FACS, and their mRNA sequenced. For 11 patients, targeted genomic DNA panel analysis for myeloma was performed.	Co-expression
SRP154382	Global mapping of polyadenylation site use in proliferating and quiescent (contact-inhibited and serum-starved) cells	Purpose: To determine genes that undergo alternative polyadenylation in proliferating versus quiescent fibroblasts. Methods: Three different biological replicates (fibroblast strains, 10-1, 12-1, and 12-2) were used for generating proliferating and quiescent (7-day contact inhibited and 7-day serum-starved) cells. RNA extracted from these cells were used for library preparation. cDNA fragments were enriched for the junction between the poly(A) site and the end of the 3' UTR using a modified high throughput sequencing protocol (GnomeGen). cDNA libraries were created according to Gnome-Gen RNA-seq library preparation kit for RNA profiling except Amgen Ampure XP beads were used instead of the Gnome-gen size selector product to remove ligation reaction products before proceeding to the reverse transcription step.  The libraries were sequenced on an Illumina HiSeq 2000 instrument. The sequencing reaction wasa run for 147 cycles. Reads from pol(A) enriched cDNA libraries were aligned to the genome using the STAR alignment algorithm after the computational removal of untemplated adenosines. Results: Polyadenylation site selection was significantly altered in approximately 10% of genes in quiescent compared with proliferating fibroblasts.  Contact inhibited and serum starved fibroblasts had similar polyadenylation site selection profiles. Conclusions: Quiescence is associated with changes in polyadenylation site selection. Overall design: Three samples of proliferating fibroblasts, three samples of contact inhibited fibroblasts and three samples of 7-day serum starved fibroblasts were analyzed with polyadenylation site-enriched RNA-Seq.	Co-expression
SRP154388	NCI Primary Human Melanocyte QTL Study	In order to create a melanocyte-specific eQTL resource, we obtained primary human melanocyte cultures isolated from foreskin of 106 healthy newborn males predominantly of European descent. Melanocytes were cultured in lot-matched culture medium in randomized batches to minimize variability that could be introduced by culturing conditions. RNA sequencing and direct SNP genotyping of these samples produced an average of ~87.9 million reads (paired-end, stranded, 126bps), and ~713,000 SNP genotypes, respectively.	Co-expression
SRP154414	Genome-wide two-step RNA splicing kinetics in human cells	Transient transcriptome sequencing and kinetic modeling reveal how the kinetics and yield of RNA splicing are encoded in the human genome.	Co-expression
SRP154428	Transcriptomic profile of Fanconi anemia (FA) epidermal stem and progenitor cells (ESPCs)	Squamous cell carcinoma (SCC) is a common cancer with global public health burden that arises from ESPCs in the skin or mucosa. To understand how genetic risk factors lay the foundation for SCC and develop effective prevention strategies, it is critical to understand the biology of ESPCs. Extreme predisposition to SCC is a hallmark of FA, an inherited disorder caused by germline loss-of-function mutations in any of 22 genes associated with the FA DNA repair pathway. Although DNA damage is the presumed cause, this does not explain the unique involvement of skin and mucosa as opposed to other solid tissues. To identify new epidermal vulnerabilities beyond DNA damage, we generated the first personalized model of FA epidermis. FA patient-derived induced pluripotent stem cells (PSCs) with a conditional FA pathway (+/-Doxycycline, DOX) were differentiated into ESPCs and 3D epidermis. The goal of this study is to uncover FA-dependent biological processes, performing transcriptome analyses of ESPCs in presence or absence of DOX in monolayer cultures. Overall design: Examination of 2 FA patient-derived ESPC lines with conditional FA pathway (+/-DOX)	Co-expression
SRP154474	RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways	It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis. Overall design: Transcriptomic profiles were obtained from palmoplantar (n = 3), scalp (n = 8), and conventional psoriatic skin (n = 8) as well as healthy control skin (n = 9) biopsies on the Illumina HiSeq 2000/4000 platforms. Multi-parameter FACS was also performed on each biopsy sample to obtain T cell populations (CD4+ T effectors, CD8+ T cells, and CD4+Foxp3+ Tregs).	Co-expression
SRP154478	MYC protein interactome profiling reveals functionally distinct regions that cooperate to drive tumorigenesis (RNA-Seq)	MYC is a potent oncogene associated with aggressive disease in many distinct tumor types. Transforming members of the MYC family (MYC, MYCL1, MYCN) encode transcription factors containing six highly conserved regions, termed MYC homology Boxes (MBs). Here, we conduct proteomic profiling of the MB interactomes, demonstrating that half of MYC interactors require one or more MBs for binding. Comprehensive phenotypic analyses revealed that two MBs are universally required for transformation. MBII interaction with acetyltransferase-containing complexes results in histone hyperacetylation and is essential for MYC-dependent tumor initiation. By contrast, MB0 interacts with transcription elongation factors through direct binding to the general transcription factor TFIIF, and deletion of MB0 severely inhibits tumor growth but is dispensable for tumor initiation. Notably, the full transforming activity of MYC can be restored upon co-expression of MB0 and MBII deletion mutants, indicating that these two regions confer unique biological functions, each required for oncogenic MYC activity. Overall design: RNA-seq analysis was conducted in TET21 cells (n=4, for each of the MYC deletion mutant ectopycally expressed) to determine the nature of the MB transcriptomes, and ChIPseq was conducted on WT-MYC TET21-expressing cells to determine MYC binding (n=1).	Co-expression
SRP154483	SULT2B11b regulates sensitivity to TNF-mediated cell death in Prostate Cancer	Single-cell mRNA sequencing (scRNA-seq) study was conducted to compare the transcriptomes of SULT2B1b knockdown (KD) versus non-targeting (Control) KD LNCaP cells.  Over 2,000 differentially expressed (DE) genes were identified along with alterations in numerous canonical pathways, including the death receptor signaling pathway. Overall design: To prepare for single-cell analysis, 2x10^5 LNCaP cells were plated in a 12-well plate coated with poly-L-lysine and allowed to adhere for 24 hours.  LNCaP cells were transfected with non-targeting (control) siRNA (Dharmacon) or SULT2B1 siRNA (IDT, HSC.RNAI.N004605.12.2), previously validated to knockdown SULT2B1b expression and function in prostate cancer cells (Figure 3.4E).234  48 hours following siRNA transfection, cells were harvested with trypsin and stained with Zombie Violet viability dye (Biolegend, 423114) according to the manufacturer's instructions.	Co-expression
SRP154536	RNA-Seq of HSV infected 293T cells	To study the function of herpes simplex virus 1 immediate early protein ICP27.	Co-expression
SRP154566	Human Multiple Myeloma CD138 Cell Population Whole Transcriptome Sequencing	Whole transcriptome sequencing (RNA-seq) of CD138+ and CD138- cell population in RPMI8226 and MM1.S multiple myeloma cell lines.	Co-expression
SRP154573	Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas [RNA-Seq]	Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. H3K27ac gain was suggested to promote tumorigenesis in H3K27M-HGGs, but how these opposing marks shape oncogenesis remains controversial. We therefore characterized the active regulatory chromatin states in H3.3K27M and H3K27 wild-type HGGs and in H3.3K27M CRISPR/Cas9 knockout tumor-derived cell lines, as an isogenic tumor model of the mutation. We show that H3.3K27M-HGGs have distinct promoter, enhancer, super-enhancer, and core transcription factor circuitries from wild-type HGGs. However, while removal of H3.3K27M restores gross H3K27ac levels to those of wild-type HGGs, we observe minimal disruption of H3K27ac deposition at these active transcriptional elements, suggesting that they are a function of the cell of origin and independent of direct H3K27M mutagenesis and active regulation. Using quantitative ChIP-seq, we show that in H3.3K27M-HGGs, H3K27ac is pervasively deposited across the genome, including at normally silent repeat elements, leading to their increased baseline expression. H3.3K27M cells respond to DNA demethylating agents and histone deacetylase inhibitors, which further increase repeat element expression, including that of specific endogenous retroviral (ERVs) families. Our findings decouple cell lineage programs from H3K27M-dependent pervasive deposition of H3K27 acetylation. De-repression of ERVs may enhance the triggering of innate immune pathways, representing a therapeutic vulnerability in H3.3K27M HGGs. Overall design: There are 6 H3.3K27WT and 7 H3.3K27M patient-derived cell lines. We sequenced unedited (7 replicates) and Crispr/Cas9 H3.3K27M-KO clones (7 replicates) for two cell lines (DIPGXIII and BT245). Furthermore, we sequenced the treated the unedited and KO clones with panobinostat, 5-azacytidine and a combination of both for each of the cell lines. We sequenced 6 H3.3K27WT and 7 H3.3K27M patient-derived cell lines as well as 17 HGG-H3.3K27M and 15 HGG-WT human tumors by RNA-seq.  We sequenced unedited (7 replicates) and Crispr/Cas9 H3.3K27M-KO clones (7 replicates) for two cell lines (DIPGXIII and BT245) as well as cells that were treated with panobinostat, 5-azacytidine and a combination of both for each of the cell lines.	Co-expression
SRP154576	Designing a single cell RNA sequencing benchmark dataset to compare protocols and analysis methods (9 cell mixture dataset).	Single cell RNA sequencing (scRNA-seq) technology has undergone rapid development in recent years and brings new challenges in data processing and analysis. This has led to an explosion of tailored analysis methods for scRNA-seq to address various biological questions. However, the current lack of gold-standard benchmarking datasets makes it difficult for researchers to evaluate the performance of the many methods available in a systematic manner. Here, we designed and generated a cross-platform benchmark dataset that has in-built truth in various forms and varying levels of biological noise. We used this dataset to compare different protocols and data analysis methods.  We found that different protocols have different data quality and ERCC spike-in works independently to endogenous RNA. We found significant differences in the results from the methods compared and we associated the results with data characteristics to identify methods that perform well in different situations. Our dataset and analysis provide a valuable resource for algorithm selection in different biological settings. Overall design: our experiment utilized the 3 human lung adenocarcinoma cell lines H2228, H1975 and HCC827. The experiment included mixtures of RNA and single cells from these cell lines. For the single cell designs, the three cell lines were mixed equally and processed by 10X chromium, Drop-seq and CEL-seq2, referred to as sc_10X, sc_Drop-seq and sc_CEL-seq2 respectively in analysis that follows. For the mixture designs, we used plate-based protocols to mix and dilute samples in 2 different ways. 9 cell mixtures from the 3 cell lines were sorted in different combinations in the cell mixture experiment and data were generated by CEL-seq2, the material after pooling from 384 wells were subsampled in either 1/9 or 1/3 to simulate cells of different sizes, with different PCR product clean up ratios ranging from 0.7 to 0.9, referred to as cellmix1 to cellmix4. For the cell mixture experiment, we also sorted wells with 10 times more cells (90 cells) to provide a pseudo bulk reference for each mixture (referred to as cellmix5).  Distinct RNA mixtures which were diluted down to create single cell equivalents (ranging from 3.75, 7.5, 15 to 30 pg per well) were generated using CEL-seq2 and SORT-seq (referred to as RNAmix_CEL-seq2 and RNAmix_Sort-seq. This is the 9 cell mixture dataset.	Co-expression
SRP154577	Differential gene expression analysis between proliferating and quiescent human dermal fibroblasts	Purpose: Quiescence is a state or reversible cell cycle arrest. A previous study using microarrays (Coller et al., PMID: 16509772) revealed gene expression changes between quiescent and proliferating human dermal fibroblasts and defined a "quiescece program" of genes that change in abundance when fibroblasts were introduced into quiescence by one of three methods. The goal of this study is to perform high throughut RNA sequencing to determine global changes in gene expression between proliferating and quiescent human dermal fibroblasts. Methods: Three different biological replicates (corresponding to two fibroblast strains, 10-5 and 12-1) were collected in proliferating and contact--inhibited (quiescent) conditions. RNA extracted from these cells were used for library preparation. The libraries were sequenced on an Illumina HiSeq 2000 instrument. Results: Among the 19,673 genes monitored, 1,993 genes (10.1%) changed in expression two-fold or more, demonstrating widespread changes in gene expression with contact inhibition-induced quiescence. Fifty-two percent of these genes were upregulated in 7dCI compared with proliferating fibroblasts, and 48% were downregulated in 7dCI fibroblasts. Conclusions: There are widespread changes in gene expression as fibroblasts transition between proliferating and quiescent states. Overall design: Three different biological replicates (corresponding to two fibroblast strains, 10-5 and 12-1) were collected in proliferating and contact--inhibited (quiescent) conditions.	Co-expression
SRP154584	Diabetes Remission Using Glucose-Responsive Insulin-Producing Human a-Cells	Natural and stable cell identity switches, where terminally-differentiated cells convert into different cell-types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic a-cells become insulin expressers upon ablation of insulin-secreting ß-cells, promoting diabetes recovery. Whether human islets also display this plasticity for reconstituting ß-like cells, especially in diabetic conditions, remains unknown. Here we show that two different islet non-ß-cell types, a- and ?–cells, obtained from deceased non-diabetic or diabetic human donors can be lineage-traced and induced to produce insulin and secrete it in response to glucose. When transplanted into diabetic mice, converted human a-cells reverse diabetes and remain producing insulin even after 6 months. Insulin-producing a-cells maintain a-cell markers, as seen by deep transcriptomic and proteomic characterization, and display hypo-immunogenic features when exposed to T-cells derived from diabetic patients. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity in islet cells, as well as in other organs, as a therapy for degenerative diseases by fostering the highly-regulated intrinsic cell regeneration. Overall design: Transcriptomic profiles of human pancreatic a-cells that convert  into insulin-producing cells were generated by deep sequencing using Illumina Hi-seq 4000	Co-expression
SRP154586	Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells	We recently described the phenotype of HepG2 and Huh-7 hepatocellular carcinoma cells deleted for histone variant macroH2A1, which acquire cancer stem cell phenotype (Lo Re O et al., Hepatology 2017, PMID: 28913935). We found that short hairpin RNA-mediated macroH2A1 knockdown induces acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolysis. As macroH2A1 is a potent transcriptional modifier we asked how KD of this histone variant might affect patterns of gene expression, and whether we could identify potential mechanistic links to the observed in vitro and in vivo HCC phenotypes. We obtained and validated an RNA-Seq dataset (Borghesan M et al., Cancer Res 2016, PMID: 26772755; Lo Re O et al., Hepatology 2017, PMID: 28913935), to conduct an unbiased comparison of the transcriptional profiles of HepG2 macroH2A1 KD cells and controls. Using a cut-off of 2 fold change, assessment of differentially expressed genes for macroH2A1 KD versus CTL showed no transcriptional overlap between the different HepG2 cell lines. Considering all differentially-expressed genes, there was significant enrichment (–log(p-value) > 1.3) in several functions and pathways that regulate pluripotency of human embryonic stem cells. Overall design: Profiling the transcriptome of hepatocellular carcinoma cells HepG2 knocked-down for macroH2A1 using RNA-Seq.	Co-expression
SRP154717	Profiling of vascular organoid endothelial cells and pericytes from iPS cells	Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. Here we report the development of a 3D blood vessel organoid culture system from human pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into interconnected capillary networks enveloped by a basement membrane. Human blood vessel organoids transplanted into mice form a stable, perfused human vascular tree, including human arteries, arterioles and venules. Exposure of blood vessel organoids to hyperglycemia and inflammatory cytokines in vitro induced thickening of the basal membrane, a hallmark of human diabetic microangiopathy. Human blood vessel, exposed in vivo to a diabetic milieu in mice, also mimick the microvascular changes in diabetic patients. We finally performed a drug screen and uncovered ?-secretase and DLL4-Notch3 as key drivers of “diabetic” vasculopathy in human blood vessels in vitro and in vivo. Thus, organoids derived from human stem cells faithfully recapitulate the structure and function of human blood vessels and are amenable to model and identify drug targets for diabetic vasculopathy, which affects hundreds of millions of patients.      Overall design: Vascular organoids were differentiated from iPSC cells and cultured in control, diabetic or diabetic media supplemented with the gamma-secretase inhibitor DAPT. Endothelial cells (CD31 positive) and pericytes (PDGFRbeta positive) were isolated by FACS and subjected to RNA Seq. Accordingly, CD31 positive endothelial cells and PDGFRbeta positive pericytes differentiated from iPS cells in 2D as a well as primary endothelial (HUVECS) and pericytes (Placenta) were FACS sorted and subjected to RNA Seq.	Co-expression
SRP154762	Effects of ethanol on human-iPSC neurons	This experiment sought to determine the effects of ethanol on induced pluripotent stem cell (iPSC) derived neurons in humans. The iPSC lines were donated by patients with alcohol use disorder (AUD) or without AUD (control) and differentiated through manipulation into neuronal lines. The neuronal lines were cultured for 12 weeks, after which each line was subsequently split into two sister-lines. For the experiment, one sister line was treated by media change with 50mM of ethanol on days 0, 2, 4, and 6 for one week and one sister line was treated by media change with no ethanol on days 0, 2, 4, and 6 for one week. RNA was harvested from both lines on the seventh day with the agent trizol. The harvested RNA was then enriched through rRNA-depletion before 100 cycles of paired amplification. The enriched and amplified RNA-sequences were then read with Illumina HiSeq 2000 and analyzed computationally.	Co-expression
SRP154763	Effects of ethanol on human-iPSC neurons	This experiment sought to determine the effects of ethanol on induced pluripotent stem cell (iPSC) derived neurons in humans. The iPSC lines were donated by patients with alcohol use disorder (AUD) or without AUD (control) and differentiated through manipulation into neuronal lines. The neuronal lines were cultured for 12 weeks, after which each line was subsequently split into two sister-lines. For the experiment, one sister line was treated by media change with 50mM of ethanol daily for one week and one sister line was treated by media change with no ethanol daily for one week. RNA was harvested from both lines on the seventh day with the agent trizol. The harvested RNA was then enriched by poly-A selection before 100 cycles of single amplification. The enriched and amplified RNA-sequences were then read with Illumina HiSeq 2000 and analyzed computationally.	Co-expression
SRP154768	Effects of ethanol on human-iPSC neurons	This experiment sought to determine the effects of ethanol on induced pluripotent stem cell (iPSC) derived neurons in humans. The iPSC lines were donated by patients with alcohol use disorder (AUD) or without AUD (control) and differentiated through manipulation into neuronal lines. The neuronal lines were cultured for 12 weeks, after which each line was subsequently split into two sister-lines. For the experiment, one sister line was treated by media change with 50mM of ethanol daily for one week and one sister line was treated by media change with no ethanol daily for one week. RNA was harvested from both lines on the seventh day with the agent trizol. The harvested RNA was then enriched with rRNA-depletion before 100 cycles of paired amplification. The enriched and amplified RNA-sequences were then read with Illumina HiSeq 2000 and analyzed computationally.	Co-expression
SRP154833	Acquisition of a side population fraction through downregulation of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 augments malignant phenotype in ovarian cancer.	Side population (SP) cells harbor malignant phenotypes, such as sphere forming capacity, single cell clonogenicity and in vivo tumorigenicity. These malignant phenotypes are related to a poor prognosis for women with ovarian cancer. The aim of this study was to identify key factor(s) that increase the proportion of ovarian cancer SP cells through a functional genomics screen. A library of 81 000 shRNAs targeting 15 000 genes was transfected into CH1 and SKOV3 cells, followed by SP analysis. We found that suppression of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 markedly increased the proportion of SP cells. Newly generated SP cells exhibit significantly greater capacity for sphere formation, single cell clonogenicity, and in vivo tumorigenicity. On the contrary, overexpression of MSL3, VPS45, ITGB3BP, TLE2, and ZNF498 significantly decreased the proportion of SP cells, sphere formation capacity and single cell clonogenicity. In ovarian cancer cases, low expression of MSL3, ZNF691 and VPS45 was related to poor prognosis. Suppression of these six genes tended to increase some stem cell-related pathways, and significantly enhanced activity of the hedgehog pathway. Cyclopamine, a hedgehog pathway inhibitor, significantly decreased the number of newly generated SP cells and their sphere forming ability. Our results provide new information regarding molecular mechanisms favoring SP cells and suggest that Hedgehog signaling may provide a viable target for improving ovarian cancer survival. Overall design: CH1 human ovarian cancer cells were transfected with TRC Lentivial shRNA of MSL3, ZNF691, VPS45 and non-silencing control. SKOV3 human ovarian cancer cells were transfected with TRX Lentivial shRNA of ITGB3BP, TLE2, ZNF498 and non-silencing control.	Co-expression
SRP154834	RNA-seq profile of expanded human ST2-transduced Tregs cultured with IL-2 and TCR in the presence or absence of IL-33	Because of the extensive data in mice supporting the concept that ST2+ Tregs might have desirable therapeutic properties, including tissue repair function, high suppressive capacity, and enhanced stability, we engineered human blood Tregs to constitutively express ST2 (IL-33R). Here we used RNA sequencing to explore the effects of short-term culture with IL-33 on human ST2-transduced Tregs. Overall design: Human naive Tregs flow-sorted from 4 independent donors were lentivirally transduced with ST2, expanded for 13 days, then stimulated with IL-2 and TCR (16 h) or IL-2, TCR, and IL-33 (16 h).	Co-expression
SRP154839	RNA-Seq in two Ewing sarcoma cell lines: A673 and SKNMC	As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition. Through integrative analysis, we identify MEIS1 as a super-enhancer-driven oncogene, which co-operates with EWS-FLI1 in transcriptional regulation, and plays a key pro-survival role in Ewing sarcoma. Moreover, APCDD1, another super-enhancer-associated gene, acting as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tumor-promoting factor in this malignancy. These data delineate super-enhancer-mediated transcriptional deregulation in Ewing sarcoma, and uncover numerous candidate oncogenes which can be exploited for further understanding of the molecular pathogenesis for this disease. Overall design: Ewing sarcoma cell lines were treated with DMSO or THZ1, and RNA-seq was performed.	Co-expression
SRP154856	RNA-seq transcriptome analyses in T47D cells treated with ActA and Palbociclib.	We performed SMAD2 ChIP-seq analysis in T47D cells with/without Palbociclib treatment. To validate whether the changes in SMAD2 binding to the genome indeed resulted in changes in target gene expression, we performed RNA-seq transcriptome analyses in T47D with/without ActA stimulation and Palbo treatment. Overall design: RNA-seq transcriptome analyses performed in estrogen receptor positive breast cancer T47D with/without ActA stimulation and Palbo treatment.	Co-expression
SRP154908	KMT9a writes the H4K12me1 histone mark and controls metabolism and proliferation of castration-resistant prostate cancer cells [RNA-seq]	The aim of the RNA-seq was to identify the KMT9 transcriptome in PC-3M cells. The MCF10A breast epithelial cells that do not express KMT9a were used to show that the siRNA against KMT9 show no off-target effects. Overall design: 12 samples correponding to 4 times 3 replicates were used for the study	Co-expression
SRP154943	Genome-wide maps of human adenocarcinomal cell PC-9 and LINC00312 knockdown PC-9 cell	We performed RNA-seq to analyze the transcriptional profiles of PC-9 cells with reduced expression of LINC00312 to better understand the molecular mechanisms by LINC00312 Overall design: Examination of 2 different expression in 2 cell types.	Co-expression
SRP154973	Reprogramming of Tumor-infiltrating Immune Cells in Early Stage of NSCLC	Comparing the relative proportions of immune cells in tumor and adjacent normal tissue from NSCLC patients demonstrates the early changes of tumor immunity and provides insights to guide immunotherapy design. We mapped the immune ecosystem using computational deconvolution of bulk transcriptome data from the Cancer Genome Atlas (TCGA) and single cell RNA sequencing (scRNA-seq) data of dissociated tumors from early-stage non-small cell lung cancer (NSCLC) to investigate early immune landscape changes occurring during tumorigenesis. Computational deconvolution of immune infiltrates in 44 NSCLC and matching adjacent normal samples from TCGA showed heterogeneous patterns of alterations in immune cells. The scRNA-seq analyses of 11,485 cells from 4 treatment-naïve NSCLC patients comparing tumor to adjacent normal tissues showed diverse changes of immune cell compositions. Notably, CD8+ T cells and NK cells are present at low levels in adjacent normal tissues, and are further decreased within tumors. Myeloid cells exhibited marked dynamic reprogramming activities, which were delineated with differentiation paths through trajectory analysis. A common differentiation path from CD14+ monocytes to M2 macrophages was identified among the 4 cases, accompanied by up-regulated genes (e.g. ALCAM/CD166, CD59, IL13RA1, IL7R) with enriched functions (adipogenesis, lysosome), and down-regulated genes (e.g. CXCL2, IL1B, IL6R) with enriched functions (TNFa signaling via NF-kB, inflammatory response). Computational deconvolution and single cell sequencing analyses have revealed a highly dynamic immune reprogramming that occurs in early stage NSCLC development, suggesting that normalizing both immune compartments may represent a viable strategy for treatment of early stage cancer and prevention of progression. Overall design: Map the immune ecosystem using computational deconvolution of bulk transcriptome data from the Cancer Genome Atlas (TCGA) and single cell RNA sequencing (scRNA-seq) data of dissociated tumors from from early-stage non-small cell lung cancer (NSCLC) to investigate early immune landscape changes occurring during tumorigenesis	Co-expression
SRP154984	Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage	Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection. Overall design: 96 nasal samples from healthy volunteers experimentally challenged with pneumococcus, 3  days after receiving live attenuated influenza vaccine or tetravalent inactivated influenza vaccine underwent RNA-Sequencing. Nasal cells were collected at baseline (D-4) before vaccination, and at 5 days after vaccination (or 2 days after pneumococcal inoculation, D+2) and at 12 days after vaccination (or 9 days after pneumoocccal inoculation, D9)	Co-expression
SRP154995	REST and Neural Gene Network Dysregulation in iPS Cell Models of Alzheimer's Disease (RNA-seq data set)	Alzheimer's disease (AD) is preceded by a long prodromal period of decades during which pathology accumulates in the brain prior to the onset of dementia.  The molecular basis of these changes as well as how and when they start are unclear. Here we have analyzed neural progenitor (NP) cells and neurons generated from induced pluripotent stem cells (iPSCs) from individuals with sporadic AD (AD) and age-matched controls.  Transcriptome analysis does not distinguish between iPSCs from individuals with SAD and age-matched controls, but shows major differences in iPSC-derived NP cells and neurons in gene networks related to neuronal differentiation, neurogenesis and synaptic transmission.  SAD NP cells exhibit accelerated neuronal differentiation, leading to the generation of neurons with increased synapse formation and electrical excitability. Network analysis of the transcriptome implicates the transcriptional repressor REST/NRSF and two components of the polycomb repressive complex 2, SUZ12 and EZH2.  Accelerated differentiation of SAD NP cells was reversed by exogenous REST expression and mimicked in normal NP cells by REST knockdown.  The phenotype of accelerated neural differentiation was recapitulated in NP cells and cerebral organoids derived from gene-edited iPSC lines that express apolipoprotein E4 (APOE4), the major genetic risk factor for AD.  Network analysis of the APOE4-related transcriptome again showed reduced function of REST, EZH2 and SUZ12 to be the major predicted regulatory changes. Reduced function of the REST repressor was due to reduced nuclear translocation and chromatin binding, and was associated with disruption of the nuclear membrane and lamina in SAD and APOE4 NP cells.  Thus, impaired function of specific transcription factors and changes in nuclear architecture may be among the earliest events in the pathogenesis of AD. Overall design: Explore the effects of isogenic editing of APOE E4 to E3 in cerebral organoids. Comparison of APOE E4 vs E3 isogenic organoids with 3 biological replicates per group.	Co-expression
SRP155026	circ-ZNF609 regulates G1-S progression in Rhabdomyosarcoma	Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from a non-canonical splicing event, ubiquitously expressed among Eukaryotes and conserved among different species. We identified a circRNA (circ-ZNF609) involved in the regulation of human primary myoblast proliferation. Upon its depletion, the percentage of proliferating myoblasts was highly reduced. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in Rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is up-regulated in biopsies from both the two major RMS subtypes, the alveolar (ARMS) and the embryonal (ERMS), and we discovered that its knock-down blocks proliferation of an ERMS-derived cell line, while it has no effect on ARMS-derived cells. To understand the mechanism through which circ-ZNF609 affects cell proliferation we compared the different effects of circ-ZNF609 depletion in ERMS and ARMS and we identified genes and pathways on which the circRNA acts. Overall design: Total RNA from wild-type human primary myoblasts treated either with a control siRNA (si-SCR) or with a siRNA specific for circ-ZNF609 (si-Circ) was analyzed by RNA-Seq. The experiment was performed in duplicate (4 samples in total). Total RNA from RD cells (Embryonal Rhabdomyosarcoma) and RH4 cells (Alveolar Rhabdomyosarcoma) treated either with a control siRNA (si-SCR) or with a siRNA specific for circ-ZNF609 (si-Circ) was analyzed by RNA-Seq. The experiment was repeated in duplicate (8 samples in total).	Co-expression
SRP155027	RNA-seq of PC9 cells tolerant to gefitinib	EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo. Overall design: The NSCLC cell line PC9 was made tolerant to gefitinib over 6-days. Replicates were performed at a minimum of duplicates. EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo.	Co-expression
SRP155035	STVI-120 Induction of differentiation in human epidermal stem cells followed by differential splicing analysis	We report the effects of induction of differentiation in human epidermal stem cells on the splicing of the transcriptome. Overall design: RNA-sequencing data following induction of differentiation in human epidermal stem cells	Co-expression
SRP155036	RNA-seq analysis of canonical and adaptive human NK cell and CD8+ T cell subsets from HCMV seropositive donors	We report our results of RNA-seq analysis on freshly isolated, sorted subsets of cytotoxic lymphocytes Overall design: RNA was isolated from sorted cells. Libraries were created using standard Illumina reagents and analyzed using a HiSeq2500.	Co-expression
SRP155045	Cellular acidosis triggers MondoA transcriptional activity by driving mitochondrial ATP production	MondoA and its transcriptional target thioredoxin-interacting protein (TXNIP) constitute a regulatory loop that senses glycolytic flux and controls glucose availability. Cellular stress also triggers MondoA activity and TXNIP expression. To understand how MondoA integrates glucose and stress signals, we studied its activation by acidosis. We found that acidosis drives mitochondrial ATP (mtATP) synthesis. The subsequent export of mtATP from mitochondria via adenine-nucleotide transporter and voltage-dependent anion channel, and the enzymatic activity of mitochondria-bound hexokinase results in the production of glucose-6-phosphate (G6P), a known activator of MondoA transcriptional activity. MondoA localizes to the outer-mitochondrial membrane (OMM), and in response to G6P, shuttles to the nucleus and activates transcription. Our data suggests that MondoA is a required feature of a glucose- and mtATP-dependent, OMM-localized signaling center. We propose MondoA functions as a coincidence detector and its ability to sense glucose and cellular stress is coupled to the concerted production of G6P. Overall design: mRNA sequencing of HeLa and HeLa:MondoA-KO cells treated with DMEM or DMEMAcidic for 4 hours	Co-expression
SRP155089	Intrahepatic MAIT cell gene expression revealed by RNA-seq	RNA-seq was carried out as described by Simone Picelli et al. with minor modifications (Genome Res 2014;24:2033-40). Briefly, RNA was extracted from 5000 cells using a miRNeasy Micro Kits (Qiagen, German). RNA quality was assessed with an Agilent RNA 6000 Pico Kit (Agilent Technologies, cat#5067-1513, USA) on an Agilent 2100 Bioanalyzer. Each library was prepared from 2ng of total RNA. After reverse transcription, cDNA was amplified for 8 cycles followed by Agencourt AMPure XP purification, the quality of cDNA library was checked on an Agilent High Sensitivity DNA Kit (Agilent Technologies, cat#5067-4626). The cDNA was sheared to a 200-500 bp size range using the Covaris AFA system. The final library was carried out by using the NEB Next ULTRA II DNA Prep Kit, and their quality and size were checked using the Agilent High Sensitivity DNA Kit. The libraries were sequenced using a Hiseq 4000 system (Illumina, USA). At least million reads were obtained for each sample. For all RNA-seq reads, we cut the 5' adaptor (AAGCAGTGGTATCAACGCAGAGTACAT GGG) using cutadapt (version 1.10) with the parameter –e 0.17, and then aligned to the hg19 genome using OSA (version 2.10.8). The aligned data were merged and count by Samtools (version 0.1.19+), and differentially expressed genes were found based on the edgeR with default parameters (Bioinformatics 2010;26:139-40). A gene was differentially expressed if (1) p < 0.05 (2) |log2(fold change)| > 1. For hierarchical clustering, the RPKM values of differentially expressed genes were log2-transformed and standardized. 1- Pearson correlation was then used as the distance for clustering. Differentially expressed genes were selected for GO analysis using R package clusterProfiler (Omics 2012;16:284-7). Overall design: Sorted mucosal-associated invariant T (MAIT) cells for RNA-Seq from tumor and peritumor tissues in five hepatocellular carcinoma (HCC) patients and normal liver tissues in five healthy donors.	Co-expression
SRP155151	N6-methyladenine DNA Modification in Glioblastoma [RNA-seq]	Genetic drivers of cancer can be dysregulated through epigenetic modifications of DNA. While the critical role of DNA 5-methylcytosine (5mC) in the regulation of transcription is recognized, the functions of other non-canonical DNA modifications remain obsure. Here, we report the  identification of novel N(6)-methyladenine (N6-mA) DNA modifications in human tissues and implicate this epigenetic regulation in human disease, the highly malignant brain cancer, glioblastoma. Glioblastoma upregulates N6-mA levels, which co-localize with heterochromatic histone modifications, namely H3K9me3. N6-mA levels are dynamically regulated by the DNA demethylase, ALKBH1, to transcriptionally silence oncogenic pathways through decreasing chromatin accessibility. Targeting the N6-mA regulator, ALKBH1, in patient-derived human glioblastoma models inhibited tumor cell proliferation and extended survival of tumor-bearing mice, supporting this novel DNA modification as a potential new molecular therapeutic target for glioblastoma. Collectively, our results uncover a novel epigenetic node in cancer through the DNA modification, N6-mA. Overall design: RNA-seq of patient derived glioblastoma stem cells in hypoxia and normoxia	Co-expression
SRP155163	A comprehensive single cell transcriptional landscape of human hematopoietic progenitors	Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products. Overall design: Single-cell mRNA sequencing of freshly isolated hematopoietic progenitors from human bone marrow. Sample HSC (Donor A) represents 1282 single cells. Sample MPP (Donor A) represents 215 single cells. Sample MLP (Donor A) represents 123 single cells. Sample PreB/NK (Donor A) represents 592 single cells. Sample MEP (Donor A) represents 1211 single cells. Sample CMP (Donor A) represents 1576 single cells. Sample GMP (Donor A) represents 1012 single cells. Sample Lin-CD34+CD164+ (Donor B) represents 6343 single cells. Sample Lin-CD34-CD164high (Donor B) represents 4434 single cells. Sample Lin-CD34lowCD164high (Donor B) represents 4266 single cells. Sample Lin-CD34-CD164low (Donor B) represents 358 single cells.	Co-expression
SRP155182	Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency	Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5 year-old child with severe pulmonary influenza at 2 years. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not interferon-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-a2b. The transcriptome induced by IFN-a2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of interferon-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus, and respiratory syncytial virus. These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV. Overall design: Total of 72 samples, 38 samples from primary fibroblasts and 34 samples from EBV-transformed B cells, were analyzed using paired-end RNA sequence data. Out of 38 samples from primary fibroblasts, 3 control samples are paired with no stimulation vs IFNa2b stimulation. Out of 34 samples from B-cells, 3 control samples are paired with no stimuliion vs IFNa2b stimulation. In addition to healthy control subjects, patients with AR complete STAT1 (STAT1 -/-) or STAT2 (STAT2 -/-) deficiency were analyzed for comparison.	Co-expression
SRP155230	Stage-specific transcriptome analysis during differentiation from pluripotency to glial restricted progenitor stages	The goals of this study are to compare NGS-derived neural transcriptome profiling (RNA-seq) and to investigate involving transcription factors at each stages Overall design: mRNA profiles of BJ, iPSC, ESC, NSC, GPLC were generated by deep sequencing, in triplicate, using Illumina Hiseq2500.	Co-expression
SRP155245	Development of a novel cell-based assay to diagnose recurrent Focal and Segmental Glomerulosclerosis	In this study we plan to compare the profiles of control sample (C) with the disease (FSGS) samples to identify differentially expressed genes. We hope to identify genes that are specifically activated in response to treatment with FSGS plasma. Overall design: Upregulated genes on incubating with plasma from recurrent FSGS plamsa sample in cultured human podocytes cells were probed	Co-expression
SRP155367	Alpha-Synuclein Induces the Unfolded Protein  Response in Parkinson's Disease SNCA Triplication  iPSC-Derived Neurons	The alpha Synuclein (SNCA) gene is one of the most commonly implicated mediator of Parkinson Disease (PD), changes in dosages are directly associated severity of PD. Here we aim to compare expression within induced pluripotent stem cells derived from a patient with a triplication of the SNCA locus to an isogenic IPSC line with normalized gene dosage through CRISPR/Cas9 mutagenesis.	Co-expression
SRP155405	Detailed genomic and molecular characterization of Indian induced pluripotent stem cell lines	We report the application of RNA sequencing technology for high-throughput profiling of control iPSC lines Overall design: RNA-seq of three iPSC lines and neural stem cells derived from the same iPSC lines.	Co-expression
SRP155415	MicroRNA-mediated suppression of the TGF-ß pathway confers transmissible and reversible CDK4/6 inhibitor resistance (RNA-Seq)	CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-ß pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday. Overall design: To analyse the binding targets of miR-432-5p we performed a mRNA pulldown using a synthetic biotin laballed miR-432-5p. RNAseq was performed to identify the captured mRNA.	Co-expression
SRP155479	Activation of Wnt signaling promotes olaparib resistant ovarian cancer.	Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10 and C18) and parental PEO1 (P1 and P2) cells was performed in order to determine mechanisms of acquired resistance in the resistant cell lines. PEO1 parental cell lines were authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Olaparib PEO1 resistant cells were generated through a step-wise escalation of olaparib (10nM to 8uM olaparib). In olaparib resistant lines an increase canonical Wnt signaling and loss of of non-canonical Wnt signaling was observed. Overall design: Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10, and C18) and parental PEO1 cells was performed in order to determine mecahnisms of acquired resistance.	Co-expression
SRP155483	White blood cells from rheumatoid arthritis patients and matched healthy donors	The experiment was designed to assess gene expression differences between rheumatoid arthritis patient and healthy donor white blood cells. Overall design: White blood cells were collected from peripheral blood (PB) of 50 RA donors and 50 age, gender and ethinicity matched healthy donors to compare whole blood transcriptomes from RA patients to healthy individuals	Co-expression
SRP155493	Widespread RNA editing dysregulation in Autism Spectrum Disorders II	Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation. Overall design: RNA-seq to examine RNA editing in Fragile X patients	Co-expression
SRP155524	HP1? is required for G9a/GLP coactivator function with the glucocorticoid receptor in Nalm6 cells	Using a genome-wide analysis, we demonstrated that HP1? is selectively required for GC-regulated expression of GR target genes that require G9a and GLP, consistent with our previous finding that automethylated G9a and GLP recruit HP1g to specific genomic GR binding sites. Overall design: We examined whether HP1g is required for GC-induced expression of the genes that require coactivators, G9a and GLP, by depleting HP1g, G9a and GLP in Nalm6 cells using shRNA and examined gene expression changes at 8 hour dexamethasone (dex) treatment compared with ethanol treatment as a control.  shRNA for a nonspecific sequence (shNS) followed by 8h of dex treatment was performed as control.	Co-expression
SRP155565	Transcriptome Analysis of Huh7 cells Infected with Adenovirus Overexpression GSTZ1 or PCK1	Purpose:To understand the change in cellular metabolism and function for the overxepression of GSTZ1 or PCK1 in hepatoma cells. Methods:Total RNAs of AdGFP- , AdGSTZ1-, or AdPCK1-infected Huh7 cells were extracted using TRIzol (Invitrogen), following the manufacturer's instructions. RNA-seq and bioinformatic data analysis were performed by Shanghai Novel Bio Ltd. Briefly, strand-specific RNA-seq libraries were prepared using the Total RNA-seq (H/M/R) Library Prep Kit (Vazyme Biotech, Nanjing, China) and were sequenced on Ion Torrent Proton sequencing platform. Raw reads in FASTQ format were subjected to quality control using FastQC. RNA-seq reads were aligned to the reference genome using Bowtie. Uniquely mapped reads were used for further analysis. Gene expression levels are expressed as RPKM (reads per kilobase per million reads) and differences in gene expression were calculated with rSeq. Results:There were 498 genes differentially expressed in AdPCK1-infected Huh 7 cells,  513 genes differentially expressed in AdGSTZ1-infected Huh 7 cells compare to the GFP control group respectively (fold change >1.5 or < 0.667; FDR < 0.05). Overall design: mRNA profiles of AdGFP1, AdGSTZ1- or AdPCK1-infected  Huh 7 cells were generated by deep sequencing in triplicate, using Ion Torrent Proton sequencing platform.	Co-expression
SRP155569	RNA-seq of Single-Cell Genotyping of Transcriptomes	Somatic cancer driver mutations may result in distinctly diverging phenotypic outputs. Thus, a common driver lesion may result in cancer subtypes with distinct clinical presentations and outcomes. The diverging phenotypic outputs of mutations result from the superimposition of the mutations with distinct progenitor cell populations that have differing lineage potential. However, our ability to test this hypothesis has been challenged by currently available tools. For example, flow cytometry is limited in its inability to resolve lineage commitment of early progenitors. Single-cell RNA sequencing (scRNA-seq) may provide higher resolution mapping of the early progenitor populations as long as high throughput technology is available to sequence thousands of single cells. Nevertheless, high throughput scRNA-seq is limited in its inability to jointly and robustly detect the mutational status and the transcriptional profile from the same cell.  To overcome these limitations, we propose the use of scRNA-seq combined with targeted mutation sequencing from transcrptional read-outs. Overall design: We apply this method to study myeloid neopasms, in which the comlex process of hematopoiesis is corrupted by mutated stem and progenitor cells.	Co-expression
SRP155573	Primary human monocytes either mock treated, infected with A/California/07/2009 and A/Victoria/361/2001	241 genes differentially expressed between two viruses Overall design: Primary human monocytes were infected for 1 hour then primary autologous NK cells were added for a 6 or 23 hr co-coculture. Post co-culture, the monocytes and NK cells were re-isolated by magnetic separation, monocyte RNA was harvested via RNA bee and sent for RNA-sequencing.	Co-expression
SRP155574	Development and Validation of a Simplified Method to Generate Human Microglia from Pluripotent Stem Cells	Comparison of published protocol (Abud et al. Neuron 2016) to simplified method of microglial differentiation which does not require hypoxia or FACS. We show each method produced highly similar microglia. Overall design: Comparison of two microglia populations to blood monocytes	Co-expression
SRP155704	ARID3a Gene Profiles are Strongly Associated with Human Interferon Alpha Production	Percentages of ARID3a-expressing low density neutrophils in SLE patients correlate with lupus disease activity and Type I IFN production. ARID3a protein levels also correlate with interferon expression in plasmacytoid dendritic cells. Gene profiles mechanistically link ARID3a with inflammatory pathway regulation. Overall design: Correlation analysis of genes associated with IFNa and/or ARID3a protein levels in neutrophils and pDCs of SLE patients.	Co-expression
SRP155705	Transcriptional single cell analysis of human umbilical cord derived mesenchymal stem cells	Mesenchymal stem cells (MSCs) are a population of multipotent cells with an attractive ability to promote tissue repair by regulating regeneration and inflammation. Ironically, the immune regulatory capacity of MSCs, regardless of their tissue origin, is endowed by inflammatory cytokines (e.g., IFNg plus TNFa). Effective application of MSCs relies on the production of relatively homogeneous MSCs. However, the cellular heterogeneity, and the differentiation trajectories of in vitro expanded MSCs remains unclear. We profiled the transcriptomes of 361 single MSCs derived from two umbilical cords (UC-MSCs). The MSCs are from different passages and culture conditions with or without inflammatory cytokine stimulation. Weighted gene correlation network analysis for the expression of their highly variable genes revealed that UC-MSCs surprisingly possess only limited heterogeneity. Cell cycle based principal component analysis showed that the limited heterogeneity identified in these UC-MSCs was strongly associated with their entrance into the G2/M phase. This was further proven by the observation that one featured gene CD168 was expressed in a cell-cycle dependent manner. When CD168high UC-MSCs were sorted and cultured in vitro, they repopulated into a new community that is similar to the original status. Our results demonstrated that in vitro expanded UC-MSCs is a well-organized population with limited heterogeneity dominated by cell cycle status. Thus, our studies argues that standardization of MSCs for disease treatment is possible. Overall design: MSCs isolation from the umbilical cord, in vitro expansion, pretreatment approach, single cell capture, and RNA sequencing. Cells isolated from two different donors are sequenced in three passages with or without cytokine stimulation.Donor1, passage5, naive, 52cells; Donor2, passage5, naive, 50cells; Donor2, passage2, naive, 50cells; Donor2, passage0, naive, 50cells; Donor1, passage5, stimulation, 59cells; Donor2, passage5, stimulation, 50cells; Donor2, passage2, stimulation, 50cells;	Co-expression
SRP155715	Does osteogenic potential of clonal human bone marrow mesenchymal stem/stromal cells correlate with their vascular supportive ability?	Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and  in developing and potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products (ATMPs) for cellular therapies. Since the healing of bone defects in larger bone grafts depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist. We tested this by assessing the lineage (i.e. adipogenic {A}, osteogenic {O} and/or chondrogenic {C}) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic {O} potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses. Our results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent.  RNAseq of individual clones defined gene fingerprints relevant to this correlation. Overall design: 16 samples from two donors (8 from each donor), possessing high or low osteogenic potential.	Co-expression
SRP155734	RNA-Seq of HSV infected Human 293T cells-part2	To study the transcription of HSV infected cells	Co-expression
SRP155751	Single cell RNA-seq profiles of primary, metastatic, drug-resistant and drug-holiday cells	We employed Single cell RNA-seq to identify the transcriptome of cisplatin sensitive, resistant and drug-holiday cells from patient-derived OSCC cells isolated from primary and metastatic sites. Overall design: Single-cell RNA-seq profiles of in sensitive and drug-resistant cells from OSCC	Co-expression
SRP155768	Integrated transcriptomic and proteomic analysis of human eccrine sweat glands	Eccrine sweat gland is an exocrine gland that is involved in the secretion of sweat for control of temperature. Malfunction of the sweat glands can result in disorders such as miliaria, hyperhidrosis and bromhidrosis. In addition, lack of reabsorption of Cl- ions from reabsorptive duct of eccrine sweat gland is a major feature of cystic fibrosis. Understanding the proteome of eccrine sweat glands is important for understanding the physiology of sweat formation. In spite of this, no systematic transcriptome or proteome analysis of eccrine sweat glands has yet been reported. To this end, we isolated eccrine sweat glands by microdissecting them from human skin and performed both RNA-seq and proteome analysis. In total, ~138,000 transcripts and ~6,100 proteins were identified. The proteome data showed the enrichment in protein digestion/absorption and salivary secretion, while the transcriptome data did not show any enrichment for a specific pathway. This study also enabled us to confirm 2 missing proteins. Integrating RNA-seq and proteomic data allowed us to identify 7 peptides from 5 novel genes. Most of the novel proteins were from short open reading frames (sORFs) suggesting that many sORFs still remain to be annotated in the human genome. The peptides mapping to the missing or novel proteins were validated by analyzing synthetic peptides. This study provides the first integrated analysis of the transcriptome and proteome of the human eccrine sweat gland and should become an invaluable resource to biomedical research community for studying sweat glands in physiology and disease. Overall design: One set of RNA sample purified from dissected sweat glands isolated from the skin dermis by microscopic dissection	Co-expression
SRP155883	Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [RNA-seq]	Tolerogenic dendritic cells (DC) are key players in maintaining immunological homeostasis, dampening immune reactions, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DC characterized by the expression of HLA-G and ILT4, play a pivotal role in promoting tolerance via T regulatory type 1 (Tr1) cells. Thus far, the absence of specific biomarkers that uniquely identify DC-10 limited their studies in vivo. By gene expression profiling of in vitro differentiated human DC, we identified CD141 and CD163 as specific surface markers for DC-10. The co-expression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of blood circulating DC-10. FACS-isolated CD14+CD16+CD141+CD163+ cells (ex vivo DC-10) from peripheral blood of healthy subjects produced spontaneously and upon activation IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4+ T cells with ex vivo isolated CD14+CD16+CD141+CD163+ cells induced the differentiation of allo-specific Tr1 cells. Finally, ex vivo isolated CD14+CD16+CD141+CD163+ cells and in vitro differentiated DC-10 exhibited a similar transcriptional profile, characterized by anti-inflammatory and pro-tolerogenic signature. These results provide new insight into the DC-10 phenotype and on the role of circulating DC-10 in modulating T cell responses and promoting Tr1 cells. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings. Overall design: Identification of the transcriptional prfile of ex vivo isolated DC-10	Co-expression
SRP155901	KLF4 as a rheostat of osteolysis and osteogenesis in prostate tumors in the bone	We previously found that KLF4, a gene highly expressed in adult prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. To test whether this anti-cancer effect of KLF4 can also prevent prostate cancer-induced damage to the bone, we ablated KLF4 in human PC3 prostate cancer cells using CRISPR/Cas9-mediated genome editing and compared their behavior to null cells transduced with a DOX inducible KLF4 expression system. KLF4 re-expression inhibited growth of PC3 null cells in monolayer and as colonies in soft agar in a dose-dependent manner. When injected into the mouse femurs, PC3 null cells proliferated rapidly, forming very large, invasive and osteolytic tumors. Induction of KLF4 expression in PC3 null cells immediately after their intra-femoral inoculation blocked the development of tumors while preserving the normal bone architecture. KLF4 re-expression in established PC3 bone tumors inhibited osteolytic effects of PC3 null cells, preventing bone fractures and inducing a significant osteogenic response with regions of new bone formation. Transcriptome analyses of PC3 cells with no or high KLF4 expression revealed KLF4-dependent osteolytic or osteogenic transcriptional programs, respectively. Importantly, these KLF4-dependent functions significantly overlapped with metastatic prostate cancers in patients. Overall design: Uninfected PC3 KLF4 wild-type cells and uninfected PC3 KLF4 null cells were grown for 48 hours and collected for RNA extraction. Another cohort of PC3 KLF4 null cells was infected with lentiviruses expressing a DOX inducible KLF4 expression construct (BFP-T2A-hKLF4) or the control empty vector (BFP-T2A). After 48 hours, DOX (10 ng/ml) was added to the culture medium to induce KLF4 expression. Control and KLF4-overexpressing cells were collected for RNA extraction after a 48-hour incubation with DOX. Total RNA was extracted using the RNeasy kit (Qiagen, CA, USA). RNA-Seq libraries were prepared with the TruSeq sample preparation kit (Illumina, CA, USA).	Co-expression
SRP155937	Oxygen Controls Metabolic Flux and Influences Global Acetylation and Methylation in Human Pluripotent Stem Cells	Purpose: The goals of this study are to compare the effects of 5% and 20% oxygen culture on human embryonic stem cells, inlcuding the impact on their transcriptomes. Overall design: mRNA profiles of two human embryonic stem cell lines (MEL1 and MEL2) cultured long term at 5% and 20% oxygen.	Co-expression
SRP155941	Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets	The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self- reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes. Overall design: RNA-seq of purified human circulating monocytes and tumor-associated macrophages (TAMs) in breast and endometrial cancers.	Co-expression
SRP155976	Transcription profiles of rectal biopsies obtained during diagnostic colonoscopy for pediatric inflammatory bowel diseases.	RNA was isolated from rectal biopsies from 190 pediatric patients undergoing diagnostic colonoscopy for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Single-end, 75-bp sequencing was performed, and raw reads aligned to the human genome using Gencode v 24 as reference.  We included 14085 protein-coding mRNA genes in downstream analyses, where cutoffs of fold change>1.5 and FDR<0.05 were considered significant. Overall design: RNA-sequencing of rectal biopsies obtained from pediatric IBD and control patients.	Co-expression
SRP155988	scRNAseq reveals mechanisms of Merkel cell carcinoma acquired immunotherapy resistance [1]	Serial blood draws from a single patient and serial tumor biopsies from the same patient  with metastatic Merkel cell polyomavirus Merkel cell carcinoma, who was treated with cellular immunotherapy targeting MCPyV (autologous endogenous T cell therapy) followed by checkpoint inhibitors (anti-PD1 and anti-CTLA4).  The patient had a 22 month clinical response followed by late/acquired resistance.  We performed scRNAseq using the 10x genomics 3'' Chromium expression assay to determine potential mechanisms contributing to immunotherapy response and late resistance Overall design: Serial blood draws from four time points, serial tumor biopsies from two time points - single cell digests were viably preserved, comparisons were performed on a within tissue basis, discovery patient for associated manuscript	Co-expression
SRP156000	Transcriptome-wide analysis of human chondrocyte expansion on synoviocyte matrix	Human chondrocytes, expanded and used in autologous chondrocyte implantation techniques, are known to rapidly de-differentiate in culture. These chondrocytes undergo both morphological and phenotypical changes and, eventually, lose the ability to produce hyaline-like matrix when cultured on tissue culture (TC) plastic. Growth on synoviocyte-derived extracellular matrix (SDECM) reduces this de-differentiation allowing for more than double the number of population doublings whilst retaining chondrogenic capacity. The goal of this study was to use RNAseq analysis to examine the differences between TC plastic-expanded and SDECM-expanded human chondrocytes over 4 passages. Human chondrocytes (3 donors) were thawed from primary stocks collected under an IRB approved protocol and cultured on TC plastic flasks or on SDECM-coated flasks at physiological oxygen tension (5%) for 4 passages. RNA was extracted from the cell layer during log expansion (70-90% confluence) phase at passages 1 and 4, column purified and DNAse treated before QC analysis and submitted for next generation RNA sequencing (RNAseq). Significant effects on gene expression were observed due to both growth substrates and passage number. These results may provide insight into the mechanism of how SDECM provides a more chondrogenesis perserving environment for cell expansion.	Co-expression
SRP156049	Transcriptome of human non-functional pancreatic neuroendocrine tumors (PanNETs)	The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells. Overall design: Evaluation of Cell of origins for non-functional PanNETs and genotype to phenotype correlations in PanNETs	Co-expression
SRP156276	The long non-coding RNA LINC00941 and SPRR5 are novel regulators of human epidermal homeostasis	Several long non-coding RNAs (lncRNAs) act as regulators of cellular homeostasis; however, few of these molecules were functionally characterized in a mature human tissue environment. Here, we report that the lncRNA LINC00941 is a crucial regulator of human epidermal homeostasis. LINC00941 is enriched in progenitor keratinocytes and acts as a repressor of keratinocyte differentiation. Furthermore, LINC00941 represses SPRR5, a previously uncharacterized molecule, which functions as an essential positive regulator of keratinocyte differentiation. Interestingly, 54.8% of genes repressed in SPRR5 deficient epidermal tissue are induced in LINC00941 depleted organotypic epidermis, suggesting a common mode of action for both molecules. Overall design: Investigating the impact of LINC00941 (on day 2 and day 3 of differentiation) or SPRR5 (on day 3 and day 4 of differentiation) depletion on the keratinocyte differentiation status in organotypic epidermal tissue cultures by high throughput sequencing.	Co-expression
SRP156289	Mechanism suppressing H3K9 trimethylation in pluripotent stem cells and its demise by polyQ-expanded huntingtin mutations [RNA-seq]	We find that HTT binds ATF7IP, a regulator of the histone H3 methyltransferase SETDB1. HTT inhibits the interaction of the ATF7IP-SETDB1 complex with other heterochromatin regulators and transcriptional repressors, maintaining low levels of H3K9 trimethylation (H3K9me3) in hESCs. Conversely, loss of HTT promotes global increased H3K9me3 levels. To test whether HTT knockdown also induces enrichment of H3K9me3 marks at specific genes, we performed chromatin immunoprecipitation (ChIP)-sequencing assays of hESCs using an antibody to H3K9me3. Overall design: We performed RNAseq in pluripotent stem cells and derived NPCs to examine how changes in HTT and ATF7IP levels change transcript levels. We have 19 samples in total:  3 replicate NPCs derived from HD iPSCs expressing Nt shRNA +  3 NPCs derived from HD iPSCs expressing ATF7IP  shRNA  to be compared with 3 NPCs derived from Control iPSCs expressing Nt shRNA; 2 replicates H9 hESCs expressing ATF7IP  shRNA to be compared with 2 replicates H9 hESCs expressing control NT shRNA; 3 replicates NPCs derived from H9 hESCs expressing HTT  shRNA to be compared with  3 replicates NPCs derived from H9 hESCs expressing control NT  shRNA	Co-expression
SRP156322	AmpliSeq Transcriptome Analysis of Human Prostate Cancer Cells With or Without Overt SRRM4 Expression	Prostate adenocarcinoma (AdPC) cells can undergo lineage switching to neuroendocrine cells and develop into therapy-resistant neuroendocrine prostate cancer (NEPC). While genomic/epigenetic alterations are shown to induce neuroendocrine differentiation via an intermediate stem-like state, RNA splicing factor SRRM4 can transform AdPC cells into NEPC xenografts through a direct neuroendocrine transdifferentiation mechanism. Whether SRRM4 can also regulate a stem-cell gene network for NEPC development remains unclear. Here, we use the Ion AmpliSeqTM Transcriptome Human Gene Expression Kit (AmpliSeq) to analyze the transcriptome of human AdPC cell line DU145 overexpressing SRRM4 via lentiviral transduction compared to the control, empty vector-transduced DU145 cells. This study reveals that SRRM4 induces a pluripotency gene network consisting of the stem-cell differentiation gene, SOX2. In summary, we report a novel mechanism by which SRRM4 drives NEPC progression via a pluripotency gene network. Overall design: Assessment of transcriptome profiles from DU145 cells with or without overt SRRM4 expression using AmpliSeq.	Co-expression
SRP156328	Next generation sequencing facilities quantitative analysis of negative control HCT116 cells and 5MP1-overexpressed HCT116 cells.	To investigate the downstream targets of eIF5 mimic protein 1 (5MP1), also known as Basic Leucine Zipper and W2 domains 2 (BZW2; Ensembl:ENSG00000136261), we performed a transcriptomic analysis using high throoughput RNA sequencing (RNA-seq). Overall design: Total RNA extracted from HCT116 cells stably expressing 5MP1 and empty vector-transfected negative control HCT116 cells was subjected to RNA-seq analysis. The sequencing libraries generated from the RNA were analyzed by Illumina Hiseq 4000. The sequencing reads were trimmed for adaptor sequence, and low-complexity or low-quality reads were removed. Subsequently, the sequencing reads were aligned to the human reference GRCh38 genome using Gencode v27 annotations by STAR. Read counts per gene were quantified using the HTSeq Python package.	Co-expression
SRP156330	Next generation sequencing facilities quantitative analysis of KMST6 cells expressing AUG-initiated c-Myc and CUG-initiated c-Myc.	To investigate the differences of transcriptional activities between AUG-initiated c-Myc and CUG-initiated c-Myc , we performed a transcriptomic analysis using high throoughput RNA sequencing (RNA-seq). Overall design: Total RNA extracted from KMST6 fibroblast cells stably expressing AUG-initiated c-Myc, CUG-initiated c-Myc, and empty vector (negative control) was subjected to RNA-seq analysis. The sequencing libraries generated from the RNA were analyzed by Illumina Hiseq 4000. The sequencing reads were trimmed for adaptor sequence, and low-complexity or low-quality reads were removed. Subsequently, the sequencing reads were aligned to the human reference GRCh38 genome using Gencode v27 annotations by STAR. Read counts per gene were quantified using the HTSeq Python package.	Co-expression
SRP156350	Single-cell analysis of adult human ovary using 10X genomics	The ovary is perhaps the most dynamic organ in the human body, only rivaled by the uterus. The molecular mechanisms that regulate follicular growth and regression, ensuring ovarian tissue homeostasis, remain elusive. We have performed single-cell RNA-sequencing using human adult ovaries to provide a map of the molecular signature of growing and regressing follicular populations. We have identified different types of granulosa and theca cells and detected local production of components of the complement system by (atretic) theca cells and stromal cells. We also have detected a mixture of adaptive and innate immune cells, as well as several types of endothelial and smooth muscle cells to aid the remodeling process. Our results highlight the relevance of mapping whole adult organs at the single-cell level and reflect ongoing efforts to map the human body. The association between complement system and follicular remodeling may provide key insights in reproductive biology and (in)fertility. Overall design: 31 tissue samples from 5 ovaries were used for single-cell and cluster analysis	Co-expression
SRP156355	Identification of lncRNA in early stage breast cancer and their prognostic implications	Breast cancer is a common malignancy among women with highest incidence rate worldwide. Increasing evidences affirm lncRNA function in tumor development and progression. The aberrant and temporal expression of lncRNA may be a fundamental event for breast tumor initiation. In this study, RNA sequencing was employed to understand lncRNA expression signature in early stage breast cancer to identify lncRNA of functional importance in tumorigenesis. Infiltrating ductal carcinoma (IDC) and Ductal carcinoma in situ along with adjacent/marginal tissues of respective IDC tissues as paired normal and tissues obtained from patients undergoing surgery for breast conditions other than malignancy were used as apparent normal samples. Tumor tissues samples were histopathologically confirmed of containing more than 70% of tumor cells. Total RNA isolated from these tissues were rRNA depleted and stranded library was synthesized.	Co-expression
SRP156387	single cell RNA-seq of human cell lines	Single cell RNA-sequencing of human cell lines performed for the benchmarking of single cell transcriptome analytics.	Co-expression
SRP156394	Transcriptomic profiling of human Lung Carcinoids (LCs)	Lung carcinoids (LCs) are rare and slow growing primary lung neoplasms that are understudied. Here, we performed targeted exome sequencing using a 354-cancer gene panel (n=29), mRNA sequencing (n=30) and DNA methylation assay (n=18) on macro-dissected lung carcinoids. The mutations we identified were enriched for genes involved in covalent histone modification/chromatin remodeling (34.5%) (MEN1, ARID1A, KMT2C and KMT2A were recurrently mutated) as well as DNA repair (17.2%) pathways. Unsupervised clustering and principle component analysis on gene expression and DNA methylation profiles showed 3 robust molecular subtypes (LC1, LC2, LC3) with distinct clinical features.  MEN1 gene mutations were found to be enriched and exclusively in the LC2 subtype (p-value<0.001).  The LC3 subtype is predominately found at endobronchial lung and earlier age of diagnosis. Immunohistochemical staining of two biomarkers, ASCL1 and S100, is sufficient to stratify the three subtypes. This molecular classification of lung carcinoids into three subtypes may help improve treatment decision and clinical management. Overall design: Genomic and Transcriptomic Characterization of Lung Carcinoids	Co-expression
SRP156403	Innate Lymphoid Cell Development in Human Tonsils	Studies in human innate lymphoid cell (ILC) development are important in understanding the pathophysiology of immune deficiencies and providing insights into the design of immunotherapies for patients with cancer, infection, and autoimmune disease. Currently, it is unclear where and how ILCs develop in humans. The overall goal of our study is to gain a comprehensive understanding of the cellular and molecular components that regulate human ILC development and function in order to best understand how they work in physiological and pathological states.	Co-expression
SRP156425	Transcriptomic analysis of the RPS3-regulated genes in HCC cell line	The human ribosomal protein S3 (RPS3), a component of the small 40S ribosomal subunit, is mainly involved in ribosomal maturation and initiation of translation through association with initiation factors. In this study, we firstly identified that RPS3 played an important role in HCC progression. We performed RNA sequencing to profile gene expression patterns before and after RPS3 knockdown. Overall design: SMMC-7721 cells were transfected with RPS3 siRNA or negative control, and overall transcriptomic changes were then examined by RNA sequencing, in duplicate, using Illumina Hiseq 2500 platform.	Co-expression
SRP156436	RNA-seq analysis of AKTi MK2206 resistant BT474 and T47D cells	BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a de-phosphorylation, nuclear translocation, and disrupts its association with SIRT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer. Overall design: Total RNA was extracted from MK2206 resistant cells for RNA sequencing. Parental cells without MK2206 resistance were used as controls.	Co-expression
SRP156443	Effects of rFVIIIFc on human macrophages	Immune responses in hemophilia A patients to replacement factor VIII can be either tolerogenic or immunogenic, the latter resulting in induction of non-neutralizing anti-factor VIII antibodies or neutralizing antibodies called inhibitors. Since these inhibitors render replacement FVIII treatment essentially ineffective, preventing or eliminating them are of top priority in disease management. The extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) is an approved therapy for hemophilia A patients. In addition, it has been reported that rFVIIIFc can induce tolerance to FVIII in hemophilia A patients that have developed inhibitors. Given that the IgG1 Fc region has the potential to interact with immune cells expressing Fc receptors and thereby affect the immune response to rFVIII, we investigated how human macrophages, expressing both Fc receptors and receptors reported to bind FVIII, respond to rFVIIIFc. We show herein that rFVIIIFc, but not rFVIII, uniquely skews macrophages towards an alternatively activated regulatory phenotype. rFVIIIFc initiates signaling events that result in morphological changes, as well as a specific gene expression and metabolic profile that is characteristic of the regulatory type Mox/M2-like macrophages. Further, these changes are dependent on rFVIIIFc-Fc receptor interactions. Our findings elucidate mechanisms of potential immunomodulatory properties of rFVIIIFc. Overall design: Human monocyte-derived macrophages (n=3) were treated with hIgG1, rFVIII or rFVIIIFc for 6h	Co-expression
SRP156444	Targeted, long-read RNA sequencing of non-coding genomic regions associated with neuropsychiatric functions.	The human brain is one of the last frontiers of biomedical research. Genome-wide association studies (GWAS) have succeeded in identifying thousands of haplotype blocks associated with a range of neuropsychiatric traits, including disorders such as schizophrenia, Alzheimer's and Parkinson's disease. However, the majority of single nucleotide polymorphisms (SNPs) that mark these haplotype blocks fall within non-coding regions of the genome, hindering their functional validation. While some of these GWAS loci may contain cis-acting regulatory DNA elements such as enhancers, we hypothesized that many are also transcribed into non-coding RNAs that are missing from publicly available transcriptome annotations. Here, we use targeted RNA capture ('RNA CaptureSeq') in combination with nanopore long-read cDNA sequencing to transcriptionally profile 1,023 haplotype blocks across the genome containing non-coding GWAS SNPs associated with neuropsychiatric traits, using post-mortem human brain tissue from three neurologically healthy donors. We find that the majority (62%) of targeted haplotype blocks, including 13% of intergenic blocks, are transcribed into novel, multi-exonic RNAs, most of which are not yet recorded in GENCODE annotations. We validated our findings with short-read RNA-seq, providing orthogonal confirmation of novel splice junctions and enabling a quantitative assessment of the long-read assemblies. Many novel transcripts are supported by independent evidence of transcription including cap analysis of gene expression (CAGE) data and epigenetic marks, and some show signs of potential functional roles. We present these transcriptomes as a preliminary atlas of non-coding transcription in human brain that can be used to connect neurological phenotypes with gene expression. Overall design: Targeted RNA capture of GWAS haplotype blocks associated with neuropsychiatric traits from four human brain regions (caudate, prefrontal cortex, primary visual cortex, superior colliculus). Following capture, samples were transcriptionally profiled using both long-read (Oxford Nanopore Technologies' PromethION) and short-read (Illumina's HiSeq 2500) RNA sequencing.	Co-expression
SRP156452	RNA-seq data	The immune system depends on a balanced interplay among a variety of specialized cell types transitioning between resting and stimulated states. While epigenome mapping efforts have focused on resting ex vivo immune cells, efforts to characterize stimulation-induced chromatin changes of diverse cell types has been limited. Thus, we collected ATAC-seq and RNA-seq data from immune cell types under resting and stimulated conditions from blood of healthy individuals, and cell types from fetal thymus samples. Overall design: 166 RNA-seq samples of 25 blood cell types from 8 healthy donors. * NOTE: The raw data of some Samples were updated on Jan 30, 2020. *	Co-expression
SRP156469	Comparative analysis of kidney organoid and adult human kidney single cell and single nucleus transcriptomes	We analyzed single cell transcriptomes over 80,000 cells isolated from 65 organoids differentiated from iPSCs and ESCs using two different protocols. We find that both protocols generate kidney organoids that contain a diverse range of kidney cells at differing ratios as well as non-renal cell types. We reconstructed lineage relationships during organoid differentiation through pseudotemporal ordering, and identified transcription factor networks associated with fate decisions. When comparing to adult human kidney, we  reveal immaturity of all kidney organoid cell types. These results define impressive kidney organoid cell diversity, identify incomplete differentiation as a major roadblock for current directed differentiation protocols and provide a human adult kidney snRNA-seq dataset against which to benchmark future progress. Overall design: Dropseq and 10X Chromium were used to profile organoid cells and adult kidney nuclei	Co-expression
SRP156474	Differential expression in wild-type and mutant neurofibroma and MPNST cell lines	Using RNA-seq we characterized gene expression changes occuring upon knockout of EZH2, EZH1, EZH1+EZH2 or SUZ12 in a neurofibroma cell line. We also investigated the transcriptional consequences of EZH1+EZH2 double knockout in a SUZ12-mutant MPNST cell line. Overall design: Examination of transcript abundance in wild-type and mutant ipNF05.5 or 88.14 cells. Two biological replicates were performed for wild-type and mutant ipNF05.5 cell lines. Three biological replicates were performed for wild-type and mutant 88.14 cell lines.	Co-expression
SRP156504	SKOV3 RBMS3 CLIP sequencing	RBMS3 is downregulated in various types of cancer, and they are associated with advanced tumor malignancy. For comprehensive understanding of the interaction between RBMS3 and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. RBMS3-binding RNAs were identified in a ovarian cancer cell line SKOV3 using flag-magnetic beads. The result shows that RBMS3 preferentially binds to DKK3, AXIN1, BACH1 and NFAT5 through AUAA binding motif, which is consistent with our previous results.	Co-expression
SRP156528	Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (RNA-seq)	Small cell carcinomas from different tissues exhibit transcriptional and epigenetic convergence and suggest common vulnerabilities for therapies Overall design: Convergent neuroendocrine cancer from distinct epithelial tissues	Co-expression
SRP156532	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [TF1_barcoding_scRNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. Overall design: A population of 25 transfected TF1 cells were expanded and forwarded to a combination of 1) ATAC-seq and single cell RNA-seq. The single-cell RNA-seq data are listed here. Meta data includes heteroplasmic variant information per cell as well as the group assigned based on the lentiviral barcoding	Co-expression
SRP156583	Transcriptome profiles of B cell subsets from healthy and SLE subjects	SLE is characterized by the production of autoantibodies that arise from the B cell lineage.  Therefore, we sought to assess the epigenetic and transcriptome profiles of distinct B cell subsets known to be expanded in SLE from healthy and SLE subjects.  These data define the differentiation heirarchy of B cell subsets and the epigenetic and transcriptional consequences of SLE on human B cells. Overall design: Five distinct B cell subsets were FACS isolated from a cohort of SLE and HC subjects.  For a subset of subjects, circulating Antibody Secreting Cells (ASC) were also isolated for comparisons.  Cells were FACS sorted into lysis buffer and RNA purified and transcriptome profiles determined by RNA-seq.	Co-expression
SRP156733	Long terminal repeat THE1B is a candidate enhancer for placenta-specific gene regulation [RNA-Seq]	The purpose of the study was to identify mRNA transcripts in human placenta that contained a THE1B element. Overall design: mRNA-seq from two human placentas with and without pre-amplification enrichment for THE1B-containing trancripts	Co-expression
SRP156757	Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis [AGO2-RIP-Seq -miRNAs]	Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA interacting protein immunoprecipitation with AGO2 for miR-124 target enrichment from neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124) and subsequent sequencing.	Co-expression
SRP156760	Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis [Timecourse RNA-Seq]	Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA profile for timecourse of neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124).	Co-expression
SRP156776	Genome-wide transcriptional analysis of human iPSC-derived healty control vs. schizophrenia cortical interneurons.	We report down-regulation of protocadeherins in schizophrenia interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Four independent iPS lines per group (total 8 iPSC lines) with three independent differentiations	Co-expression
SRP156784	Expanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6-thioguanisine	RNA-sequencing (RNA-seq) measures RNA abundance in a biological sample but does not provide temporal information about the sequenced RNAs. Metabolic labeling can be used to distinguish newly made RNAs from pre-existing RNAs. Mutations induced from chemical recoding of the hydrogen bonding pattern of the metabolic label can reveal which RNAs are new in the context of a sequencing experiment. These nucleotide recoding strategies have been developed for a single uridine analogue, 4-thiouridine (s4U), limiting the scope of these experiments. Here we report expansion of TimeLapse sequencing (TimeLapse-seq) to the guanosine analogue, 6-thioguanosine (s6G), which can be recoded under RNA-friendly nucleophilic-aromatic substitution conditions to produce adenine analogues (substituted 2-aminoadenosines). We demonstrate the first use of s6G recoding experiments to reveal transcriptome-wide RNA population dynamics. Overall design: Distinguishing newly made from preexising RNA using RNA-sequencing of 6-thioguanosine containing RNA, which was subjected to TimeLapse chemistry to induce G to A mutations in newly-made RNA.	Co-expression
SRP156880	Homo sapiens Transcriptome or Gene expression	Cervical cancer cell line C33A	Co-expression
SRP156923	Oncogenic Ras Interactome RNA Sequencing	RNA sequencing of target protein knockdown and overexpression to examine transcriptional impacts.	Co-expression
SRP157044	Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [RNA-Seq]	Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conduct single-cell RNA- sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Intercellular heterogeneity of gene expression programs within each tumor was variable and largely correlated with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation was predictive of long-term outcomes for TNBC patients in a large patient cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease. Overall design: Single cell RNA sequencing of 1,534 cells in six fresh triple negative breast cancer tumors.	Co-expression
SRP157215	Heterogeneity of Androgen Receptor Splice Variant-7 (AR-V7) Protein Expression and Response to Therapy in Castration Resistant Prostate Cancer (CRPC)	Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival (OS) from endocrine therapies in castration resistant prostate cancer (CRPC). However, these studies provide little information pertaining to AR-V7 biology and expression in prostate cancer (PC) tissue. Following generation and validation of a novel AR-V7 antibody for immunohistochemistry (IHC); nuclear AR-V7 protein expression was determined for 358 primary prostate samples (358 patients) and 293 metastatic biopsies (194 patients). Associations with disease progression, nuclear AR full length (AR-FL) expression, response to abiraterone and/or enzalutamide, and gene signatures (from three independent cohorts) was determined. Overall design: RNA sequencing of metastases from individuals with castration resistant prostate cancer (CRPC) using Illumina HiSeq 2500.	Co-expression
SRP157582	The Estrogen Receptor variants ß2 and ß5 Induce Stem Cell Characteristics and Chemotherapy Resistance in Prostate Cancer through activation of Hypoxic Signaling	Chemotherapy resistant prostate cancer is a major clinical problem. When the prostate cancer has become androgen deprivation resistant, one of the few treatment regimens left is chemotherapy. There is a strong connection between a cancer's stem cell like characteristics and drug resistance. By performing RNA-seq we observed several factors associated with stem cells being strongly up-regulated by the estrogen receptor ß variants, ß2 and ß5. In addition, most of these factors were also up-regulated by hypoxia. One mechanism of chemotherapy resistance was expression of the hypoxia-regulated, drug transporter genes, where especially ABCG2 and MDR1 were shown to be expressed in recurrent prostate cancer and to cause chemotherapy resistance by efficiently transporting drugs like docetaxel out of the cells. Another mechanism was expression of the hypoxia-regulated notch3 gene, which causes chemotherapy resistance in urothelial carcinoma, although the mechanism is unknown. It is well known that hypoxic signaling is involved in increasing chemotherapy resistance. Regulation of the hypoxic factors, HIF-1a and HIF-2a is very complex and extends far beyond hypoxia itself. We have recently shown that two of the estrogen receptor ß variants, estrogen receptor ß2 and ß5, bind to and stabilize both HIF-1a and HIF-2a proteins leading to expression of HIF target genes. This study suggests that increased expression of the estrogen receptor ß variants, ß2 and ß5, could be involved in development of a cancer's stem cell characteristics and chemotherapy resistance, indicating that targeting these factors could prevent or reverse chemotherapy resistance and cancer stem cell expansion. Overall design: Examination of the transcriptome changed by two estrogen reseptor beta variants (ERbeta2 and ERbeta5). Control (lacking expression) and  variant expressing cells in two repeats	Co-expression
SRP157585	Comparative Transcriptomics Unravels Prodigiosin's Potential Cancer-Specific Activity Between Human Small Airway Epithelial Cells and Lung Adenocarcinoma Cells	Objective: Non-small cell lung cancer (NSCLC) is extremely lethal upon metastasis and requires safe and effective systemic therapies to improve a patient's prognosis. Prodigiosin (PG) appears to selectively and effectively target cancer but not healthy cells. However, PG's cancer-specific activity has remained elusive until recently. Methods: PG's cancer-specific performance was compared to Docetaxel (DTX), Paclitaxel (PTX), and Doxorubicin (DOX) against human lung adenocarcinoma (A549) and human small airway epithelial cells (HSAEC). Combination of PG with DTX, PTX, or DOX in a 1:1 ED50 ratio was also evaluated. MTT assay was used to determine the post-treatment cell viability. RNA-sequencing was used for comparative transcriptomics analysis between A549 and HSAEC treated with 1.0µM PG for 24 h. Results: PG reduced A549 cell viability by four-folds greater than HSAEC. In comparison to DTX, PTX and DOX, PG was ~1.7 times more toxic toward A549, and 2.5 times more protective toward HSAEC. Combination of PG in 1:1 ED50 ratio with DTX, PTX, or DOX failed to exhibit synergistic toxicity toward A549 or protection toward HSAEC. In A549, genes associated in DNA replication were downregulated, while genes directly or indirectly associated in lipid and cholesterol biogenesis were upregulated. In HSAEC, co-upregulation of oncogenic and tumor suppressive genes was observed. Conclusion: An overactive lipid and cholesterol biogenesis could have caused A549's autophagy while a balancing-act between genes of oncogenic and tumor-suppressive nature could have conferred HSAEC heightened survival. Overall, PG appears to be a smart chemotherapeutic agent that may be both safe and effective for NSCLC patients. Overall design: HSAEC, A549 and HCT116 cells derived from American Type Culture Collection (ATCC) were subjected to 1.0µM PG treatment for 24 hours in vitro (biological triplicates). Total RNA was extracted and mRNA was purified with the Illumina® TruSeq® Stranded messenger RNA Sample Prep Kit. The library preparation output which was cDNA fragments were paired-end sequenced at read lengths of 100 nucleotides via the Illumina® HiSeq 2500 (Illumina) platform.	Co-expression
SRP157750	RNA-Seq of osteosarcoma cell lines	The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma.  While the precise mechanisms underlying the ALT pathway are unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3, correlate with ALT status. ATRX and DAXX facilitate deposition of the histone variant H3.3 within heterochromatic regions including the telomere suggesting that loss of ATRX, DAXX, and/or H3.3 lead to defects in heterochromatin maintenance at telomeres, ultimately contributing to ALT activity.  Previous studies have detected genetic mutations in ATRX, DAXX, and H3.3 in ALT cell lines and tumor samples. However, a subset of ALT samples show loss of ATRX or DAXX protein expression or localization without evidence of genetic alterations, indicating a role for other defects in ATRX/DAXX/H3.3 function. Here, using Next Generation Sequencing, we identified a novel gene fusion event between DAXX and the kinesin motor protein, KIFC3, which leads to the translation of a chimeric DAXX-KIFC3 fusion protein.  Here, we demonstrate that the fusion of KIFC3 to DAXX leads to defects in DAXX function and likely perpetuates ALT activity.  These data highlight a previously unrecognized mechanism of DAXX inactivation in ALT positive osteosarcoma and provide rationale for thorough and comprehensive analyses of ATRX/DAXX/H3.3 proteins in ALT positive cancers. Overall design: 13 cell lines sequenced in triplicate, totaling 39 sequencing samples	Co-expression
SRP157753	Transcriptomic analysis of trametinib-resistant HCT116 colorectal carcinoma cells compared to the parental control cells	HCT116 cells were treated with with increasing concentrations of trametinib over 2 months. Drug-resistant clones emerged and were cultured in the presence of 30 nmol/L trametinib. These cells exhibited a greater than 10-fold increase in the GI50 for trametinib compared to the parental cell line. RNA-seq of the resistant clone HCT116_R4 versus the parental cells identified differentially expressed genes potentially involved in resistance. Overall design: For the parental and resistant clone, 3 replicates each were analysed by RNA-seq.	Co-expression
SRP157910	Genome wide expression change by RNF168 knocking down in NEC cells	We aim to the investigate the role of RNF168 in breast cancer progression. NEC cells were used as the model and RNF168 was silenced by siRNA. Overall design: The NEC cells were treated with 50nM stramble siRNA and siSMURF1. After 48 hours, cells were harvested and the total RNA was extacted by Qiagen kit. The RNA sample was sent to BGI for RNA expression anaylsis.	Co-expression
SRP157918	Quantitative Analysis of p53 and/or TGFBR2 Knockdown Endothelial Transcriptomes after Irradiation	Transcriptional profiling p53 or TGFBR2 knockdown HUVECs with or without irradiation. Overall design: mRNA profiles of control, p53 knockdown, TGFBR2 knockdown, and p53+TGFBR2 knockdown endothelial cells with or without irradiation were generated by deep sequencing using Illumina HiSeq 2500. HUVEC cells were collected 48 hrs post-irradiation. Two biological replicates for each condition were pooled together and sequenced.	Co-expression
SRP157936	Transcriptomic analysis of T84 colon carcinoma cell line treated with trametinib, JQ1 or their combination	T84 cells were treated with DMSO, 30nM trametinib (MEKi), 1µM JQ1 (BRD4i) or the combination of trametinib and JQ1 (combo) for 24h. Overall design: 3 replicates per condition were analyzed by RNA-seq.	Co-expression
SRP157946	RNA-seq of cholesterol treated PC-3 cells	This study goal is to obtain the different expression genes induced by cholesterol.	Co-expression
SRP157976	Acetyl-CoA carboxylase inhibition regulates microtubule dynamics and intracellular transport in cystic fibrosis epithelial cells	In this study, we hypothesize that acetyl CoA carboxylase (ACC) is an important intermediate in Cystic fibrosis (CF) inflammatory signaling cascade.  Here, we demonstrate that ACC inhibition mimics the cellular effects of ibuprofen promoting both redistribution of intracellular cholesterol and increased rates of microtubule reformation, while decreasing RhoA expression in CF epithelial cell models.  Inhibiting ACC polymerization with citrate increases RhoA expression and decreases microtubule reformation rates in wild-type epithelial cells, suggesting pro-inflammatory signaling.  Together, these findings demonstrate a novel mechanism of high-dose ibuprofen efficacy and point to a potential new therapeutic target for anti-inflammatory drugs in CF. Overall design: Compare broader impact of ACC inhibition on TOFA-treated (5-(Tetradecyloxy-2-furoic acid) CF HNE cells	Co-expression
SRP158109	Next Generation Sequencing of ovarian CA-MSC & MSC Transcriptomes	Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes,  promote tumor cell growth,  increase cancer 'stemness' and  chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression.  Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs.    Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation.  Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes,  promote tumor cell growth,  increase cancer 'stemness' and  chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression.  Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs.    Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Overall design: mRNA profiles of 4 normal omental MSCs and 10 ovarian CA-MSCs using Illumina TruSeq RNA Sample Preparation kit and Illumina HiSeq 100bp PE sequencing.	Co-expression
SRP158121	A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells [RNA-Seq]	Self-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. We use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm. Overall design: examine gene expression changes in ZNF207 knock down hESCs	Co-expression
SRP158127	RNAseq of unstimulated human neutrophil granulocytes.	Human neutrophils were isolated with negative selection (Miltenyi MacsXpress, purity > 99%) from fresh venous blood. RNA was isolated directly after without stimulating the cells. Overall design: Neutrophil transcriptome in the unstimulated cell.	Co-expression
SRP158196	AmpliSeq Transcriptome Analysis of cells stimulated with polyIC in presence of GFP or NS5 protein	We compared polyIC stimulated cells in the presence of either GFP or NS5 protein Overall design: A549 cells presence with GFP- or NS5-expressing plasmid using Polyjet (Signagen) according to manufacturer instructions, and 30 hours later stimulated with polyIC (Tocris) as previously described (Marazzi et al., 2012). At 12 hours post-stimulation, total cellular RNA was purified by RNeasy column (Qiagen).	Co-expression
SRP158284	Repeat-selective screening identifies microtubule inhibitors that reduce toxic CUG RNA	Myotonic dystrophy type 1 (DM1) is the most common adult onset muscular dystrophy. It is caused by a CTG microsatellite expansion in the DMPK gene. Transcription of the CTG repeats gives rise to CUG repeat RNA with a toxic gain-of-function. The toxic CUG RNA sequesters the muscleblind-like (MBNL) family of RNA-binding proteins and disrupts their normal cellular function causing global mis-regulation of RNA processing. We carried out unbiased chemical screening to identify compounds that selectively reduce toxic CUG RNA levels leading to the identification of multiple microtubule inhibitors. Colchicine, and FDA-approved microtubule destabilizing agent was used to treat patient-derived myotubes and the HSALR DM1 transgenic mouse model. Colchicine treatment selectively reduced toxic RNA levels and partially rescued mis-splicing of multiple MBNL-dependent pre-mRNA events with minimal off-target effects on gene expression.	Co-expression
SRP158293	Phosphorylation of SRSF1 at Tyr-19 promotes cell proliferation in pediatric acute lymphoblastic leukemia	we identified for the first time that the phosphorylation state of SRSF1 is linked to different phases in ALL. Our results underscore the phosphorylation of SRSF1 at the Tyr-19 residue disrupts subcellular localization of SRSF1 and promotes cell proliferation in leukemic cells by accelerating cell-cycle progression. Targeting Tie2 kinase is able to catalyze Tyr-19 phosphorylation of SRSF1, and offer a promising therapeutic target for the treatment of pediatric ALL. These findings undoubtedly add a new layer in understanding of how post-translational mechanism supports leukemia progression. Overall design: The mRNA profiles of stable leukemic cell line overexpressed wild-type SRSF1, mutants (SRSF1-Y19D or SRSF1-Y19F) or the empty vector were generated by deep sequencing using Illumina  HiSeq 4000 platform	Co-expression
SRP158325	Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study [bulk]	Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounds such as passaging effects and progenitor storage. Single cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility. Overall design: RNAseq profiles of 57 bulk Human iPSC-Derived Neurons differentiated across five laboratories were generated in triplicates at two different time points and sequenced on 1 lane of HiSeq4000 at 75bp paired end. RNAseq profiles of .... single cells extracted from 2 of the 5 laboratories at the later time point were isolated by FACS onto 96-well plates and sequenced on 1 lane of HiSeq4000 at 75bp paired end.	Co-expression
SRP158328	Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200	RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease. Overall design: Gene expression profiling of Pol III transcripts in control and POLR3A-mutated cell lines (HEK293 and MO3.13) using RNA-seq and small RNA-seq; ChIP-seq of FLAG-tagged POLR3A-WT and mutated POLR3A-M852V	Co-expression
SRP158338	Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high-throughput sequencing	Circular RNAs (circRNA) are special non-coding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs. They can regulate target gene mRNA expression and play important roles in many biological processes. However, expression profile and function of circRNAs in human TSCC haven't been reported. High-throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues. A separate set (n=20) of human TSCCs and corresponding adjacent tissues were subjected to RT-PCR for validation of circular RNAs expression profile. GO functional analysis, KEGG pathway analysis, and circRNA–microRNA network analysis were also performed to predict the function of circRNA in TSCC.A total of 12,156 circRNAs were identified and annotated, most of the circRNAs were novel (n=6,231) and exonic (62.09%). Statistical analysis revealed 322 differentially expressed (DE) circRNAs. RT-PCR results showed that circRNA expression in TSCC was higher than that in adjacent tissues. GO functional analysis, KEGG pathway analysis, and circRNA–microRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain extent. The present study is the first to systematically characterize and annotate circRNA expression in TSCC, the majority were novel circRNAs. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor-relevant microRNAs, indicating that circRNAs might be promoted development and progression of  TSCC. Overall design: High-throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues.	Co-expression
SRP158380	Transcriptome-wide analysis of adipose circular RNAs reveals their dynamic regulation in obesity and functional role in adipogenesis	Non-coding RNAs are emerging as novel regulators in adipocyte differentiation and function. Circular RNAs (circRNAs) are a new class of non-coding transcripts generated across all eukaryotic tissues, but their function in adipose biology remains unknown. Here we perform deep sequencing of visceral and subcutaneous fat to discover thousands of adipose circRNAs, many of which are species-conserved, tissue-specific and dynamically regulated during adipogenesis and obesity. We identified circTshz2-1 and circArhgap5-2 as indispensable regulators of adipogenesis in vitro. To characterize the function of circRNAs in vivo, we injected adenoviral shRNA targeting circArhgap5-2 into mouse inguinal tissue and found that the expression of this circRNA was essential in maintaining the global adipocyte transcriptional programme involved in lipid biosynthesis and metabolism. Furthermore, we demonstrated that the pro-adipogenic function of circArhgap5-2 is conserved in human adipocytes. Our results provide important evidence that circRNAs serve as important regulators in adipocyte differentiation and metabolism. Overall design: Discovery of circular RNA in adipocytes using RNA-seq	Co-expression
SRP158392	UGDH knockdown in MDA-MB-231	Transcriptome profiling (RNA-Seq) to evaluate the connection the metabolic enzyme UGDH on gene expression. The RNA libraries were prepared and sequenced at University of Houston Seq-N-Edit Core per protocols. Total libraries were prepared with Ovation® Universal Plus mRNA-Seq (NuGen) using 200 ng input RNA. The size selection for libraries were performed using SPRIselect beads (Beckman Coulter) and purity of the libraries were analyzed using the High Sensitivity DNA chip on Bioanalyzer 2100 (Agilent). The prepared libraries pooled and sequenced using NextSeq 500 (Illumina), generating ~15 million 2×76 bp paired-end reads per samples. The RNA-seq raw fastq data were processed with RNA-Seq Express app within the Illumina BaseSpace app suite (www.basespace.illumina.com), which performed alignment with STAR aligner, assignment of aligned reads to genes, and differential gene expression with DESeq2 Analysis was performed comparing controls (shNT) against individual knockdowns (shU1 or shU2). Then, results from both analyses were compared for the intersection to identify commonly altered genes. Overall design: mRNA profiles of MDA-MB-231 cells carrying either a control shRNA (shNT) or one of two independent shRNAs targeting UGDH (shUGDH-1, shUGDH-2) were generated by deep sequencing, in triplicate, using Illumina NextSeq 500.	Co-expression
SRP158414	ISG knockdown effects on gene expression	Inteferon induced gene effects on cell gene expression	Co-expression
SRP158425	Assessment of a highly multiplexed RNA sequencing platform and comparison to existing high-throughput gene expression profiling techniques [3pDGE]	In this study, we report the performance of one such technique denoted as sparse full length sequencing (SFL), a ribosomal RNA depletion-based RNA sequencing approach that allows for the simultaneous sequencing of 96 samples and higher.  We offer comparisons to well established single-sample techniques, including: full coverage Poly-A capture RNA-seq and microarray, as well as another low-cost highly multiplexed technique known as 3' digital gene expression (3' DGE). Data was generated for a set of exposure experiments on immortalized human lung epithelial (AALE) cells in a two-by-two study design, in which samples received both genetic and chemical perturbations of known oncogenes/tumor suppressors and lung carcinogens.  SFL demonstrated improved performance over 3' DGE in terms of coverage, power to detect differential gene expression, and biological recapitulation of patterns of differential gene expression from in vivo lung cancer mutation signatures. Overall design: 3' Digital Gene Expression (3'DGE) for immortalized human bronchial epithelial cells (AALE) exposed to chemical and genotypic perturbations	Co-expression
SRP158433	Comparative analysis of mesenchymal stem cells derived from amniotic membrane, umbilical cord and chorionic plate under serum-free condition	We performed RNA-Seq and identified the differnetially expressed gene information among human AM-MSC, UC-MSC, and CP-MSC(or named P-MSC). Overall design: mRNA profiles of  AM-MSC, UC-MSC, and CP-MSC from four individual donors were generated by deep sequencing.	Co-expression
SRP158445	Next-generation sequencing of control (scramble) and Myo1c knockdown human podocytes, with and without TGF-ß treatment	Purpose: Next-generation sequencing (NGS) was used to identify cellular pathways and genes through systems-based analysis. The goals of this study are to identify NGS-derived transcriptome profiling (RNA-seq) in control and Myo1c knockdown human podocytes upon TGFß stimulation. These high-throughput data were further validated through qRT–PCR methods to confirm the cellular pathways and genes affected due to genetic knockdown of Myo1c and TGF-ß stimulation. Methods: Human control and Myo1c knockdown podocytes were differentiated for 14 days by thermoswitching from 33°C to 37°C and removal of growth factors, insulin-transferrin-selenium from the medium. These podocytes were incubated overnight in RPMI medium with 0.1% FBS and stimulated with 5ng/ml of TGF-ß in the same medium for a period of 48 hours. Control and TGF-ß stimulated podocytes were processed for RNA isolation and submitted to Novogene for RNA-Seq. All the experiments were performed in triplicates. Conclusions: Our study is first to describe the detailed analysis of TGF-ß stimulated Myo1c knockdown podocyte transcriptomes using the RNA-seq technology. A comparative analysis of the differential expression profile was obtained between control vs. Myo1c knockdown podocytes, and control vs. Myo1c knockdown podocytes that were stimulated with TGF-ß. Complex genetic network and genes effected due to Myo1c knockdown and TGF-ß stimulation will provide a platform to define biological pathways in podocytes where Myo1c participates. Overall design: Human podocytes mRNA profiles in control (scramble) and Myo1c knockdown cells were generated by deep sequencing, in triplicate, using Illumina. Contributor: Novogene Corporation	Co-expression
SRP158480	Identification of grade and origin specific cell populations in serous epithelial ovarian cancer by single cell RNA-seq	Here we investigated different cell populations within ovarian cancer using single-cell RNA seq: fourteen samples from nine patients with differing grades (high grade, low grade and benign) as well as different origin sites (primary and metastatic tumor site, ovarian in origin and fallopian in origin). Overall design: Examination of cellular heterogeneity of primary and metastatic tumor samples from nine patients with differing stage of serous epithelial ovarian cancer.	Co-expression
SRP158491	Gene expressions of T cells in each developmental stages in healthy volunteers and patients with rheumatoid arthritis	We collected and compared samples from the cohort consisted of six groups as follows: methotrexate (MTX) monotherapy, combination therapy of MTX and infliximab (IFX), tocilizumab (TCZ) monotherapy, age- and gender-matched HC, and a small number of synovial fluid samples. In order to reduce variation due to the proportion of cells at each developmental stage, we performed transcriptome analysis after sorting CD4+ and CD8+ T cells according to developmental stage. We created a gene list that was significantly expressed in RA T cells, and revealed that pathways such as mTORC1, IL-2-stat5, Cell cycle and interferon-related genes were significantly enriched among them. Overall design: Examination among healthy controls and patients with rheumatoid arthritis, including before and after treatment	Co-expression
SRP158502	Transcriptomes of activated naïve CD4 T cells from young and older individuals	The goal of this study was to identify age-associated differences in T cell responses. Naïve CD4 T cells isolated from healthy young and older individuals were activated with anti-CD3/CD28 beads for 5 days. Libraries were prepared using the Ovation Human FFPE RNA-Seq Library Systems (NuGEN) and sequenced on an Illumina NextSeq 500.	Co-expression
SRP158524	Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation I	The transcriptional profile of A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs) Overall design: A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs)	Co-expression
SRP158525	Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation II	The transcriptional profile of A673 parental,  and SP-2509 drug resistant washout cells (4 and 6 months) Overall design: Following generation of A673 SP-2509 drug resistant cells (chronic exposure for 7 months), drug was withdrawn with cell pellets collected 4 and 6 months after removal.	Co-expression
SRP158544	Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [RNA-seq]	Purpose: LMNA-DCM accounts for 5-10% of DCM cases and has an age-related penetrance whose onset typically appears between the ages of 30 and 40. However, the precise mechanisms linking the LMNA mutation to increased arrhythmogenicity are still unknown. Methods: We utilized human iPSC-CMs RNA-seq, ChIP-seq, and ATAC-seq technologies. Results: The electrophysiological studies of iPSC-CMs identify the LMNA mutation as a cause of increased arrhythmogenicity in mutant iPSC-CMs through abnormal calcium homeostasis. We find that the mutations in LMNA disrupt the global chromatin conformation, resulting in hyper-activation of the platelet-derived growth factor (PDGF) signaling pathway in LMNA-mutant iPSC-CMs. Inhibition of the PDGF signaling pathway can rescue the arrhythmic phenotype of mutant iPSC-CMs. Conclusions: These findings were corroborated in cardiac tissues from healthy and LMNA-DCM patients, thus confirming a novel mechanism of LMNA-DCM pathogenesis both in vitro and in vivo. Overall design: RNA-seq of iPSC-CMs.	Co-expression
SRP158590	Molecular Signatures of Multiple Myeloma Progression through Single Cell RNA-Seq	Multiple myeloma (MM) is a malignant plasma cell disorder with well-defined clonal genetic/cytogenetic abnormalities.  However, cellular heterogeneity is a key factor in MM's progression, therapeutic decision, and response to treatment. Single cell whole transcriptome profiling (scRNA-Seq) offers an opportunity to dissect this molecular heterogeneity during MM progression to better understand the disease and guide rational therapy.  Here, we examined 597 CD138 positive cells from 15 patients at different stages of MM progression using scRNA-Seq.  We selected 790 genes based on a Coefficient of Variation (CV) approach which organized cells into four clusters (L1-L4) based on unsupervised clustering. Plasma cells from each patient contained a mixed population of plasma cells at different state of aggressiveness based on gene expression signature reflecting the inter-cellular heterogeneous nature of MM.  Cells in the L1 group is characterized by low level expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathway having most cells from MGUS patients (p < 1.2x10-14).  In contrast, low level of these genes in L1 group increased progressively and were the highest in the L4 group containing only cells from high-risk MM patients with t(4;14) translocations.   Furthermore, 44 genes consistently overexpressed by pair-wised comparisons of the four groups strongly associated with a reduced overall survival in MM patients (APEX trial, p < 0.0001; Hazard Ratio (HR), 1.83; 95% CI, 1.33 to 2.52), particularly those in the bortezomib treated group (p < 0.0001; HR, 2.00; 95% CI, 1.39 to 2.89).  No survival significance was observed for the dexamethasone treated group.   Our study at the resolution of single cells showed that there is a mixed population of cells in each patient at different stages of MM progression and these cells can be organized into four different subgroups (L1 to L4).  Consistent overexpression of the 44 genes from L1 to L4 groups is associated with patient outcome and treatment response.  Our results show that oxidative phosphorylation, Myc target, and mTORC1 signaling genes are significant pathways for MM progression and affect MM prognosis and treatment stratification. Overall design: 597 single cell libraries passed QC and were included in the downstream analysis	Co-expression
SRP158607	ATO treatment on mesenchymal stem cells (MSCs) interacting breast cancer cells	Based on next generation RNA-seq, we examed Arsenic trioxide treatment (ATO) effect on MSCs-interacting MCF7 cells in 3D cultures. We found gap junction protein Cx43 is dramatically downregulated after ATO treatment.. Overall design: human breast cancer cell line MCF-7 cells cocultured with mouse MSCs in 3D culture, with or without ATO treatment, are subject to NGS and then analyzed.	Co-expression
SRP158622	Flura-seq identifies organ-specific adaptations in metastasis-initiating cells	Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics.  We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with unprecedented sensitivity.  Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, covalently labeling nascent RNA for purification and sequencing. Flura-seq revealed that breast cancer micrometastases in lung and brain exhibit unique, reversible gene signatures depending on the microenvironment. Specifically, the mitochondrial electron transport Complex I and the NRF2-driven antioxidant programs were induced in oxygen-rich pulmonary micrometastases, compared to mammary tumors or brain micrometastases. Loss of Complex I activity, and antioxidant supplementation potentiated pulmonary metastatic growth. We confirm lung metastasis-specific NRF2 overexpression in clinical samples, thus validating Flura-seq's utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research. Overall design: Examination of 5-FU labeled RNAs in cancer cells present in different organs	Co-expression
SRP158623	Expression profiling of NRAS knockout in embryonal rhabdomyosarcoma (ERMS) cells	Targeted disruption of NRAS was performed in a stable 381T ERMS cell line harboring tamoxifen inducible CRISPR/Cas9 gRNA against NRAS Overall design: RNA sequencing was performed using RNA extracted from uninduced control 381T ERMS cells as well as tamoxifen (TAM)-induced ERMS cells with NRAS CRISPR/Cas9-mediated knockout. Each in 3 biological replicates.	Co-expression
SRP158625	Sequencing of polysome-associated mRNA in VSV infected HeLa cells	Infection of mammalian cells with vesicular stomatitis virus (VSV) results in the inhibition of cellular gene expression. This host shut-off is achieved through viral mediated inhibition of cellular gene expression at multiple levels including transcription, mRNP nuclear-cytoplasmic export, and translation. To interrogate the effects of VSV infection on translation, we infected HeLa cells at MOI 10 for 2 or 6 hours and performed polysome profiling and deep sequenced total cytoplasmic mRNA as well as monosome- and polysome-associated mRNAs. Our data support a model where viral mRNA abundance contributes to host shut-off by dominating the pool of cytoplasmic mRNA.	Co-expression
SRP158649	RNA-Seq of meibomian gland carcinoma	Pro?ling and functional analysis of mRNAs and long non-coding RNAs (lncRNAs) in Meibomian gland carcinoma (MGC), the most common ocular SGC, has not yet been studied. Therefore, we used RNA-Seq, gene ontology (GO), ClueGO, Ingenuity Pathway Analysis and co-expression network analyses to pro?le the expression and regulation patterns of lncRNAs and mRNA in MGC.	Co-expression
SRP158659	A novel CD4+ T cell population expanded in SLE blood provides B cell help through IL10 and succinate	A better understanding of the mechanisms involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR5- CXCR3+ PD1hi CD4+ T cell 'helper' population distinct from follicular helper T cells (Tfh) and expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFN??and high levels of IL10. Additionally, they accumulate high amounts of mitochondrial ROS (mtROS) as the result of reverse electron transport (RET) fueled by succinate.  These cells provide potent help to B cells through the synergistic effect of IL10 and succinate. Cells with similar phenotype and function are generated in vitro upon priming naïve CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)-activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 9 total samples; 3 groups of 3 biological replicates: control group Th0, co-culture group CpGA-pDC, and co-culture group Ox mtDNA-pDC	Co-expression
SRP158689	Influence of miR-21-regulated pathways on T cell responses	The goal of this study was to examine how miR-21 upregulation influences T cell responses. miR-21 was antagonized by lentiviral overexpression of anti-sense miR-21 during activation of naive CD4 T cells from healthy adults. On day 5 after activation, libraries of miR-21 high and miR-21 low cells were prepared using the Ovation Human FFPE RNA-Seq Library Systems (NuGEN) and sequenced on an Illumina HiSeq 2500.	Co-expression
SRP158704	Comparative analysis of WT and ZEB1 KO cells in different stages during differentiation	We performed RNA-Seq and identified the differnetially expressed gene information among WT and ZEB1 KO cells Overall design: mRNA profiles between 2 cell types during differentiation	Co-expression
SRP158717	Expression alterations induced by restoration of AXIN1 expression in SNU449 hepatocellular carcinoma cells	Aberrant activation of Wnt/ß-catenin signaling is observed in numerous cancers. In hepatocellular carcinoma activating mutations in CTNNB1 (20-25%) or loss of function mutations in AXIN1 (10%), AXIN2 (2%) and APC (1-2%) are observed. All these mutations lead to aberrant stabilization of ß-catenin, which constitutively activates downstream Wnt/ß-catenin target genes and triggers a genetic program resulting in tumor formation. However, in relation to AXIN1 mutations some reports have challenged whether these indeed result in tumor growth by enhancing ß-catenin signaling (e.g. PMID: 16964294, 29525529). Several alternative pathways have also been linked to AXIN1 (ENSG00000103126), such as TGFß, SAPK/JNK, p53, YAP/TAZ and c-myc. To identify which one of these or other unknown signaling routes are linked to AXIN1, using CRISPR-Cas9 genome editing, we have successfully repaired the homozygous p.R712* AXIN1 mutation present in the SNU449 hepatocellular carcinoma cell line. Next, using RNA sequencing the RNA expression patterns of 3 independent repaired clones were compared with 3 clones retaining the AXIN1 mutation. Surprisingly, only 5 genes were significantly altered in the repaired clones, among which AXIN2, a well-established ß-catenin target gene. Thus, this analysis leads to the surprising observation that a commonly observed mutation in a hepatocellular tumor suppressor gene, is associated with minimal alterations in gene expression, at least in the SNU449 cell line. Overall design: Comparison of 3 independent repaired SNU449 clones with 3 clones retaining the AXIN1 mutation	Co-expression
SRP158719	RNA sequencing of RPA KO cells	The goal of this study was to identify transcriptomic differences in A549 lung cancer cell line following knockout of the RPA1 gene. A549 cells, and many lung tumors, carry constitutive NRF2 activation. Understanding how RPA1 modulates transcription, particularly NRF2-mediated transcription, is relevant for future cancer therapeutics.	Co-expression
SRP158730	Separation of breast cancer and organ microenvironment transcriptomes in metastases	The seed-and-soil hypothesis was described over a century ago to describe why cancer cells (seeds) grow in certain organs (soil). Since then, the genetic properties that define the cancer cells have been heavily investigated, however, the genetic mediators within the organ microenvironment that mediate successful metastatic growth are less understood. In these studies, a set of human breast cancer patient-derived xenograft (PDX) metastasis models were utilized. Mammary tumors and metastases to the liver, lung, and brain were RNA-sequenced with the goal of identifying complementary cancer and organ-specific genetic properties that mediate metastatic growth. During metastatic growth of PDXs, the genetic changes that occurred in the liver and lung microenvironment were more consistent and higher in magnitude than the cancer cell transcriptomes . Integration of the liver microenvironment gene signature into genetic data from liver metastasis autopsy samples or fine-needle aspirates revealed the contribution of the microenvironment to the metastatic transcriptome. These insights identify cancer and organ-specific genetic drivers  of metastasis. Overall design: Mammary tumors and metastases to the liver, lung, and brain were RNA-sequenced with the goal of identifying complementary cancer and organ-specific genetic properties that mediate metastatic growth.	Co-expression
SRP158762	Effect for target mRNA degradation by methylated microRNAs	To confirme the function of methylated micro RNAs (miR-17 and let-7a), we transfected methylated or non-methylated microRNAs to DICER KO HCT116 cell line. mRNA were isolated at 48 houes after transfection. This data show that the function were different between methylated or non-methylated microRNAs. Overall design: Methyated or non-methyated microRNAs were transfected in dicer KO HCT116 cell lines.	Co-expression
SRP158772	A novel long non-coding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1	Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown.  By using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull down-mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer.Together, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy. Overall design: RNA-seq analysis of HOXC-AS3 and YBX1 knockdown in one cell type	Co-expression
SRP158776	RNA sequencing of FHR1-treated human monocytes	The plasma protein FHR1 induces release of inflammatory cytokines IL-1ß, IL-6, IL-18 or TNFa from blood-derived human monocytes. RNA sequencing was performed from RNA of BSA- or FHR1-treated monocytes from 4 different donors. In response to FHR1, 522 monocytic genes were upregulated (gene ontology enrichment analysis), including 35 inflammation related genes, e.g. TNF. Also, G protein-coupled receptors such as EMR2/ADGRE2 were upregulated in response to FHR1. Overall design: Blood-derived monocytes were treated with BSA or FHR1, after 4h RNA was isolated. RNA of 4 donors were combined and sequenced.	Co-expression
SRP158789	Induction of Apoptosis in human hepatoma cells by BCP &PC mutant of geenotype D1 hepatitis B virus	RNA seq of WT and BCP&amp;PC mutant of HBV infected Hepatoma cells (HepG2) using Illumina 2500	Co-expression
SRP158794	Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny	We report here the multi-omics analysis of esthesioneuroblastomas, which is a rare cancer arising from the olfactory bulb. We discovered ENB can be grouped in two subtypes, namely basal and neural ENBs. We also uncovered high rates of mutations (~35%) in basal ENB subgroup. Overall design: We report here the multi-omics analysis of esthesioneuroblastomas using whole-exome sequencing (n=27), RNA sequencing (n=19) and DNA methylation profiling (n=26).	Co-expression
SRP158826	Type 3 inflammation drives liver fibrosis by enhancing TGF-beta signaling through activation of MAPKS	Type 3 inflammation characterized by increased production of IL-22 is a common driver of liver fibrosis during chronic liver injury through enhancement of TGF-ß signaling in a p38 MAPK dependent manner. Overall design: Three lots of human primary hepatitic stellate cells. Each lot was stimulated for 48h with either PBS, TGFlo (0.1ng/mL), TGFhi (2,5ng/mL), IL-17A (40ng/mL), IL-17A + TGFlo, IL-22 (40ng/mL) or IL-22 + TGFlo. Each lot comes from a single donor.	Co-expression
SRP158866	Transcriptome characterization of patient-derived xenografts and cancer cell lines from nasopharyngeal carcinoma	Nasopharyngeal carcinoma (NPC) is rare worldwide but common in southern China, including Hong Kong. The lack of representative NPC models has hampered research in the carcinogenesis and preclinical studies in NPC. We have recently established four patient-derived xenografts (PDXs) and three cancer cell lines from NPC tissues. Their genetic background has well characterized using genomic next-generation sequencing. To further delineate the transcriptome profiles of these newly established PDXs and cell lines, and further comprehensively compare the transcriptome differences between Epstein-Barr virus (EBV)-positive and –negative NPC, we performed RNA sequencing to determine the gene expression levels.	Co-expression
SRP158917	Transcriptomes change differerntly in differernt cancer cells upon EPZ-6438 treatment	Purpose: The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) to find out the difference between EZH2 inhibitor treatment and DMSO group in each cancer cell line, and find the relationship between transcriptomes change and drug sensivitity. Methods: mRNA profiles of cell lines were generated using  Illumina PE150, then GSEA was used for cellular pathways analysis Results:  The result showed 53 common oncogenic signatures were enriched in RNA-seq data. For example, KRAS.300_UP.V1_UP, MEK_UP.V1_UP were statistically enriched in the RNA-seq data. In addition, some oncogenic signatures were only enriched in certain cancer cell lines. For example, 101 and 12 signatures from the RNA-seq were statistically enriched in U2932 and SMMC-7721, respectively. Conclusions: Our study systematically examined the cellular transcriptomes affected by EPZ-6438, with biologic replicates, generated by RNA-seq technology. EZH2 inhibition results in the transcriptional activation of multiple onco-pathways in a cell-context dependent manner, which may underline the resistance to EZH2 inhibition. Overall design: mRNA profiles of 3 cancer cell lines treated with 1 µM EPZ-6348 or DMSO for 6 days, using NEBNext® UltraTM RNA Library Prep it for Illumina® (NEB, USA).	Co-expression
SRP158943	Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in chronic lymphocytic leukemia	Cancer evolution is fueled by genetic and epigenetic diversity, and intra-tumoral heterogeneity in DNA methylation has been shown to co-operate with genetic heterogeneity to empower evolutionary capacity of cancers such as chronic lymphocytic leukemia. Here, we show that epigenetic diversification leads to decreased coordination across layers of epigenetic information, likely reflecting an admixture of cells with diverging epigenetic identities. This manifests in incomplete gene silencing by the Polycomb complex, unexpected co-occurrence of typically mutually exclusive activating and repressing histone modifications, and greater cell-to-cell transcriptional heterogeneity. Overall design: Given the importance of histone modifications to lineage plasticity in cancer15-17, intra-leukemic epigenetic heterogeneity may extend to histone modifications, likely promoting lineage plasticity by enabling permissive chromatin states. To address this question, we complemented DNAme analysis with a chromatin immunoprecipitation sequencing (ChIP-seq) compendium of histone post-translational modifications (H3K4me3, H3K27ac, H3K4me1, H3K27me3, H3K9me3 and H3K36me3) and transcriptome sequencing (RNA-seq) in a cohort of primary CLL and healthy B lymphocytes samples (CLL IGHV unmutated, n = 12; CLL IGHV mutated, n = 10; peripheral blood NBCs [CD23+CD19+CD27-IgD+], peripheral blood memory B cells [GCBs; CD23+CD19+CD27+IgD-], peripheral blood CD20+ cells.	Co-expression
SRP158979	Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nuceolin-AKT pathway.	We found that CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival in pateints. In this study, we used an siRNA to decrease CITED2 expression in PC3 cells. A RNA-seq approach was utilized in order to determine global gene expression changes  in CITED2 knockdown cells compared to control cells. Overall design: PC3 cells transfected with control siRNAs were used as controls. Cells transfected with siRNAs targeting CITED2 were used as experimental group. Cells were transfected for 72 hr and the analyses were done.	Co-expression
SRP158981	Transcriptome analysis of the effect of enrichment and regulation of m6A by synthetic writer and reader in human cells	To investigate the basic principles of epigenetic control, we established an orthogonal epigenetic regulatory system in mammalian cells using N6-methyladenine (m6A), a DNA modification not commonly found in metazoan epigenomes. We developed a synthetic initiator module (synI) capable of establishing m6A marks in a sequence-specific manner at designer reporter loci integrated in the human genome, and a synthetic readout module (synR) which selectively reads m6A and consequently induces transcriptional changes. To ensure our orthogonal m6A system has minimal interaction with endogenous human transcriptional machineries, we performed RNA-sequencing analysis and determined that both synI and synR expression have minimal effect on 293FT transcriptome.	Co-expression
SRP158994	Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection	Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq to characterize immune function in peripheral blood before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. This innate response coincides with a decrease in B cell transcriptional signatures. These results represent the first longitudinal transcriptomic characterization of human immune function in acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure. Overall design: mRNA-Seq of peripheral blood mononuclear cells (PBMC) collected from individuals before, during, and after acute HCV infection. Acute HCV infection resulted in spotaneous viral resolution (n=6) or chronic infection (n=8). Four time points were examined per subject: i) Pre-infection baseline (Variable); ii) Early acute (2-9 weeks, mean 6 weeks); iii) Late acute (15 – 20 weeks, mean 17 weeks); and iv) Follow up (25 – 71 weeks, mean 52 weeks)	Co-expression
SRP159013	Gene exression in single T cells across division states.	Purpose: To compare diversity of primary human CD8+ T cells that have divided 0, 1, or 2 times on day 3 of ex vivo expansion from naïve resting state. Methods: Naïve T cells were enriched from human peripheral blood monoluclear cells (PBMCs), labeled with CFSE dye, and expanded for 3 days using rapid expansion protocol (Li, Y. & Kurlander, R.J. Journal of Translational Medicine, 2010). On day 3, 10,000 single live CFSE+ CD8+ T cells from each of divisions 0, 1, and 2 were sorted and immediately processed using 10X Genomics single-cell RNA-sequencing platform. Results: We found that undivided cells display the highest gene expression diversity. Using 1,000 most variably expressed genes, we created a force-directed layout, representing a phenotypic map of cellular differentiation across division states. To understand the basis of T-cell diversity, we defined and quantified regions of interest on this map based on diffusion pseudo-time (DPT), a metric of cell differentiation state. Finally, we examined gene expression in cells from each region and found that undivided cells acquire gene expression associated with effector cell function, while remaining cells go on to grow and differentiate. Conclusions: Our study provides insights into T-cell differentiation within an ex vivo expansion system for cancer immunotherapy applications. Overall design: A total of 4,060 cells (division 0: n = 552 cells, division 1: n = 1,777 cells, division23: n = 1,731 cells) were sequenced to an average of 52,040 post-normalization reads per cell capturing a median of 18,770 unique molecular identifier (UMI) counts per cell mapping to 3,544 unique genes per cell.	Co-expression
SRP159023	Acquisition of a hybrid E/M state is essential for tumorigenicity of basal breast cancer cells	Using the recently described CD104+/CD44hi antigen combination we demonstrate that tumorigenicity depends on individual cells residing in a hybrid E/M state. Acquisition of this E/M hybrid state is facilitated by the differential expression of EMT- TFs, like Snail accompanied by the expression of adult stem-cell programs. Transition from the highly tumorigenic E/M state to a fully mesenchymal phenotype, achieved by constitutive ectopic expression of Zeb1, is sufficient to drive cells out of the E/M hybrid state into an extreme mesenchymal (xM) state, which is accompanied by a substantial loss of tumorigenicity and a switch from canonical to non-canonical Wnt signaling. Overall design: Performing RNASeq with HMLE (immortalized human mammary epithelial cells) in different EMT stages, either in the E state the hybrid E/M state or the extreme mesenchymal (xM) state as determined by sorting for CD104 and CD44. And performing RNASeq with HMLE cells locked in the xE state by Zeb1KO (xE-SCC-Zeb1KO), from there transferred to the hybrid E/M state by Snail overexpression (E-SCC-Zeb1KOSn) or rescued and transitioned to an xM state with CRISPR resistant Zeb1 wobble mutant (mt) (E-SCC-Zeb1KOSnZmt).	Co-expression
SRP159024	Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy	The presence of disseminated tumour cells (DTCs) in bone marrow predicts poorer metastasis-free survival of breast cancer patients with localized disease, and their eradication improves long-term prognosis. DTCs persist in distant tissues despite administration of adjuvant chemotherapy, ostensibly because the majority of DTCs are quiescent. Here, we provide evidence that the microenvironment of DTCs protects them from chemotherapy independent of cell cycle status. We show that chemoresistant DTCs associate with the perivascular niche (PVN) of distant tissues, and that they are protected from therapies by vascular endothelium. Inhibiting key integrin-mediated interactions between DTCs and the PVN, driven partly by endothelial-derived von Willebrand Factor, sensitizes DTCs to chemotherapy and prevents bone metastasis. Importantly, chemosensitization is achieved without inducing DTC proliferation, or exacerbating chemotherapy-induced toxicities. These results suggest that prefacing adjuvant therapy with integrin inhibitors is a viable clinical strategy to eradicate DTCs and prevent metastasis. Overall design: RNA sequencing of bone marrow mesenchymal stem cells (MSCs) and bone marrow microvascular niches (MVNs) by RNAseq using Illumina HiSeq 2500.	Co-expression
SRP159066	Effect of TGF-beta treatment on circRNAs biogenesis	circRNAs profile were examined upon TGF-beta treatment in A549 cells Overall design: Examination of circRNAs profile in TGF-beta treated and TGF-beta+ SIS3 inhibitor group	Co-expression
SRP159079	Human Treg IL-12 stimulation	Human Tregs isolated from PBMCs were cultured in the absence or presence of IL-12 (20ng/ml) for four days and were performed mRNA-seq. Overall design: mRNA profiles of human Treg stimulated with IL-12 (Th1 condition)	Co-expression
SRP159081	Human Treg NaCl stimulation	Human Tregs isolated from PBMCs were cultured in the absence or presence of additional NaCl (40mM) for four days and were performed mRNA-seq. Overall design: mRNA profiles of human Treg stimulated with additional NaCl	Co-expression
SRP159087	HOXC10 Overexpression Promotes Cell Proliferation and Migration through Regulation of CST1 Expression in Gastric Cancer	This study propose HOXC10 overexpression by reduced DNA methylation promotes gastric cancer progression through regulation of CST1 and S100P. Overall design: control cells, HOXC10 overexpressed cells	Co-expression
SRP159095	Short-term effect of Boost versus Radical doses of Intraoperative electron Radiotherapy in breast cancer tumor bed using high-throughput approaches	Importance: Intra-operative electron Radiation Therapy as a partial-breast single high dose radiotherapy, leads to decrease the local recurrence through tumor bed modification. Objective: This study designed to investigate short-term effect of the dose- dependent and -independent molecular mechanisms and biological pathway of tumor bed modification induced by Intra-operative electron Radiation Methods: Six random selected breast cancer patients entered into our study and all patients by referee to their pathological report were treated by doses of 12Gy as a Boost dose and 21Gy as a Radical dose and the samples were categorized into three groups which included: Margin Before irradiation, Margin After immediately irradiation and Margin 24 hours After irradiation. Resluts: Using mRNA-sequencing, ~6 Giga base clean data (20 Million Reads, 150 base pair) per individual sample and totally 125.3 million reads of transcriptome sequence were generated from the patient samples. Discussion: Appropriate Intra-operative electron Radiation Therapy short-term effects of molecular mechanisms in tumor bed seems to be dose-independent. Overall design: A single high dose 12Gy of Intra-operative electron Radiation Therapy as a Boost dose and 21Gy as a Radical dose after breast-conserving surgery (BCS) immediately and 24 hours after irradiation on tumor bed compared with tumor bed before irradiation.	Co-expression
SRP159099	Determination of the Forkhead box A2 (FOXA2) Cistrome in the Human Endometrium	Uterine glands are central to endometrial function and fertility, however the mechanisms regulating their development and function are not well understood. The pioneer forkhead box A2 (FOXA2) transcription factor is distinctively expressed in the glands of the endometrium in both the human and mouse uterus. Studies in mice established that FOXA2 is a critical regulator of gland development in the neonatal uterus as well as differentiated gland function in the adult uterus. An integrative approach was used here to define the FOXA2 cistrome in the human endometrium. Genome-wide mapping of FOXA2 binding sites by chromatin immunoprecipitation sequencing (ChIP-Seq) was performed on proliferative (P) and mid-secretory (MS) phase endometrium and combined with the transcriptome determined by RNA sequencing (RNA-Seq). Distinctive binding of FOXA2 was observed between the P and MS endometrium, and FOXA2 binding intervals were enriched for different transcription factor binding motifs between the phases of endometrium. Pathway analysis revealed different biological processes regulated by FOXA2 bound genes in the P and MS endometrium. Thus, FOXA2 is proposed to regulate gene expression in concert with other transcription factors to influence gland function in a cycle phase-dependent manner. Further analysis identified potential FOXA2 regulated genes that influence endometrial growth, uterine receptivity, and stromal cell decidualization. This analysis of the FOXA2 cistrome provides a foundation essential to understanding fundamental aspects of uterine gland development, differentiation, function, and disease. Overall design: (6) proliferative phase and (5) mid-secretory phase human endometrium biopsies	Co-expression
SRP159142	ZIKV infection increases HUVECs endothelial barrier permeability and activates inflammatory cytokines	The objective of this assay was to determine the effects of ZIKV on HUVEC cells Overall design: Purified HUVECs were infected with two strains of ZIKV (PRVABC59 and IBH30656) and mRNA was subjected for differential gene expression	Co-expression
SRP159156	Differential gene expression analysis in BRD4-PROTAC treated diffuse large B-cell lymphoma cell lines	We identified differential gene expression after treatment with BRD4-PROTAC ARV771 in two ABC-like diffuse large B-cella lymphoma cell lines. We have identified cluster of gene expression regulated after BRD4 inhibition which are criticaly important for DLBCL malignancy. Overall design: Two ABC-DLBCL cell lines were used to identify the changes in gene expression profile after BRD4-PROTAC (ARV771) treatment.	Co-expression
SRP159180	Changes in CD34 and Erythroid Progenitor Transcriptome After RUNX3 Kock-down	The associated publication describes a RUNX3-dependent defect in primary human CD34+ HSPC differentiation into the erythroid lineage. This study was designed to determine which genes are potential targets of RUNX3, and could contribute to regulation of erythropoiesis. Overall design: Undifferentiated human CD34+ HSPCs were subjected to lentiviral knock-down of RUNX3. After selection, cells were either harvested as undifferentiated CD34+ cells, or grown for 24 hours in erythroid medium and then harvested. Samples underwent processing using the Qiagen RNeasy kit, and RNA was quantified using a Thermo Fisher Scientific Nanodrop One spectrophotometer. Sequencing was performed by Hudson Alpha Genomic Services Laboratory (ribosomal reduction, 100bp, paired-end, 50M reads, strand-specific) and data processing was performed using Galaxy Suite tools. Analysis across the three biological replicates included comparisons between erythroid and undifferentiated cells, as well as empty vector compared to RUNX3 knock-down in both erythroid and undifferentiated cells.	Co-expression
SRP159196	Generation, transcriptome profiling, and functional validation of cone-enriched human retinal organoids	The macula of the retina has a high ratio of cones to rods and is critical for central vision and visual acuity. Macula degenerations affect vision the most and are incurable. Here we report the generation, transcriptome profiling, and functional validation of cone-enriched human retinal organoids differentiated from hESCs. Transcriptome profiling using bulk RNA-seq demonstrated that retinal differentiation in vitro recapitulated retinogenesis in vivo in the temporal expression of cell differentiation markers and retinal disease genes, as well as in mRNA alternative splicing. Single-cell RNA-seq of 8-month retinal organoids identified clusters of cone and rod photoreceptors and confirmed the cone enrichment initially revealed by immunostaining. Notably, comparisons of single-cell transcriptomes demonstrated the similarity between retinal organoids and human macula in cones and rods. Cones in retinal organoids exhibited electrophysiological functions. Collectively, we have established cone-enriched retinal organoids and a reference of transcriptomes that are rich resources for retinal studies. Overall design: To globally characterize the transcriptomes during human retinal cell differentiation, we performed bulk RNA-seq of retinal organoids at multiple time points (15 days, 1, 3, 6.5, and 9 months, three replicates per time point, Supplemental Table S1), starting from the stage preceding retinal ganglion cell differentiation to the stage when photoreceptors display outer segments.	Co-expression
SRP159204	single cell RNA-seq raw reads of estrogen-stimulated breast cancer cell line MCF7 (high throughput)	Single-cell RNA-seq reveals dynamic estrogen-stimulated metabolic reprogramming in breast cancer cell lines	Co-expression
SRP159243	RNA Sequencing Facilitates Quantitative Analysis of differentially expressed genes during  human erythroipoiesis	Purpose: The goals of this study are to determine the differentially expreseed non-coding RNAs during human erythropoiesis Methods:gene expression profiling with cells on days 4,8,11,14 during erythroid differentiation, with two replicated using Illumina Genome Analyzer IIx. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: ncRNAs were differentially expressed during erythroid differentiation Overall design: mRNA profiles of day4,8,11,14 erythroid cells were generated by deep sequencing, in duplicate.	Co-expression
SRP159261	Molecular Pathology of adverse local tissue reaction caused by metal-on-metal implants	RNA-sequencing analysis of periacetabular synovial tissue collected from patients undergoing a revision total hip arthroplasty (rTHA) after failure of a Cobalt Chromium implant. Comparisons were made to periacetabular synovial tissue collected from patients undergoing primary THAs (pTHA). Results: Analysis of tissue biopsies by RNA-sequencing revealed that MoM patient samples exhibit significantly increased expression of immune response genes but decreased expression of genes related to extracellular matrix (ECM) remodeling. Overall design: RNA was extracted from 3 pTHA and 3 rTHA samples and used for RNA-sequencing. Comparative analysis was performed using RPKM values obtained after processing of sequencing data.	Co-expression
SRP159264	RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [RNA-Seq]	Alteration in RNA editing has been connected to tumor progression and many other important human diseases. However, the role of RNA editing in intrahepatic cholangiocarcinoma (ICC) remains unclear. Here we conducted a transcriptome-wide investigation in ICCs, and revealed ADAR-associated over-editing occurred uniformly in ICCs. Collectively, these results reveal a previously unrecognized role of RNA editing in malignant transformation into ICC, and ADAR1 inhibition may obviate progression and relapse of this malignancy. Overall design: We performed RNA-seq using Illumina HiSeq2000 on 15 pairs of ICC tumors and matched non-tumor liver tissues, with a mean of 30 million paired-end reads per sample. RNA-seq was performed by MyGenostics Inc. (Beijing, China).	Co-expression
SRP159277	Inhibition of the integrin alpha-V beta-3 reverts the paradoxical effect of levothyroxine replacement during bexarotene therapy in cutaneous T-cell lymphoma	Bexarotene is a specific RXR agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). The mechanism of action is pleiotropic but impacts directly on CTCL cell proliferation, chemotaxis and apoptosis, and indirectly on lymphoma immunity. Bexarotene causes hypothyroidism in more than 90% of patients thus requiring the concomitant administration of levothyroxine. Hereon we investigated the consequence of levothyroxine administration to the antineoplastic effect of bexarotene in CTCL. We found that bexarotene induces transcriptional and biological changes in CTCL cells related to decreased cell proliferation and chemotaxis, as well as increased proliferation and interferon response. Although lack of levothyroxine supplementation during bexarotene treatment increased apoptosis and decreased cell proliferation of CTCL cells in vitro and in vivo, it also decreased the lymphoma immunity. Since levothyroxine activates both the ubiquitous TRA nuclear receptor and the more restricted integrin ?V?3 membrane receptor that is overexpressed in CTCL cells, we investigated their role in bexarotene treatment. We demonstrated that genetic and pharmacologic inhibition of the integrin ?V?3 receptors resulted in improved bexarotene-induced effects on apoptosis, cell proliferation and chemotaxis while maintaining the lymphoma immunity. Our results provide a mechanistic rationale for evaluating the addition of the integrin ?V?3 inhibitor cilengitide to CTCL therapeutic regimens that are based on bexarotene and levothyroxine supplementation. Overall design: RNA was isolated from HuT 78 cells transfected with siRNA for integrins (si-ITGAV/B3); TRA (si-TR) or non-target sequences (si-CT) followed by treatment with bexarotene in the presence of physiological concentrations of TH, for 6 hours using TRI-REAGENT	Co-expression
SRP159286	Generation, transcriptome profiling, and functional validation of single cells from cone-enriched human retinal organoids	The macula of the retina has a high ratio of cones to rods and is critical for central vision and visual acuity. Here we report the generation, transcriptome profiling, and functional validation of single cells from cone-enriched human retinal organoids differentiated from hESCs.  Single-cell RNA-seq of 8-month retinal organoids identified clusters of cone and rod photoreceptors and confirmed the cone enrichment initially revealed by immunostaining. Collectively, we have established cone-enriched retinal organoids and a reference of transcriptomes that are rich resources for retinal studies. Overall design: To globally characterize the transcriptomes during human retinal cell differentiation, we performed single cell RNA sequencing  of 8M retinal organoids.	Co-expression
SRP159512	The SUMO Pathway as a Therapeutic Option in Pancreatic Cancer	Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with overall five-year survival of 8%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC, however subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumor biology. It is clear that hyperactivation of MYC generates dependencies, which can be exploited therapeutically. To find MYC-associated dependency we analyzed human PDAC expression dataset. We observed that MYC is connected to the sumoylation machinery in PDAC. Components of the SUMO pathway mark a PDAC subtype with worse prognosis and we provide evidence that PDACs with a MYChigh/SUMOhigh phenotype respond to a novel SUMO inhibitor, offering the opportunity to develop novel stratified PDAC therapies Overall design: IMIM-PC1 cells stably expressing the MYC-ER fusion protein were treated with 500nM 4-OHT for an interval of 24h.	Co-expression
SRP159553	Septin 9 over expression in MCF7	Septin 9 (SEPT9), a member of the septin gene family, is strongly linked to cancer, particularly breast cancer, where genomic amplification occurs in ~11% of cases. SEPT9 is a putative oncogene as it is amplified in the form of double minute chromosomes in murine models of breast cancer, is a fusion partner of mixed lineage leukemia (MLL) gene in leukemia, and it is a known hot spot of retroviral tagging insertion. SEPT9 contributes to cytoskeleton dynamics, thus oncogenic functions have been proposed based on the broad range of cellular functions it partakes. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies indicate that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while its downregulation inhibits this process. The degradation pattern is associated with focal adhesions (FA) at the cell periphery. Increased extracellular matrix digestion during epithelial–mesenchymal transition digestion is significantly associated with increased expression of matrix metalloproteinases. In SEPT9 over expressing cells, MMP3 is secreted to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filaments assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells. Overall design: MCF7_SEPT9_v1, MCF7_SEPT9_v2, and MCF7_SEPT9_v3-overexpressing cell lines and the MCF7 control cells (MCF7_C) were used. A total of 12 samples were used for RNA-Seq analysis (three biological replicates from each of the MCF-7 isoforms and control cells).	Co-expression
SRP159632	CROP-Seq in Primary Human T Cells	We adapted sgRNA lentiviral infection and Cas9 electroporation (SLICE) to allow for CROP-Seq (Datlinger et al, Nat Med 2017) in primary cells. We used a library of 48 sgRNA, derived from GW screens, to explore transcriptional changes downstream of CRISPR-KO. Overall design: Pooled CRISPR screen with single cell RNASeq readout (Perturb-Seq / CROP-Seq) in primary human T cells. Dataset includes CD8 T cells from two donors, for two conditions: with TCR stimulation or No stimulation.	Co-expression
SRP159647	Fibroblast RNA-Seq data from three genodermatoses (RDEB, XPC and KS)	Recessive dystrophic epidermolysis bullosa, Kindler syndrome and xeroderma pigmentosum C, are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the contributing role of the stromal microenvironment in the pathology of these disorders. To investigate common mechanisms that contribute to the pathogenic role played by dermal fibroblasts, we conducted a comparative gene expression analysis by RNA-Seq. Overall design: 3 healthy controls, 9 RDEB, 3 XPC and 3 KS patients	Co-expression
SRP159651	Single-cell RNA-seq analysis of human tonsil CD4 T cells	We performed single-cell RNA-seq on CD4 T cells isolated from the tonsils of one healthy donor. We used the 10x chromium technology. Overall design: Tonsil CD4 T cells were enriched by negative selection using magnetic beads. Cell populations (CXCR5+PD-1low T cells, CXCR5+PD-1int T cells and CXCR5+PD-1high T cells ) were further isolated by cell sorting. Cellular suspensions (3500 cells) were loaded on a 10X Chromium instrument (10X Genomics) according to manufacturer's protocol.	Co-expression
SRP159657	Effects of HOTAIR RNAi on Transcriptomes in H23 Cells	We profiled transcriptomes in human lung cancer cell line H23 when the expression of HOTAIR was knockdown by the siRNA specific to an HOTAIR isoform HOTAIR-N (NR_047517). Overall design: H23 cells were cultured in RPMI1640.  HOTAIR-N-specific and control siRNAs were transfected into H23 cells using RNAiMAX. Total cell RNA was extracted at 48 hrs after transfection. Three independent transfections were carried out for each siRNA. The extracted RNA was processed for RNA-SEQ on Illumina HIGHSEQ 2500.	Co-expression
SRP159658	Effects of HOTAIR RNAi on Transcriptomes in T47D Cells	We profiled transcriptomes in human breast cancer cell line T47D when the expression of HOTAIR was knockdown by the siRNA specific to an HOTAIR isoform HOTAIR-N (NR_047517). Overall design: T47D cells were cultured in RPMI1640.  HOTAIR-N-specific and control siRNAs were transfected into T47D cells using RNAiMAX. Total cell RNA was extracted at 48 hrs after transfection. Three independent transfections were carried out for each siRNA. The extracted RNA was processed for RNA-SEQ on Illumina HIGHSEQ 2500.	Co-expression
SRP159659	Effects of Bloom RNAi on Transcriptomes in A549 Cells	We profiled transcriptomes in human lung cancer cell line A549 when the expression of Bloom was knockdown by the siRNA specific to Bloom. Overall design: A549 cells were cultured in DMEM.  Bloom-specific and control siRNAs were transfected into A549 cells using RNAiMAX. Total cell RNA was extracted at 48 hrs after transfection. Three independent transfections were carried out for each siRNA. The extracted RNA was processed for RNA-SEQ on Illumina HIGHSEQ 2500.	Co-expression
SRP159660	Comparison of Transcriptomes between A549 and H23 Cells	We profiled transcriptomes in human lung cancer cell lines H23 and A549 cells. Overall design: H23 and A549 were cultured to ~80% confluent. Total cell RNA was extracted using Trizol. Three independent cultures of each cell line were lysed for RNA. The extracted RNA was processed for RNA-SEQ on Illumina HIGHSEQ 2500.	Co-expression
SRP159677	Differential expression in wild type and mutant HAP1 cells [RNA-seq II]	Characterization of gene expression changes occuring upon knockout of RING1A, RING1B, and BAP1. Overall design: Four Samples	Co-expression
SRP159805	Fate-mapping within human iPSC-derived kidney organoids reveals conserved mammalian nephron progenitor lineage relationships.	Early human kidney development is poorly documented due to tissue inaccessibility and a lack of genetic tractability. Here we combine reprogramming, CRISPR/Cas9 gene-editing and organoid technologies to study the nephron lineage in a human context. We confirm the presence of a SIX2+ population in early kidney organoids with a transcriptional profile akin to human fetal nephron progenitors. Using lineage-tracing analyses, we show that SIX2-expressing cells contribute to nephron formation but not to the putative collecting duct epithelium. Labeling of SIX2+ cells at various time-points during organoid differentiation revealed a markedly reduced capacity for these cells to contribute to nephron formation over time. This suggests human kidney organoids lack a true nephron progenitor niche, as the developing kidney does in vivo, capable of both self-renewal and ongoing nephrogeneis. Nonetheless, human iPSC-derived kidney tissue maintains previously identified lineage relationships, which supports the utility of in vitro organoid models for interrogating the molecular and cellular basis of early human development. Overall design: Single cell RNA-seq generated on a 10x Chromium genomics platform from iPSC-derived human kidney organoids. Each sample represents 6 pooled organoids derived from a single well of a transwell plate, generated from individual iPSC-derived reporter lines and harvested at either Day 18 (D18) or Day 25 (D25) of the differentiation protocol. The aggregated data contains 5365 cells (1865 from D18 and 3500 from D25) that passed QC and contains populations representing stroma, early/late nephron segments (podocytes, progenitors and proximal tubule) and distal tubule/collecting duct, as well as small off-target populations with similarity to neurons and muscle.	Co-expression
SRP159842	RNA sequencing of Asthmatic Human Airway Smooth Muscle Cells I	The goal of the was to evaluate the mRNA expression profile of non-asthmatic and asthmatic airway smooth muscle. Overall design: RNA Seq was performed on nonasthmatic (n=5 individuals) and asthmatic (n=5  individuals) human airway smooth muscle cells.	Co-expression
SRP159868	Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model	ER+ PDX (COH-SC31) were exposed to PBDE mixture for 1 weeks. RNA-sequencing analysis was performed to evalaute the gene expression changes. Overall design: RNA-Seq gene expression was compared between control (DMSO, dimethyl sulfoxide) and treatment with mixture of PBDEs.	Co-expression
SRP159905	Precise Gene Editing Preserves Hematopoietic Stem Cell Function Following Transient p53-Mediate DNA Damage Response [scRNA-seq]	We performed single-cell (sc)RNA-Seq on male donors FACS-sorted “primitive” (CD34+ CD133+ CD90+) and “progenitor” (CD34+ CD133+ CD90-) HSPC cells treated with IL2RG ZFN,  High Specificity (HS), (Low Specificity (LS) or control RNP in a ratio 1 to 1. We also included HS RNP and the cognate repair template containing a GFP expression cassette delivered by AAV6 and sorted for targeted integration (HS/AAV6 GFP+ vs. HS/AAV6 GFP-) Overall design: We analysed  cells 24h after nucleases delivery. In order to identify cell subpopulations within samples and better enable comparison across datasets, we performed multi-set canonical correlation analysis and segregated cell clusters using the Louvain graph-based clustering approach. We computed the significant components using a supervised approach and we identified 6 clusters, 2 of which were enriched for HSC/MPP marker genes and depleted of lineage-associated markers. The analysis of the transcriptional landscape of cells  indicate that p53 pathway activation and modulation of cell cycle progression genes are consistently observed upon nuclease treatment across different HSPC types/states, including the most primitive subset as putatively identified in our single-cell. analysis	Co-expression
SRP159911	Supraphysiological Androgens Repress Prostate Cancer Growth and Induce DNA Damage Augmented by PARP Inhibition	Prostate cancer (PC) is initially dependent on androgen receptor (AR) signaling for survival and growth. Therapeutics designed to repress AR activity, such as those reducing circulating androgen levels, serve as the primary intervention for advanced disease. However, supraphysiological androgen (SPA) concentrations, can produce a paradoxical response leading to growth inhibition. We sought to determine the mechanisms by which SPA represses PC growth and determine if molecular context associates with anti-tumor effects. Overall design: RNA sequencing of LNCaP human prostate tumor cell lines using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.	Co-expression
SRP159956	Inhibition of Enhancer of Zeste Homologue 2 attenuates TGF-ß dependent hepatic stellate cell activation and liver fibrosis	We report the effect of TGFß  vs PDGF 2h treatment in hepatic stellate cells. We also report the effect of TGFß treatment for 48h in human hepatic stellate cells. Overall design: RNA sequencing was performed after treating human hepatic stellate cells with TGFß and PDGF for 2h and also with TGFß for 48h	Co-expression
SRP160142	Acidification of tumor: stromal boundaries drive transcriptome alterations associated with aggressive phenotypes	We report RNA splicing changes in response to extracellular acidification Overall design: MDA-MB-231 and 4T1 mammary carcinoma cell lines were exposed to 48hrs of low pH conditions generated by changes in sodium bicarbonate concentrations.	Co-expression
SRP160391	Generation of induced neural stem cells from urine derived cells by synthetic mRNA	Analysis of induced neural stem cells from urine derived cells by synthetic mRNA vs. H9 embryonic stem cell derived neural stem cells and urine derived cells. Results provide insight into molecular similarities between induced neural stem cells and H9 embryonic stem cells derived neural stem cells. Overall design: Total RNA profiles of induced neural stem cells, H9 embryonic stem cells derived neural stem cells and urine derived cells were generated by RNA sequencing, in duplicate.	Co-expression
SRP160392	Defective transcription elongation in a subset of cancers confers immunotherapy resistance (BGI12 RNA-Seq)	The nature and the role of global transcriptional deregulations in cancers are not fully understood. We report a phenotype in a significant portion of cancers characterized by widespread defects in mRNA transcription elongation (TE). Cancers with TE defects (TEdeff) were characterized by spurious transcription and defective mRNA processing, specifically in a large set of genes characterized by long genomic length, poised promoters and inducible expression. As such, signaling pathways regulated by such genes, such as interferon/JAK/STAT and TNF/NF-?B pathways, were consistently suppressed in TEdeff tumors. Remarkably, TEdeff significantly correlated with the poor response and outcome in immunotherapy, but not chemo- or targeted therapy, -treated renal cell carcinoma and metastatic melanoma patients in 4 different cohorts. Importantly, forced pharmacologic or genetic induction of TEdeff in tumor cells impaired the expression of the interferon/JAK/STAT and TNF/NF-?B pathways, and imposed resistance to the innate and adaptive anti-tumor immune responses and checkpoint inhibitor therapy in vivo. Therefore, defective TE is a novel epigenetic mechanism in the tumor arsenal of immune resistance tools, which warrants its assessment in cancer patients undergoing immunotherapy. Overall design: The nature and the role of global transcriptional deregulations in cancers are not fully understood. We report a phenotype in a significant portion of cancers characterized by widespread defects in mRNA transcription elongation (TE). Cancers with TE defects (TEdeff) were characterized by spurious transcription and defective mRNA processing, specifically in a large set of genes characterized by long genomic length, poised promoters and inducible expression. As such, signaling pathways regulated by such genes, such as interferon/JAK/STAT and TNF/NF-?B pathways, were consistently suppressed in TEdeff tumors. Remarkably, TEdeff significantly correlated with the poor response and outcome in immunotherapy, but not chemo- or targeted therapy, -treated renal cell carcinoma and metastatic melanoma patients in 4 different cohorts. Importantly, forced pharmacologic or genetic induction of TEdeff in tumor cells impaired the expression of the interferon/JAK/STAT and TNF/NF-?B pathways, and imposed resistance to the innate and adaptive anti-tumor immune responses and checkpoint inhibitor therapy in vivo. Therefore, defective TE is a novel epigenetic mechanism in the tumor arsenal of immune resistance tools, which warrants its assessment in cancer patients undergoing immunotherapy.	Co-expression
SRP160396	Defective transcription elongation in a subset of cancers confers immunotherapy resistance (human cell lines RNA-Seq)	The nature and the role of global transcriptional deregulations in cancers are not fully understood. We report a phenotype in a significant portion of cancers characterized by widespread defects in mRNA transcription elongation (TE). Cancers with TE defects (TEdeff) were characterized by spurious transcription and defective mRNA processing, specifically in a large set of genes characterized by long genomic length, poised promoters and inducible expression. As such, signaling pathways regulated by such genes, such as interferon/JAK/STAT and TNF/NF-?B pathways, were consistently suppressed in TEdeff tumors. Remarkably, TEdeff significantly correlated with the poor response and outcome in immunotherapy, but not chemo- or targeted therapy, -treated renal cell carcinoma and metastatic melanoma patients in 4 different cohorts. Importantly, forced pharmacologic or genetic induction of TEdeff in tumor cells impaired the expression of the interferon/JAK/STAT and TNF/NF-?B pathways, and imposed resistance to the innate and adaptive anti-tumor immune responses and checkpoint inhibitor therapy in vivo. Therefore, defective TE is a novel epigenetic mechanism in the tumor arsenal of immune resistance tools, which warrants its assessment in cancer patients undergoing immunotherapy. Overall design: RNAseq was performed on a panel of human breast cancer cell lines to illustrate transcription elongation defects existed in a subset of samples. The data was also used to illustrate that results obta	Co-expression
SRP160423	CHD7 is Suppressed in the Perinecrotic/Ischemic Microenvironment and is a Novel Regulator of Angiogenesis	In a study focused on the role for CHD7 in angiogenesis we completed RNA-sequencing of D456, a glioblastoma xenograft line and neural precursor cells after CHD7 knockdown Overall design: RNA-sequencing after shRNA KD of CHD7 in two cell lines	Co-expression
SRP160510	Transcription-dependent control of stem cell self-renewal and differentiation by the splicing factor U2AF1	Purpose: Here we describe the modulation of a gene expression program involved in cell fate. Methods: We depleted U2AF1 in human induced pluripotent stem cells (hiPSCs) to the level found in differentiated cells using an inducible shRNA system, followed by high-throughput RNAseq, revealing a gene expression program involved in cell fate determination. Results: Approximately 85% of the total raw reads were mapped to the human genome sequence (GRCh37), giving an average of 200 million human reads per sample for total RNA and 15 million human reads per sample for small RNA libraries. Conclusions: Our results show that transcriptional control of gene expression in hiPSCs can be set by the CSF U2AF1, establishing a direct link between transcription and AS during cell fate determination. Overall design: hiPSCs were differentiated into the three germ layers following the described protocol in the study (Gifford et al., 2013).	Co-expression
SRP160904	Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease (human)	Pre-clinical studies of cysteamine bitartrate demonstrate its narrow therapeutic window, where toxicity at millimolar levels correlates with a marked induction of hydrogen peroxide production.  At micromolar range concentrations, cysteamine bitartrate yielded a survival benefit in RC disease subject fibroblasts, and protection from brain death in RC complex IV deficient zebrafish.  Mitochondrial oxidative stress and membrane potential were significantly improved by micromolar cysteamine bitartrate in RC complex I disease worms, translating to a modest improvement of animal development and fecundity but not lifespan.  Overall, these data suggest that cysteamine bitartrate may hold therapeutic potential but requires careful consideration of safe and effective dose to further evaluate in clinical trials of human subjects with primary mitochondrial disease. Overall design: Rrimary human fibroblast cell lines (FCLs) derived from genetically-confirmed RC complex I NDUFS8 deficient and multiple RC deficient FBXL4 disease human subjects; treated with cysteamine for 6 or 24 hours.	Co-expression
SRP161171	Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 1: RNA-seq)	By taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we performed an in-depth comparison of transcriptomic responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells in humanized mice promotes transcriptomic responses akin to those of human vaccinees Overall design: The transcriptome of human PBMCs from different humanized mouse models (conventional model: 3 cohorts/samples of 5 mice each; NFA2-HIS/Fluc model: 2 cohorts/samples of 4 mice each; NFA2-HIS/Flt3LG model: 3 cohorts/samples of 4 mouse each) was determined by RNA-Seq prior (day 0 post infection; control) and after YFV-17D infection (day 11 post infection; post infection). Resulting data sets of differentially expressed genes were compared to data sets from human vaccinees (GSE13485 and GSE13699). Total number of samples processed for RNA-seq: 16	Co-expression
SRP161172	Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 2: scRNA-seq)	We performed an in-depth characterization and comparison of the immune system diversity and complexity in the spleen of conventional NRG-HIS mice and NFA2-HIS/Ftl3LG mice upon YFV-17D infection, a live-attenuated virus that induce that induce potent protective immunity in human. To do so, we employed Seq-Well, a recently developed platform for massively parallel single-cell RNA-Seq (scRNA-Seq), on splenocytes from NRG-HIS mice and NFA2-HIS/Flt3LG mice at six-weeks post YFV-17D infection. Our data provide an in-depth view of the cellular composition of the HIS in conventional and second-generation humanized mice. They also highlight the enhanced engraftment and functionality of the critical role of the myeloid and NK cell compartment in NFA2-HIS/Flt3LG mice, which is likely critical in promoting an enhanced transcriptomic, cellular and humoral response to YFV-17D. Overall design: We isolated splenocytes from two NRG-HIS mice and two NFA2-HIS/Flt3LG mice at six-weeks post YFV-17D infection and sorted these cells by human CD45 (hCD45) or human CD33 (hCD33) expression. We ran parallel Seq-Well arrays for each sorted population, enabling both unbiased characterization of the relative abundances of all lymphocytes, as well as a deeper examination of the cellular diversity within the myeloid compartment.	Co-expression
SRP161185	HiSeq analysis of human gene expression profile following infection with highly pathogenic avian influenza A virus (H5N1; A/Chicken/Vietnam/0008/04)	Current prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II (ATII) cells infected with highly pathogenic avian influenza H5N1 virus. We employed primary human ATII cells isolated from normal human lung tissue donated by patients that underwent lung resection. Human host gene expression following HPAI H5N1 virus (A/Chicken/Vietnam/0008/04) infection of primary ATII cells was analyzed using Illumina HiSeq deep sequencing. Overall design: Human non-tumor lung tissue samples were donated by three anonymous patients undergoing lung resection at Geelong Hospital, Barwon Health, Australia. The research protocols and human ethics were approved by the Human Ethics Committees of Deakin University, Barwon Health and the Commonwealth Scientific and Industrial Research Organisation (CSIRO). An informed consent was obtained from all tissue donors. All research were performed in accordance with the guidelines stated in the National Statement on Ethical Conduct in Human Research (2007). The sampling of normal lung tissue was confirmed by the Victorian Cancer Biobank, Australia.	Co-expression
SRP161484	Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer	In this study, we used RNA-seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in 10 paired tumor and normal pancreatic samples from patients Overall design: 10 paired tumor and normal pancreatic samples from patients	Co-expression
SRP161504	Single cell transcriptomes of replicatively cellular senescenct cells and ionizing radiation induced senescent cells	In order to identify the transcriptome change and heterogeneity in replicative senescent cells and stress-induced senescent cells, =we measured 1600 single cell transcriptomes of young quiescent cells at a population doubling (PD) number of 38, middle age quiescent cells (PD = 48), replicative senescent (PD = 71) cells and 50Gy X-ray induced senescent cells of PD38 control cells by Drop-seq. Overall design: Drop-seq of RS and SIPS cells.	Co-expression
SRP161553	CHROMATIN LANDSCAPES REVEAL DEVELOPMENTALLY ENCODED TRANSCRIPTIONAL STATES THAT DEFINE GLIOBLASTOMA [RNA-Seq]	Glioblastoma is an incurable brain cancer characterized by high genetic and pathological heterogeneity. Here we mapped active chromatin landscapes with gene expression, whole-exomes, copy number profiles, and DNA methylomes across 44 glioblastoma stem cell (GSCs) models, 50 primary glioblastomas, and 10 neural stem cells (NSCs) with the goal of identifying essential super enhancer (SE)-associated genes and the core transcription factors that establish them and glioblastoma identity. Glioblastomas segregate with two dominant enhancer profiles that coopt unique developmental transcription factor regulatory programs to enforce tumor identity. From group specific enhancer profiles, we inferred core transcription factors that define subgroup identity. These transcription factors show higher activity in glioblastomas versus normal neural stem cells, are associated with poor clinical outcomes, and are required for glioblastoma growth in vitro and in vivo. Given challenges with genetically-defined targeted therapies for glioblastoma, we propose targeting underlying transcriptional identity may serve as an important therapeutic strategy. Overall design: Dataset consists of total RNA isolated from either glioblastoma primary tissue or gliblastoma stem cell models and an analysis of gene expression signatures. For primary GBM samples, we have 50 GBM samples in total, 46 of which have H3k27ac ChIPseq data, 45 of which have RNAseq data, and 39 of which have methylation data (GBM74 has replicate data). For glioblastoma stem cell samples, we have 44 GSC samples in total, 43 of which have H3k27ac ChIPseq data, 44 of which have RNAseq data, and 41 of which have methylation data. For neural stem cell samples, we have 10 NSC samples in total, 9 of which have H3k27ac ChIPseq data, 9 of which have RNAseq data, and 9 of which have methylation data.	Co-expression
SRP161576	HOIL-1/RBCK1 promotes p53 degradation in Renal cancer cells	We performed RBCK1 depletion in renal cancer cells along with RNA sequencing. The expression profiling showed p53 signaling as a potential RBCK1 target and the conclusions were also verified in clinical samples. Overall design: RNA sequencing in 1 renal cell lines with si-Control or si-HOIL-1/RBCK1	Co-expression
SRP161584	A novel lncRNA lncRNA-AF339830 promotes colorectal carcinogenesis and glucose metabolism by stabilizing and specifying the transcription modification pattern of c-Myc [RNA-Seq]	To elucidate whether  lncRNA-AF339830 plays a role in  colorectal cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of  lncRNA-AF339830 siRNA and control siRNA transfectants. Overall design: RNA-seq was performed in colorectal cancer cells after lncRNA-AF339830 knock down	Co-expression
SRP161678	Deconstructing Retinal Organoids: single cell RNA-Seq reveals the cellular components of human pluripotent stem cell-derived retina	The rapid improvements in single cell sequencing technologies and analyses methods afford greater scope for dissecting organoid cultures composed of multiple cell types and create an opportunity to interrogate these models to understand tissue biology, cellular behaviour and interactions. To this end, retinal organoids generated from human embryonic stem cells (hESCs) were analysed by single cell RNA-Sequencing at three time points of differentiation. Combinatorial data from all time points revealed the presence of nine clusters, five of which corresponded to key retinal cell types, namely retinal pigment epithelium (RPE), retinal ganglion cells (RGCs), cone and rod photoreceptors and Müller glia cells. The remaining four clusters expressed genes typical of mitotic cells, extracellular matrix (ECM) components and those involved in retinal homeostasis. The cell clustering analysis revealed the decreasing presence of mitotic cells and RGCs, formation of a distinct RPE cluster, the emergence of cone and rod photoreceptors from photoreceptor precursors and an increasing number of Müller Glia cells over time. The pseudotime analysis resembled the order of cell birth during retinal development, with the mitotic cluster commencing the trajectory and the large majority of Müller glia being the latest. Together, these data demonstrate the feasibility and potential of single cell RNA-Seq to dissect the inherent complexity of the organoids and the orderly birth of key retinal cell types. Overall design: A hESC (H9) cell line harbouring a CRX-GFP reporter was differentiated to retinal organoids 25. Samples were collected at 60, 90 and 200 days, dissociated, partitioned into single cells using the Fluidigm C1 Single-Cell mRNA-Seq HT IFC and processed for scRNA-Seq.	Co-expression
SRP161680	Identification of human gene expression induced by 4MU-xyloside treatment	The Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer element PGSE, which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway. Overall design: Three control samples (DMSO-treated) and three 4MU-xyloside-treated samples	Co-expression
SRP161704	Molecular Determinants of Post-Mastectomy Breast Cancer Recurrence	Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls.  We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy.  This included 32 LRR, 34 DM and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM or controls.  DNA analysis on 57 primary tumors (17 LRR, 15 DM and 25 controls) identified significantly more NF1 mutations and mitogen activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p<0.0001 and p=0.0070, respectively).  Three patients had matched primary vs LRR samples, one patient had a gain of a NF1 mutation in the LRR.  There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression.  The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) versus controls (14%,p= 0.0045).  In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype.  Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence. Overall design: This is a multicenter retrospective study of patients who underwent mastectomy at a participating Translational Breast Cancer Research Consortium (TBCRC) institution.  Study centers included Memorial Sloan Kettering Cancer Center, University of Pittsburgh, Duke University, Dana Farber Cancer Institute, University of North Carolina at Chapel Hill, Georgetown University, University of Michigan at Ann Arbor, Vanderbilt University, University of Alabama at Birmingham and MD Anderson Cancer Center.  Eligible patients included those patients who underwent mastectomy without radiation for T stage 1-3 and N stage 0-1 breast cancer, and for whom archived tissues and outcome data were available. Patients with any recurrence, loco-regional (LRR) or with distant metastasis (DM), were treated from 1997 to present time as this was felt to represent an era when treatment recommendations would be the most uniform and consistent. Patients with LRR could have a subsequent DM as long as this DM was diagnosed at least 3 months after the LRR. Patients who developed LRR after developing distant metastases were placed in the DM group. Control patients were treated from 1997 to 2007 to allow at least five years follow-up with a disease-free interval.  Controls were matched to cases for age, ER/PR status, chemotherapy and endocrine therapy regimens and year of diagnosis.  All patients were treated with an upfront mastectomy followed by systemic therapy if indicated, which included chemotherapy, endocrine therapy or both.  Patients were ineligible if they received post-mastectomy radiation therapy, neoadjuvant chemotherapy, had a T4 primary tumor, N2 nodal disease, were HER2 positive, had positive margins after mastectomy, had fewer than 10 lymph nodes retrieved at axillary lymph node dissection, or had inadequate follow-up (<5 years) if a control patient.  If specimens were available from the recurrent tumors, these were also collected for exploratory analysis.	Co-expression
SRP161727	The Genetic Landscape of Diamond-Blackfan Anemia	Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). We identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported ribosomal protein (RP) encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in individual-derived cell lines. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in 7 previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this report should not only inform clinical practice for DBA individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders. Overall design: 9 individuals with DBA with putative splice mutations and 5 control individuals were processed for RNA-seq.	Co-expression
SRP161784	SMARTer single cell total RNA sequencing [SHSY5Y-MYCN-TR]	single cell polyA+ and total RNA-seq data was generated for NGP, SK-N-BE-2C and SHSY5Y-MYCN-TR cells Overall design: This submission consists of SHSY5Y-MYCN-TR cell line data.	Co-expression
SRP161830	Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer (RNA-Seq)	Constitutively active androgen receptor (AR) signaling confers resistance to AR-targeted therapies. Here we show that the ubiquitin-mediated proteolysis pathway plays a critical role in the degradation of AR and its variants, particularly variant 7 (AR-V7). AR/AR-V7 proteinhomeostasis (proteostasis) requires interaction of the E3 ubiquitin ligase STUB1 and HSP70complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 reduces AR/AR-V7 expression which significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason scores prostate tumors. Our results reveal a novel mechanism of AR-V7 modulation via proteostasis which could be targeted to reduce AR-V7 expression and overcome resistance to AR-targeted therapies. Overall design: A total of 6 samples were analyzed in this study. The study included 2 different castration-resisatnt prostate cancer (CRPC) cell lines, LNCaP-C42B-MDVR and CWR22Rv1. Individual cultures of each cell line were treated with DMSO vehicle control, apoptozole, or VER155008. Following treatment of the cells for 48 hours, total RNA was isolated and then submitted for RNA-sequencing analysis.	Co-expression
SRP161949	Profiling of gene expression using RNA-Seq in fibroblasts, iPSCs, iPSC-derived neurons and cells overexpressing Onecut transcription factors	Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we here used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced neuronal morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights the potential of ONECUT transcription factors for direct neuronal reprogramming. Overall design: Each RNA-Seq experiment was performed in duplicate (library constructed from different wells of the same cell line in the same cell culture experiment). Bclxl controls were generated for the overexpression. experiments.	Co-expression
SRP161982	Clinically relevant biomarker discovery in high-risk recurrent neuroblastoma	12 high-risk neuroblastoma cell lines sequenced using the Illumina Hi-Seq 2000 platform.	Co-expression
SRP161997	Unveiling the Role of the Most Impactful Cardiovascular Risk Locus Through Haplotype Editing at Cell	The 9p21.3 cardiovascular disease locus is the most influential common genetic risk factor for coronary artery disease, accounting for ~10-15% of disease among non-African populations. The ~60kb risk haplotype is human-specific and lacks coding genes, hindering efforts to decipher its function. Genetic studies implicate the 9p21.3 locus and other risk genes to effects in the vascular wall. Here,  we use genome editing to delete the entire risk on non-risk haplotype from the genomes of human iPSCs and perform genomewide transcriptional profiling along the timecourse of their differentiation into vascular smooth muscle cells (VSMCs). These studies identify a network of ~3000 genes governed by the risk haplotype in VSMCs that predict deficits in cell division, adhesion and contraction, which we confirmufunctionally. Remarkably, deleting the risk haplotype reverts VSMCs to resemble the non-risk VSMCs, suggesting that the risk region drives a cell state transition.  transcriptionally and functionally. . Deleting the risk haplotype reverts these cells to reverted to the non-risk of iPSCs we show that the non-risk haplotype has little effect on locus we produce iPSCs from risk and non-risk individuals, delete each haplotype using genome editing and generate vascular smooth muscle cells (VSMCs). We show that risk VSMCs exhibit aberrant adhesion and contraction, concomitant with dramatically altered global transcriptional changes that are enriched in previously identified cardiovascular disease genes and pathways. Unexpectedly, deleting the risk haplotype rescues VSMC transcriptional identity and function, while expressing the 9p21.3-associated long non-coding RNA ANRIL induces risk phenotypes in non-risk VSMCs. This studies shows that the risk haplotype dominantly predisposes VSMCs to adopt perturbed phenotypes associated with cardiovascular disease and establishes haplotype-edited iPSCs as powerful tools for functionally annotating human-specific variation in non-coding genomic regions. Overall design: RNA-seq proiles of 3 stages of human SMC differentiation starting from iPSC	Co-expression
SRP162003	Liver macrophages regulate metabolism through non-inflammatory factors	It is currently debated as to whether liver macrophage (LM) activation from an anti-inflammatory to pro-inflammatory phenotype contributes to obesity-induced metabolic diseases. Here we report that LMs do not undergo a pro-inflammatory phenotype switch in obesity-induced insulin resistance in mice and humans. Remarkably, immune response related genes remained also unchanged in fly immune cells (haemocytes) upon high fat feeding. However, unbiased transcriptomic analyses revealed that LMs produce non-inflammatory factors, such as insulin like growth factor binding protein 7 (Igfbp7), that directly regulate liver metabolism. Using a unique method to manipulate gene expression only in LMs in vivo, we discovered that IGFBP7 specifically produced by LMs binds the insulin receptor and induces lipogenesis and gluconeogenesis, two major pathways increased in metabolic diseases. This study shows that macrophages could contribute to insulin resistance independently of their inflammatory status and that targeting non-inflammatory factors produced by macrophages might represent a better strategy than anti-inflammatory drugs to tackle metabolic diseases.	Co-expression
SRP162014	Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts	The Wnt/b-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/b-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression. However, studies on the combined action of 1,25(OH)2D3 and Wnt factors in colon fibroblasts are lacking. Here we show by global transcriptomic studies that 1,25(OH)2D3 and Wnt3A have profound, additive, partially overlapping effects on the gene expression profile of CCD-18Co human colon myofibroblasts. Moreover, 1,25(OH)2D3 and Wnt3A inhibit CCD-18Co cell proliferation and migration, while 1,25(OH)2D3 reduces, but Wnt3A increases, their capacity to contract collagen gels (a marker of fibroblast activation). These data were largely confirmed in patient-derived primary colon normal fibroblasts and CAFs, and in fibroblasts from other origins. Our results indicate that 1,25(OH)2D3 and Wnt3A are strong regulators of colon fibroblast biology and contribute to a better knowledge of intestinal homeostasis and stromal fibroblast action in CRC. Overall design: RNA-sequencing analysis of three independent experiments of CCD-18Co human normal colon myofibroblasts treated with 1a,25-dihydroxyvitamin D3, Wnt3A, both, or vehicle for 24 hours	Co-expression
SRP162020	Antiviral and anti-inflammatory properties of novel anti-HIV candidate ABX464 promotes specifics RNA splicing while preserving cellular RNA integrity.	Purpose: To ensure that ABX464 acted specifically on HIV splicing and did not significantly or globally affect the splicing events of human genes, we used an assembly approach of HIV (YU2 strain) putative transcripts and human long non-coding sequences from paired-reads (2x75bp) captured on a NimbleGen SeqCap® EZ Developer Library (Roche/NimbleGen). Methods: Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal, followed by high-throughput RNAseq from custom SeqCap EZ capture libraries. Each raw dataset of the samples contained between 5 and 30 million paired-end reads (75 bp), with an average of approximately 12 million raw reads per sample. Results: The raw reads were then cleaned and assembled per library to generate contigs, giving an average of 930 contigs per sample for further analyses. Conclusions: Our results show that high-throughput analyses coupled with bioinformatics-specific tools offers a comprehensive and more accurate view of mRNA splicing within a cell. Overall design: We used buffy coats from HIV-negative individuals were obtained from the local blood donation center, then human peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll (Histopaque, Sigma) gradient centrifugation. Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal.	Co-expression
SRP162023	HantavaxTM vaccinated peripheral blood mononuclear cells (PBMCs) and sera analyses by transcriptomic and metabolomic profilings	Purpose: To annotate vaccine-induced protective immunity following vaccination and identify the dynamics of enriched modules over time, and determine whether and how transcriptomics and metabolomics data correlates. charge ratio) within a range of ions set from 50 to 1,000 from mass spectral data. The data from triplicate run were averaged and statistically analysed using SIMCA 14.1 Results: Based on neutralizing antibody titers, subjects were subsequently classified into three groups; non responders (NRs), low responders (LRs) and high responders (HRs). Post vaccination differentially expressed genes (DEGs) associated with innate immunity and cytokine pathways were highly upregulated. DEG analysis revealed a significant induction of CD69 expression in the HRs. High resolution metabolomics (HRM) analysis showed that correlated to the antibody response, cholesteryl nitrolinoleate and octanoyl-carnitine were significantly elevated in HRs, while chenodeoxycholic acid and methyl palmitate were upregulated in NRs and LRs, but not HRs. Additionally, gene-metabolite interaction revealed upregulated gene-metabolite couplings in, folate biosynthesis, nicotinate and nicotinamide, arachidonic acid, thiamine and pyrimidine metabolism in a dose dependent manner in HR group. Conclusions: Our data provide new insight into the underlying mechanisms of the HantavaxTM-mediated immunogenicity in humans. Our study illustrate the potential for transcriptomics and untargeted metabolomics to identify genes and metabolites involved in immune responses which may propose a targeted vaccine design in future. Overall design: Systems vaccinology analyses were performed based on two different approaches: vaccination instance and responsiveness to the vaccine. In our study we vaccinated a total of 20 subjects with 4 doses. However, 1 subject (subject or sample # 3) was excluded from transcriptomic study after first vaccination due to abnormal antibody titer.  Hence, we have 19 subjects vaccinated 4 time but the samples were collected before 1st and after 2nd, 3rd and 4th vaccination (i.e., sample collections was performed at 4 time points).  This Series contains a total of 76 samples (19 x 4).	Co-expression
SRP162073	Transcriptome profiling of patients with critical illness myopathy	Critically ill, immobilized and mechanically ventilated intensive care unit (ICU) patients develop severe muscle wasting and impaired muscle function. This condition is referred to as critical illness myopathy (CIM). This study aimed to obtain the gene signature of CIM. Percutaneous conchotome muscle biopsies from the tibialis anterior muscle was used for RNA sequencing from seven mechanically ventilated ICU patients and six control subjects.	Co-expression
SRP162125	Pharmacodynamic Biomarkers and Differential Effects of TNF- and GM-CSF-Targeting Biologics in Rheumatoid Arthritis	A major unmet need in rheumatoid arthritis (RA) is the choice of treatment options for patients with an inadequate response to anti-TNF agents (anti-TNF–IR). In order to identify pharmacodynamic biomarkers and assess differential effects of TNF- and non–TNF-targeting agents on RA patients with an inadequate response to anti-TNF–IR in comparison with biologic-naïve patients, peripheral protein markers and gene expression levels in association with clinical response posttreatment in two disease strata were assessed in disease-modifying antirheumatic drug (DMARD)-IR and anti-TNF-IR patients. Serum proteomics results indicated the existence of specific pharmacodynamic markers for golimumab and mavrilimumab, regardless of prior anti-TNF treatment. In contrast, both antibodies induced early and sustained suppression of RA disease markers, including IL-6, CRP, IL2RA, and MMP1, in DMARD-IR patients. Golimumab-induced early changes rapidly returned toward baseline concentrations in anti-TNF–IR patients, whereas mavrilimumab-induced changes were maintained through Day 169. RNA sequencing demonstrated gene expression changes at Day 169 after administration of mavrilimumab but not golimumab in anti-TNF–IR patients. Additionally, receiver operating characteristic curve and regression analysis showed the association of early IL-6 change and subsequent clinical responses to golimumab in anti-TNF-IR patients. Our results revealed golimumab- and mavrilimumab-specific pharmacodynamic biomarkers, and demonstrated differential biomarker-treatment relationships in anti-TNF–IR and DMARD-IR patients respectively. Early IL-6 change after anti-TNF antibody treatment may be a potential predictive biomarker for selection of different treatment regimens in anti-TNF-IR patients. Overall design: For RNAseq study, PAXgene whole blood tubes were collected from 75 DMARD-IR and 63 anti-TNF-IR RA patients at baseline and at day 169 of post-treatment by golimumab and marvrilimumab. Whole transcriptome profiles of these patients and 20 health donors were generated from RNAseq data. Differentially expressed genes (DEG) resulted from drug-treatment were identified by pairwise comparisons between post-treatment and baseline data of the same patients. DEGs related with RA disease were identified by comparing baseline data with the data of health donors.	Co-expression
SRP162136	Profiling of RNAs downregulated by influenza A virus PA-X ribonuclease	The goal of this analysis was to investigate the targets of the influenza A host shutoff ribonuclease PA-X. We profiled the relative levels of cellular RNAs in cells infected with influenza A virus (A/PuertoRico/8/1934 H1N1) comparing wild-type and mutants that make reduced levels of PA-X and/or make a truncated and inactive PA-X. We also profiled relative RNA levels in cells overexpressing wild-type PA-X or a catalytically inactive mutant (D108A). Overall design: for extopic expression, PA-X (from the A/PuertoRico/8/1934 H1N1 (PR8) strain) was expressed in A549 cells using a doxycyline-inducible transgene for 18 hrs; for infection, A549 cells were infected with the wild-type PR8 strain or mutant strain that carried mutations that reduce PA-X production or activity for 15 hrs. rRNA deplete RNA was subjected to high-throughput sequencing	Co-expression
SRP162148	Simultaneous profiling of sexually transmitted bacterial pathogens, microbiome, and concordant host response in cervical samples using whole transcriptome sequencing analysis	We examined the potential for characterization of host, pathogen and microbiome interactions at a molecular level and identification of novel, outcome-relevant biomarkers in a single, easily obtained, clinical specimen using total RNA-seq. Overall design: Examination of human cervical swabs via total RNA-seq CT = Chlamydia trachomatis GC = Neisseria gonorrhoeae MG = Mycoplasma genitalium TV = Trichomonas vaginalis	Co-expression
SRP162175	Identifying transcripts that are transcriptinoally regulated by CBFB and RUNX1 using RNAseq	Using RNAseq to identify differentially expressed transcripts between CBFB wild type (WT) and knockout (KO) or between RUNX1 wild type (WT) and knockout (KO) MCF10A cells. Overall design: Three repeats for CBFB KO and CBFB WT MCF10A cells. Four repeats for RUNX1 KO and RUNX1 WT MCF10A cells. One CBFB KO clone (#751) and two RUNX1 KO clones (5008 and 5010) were used.	Co-expression
SRP162188	Bulk RNA-seq U2OS cells treated with small molecules	We report the transcriptional changes associated with treatment of U2OS osteosarcoma cell line with DMSO, AML108, AMN107, BGW675, JAA804, LEE837 and LHD510. Overall design: U2OS cells were treated with 100nM, 1000nM and 10000nM of DMSO, AML108, AMN107, BGW675, JAA804, LEE837 and LHD510 for 12 hrs and subjected to RNA-seq.	Co-expression
SRP162214	Human Bone Marrow Assessment by Single Cell RNA Sequencing, Mass Cytometry and Flow Cytometry [scRNA]	New techniques for single-cell analysis have led to insights into hematopoiesis and the immune system, but the ability of these techniques to cross-validate and reproducibly identify the biological variation in diverse human samples is currently unproven. We therefore performed a comprehensive assessment of human bone marrow cells using both single-cell RNA sequencing and multiparameter flow cytometry from twenty healthy adult human donors across a broad age range. These data characterize variation between healthy donors as well as age-associated changes in cell population frequencies. Direct comparison of techniques revealed discrepancy in the quantification of T lymphocyte and natural killer cell populations. Orthogonal validation of immunophenotyping using mass cytometry demonstrated good correlation with flow cytometry. Technical replicates using single-cell RNA sequencing matched robustly, while biological replicates showed variation. Given the increasing use of single-cell technologies in translational research, this resource serves as an important reference dataset and highlights opportunities for further refinement. [Funding source] Project Number: 1ZIAHL006163-05 Contact PI / Project Leader: HOURIGAN, CHRISTOPHER Title: DETECTION, PREVENTION AND TREATMENT OF ACUTE MYELOID LEUKEMIA (AML) RELAPSE. Awardee Organization: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE Overall design: Using standard operating procedures, mononuclear cells from 20 healthy donors' bone marrow aspirates were isolated using Ficoll density gradient separation and cryopreserved in 90% FBS/ 10% DMSO for storage in 72 liquid nitrogen. scRNAseq was performed using 10X Genomics Single Cell 3' Solution, version 2 according to manufacturer's instructions (protocol rev A). Libraries were sequenced on HiSeq3000. Droplet-based scRNAseq of bone marrow mononuclear cells for all donor samples was performed with goal minimum sequencing depth of 50,000 reads/cell and detected a mean of 880 genes/cells (range 575-1,390 gene/cell).	Co-expression
SRP162245	MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.	p493 RNA-seq in the MYC on and MYC off conditions Overall design: For RNA-seq analysis of MYC-ON versus MYC-OFF states, the P493-6 cells, which were engineered to have tetracycline-repressible ectopic MYC, were supplemented with 0.1 µg/mL tetracycline (Sigma) for 48 hours before harvesting for the MYC-OFF state. The RNA from these cells were compared with MYC-ON cells that had continuously expressed MYC for 48 hours grown contemporaneously with the MYC-OFF cells.	Co-expression
SRP162268	In situ 10-cell RNA sequencing in tissue and tumor biopsy samples	We combined the tissue preservation and single-cell resolution of laser capture with an improved preamplification procedure enabling RNA sequencing of 10 microdissected cells.  This in situ 10-cell RNA sequencing (10cRNA-seq) can exploit fluorescent reporters of cell type in genetically engineered mice and is compatible with freshly cryoembedded clinical biopsies from patients.   By using small pools of microdissected cells, 10cRNA-seq thus results in improved per-cell reliability and sensitivity beyond existing approaches for single-cell RNA sequencing (scRNA-seq).  Accordingly, in multiple tissue and tumor settings, we observe 1.5–2-fold increases in genes detected and overall alignment rates compared to scRNA-seq.  Combined with existing approaches to deconvolve small pools of cells, 10cRNA-seq offers a reliable, unbiased, and sensitive way to measure cell-state heterogeneity in tissues and tumors. Overall design: 10-cell samples from various tissue sources captured by laser capture microdissection. mRNA was extracted and PCR amplified for RNA-sequencing	Co-expression
SRP162274	RNA-seq of MDA-MB-231 siCt and siAXL	Triple-Negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with poor prognosis due to its propensity to form metastases. Unfortunately, the current treatment options are limited to chemotherapy such that identification of actionable targets are needed. The receptor tyrosine kinase AXL plays a role in the tumor cell dissemination and its expression in TNBC correlates with poor patients? survival. Here, we explored whether exploiting an AXL knockdown gene signature in TNBC cells may offer an opportunity for drug repurposing. To this end, we queried the PharmacoGx pharmacogenomics platform with an AXL gene signature which revealed Phenothiazines, a class of Dopamine Receptors antagonists (Thioridazine, Fluphenazine and Trifluoperazine) typically used as anti-psychotics. We next tested if drugs may be active to limit growth and metastatic progression of TNBC cells, similarly to AXL depletion.  We found that the Phenothiazines were able to reduce cel  l invasion, proliferation and viability, and also increased apoptosis of TNBC cells in vitro. Mechanistically, these drugs did not affect AXL activity but instead reduced PI3K/AKT/mTOR and ERK signaling. When administered to mice bearing TNBC xenografts, these drugs showed were able to reduce tumor growth and metastatic burden. Collectively, these results suggest that these antipsychotics are novel anti-tumor and anti-metastatic agents that could potentially be repurposed, in combination with standard chemotherapy, for use in TNBC. Overall design: RNA-seq of the Triple Negative Breast Cancer cell line MDA-MB-231 treated with siCt or siAXL Differential gene expression profile between MDA-MB-231 siCt and siAXL by RNA sequencing (Illumina HiSEq 2000)	Co-expression
SRP162285	RNA-seq of human adnexal tumors	Transcriptome analysis and comparisons of human adnexal tumors of the skin to find tumor subtypes, disease bio-markers, drivers, to compare their gene profiles to the ones of adenoid cystic carcinoma of salivary glands. Improving the understanding of this disease in context to other cancer.	Co-expression
SRP162300	Vertebrate species Raw sequence reads	Skeletal stem and progenitor cells from vertebrate species	Co-expression
SRP162329	CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary (I)	Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The role of SMARCA4 in SCCOHT cells. Total RNA was quantified using a NanoDrop Spectrophotometer ND-1000 (NanoDrop Technologies, Inc.) and its integrity was assessed using a 2100 Bioanalyzer (Agilent Technologies). Libraries were generated from 250 ng of total RNA using  the TruSeq stranded mRNA Sample Preparation Kit (Illumina), as per the manufacturer's recommendations. Libraries were quantified using the Quant-iT™ PicoGreen® dsDNA Assay Kit (Life Technologies) and the Kapa Illumina GA with Revised Primers-SYBR Fast Universal kit (Kapa Biosystems). Average size fragment was determined using a LabChip GX (PerkinElmer) instrument.	Co-expression
SRP162331	CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary (II)	Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.	Co-expression
SRP162332	Human Pancreatic Islets Expressing HNF1A Variant Have Defective ß cell Transcriptional Regulatory Networks	Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found donor islets contained ß cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in hepatocyte nuclear factor 1 alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment. Overall design: Total of 12 samples were analyzed, 10 were non-diabetic control donors and 2 were  HNF1A donors. GEO accession number for non-diabetic controls are GSE116559(ß cell controls) and GSE106148 (a cell controls).  a cells and ß cells were FACS-sorted and RNA was extracted from each of these samples. RNAseq was performed on all 12 samples	Co-expression
SRP162342	RNA-Seq of LRRK2 G2019S Parkinson's iPSC-derived astrocytes	Non-neuronal cell types such as astrocytes can contribute to Parkinson's disease (PD) pathology. The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is one of the most common known causes of familial PD. To characterize its effect on astrocytes, we developed a protocol to produce midbrain-patterned astrocytes from human induced pluripotent stem cells (iPSCs) derived from PD LRRK2 G2019S patients and healthy controls. In order to understand the effect of this mutation on astrocyte function, we compared the gene expression profiles of iPSC-derived midbrain-patterned astrocytes from PD patients with those from healthy controls. Overall design: Bulk RNA-Seq profiles of human iPSC-derived midbrain-patterned astrocytes from 7 donors, including 4 patients with Parkinson's disease who carry the LRRK2 G2019S mutation, and 3 healthy control individuals	Co-expression
SRP162356	Global Long Terminal Repeat activation participates in establishing the unique gene expression program of classical Hodgkin Lymphoma [Primary RNA-Seq]	Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported that a member of the THE1B class of LTR elements in classical Hodgkin Lymphoma (cHL) acted as a promoter for the growth factor receptor gene CSF1R and that expression of this gene is required for tumor survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression program is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases. Overall design: RNA-Seq in laser capture microdissected (LCM) tumour (TU) and non tumour cells (NTC) primary HL material from patient samples	Co-expression
SRP162358	Global Long Terminal Repeat activation participates in establishing the unique gene expression program of classical Hodgkin Lymphoma [RNA-Seq]	Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported that a member of the THE1B class of LTR elements in classical Hodgkin Lymphoma (cHL) acted as a promoter for the growth factor receptor gene CSF1R and that expression of this gene is required for tumor survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression program is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases. Overall design: RNA-Seq in HL, NHL, NHL+PMA cell lines	Co-expression
SRP162384	Genomic expression analysis of K562 cells expressing shRNA targeting lncRNA-IIRX and control cells	LncRNA-IIRX plays critical role in Bcr-Abl-induced tumorigenesis. To discover its mechanisms underlying cellular transformation by Bcr-Abl oncogene, genome-wide mRNA expression was measured by RNA-seq in K562 cells expressing shRNA targeting lncRNA-IIRX and control cells. We identified many genes with differential expression in K562 cells after knocking down lncRNA-IIRX. Overall design: RNA samples from K562 cells expressing shRNA targeting lncRNA-IIRX and control cells were collected. Six total RNA samples from three independent experiments were extracted and used for RNA-seq.	Co-expression
SRP162430	Intrinsic immunity employs 2',5'-oligoadenylate signaling to establish privileged translation of interferons ß and l	RNAseq of control vs poly-IC treated A549 cells shows IFN induction. Overall design: Poly-A pulldown and RNAseq	Co-expression
SRP162455	Next Generation Sequencing Facilitates Quantitative Analysis of Gene expression profile in CD8+ T cells with TOX-overexpression	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived TOX associated transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis. Methods: mRNA profiles of human CD8+ T cell overexpressed by TOX lentivirus or NC lentiviruswere generated by deep sequencing, in triplicate, using Illumina. qRT–PCR validation was performed using TaqMan and SYBR Green assays          Conclusions: Our study represents the first detailed analysis of TOX associated transcriptomes generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: Gene expression profile in CD8+ T cells with TOX-overexpression	Co-expression
SRP162461	Placenta and decidua single cell RNA-seq.	No description.	Co-expression
SRP162465	STX4 Over-Expression in Human islets	We have used RNA-seq to identify transcripts expressed in human islets harboring beta cells transduced  to overexpress STX4 and induce chemokine ligand by adenoviral transduction Overall design: 3 human islets preparations examed under 2 conditions, beta cell specific expressed STX4 and control GFP. A human islets preparation tested under no tranduction and ctrol GFP transduction by adenovirus.	Co-expression
SRP162503	Vitiligo patient iPSCs and iPSCs-derived melanocytes	To detect the molecular feature of patient iPSCs-derived melanocytes.	Co-expression
SRP162524	Characterization and therapeautic application of mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells	Here, human pluripotent stem cells (including hiPSC and hESC) were induced to differentiate to mesenchymal stem cells (MSC) through the intermediate stage of neuromesoderm (NMP). We sequenced mRNA samples at different stages during NMP-MSC differentiation of human pluripotent stem cells to generate the gene expression profiles of these cells. Overall design: 12 samples, including undifferentiated hPSC (hiPSC, H1, and H9), hPSC-NMP-derived paraxial mesoderm (hPSC-NMP-PM; including hiPSC-NMP-PM, H1-NMP-PM, and H9-NMP-PM), hPSC-NMP-MSC (Passage 5; including hiPSC-NMP-MSC, H1-NMP-MSC, H9-NMP-MSC1, and H9-NMP-MSC2), BMSC1 (Passage 5), and BMSC2 (Passage 5), were analyzed.	Co-expression
SRP162552	Human Bone Marrow Assessment by Single Cell RNA Sequencing, Mass Cytometry and Flow Cytometry [bulk]	Bulk RNA Sequencing of Healthy Bone Marrow Mononuclear Cells Overall design: Using standard operating procedures, mononuclear cells from bone marrow aspirates were isolated using Ficoll density gradient separation and cryopreserved in 90% FBS/ 10% DMSO for storage in liquid nitrogen. RNA was harvested from thawed cell vials of BMMCs using AllPrep kits (QIAGEN). Libraries were prepared using TruSeq Stranded Total RNA Sample Preparation Kit (Illumina) with 1ug of RNA input. Sequencing was performed by paired-end 75 nt on Illumina HiSeq 3000.	Co-expression
SRP162572	Gene expression perturbation upon over-expression of a new PPARG isoform	PPAR? regulates glucose and lipid homeostasis, insulin signaling and adipocyte differentiation. Here we report the skipping of exon 5 as legitimate splicing event generating PPAR??5, a new truncated isoform lacking the ligand binding domain. PPAR??5 is endogenously expressed in human adipose tissue and during adipocyte differentiation, lacks the ligand-dependent transactivation ability and acts as dominant negative reducing PPAR? activity. Ligand-mediated PPAR? activation induces exon 5 skipping in a negative feedback loop, suggesting alternative splicing as a new mechanism regulating PPAR? activity. PPAR??5 over-expression modifies PPAR?-induced transcriptional network, significantly impairing the differentiation ability of adipocyte precursor cells. Additionally, PPAR??5 expression in subcutaneous adipose tissue positively correlates with BMI in two independent cohorts of obese and diabetic patients. From a functional perspective, PPAR??5 mimics PPARG dominant negative mutated receptors, possibly contributing to adipose tissue dysfunctions. These findings open unexplored scenario in PPARG regulation and PPAR?-related diseases. Overall design: Three samples analyzed: 1) HEK293 cells treated with troglitazone; 2) HEK293 cells treated with troglitazone and over-expressing PPARG (plasmid vector); 3) HEK293 cells treated with troglitazone and co-expressing canonical PPARG and PPARD5 (plasmid vectors).	Co-expression
SRP162574	Next Generation Sequencing Analyzes Transcriptome after  TMEM126A overexpression and knockdown	Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to identify the differential expression genes after TMEM126A overexpression or knockdown. Methods:Total cell mRNA profiles of TMEM126A-knockdown MDA-MB-231 cells (sh-NC vs shT126A) and TMEM126A-overexpression MCF10-Ca1a cells(pCDH vs T126A) were generated by deep sequencing, using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the gene-level quantification, analysis of differentially expressed genes (DEGs), cluster analysis, GO and KEGG enrichment and qRT–PCR validation was performed using SYBR Green assays. Conclusions: Our study represents the first detailed analysis of TMEM126A overexpression and knockdown transcriptomes, with 2 cell lines, generated by RNA-seq technology. Our results show that NGS offers a comprehensive information for the downstream molecular mechanism. Overall design: Using Next Generation Sequencing to analyze the differential gene expression beteewn pCDH vs TMEM126A overexpression in MCF10-Ca1a and sh-NC vs TMEM126A knockdown in MDA-MB-231.	Co-expression
SRP162662	The Human Testis Cell Atlas via Single-cell RNA-seq (Infant scRNA-seq data set)	Human adult spermatogenesis involves a balance of spermatogonial stem cell self renewal and differentiation, alongside complex germline-niche interactions. To better understand, we performed single cell RNA sequencing of ~7000 testis cells from three healthy men of peak reproductive age. Our analyses revealed multiple distinctive transcriptional 'states' of self-renewing and differentiating spermatogonia, the cellular stages of gametogenesis, five niche cells (Leydig, Myoid, Sertoli, Endothelial, macrophage) and insights into germline-niche communication. Spermatogenesis was reconstructed computationally, which identified sequential coding, noncoding, and repeat-element transcriptional signatures. A new, developmentally early and likely quiescent spermatogonial state is identified (GFRA1-/ETV5-/ID4+/UTF1+/FGFR3+). Notably, certain epigenetic features combined with nascent transcription analyses suggest considerable plasticity within certain spermatogonial populations/states. Key findings were validated via RNA and protein staining. Taken together, we provided the first “Cell Atlas” of the adult human testis, and provide multiple new insights into germ cell development and germ cell – niche interaction. Overall design: We isolated single testicular cell from two infant (13 months old). Two technical replicates were performed for each individual.	Co-expression
SRP162743	Dilated cardiomyopathy vs Myocarditis	Sequencing data of biopsies from Myocarditis and DCM patients Overall design: Sequencing from 11 DCM and 5 myocarditis heart biopsy samples	Co-expression
SRP162816	RNA sequencing of CFU-GM derived from CD34+ cells expressing PRR14L shRNA or a scramble control	Here we are using RNA-Seq to study the effect of PRR14L knockdown on transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage. Overall design: RNAseq was performed on individual CFU-GM with shRNA-mediated PRR14L knockdown and scramble control to study the effects of PRR14L knockdown on the transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage.	Co-expression
SRP162841	Transcriptome measurements after knocking out the UMLILO lncRNA	Purpose: Assess whether knocking out the UMLILO lncRNA altered the expression of genes transcribed within the CXCL chemokine TAD Outcome:  To confirm whether the effect of UMLILO was limited to the CXCL TAD. Adeno-associated viral vectors (AAVs) were constructed that contain CRISPR/Cas9 and guides targeting UMLILO to delete the full length UMLILO transcript. RNAseq was performed on a transduced THP-1 population to verify genome-wide effects of UMLILO depletion. This revealed that IL8, CXCL1, 2, 3 transcription was abrogated, but a similar effect was not seen for genes located outside of the CXCL TAD boundary Overall design: AAVs were constructed that contain CRISPRs that harness non homologous end joining (NHEJ) to target UMLILO by deleting the genomic region encoding UMLILO, but not its promoter. The THP-1 monocytic cell line was transduced with the AAVs containing the CRISPRs for 1.5 weeks. Controls were transduced with AAV vector plasmids expressing SpCas9.	Co-expression
SRP162873	RNA sequencing in healthy controls, intermittent claudicant, and CLI patient skeletal muscle	Gastrocnemius muscle biopsies were obtained from 15 health older adults without peripheral artery disease (PAD), 20 PAD patients with intermittent claudication, and 16 patients with critical limb ischemia undergoing limb amputation.  Gene expression analysis was performed using RNA sequencing analysis. Overall design: Examination of gene expression differences across the clinical spectrum of PAD (healthy vs. claudicant vs. critical limb ischemia)	Co-expression
SRP162879	The Regulation of IFN Type I Pathway Related Genes RSAD2 and ETV7 Specifically Indicate Antibody-Mediated Rejection After Kidney Transplantation	We performed  total RNA-Seq and compared expression levels of genes of whole blood cells isolated from patients after kidney transplantation with stable graft function, antibody mediated- and t cell mediated graft rejection. Overall design: Whole blood cells were isolated from 6 patients with stable graft function, 6 patients with histologically verified antibody mediated graft rejection episode and 4 patients with histologically verified T cell mediated graft rejection after kidney transplantation. Total RNA was extracted and cDNA libraries for total RNA sequencing were generated using “TruSeq® Stranded Total RNA Library” kit (Illumina, San Diego, CA, USA).	Co-expression
SRP162931	Genomic Analysis of DNA Repair Genes and Androgen Signaling in Prostate Cancer	Abstract    Background. The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has important translational implications.    Methods. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription.    Results. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells.    Conclusions. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer. Overall design: RNA was extracted from PC3-AR, VCaP, and LNCaP cells under untreated and androgen (2 nM, R1881) treated conditions. A total of 21 samples were sequenced with 3 replicates for each condition.	Co-expression
SRP162991	Gene expression analysis in response to hypoxic pathway inhibition	Gene expression analysis of HeLa cells exposed to hypoxia (1% Oxygen), treated with a PHD inhibitor (IOX2) or treated with a VHL inhibitor (VH032) for 16 hours Overall design: 3 biological replicates of HeLa cells exposed to hypoxia (1% Oxygen), PHD inhibitor (250 µM of IOX2) or  VHL inhibitor (250 µM VH032), comparing to vehicle control (0.05% DMSO). Treatments were performed for 16 hours	Co-expression
SRP163027	Differential analysis of gene expression profiles in peripheral blood cells of patients with cervical lesions	Using RNA-sequencing analysis of peripheral blood cells from 11 cervical cancer patients, 21 cervical intraepithelial neoplasia patients and 19 healthy controls, we identified a group of differentially expressed genes. A real time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to the validation of candidate markers in the blood of 115 patients and 46 healthy controls. The results suggest that a six-gene predictor set (GZMB, NDUFA1, GPR84, NUAK1, AGAP1 and CIR1) can be used as candidate genes for the detection of cervical cancer. Overall design: The mRNA profiles of peripheral blood cells from 11 cervical cancer patients, 21 cervical intraepithelial neoplasia patients and 19 healthy control participants were sequenced using Illumina 2500.	Co-expression
SRP163035	CRISPR activation of long non-coding RNAs transiently expressed during cortical neuron differentiation associated with Field, et al, Stem Cell Reports 2018	4 transiently expressed long non-coding RNAs that were identified in human and non-human primate cortical organoid differentiation were activated out of context in HEK293FT cells using CRISPRa. Overall design: 5 sgRNAs targeting TrEx lncRNAs or non-targeting controls were co-transfected with dCas9-VP64 into HEK293FT cells. Successfully transfected cells were selected by puromycin at 24 hours and harvested for RNA at maximal expression, 48 hours post transfection. RNA-seq libraries were prepared in biological triplicates with the NEXTflex Rapid Directional qRNA-Seq Library Prep Kit (PerkinElmer).	Co-expression
SRP163049	Beta catenin knock out in hESC	Comparing beta catenin knock out hESCs and wildtype hESCs to understand transcript differences between the two cell types	Co-expression
SRP163059	GREB1 amplifies androgen receptor output in prostate cancer and contributes to antiandrogen resistance	Genomic amplification of the androgen receptor (AR) is an established mechanism of antiandrogen resistance in prostate cancer.  Here we show that the magnitude of AR signaling output, independent of AR genomic alteration or expression level, also contributes to antiandrogen resistance, through upregulation of the coactivator GREB1.  We demonstrate 100-fold heterogeneity in AR output within cell lines and show that cells with high AR output have reduced sensitivity to enzalutamide.  Through transcriptomic and shRNA knockdown studies, together with analysis of clinical datasets, we identify GREB1 as a gene responsible for high AR output.  We show that GREB1 is an AR target gene that amplifies AR output by enhancing AR DNA binding and promoting p300 recruitment.  GREB1 knockdown in high AR output cells restores enzalutamide sensitivity in vivo.  Thus, GREB1 is a candidate driver of enzalutamide resistance through a novel feed forward mechanism. Overall design: RNA-seq was performed on following samples, LNCaP prostate cancer cells with 1) low or high AR activity (AR-low vs AR-high), 2) high AR activity infected with shRNA against Renilla or GREB1, treated with vehicle or DHT (AR-high shRenilla veh or DHT vs. AR-high shGREB1 veh or DHT)	Co-expression
SRP163126	mRNA-seq for etoposide-treated TLP-knockdown cells	We explored the mechanism by which TLP affects DNA damage response. We performed mRNA-seq analysis of non-treated and etoposide-treated samples in control and TLP-knockdown cells. We show that TLP is critical for global transcriptional repression after double-strand DNA breaks (DSBs). Overall design: Examination of non-treated and etoposide-treated samples in control and TLP-knockdown cells	Co-expression
SRP163150	Genome-wide expression analysis of human hTert immortalized fibroblasts after downregulation of MCM2	Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM2	Co-expression
SRP163151	Genome-wide expression analysis of human hTert immortalized fibroblasts after donwregulation of MCM7	Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM7	Co-expression
SRP163173	Integrative epigenetic taxonomy of primary prostate cancer [RNA-Seq]	The Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most epigenetic profiling has been performed in cell lines or limited tissue samples. To comprehensively study the epigenetic landscape, we complemented RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) in 100 primary prostate carcinomas. Integrative molecular subtyping of the five data streams revealed three major subtypes of which two were clearly TMPRSS2-ERG dictated. Importantly, a third novel subtype was identified, with low AR chromatin binding and activity, even though the receptor was clearly expressed. While positive for neuroendocrine-hallmark genes, these tumors were copy number-neutral with low mutation burden, significantly depleted for genes characteristic of poor-outcome associated luminal B-subtype. We present a rich novel resource on transcriptional and epigenetic control in prostate cancer, revealing a tight control of gene regulation differentially dictated by AR over the three subtypes. Overall design: RNA-seq data for primary prostate carcinomas	Co-expression
SRP163265	Next-generation RNA sequencing to determine changes in gene expression during breast cancer progression	Purpose: The goal of the study is to compare NGS-derived transcriptome in an isogenic breast cancer progression model cell line system. By comparing the protein-coding and noncoding gene expression of normal versus tumorigenic breast cancer cell lines, we will be able to identify genes that show aberrant expression during breast cancer progression. Methods: We isolated poly A + RNA from four isogenic mammary epithelial cell lines showing various stages of breast cancer progression. The model system comprises of 4 isogenic cell lines, categorized as M1-M4. M1 represents the normal, non-tumorigenic, immortalized MCF10A cells. Transfection of MCF10A with activated T24-HRAS and selection by xenografting generated the M2 (MCF10AT1k.cl2) cell line, which is highly proliferative and gives rise to premalignant lesions with the potential for neoplastic progression. M3 (MCF10Ca1h) and M4 (MCF10CA1a.cl1) were derived from occasional carcinomas arising from xenografts of M2 cells. M3 gives predominantly well-differentiated low-grade carcinomas on xenografting, while M4 gives rise to relatively undifferentiated carcinomas and colonizes to the lung upon injection of these cells into the tail vein. We performed paired-end deep sequencing (190-260 million reads/sample) of poly A+ RNA isolated from these cells that were cultured as 3D acini in biological duplicates. Reads of the samples were trimmed for adapters and low-quality bases using Trimmomatic software before alignment with the reference genome (Human - hg19) and the annotated transcripts using STAR. The average mapping rate of all samples is 96%. Unique alignment is above 87%. There are 3.74 to 4.07% unmapped reads. The mapping statistics are calculated using Picard software. The samples have 0.59% ribosomal bases. Percent coding bases are between 67-72%. Percent UTR bases are 23-26%, and mRNA bases are between 94-96% for all the samples. Library complexity is measured in terms of unique fragments in the mapped reads using Picard's MarkDuplicate utility. The samples have 31-52% non-duplicate reads. In addition, the gene expression quantification analysis was performed for all samples using STAR/RSEM tools. Both the normalized count and the raw count are provided as part of the data delivery. Results: Using an optimised data analysis workflow, we mapped ~190-250 million reads/sample and identified expression of 17396 protein-coding genes and 11509 long noncoding RNA genes. We initially compared gene expression between M1 and M4 cells. 4668 genes (2815 protein coding and 1853 lncRNAs) showed ~2 fold change in their expression between M1 and M4 cells in both biological repeats. 1159 out of the 1853 deregulated lncRNAs showed 2-fold upregulation in M4 cells in both repeats. On the other hand, 694 of lncRNAs displayed reduced levels in M4 compared to M1 cells. Further, we noticed that natural antisense transcripts (NATs) comprised one of the largest types of lncRNAs (504 out of 1853) that showed deregulation in M4 cells. Conclusion: Our study revealed differential expression of thousands of protein-coding and long noncoding RNAs during breast cancer progression using the isogenic cell line model system. This data set will act as a rich resource for downstream mechanistic studies to determine the role of these differentially expressed genes in breast cancer progression. Overall design: Poly A+ RNA from M1, M2, M3 and M4 cells (all grown in 3D acini in matrigel as biological duplicates) for 8-10 days were sequenced on HiSeq using Illumina TruSeq mRNA Prep Kit RS-122-2101 and paired-end sequencing. The samples have 163 to 256 million pass filter reads with a base call quality of above 94% of bases with Q30 and above.	Co-expression
SRP163419	Transcriptomic Profile of OCI-AML-20 Cell Line	Acute myeloid leukemia (AML) is a complex, heterogeneous disease with variable outcomes following curative intent chemotherapy. AML with inv(3) is a genetic subgroup characterized by low response rate to induction type chemotherapy and hence is among the worst long term survivorship of the AMLs. Here, we present RNA-Seq transcriptome data from OCI-AML-20, a new AML cell line with inv(3) and deletion of chromosome 7. Overall design: RNA-Seq transcriptome analysis of OCI-AML-20 cell line with three biological replicates.	Co-expression
SRP163432	Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes is Associated with Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy [RNA-Seq]	Mutations in the LMNA gene causes set of disorders collectively referred to as laminopathies that  include dilated cardiomyopathy. Lamin A/C proteins a components of nuclear lamina forms distinct nuclear domains called lamina associated domains (LADs). The roles of LADs in DCM is not known.  To identify LADs and characterize their associations with CpG methylation and gene expression in human cardiac myocytes isolated from patients with DCM and controls we performed   Chromatin immunoprecipitation-sequencing (ChIP-Seq), reduced representative bisulfite sequencing (RRBS), and RNA-sequencing (RNA-Seq) in 5 control and 5 DCM hearts with defined pathogenic variants in the LMNA gene. LADs are redistributed in DCM, are associated with CpG methylation and suppressed transcription, contributing to the pathogenesis of DCM in laminopathies. Overall design: integrated analysis  of  ChIP-seq for LMNA from Cardiac myocytes and RNA-seq and RRBS  from  5 control and 5 DCM human heart sample	Co-expression
SRP163470	RNAseq of CD8+ and CD8- MAIT cells in human peripheral blood	Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8a co-receptor (CD8+), with a smaller subset lacking both CD4 and CD8 (DN). However, it is unclear if these two MAIT cell sub-populations distinguished by CD8a represent functionally distinct subsets. To address this, we investigated the phenotypic, transcriptional, and functional differences between CD8+ and DN MAIT cells using human samples from peripheral blood, mucosal tissues, and fetal tissues. Overall design: We FACS sorted CD8+ and CD8- MAIT cells from human peripheral blood and performed bulk RNAseq on these cells	Co-expression
SRP163478	Wipi1 is a Genetic Hub that Mediates Right Ventricular Failure	Right ventricular dysfunction (RVD) independently predicts worse outcomes in both heart failure (HF) and pulmonary hypertension (PH), irrespective of their etiologies. Yet no evidence-based therapies exist for RVD and progression towards RV failure (RVF) can occur in spite of optimal medical treatment of HF or PH. This disparity reflects our insufficient understanding of the molecular pathophysiology of RVF. To identify molecular mechanisms that may uniquely underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using weighted gene co-expression network and module-phenotype analyses, we identified a 279-member gene module that correlated significantly and specifically with RVF. Within this module, WIPI1 served as a genetic hub, HSPB6, SNAP47, and MAP4 as drivers, and PRDX5 as a repressor of RVF. We subsequently confirmed the ventricular specificity and temporal relationship of Wipi1, Hspb6, and Map4 transcript expression changes in murine models of pressure overload induced RV failure versus LV failure and subsequently uncovered differential dysregulation of autophagy in the failing RV versus the failing LV, namely a shift towards excessive non-canonical, Beclin1-independent, Wipi1/LC3II-mediated autophagy in RVF. In vitro siRNA silencing of Wipi1 partially protected isolated neonatal rat ventricular cardiac myocytes against aldosterone-induced failing phenotype. Moreover, silencing Wipi1 blunted mitochondrial superoxide production and limited non-canonical autophagy in this in vitro RVF model. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and autophagy in cardiac myocytes. Inhibition of Wipi1 may hold promise as a therapeutic target for RVF. Overall design: Examination of RNAseq results from Left and Right Ventricles of 15 individuals, 5 control, 5 left-sided Heart Failure, 5 bi-ventricular Heart Failure	Co-expression
SRP163491	MYCN knock-down leads to DNA-repair deficiency in human neuroblastoma (RNA-Seq)	We knock down MYCN in human neuroblastoma cell line by RNAi. MYCN knock-down caused global epigenome change, including nucleosome gain on key DNA-repair genes and promoter H3K9ac down regulation. Overall design: mRNA gene expression profiles of ctrl/MYCN-kd in human neuroblastoma cell line BE2C..	Co-expression
SRP163514	A genome-wide framework for mapping gene regulation via cellular genetic screens	Over one million candidate regulatory elements have been identified across the human genome, but nearly all are unvalidated and their target genes uncertain. Approaches based on human genetics are limited in scope to common variants, and in resolution by linkage disequilibrium. We present a multiplex, eQTL-inspired framework for mapping enhancer-gene pairs by introducing random combinations of CRISPR/Cas9-mediated perturbations to each of many cells, followed by single-cell RNA-seq. Across two experiments, we used dCas9-KRAB to perturb 5,920 candidate enhancers with no strong a priori hypothesis as to their target gene(s), measuring effects by profiling 254,974 single-cell transcriptomes. We identified 664 (470 high-confidence) cis enhancer-gene pairs, which were enriched for specific transcription factors, non-housekeeping status, and genomic and 3D conformational proximity to their target genes. This framework will facilitate the large-scale mapping of enhancer-gene regulatory interactions, a critical yet largely uncharted component of the cis-regulatory landscape of the human genome. Overall design: Three scRNA-seq datasets of a low multiplicity-of-infection (MOI) pilot gRNA screen, high MOI pilot, and at-scale screen, in addition to bulkRNA-seq used to validate individual enhancer-gene pairs from the screens.	Co-expression
SRP163524	Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle	In our study, we investigated for contractile activity-specific changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle at baseline (after long term training). Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (baseline condition, 48 h after exercise), 1 and 4 h after the one-legged exercise from m. vastus lateralis of either leg. Comparison of gene expression in exercised leg with that in non-exercised [control] leg allowed us to identify contractile activity-specific genes in both untrained and trained skeletal muscle, i.e., genes that play a key role in adapting to acute exercise, regardless of the level of fitness. RNA-sequencing (84 samples in total; ~47 million reads/sample) was performed by NextSeq 500 and HiSeq 2500 (Illumina). Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in the incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. Contractile activity-specific changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, transcriptome responses specific for contractile activity in trained muscle substantially decreased relative to those in untrained muscle. We found out that adaptation of skeletal muscle to regular exercise is associated not only with a transient change in the transcriptome after each stress (acute exercise), but also with a marked change in baseline expression of many genes after repeated stress (e.g., long term training). Overall design: Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity (at ~65% of the maximal power determined in the one-legged knee extension ramp test) before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (baseline condition, 48 h after exercise), 1 and 4 h after the one-legged exercise from m. vastus lateralis of either leg. Comparison of gene expression in exercised leg with that in non-exercised leg allowed us to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness as well as a change in baseline transcriptome after long term training. RNA-sequencing (84 samples in total; ~47 million reads/sample) was performed by NextSeq 500 and HiSeq 2500 (Illumina). Symbols in file names: 'Ex' – exercised leg; 'NE' – non-exercised leg; 'baseline' – prior to the one-legged exercise; '+1 h' – 1 h after the one-legged exercise; '+4 h' – 4 h after the one-legged exercise; 'untrained' – before a 2 month aerobic training programme; 'trained' – after a 2 month aerobic training programme; the last symbol in file name – subject's ID.	Co-expression
SRP163643	Inherent DNA binding specificities of the HIF-1a and HIF-2a transcription factors in chromatin (RNA-seq)	Hypoxia inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-a isoforms, HIF-1a and HIF-2a, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1b to activate a broad range of transcriptional responses. Here we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-a isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter proximal binding of HIF-1 and promoter distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently. Overall design: RNA_seq analysis of hypoxic gene regulation in HKC8 and HepG2 cell lines and in RCC4 cell lines stably transfected with wtVHL	Co-expression
SRP163660	Differential expression of genes in AD169-infected MRC5.	We studied changes in a whole transcriptome during HCMV infection. Overall design: Fibroblasts (MRC5) were infected with HCMV and total RNA was isolated at 48. Total 2 individual samples were used. There were 3 replicates analyzed per individual sample.	Co-expression
SRP163661	Differential expression of genes in fibroblasts and epithelial cells infected with dsDNA viruses	We studied changes in a whole transcriptome during dsDNA virus infection. Overall design: Fibroblasts (MRC5 & HFF) and epithelial cells (ARPE19) were infected with HCMV, HSV1 or Ad5 and total RNA was isolated at 48, 9, or 24 hpi, respectively. Total 15 treatments were used. There were 2 biological replicates analyzed per each treatment.	Co-expression
SRP164309	Leprosyl whole blood transcriptome	Transcriptome profiles of the peripheral whole blood of leprosy patients with different clinical forms Overall design: Whole blood  from leprosy blood were collected and RNA sequencing was performed on a total of 58  samples	Co-expression
SRP164578	IFN-? selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate M1-like macrophage polarization [RNA-seq]	Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-? and LPS. Synergistic activation of canonical inflammatory NF-?B target genes by IFN-? and LPS is well appreciated, but less is known about whether IFN-? negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-? selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-?-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-?-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-?. These findings reveal that IFN-? suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-? selectively inhibits TLR4-induced transcription. Overall design: RNA-seq analysis of transcriptional changes in human macrophages that were cultured with or without IFN-? and then stimulated with LPS	Co-expression
SRP164659	Mycobacterium leprae induced genes in human monocyte derived macrophages	Transcriptome analysis of human macrophages infected with Mycobacterium leprae from one heathy donor for different time points. Overall design: RNA sequencing of human monocyte differentiated macrophages infected with Mycobacterium leprae at a multiplicity of infection of 10 from one heathy donor for 0h (uninfected control), 1, 2, 24 and 48h	Co-expression
SRP164707	Comparison of the mRNA profile of GDC0032-resistant and GDC0032-sensitive IGROV1 cells	The goal was to find pathways which were enriched in the resistant group of cells. Overall design: mRNA profiles of both cell lines were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP164734	Deciphering clonal evolution and dissemination of Multiple Myeloma cells in vivo	Clonal evolution drives tumor progression, dissemination and relapse in cancer, and dissemination or metastasis of the tumor cells from primary site to other organs is the leading cause of death for cancer patients. This multi-stage process requires tumor cells to survive in the circulation, extravasate at distant sites, then colonization. The whole process involves contributions from both the tumor cells and microenvironment. Here we developed and applied a clonal tracking 'rainbow' system into a tumor dissemination xenograft mouse model (SCID-mu) to study the clonal behaviors with the presence of a bone marrow environment showing that only a few subclones successfully remodeled by BM environment can exit the primary site and further colonize in distant tissues. RNA-sequencing results of primary and disseminated MM tumor cells revealed a metastatic signature, which is sequentially activated during human MM progression and significantly associated with overall survival when evaluated against a public patient dataset suggesting SCID-mu model characterizes MM dissemination phenotypically and mechanistically. Overall design: To explore the underlying molecular mechanisms that contribute to tumor metastasis, we performed RNA sequencing on three human cell lines MM.1S, IM9 and OPM2 that were harvested from primary bone chips and metastatic BM using SCID-mu xenograft model.	Co-expression
SRP164913	Comprehensive Analysis of TCR-ß Repertoire in Patients with Neurological Immune-mediated Disorders	Infiltrating T-lymphocytes from the peripheral blood into the central nervous system (CNS) play a dynamic role in the development of a neurological immune-mediated diseases. HAM/TSP is a chronic progressive inflammatory neurological disorder associated with human T-cell lymphotropic virus type I (HTLV-I) infection. In this chronic myelopathy, virus-infected circulating T-cells infiltrate the CNS and an immune response is initiated against the components of CNS. As the HTLV-I proviral load (PVL) has been used as the best clinical marker for patient diagnostic with HAM/TSP, we hypothesized there might be a signature on T-cell receptor (TCR) clonal repertoire in these patients, which could distinguish HAM/TSP patients from the healthy population, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease as multiple sclerosis (MS). With this in mind, we applied an innovative unbiased molecular technique – unique molecular identifier (UMI) library-strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR ß-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). To address whether the clonal expansion correlates with the patient's PVL level, analysis of longitudinal TCR repertoire was performed in 2 HAM/TSP patients. Over 5.6 million TCR sequences were generated per sample on HiSeq 2500 Illumina system and analyzed through the molecular identifier groups-based error correction pipeline (MiGEC). Bioinformatic analysis showed that clones with more than 8 reads had a lower coefficient of variation (CV) and then could be used with confidence to evaluate the TCR clonal expansion. While HAM/TSP patients showed the higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subject's group. In addition, correlation of the PVL with TCR clonal expansion was observed in HAM/TSP patients at longitudinal time-points. Surprisingly, MS patients showed a higher diversity of TCR repertoire along with a very slight clonal T-cell expansion in comparison to either HAM/TSP patients or HC. Despite of the higher TCR clonal expansion in HAM/TSP patients, a non-shared or “private” TCR repertoire was observed in these patients. No clones that shared the same CDR3 amino acid sequences were seen in HC and MS patients. However, a cluster of related CDR3 amino acid sequences were observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. It suggestes that a TCR-repertoire signature might characterize patients with MS. Our findings suggest that even though a unique TCR-b repertoire shapes the immune response in patients with neurological immune-mediated disease, a relatedness on clonal T-cell repertoire exist in MS. Overall design: TCR-ß profiles for 68 human samples were generated via deep sequencing using the Illumina HiSeq 2500 system and reagents. Of those profiled, 20 were not diagnosed as having HAM/TSP or MS (i.e., Healthy Control, "HC"), 14 were diagnosied as having HAM/TSP, and 34 were diagnosed as having MS.	Co-expression
SRP164914	Human macrophages exhibit high activity to clear intracellular biovar Microtus strain of Y. pestis	human peripheral lymphocytes were infected with the full virulent strain 141 or human avirulent Microtus strain 201, and their transcriptomes were determined and compared. The most impressive finding is that robust responses of lysosome, TLR signaling and Fc?R mediated phagocytosis pathways were provoked at 2 hpi in 201- but not in 141-infected lymphocytes, suggesting that human lymphocytes might be able to constrain infection caused by strain 201 but not 141. Overall design: We used RNA-sequencing technology to analyze transcriptomic of human peripheral lymphocytes infected with the full virulent strain 141 or human avirulent Microtus strain 201, and these transcriptomes were  further compared and functionally validated.	Co-expression
SRP164926	Trisomy of a 'Down syndrome critical region' globally amplifies transcription via HMGN1 overexpression [SLAM-Seq]	Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes in cells with trisomy 21, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute per cell normalization unmasked global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulated the transcriptional changes seen with triplication of a “Down syndrome critical region” on distal chromosome 21. Absolute exogenous normalized ChIP-seq (ChIP-Rx) also revealed a global increase in histone 3 lysine 27 acetylation caused by HMGN1. Genes most amplified downstream of HMGN1 were enriched for tumor- and developmental stage-specific programs of B-cell acute lymphoblastic leukemia dependent on the cellular context. These data offer a mechanistic explanation for DS transcriptional patterns, and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted. Overall design: SLAM-seq in NALM6 human pre-B cells with engineered HMGN1 overexpression	Co-expression
SRP164934	Vitamin C Promotes Apoptosis in Breast Cancer Cells by Increasing TRAIL Expression	In this study we show that ascorbate (vitamin C) shifts the transcriptome of MDA-MB-231 cells and increases apoptosis. Overall design: Examination of transcriptome in vitamin C treated  or control MDA-MB-231 cells	Co-expression
SRP164936	Epigenetic reprogramming of melanoma cells by vitamin C treatment	In this study we show that ascorbate (vitamin C) shifts the  transcriptome of melanoma cells, and decreases malignant phenotypes. Overall design: Examination of transcriptome in vitamin C treated  or control A2058 melanoma cells	Co-expression
SRP164953	Selective Disruption of Core Regulatory Transcription [RNA-seq]	Activation of identity determining transcription factors (TFs), or core regulatory TFs, is governed by cell-type specific enhancers, an important subset of these being super enhancers (SEs). This mechanism is distinct from constitutive expression of housekeeping genes. The characterization of drug-like small molecules to selectively inhibit core regulatory circuitry is of high interest for treatment of cancers, which are addicted to core regulatory TF function at SEs. Surprisingly, we find histone deacetylases (HDAC) to be an indispensable component of SE-driven transcription. While histone acetylation is a marker for active genes, over accumulation of acetylation selectively halts core regulatory transcription. We show this conundrum may in part be explained by a SE-specific need for resetting histones to maintain SE boundaries, to facilitate enhancer-promoter looping and high levels of transcription. Overall design: RNA-seq data for FP-RMS cells treated with various concentrations of various small molecules modulators of epigenetic processes.	Co-expression
SRP165202	Three-component mixed cell lines RNA-seq experiment	To generate this dataset in RNA-seq, we performed a mixing experiment, in which we mixed mRNAs from three cell lines: lung adenocarcinoma in humans (H1092), cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TIL), at different proportions to generate 32 samples, including 9 samples that correspond to three repeats of a pure cell line sample for three cell lines. The RNA amount of each tissue in the mixture samples was calculated on the basis of real RNA concentrations tested in the biologist's lab. This dataset was generated in house and then used to generate the count table that counts the number of reads mapped to each exon for all the samples. This count data will be pre-processed by total count normalization and genes that contained zero counts are removed. Overall design: We run the RNA samples at 8-plex/lane at the Illumina sequencing core. We fit 4 sequencing lanes for 32 samples total at 76bp PE, and prepare 2 lanes for each sample.	Co-expression
SRP165235	Effect of Influenza virus infection on lncRNA expression in A549 cells	Long non-coding RNAs (lncRNAs) are a new arm of gene regulatory mechanism as discovered by sequencing techniques and follow-up functional studies. There are only few studies on lncRNAs as related to gene expression regulation and anti-viral activity during influenza virus infection. We sought to identify and characterize lncRNAs involved in influenza virus replication. In the current study, we identified dys-regulated lncRNAs in influenza virus-infected human lung epithelial A549 cells using RNA sequencing in A549 cells. Overall design: RNA sequencing of A549 cells with Influenza virus and MOCK infection.	Co-expression
SRP165240	Transcriptional profiling of isogenic Friedreich ataxia iPSC-derived neurons	Friedreich ataxia (FRDA) is a rare childhood neurodegenerative disorder with no effective treatment. FRDA is caused by the transcriptional silencing of the FXN gene and consequent loss of the essential mitochondrial protein frataxin. We derived a set of isogenic iPSC lines that differ only in the length of the GAA·TCC repeats, using “scarless” gene-editing methods (helper-dependent adenovirus-mediated homologous recombination). To uncover the gene expression signature due to GAA•TCC repeat expansion in FRDA neuronal cells , we performed transcriptomic analysis of iPSC-derived neurons by RNA sequencing. We find that multiple cellular pathways are affected by the loss of frataxin in central nervous system neurons.	Co-expression
SRP165263	Impact of the mineralocorticoid receptor on differential gene expression in endothelial cells	Comparative transcriptome analysis by RNAseq of human umbilical vein endothelial cells (HUVECs) after aldosterone (100nM) stimulation and siRNA knockdown of the mineralocorticoid receptor versus respective controls.	Co-expression
SRP165626	Homos sapiens neutrophils with and without Helicobacter pylori infection.	Helicobacter pylori is a Gram-negative bacterium that infects the stomach of over half the global population causing a spectrum of disease including gastritis, peptic ulcers, and gastric adenocarcinoma. The infection initiates a chronic, neutrophil-dominant inflammatory response. We demonstrated that upon direct co-culture with H. pylori, human neutrophils undergo subtype differentiation characterized by profound nuclear hypersegmentation, changes in surface marker expression, and proinflammatory cytokine secretion. We further showed that neutrophil transcription and translation are required for this subtype differentiation. Due to the unique morphology of the nuclei of H. pylori-infected neutrophils and the requirement of transcription for neutrophil subtype differentiation, we examined the transcriptional profile of H. pylori-infected human neutrophils by RNA-sequencing. Freshly isolated human neutrophils from 3 donors were left uninfected for 0, 6, or 24 h or infected with Helicobacter pylori strain NCTC11637 (ATCC 43504) for 6 or 24 h before RNA was isolated. Results revealed that H. pylori induced extensive changes in neutrophil gene expression at both 6 and 24 h post-infection, with 1459 transcripts upregulated and 726 transcripts downregulated in neutrophils that had been infected for 24 h compared to neutrophils that had been aged for 24 h. Pathway analysis to probe for altered cellular functions suggested that groups of genes involved in cellular maintenance as well as cell death and survival were the most significantly altered. Additionally, there were eight H. pylori transcripts that were upregulated at 24 h post-infection versus 6 h post-infection, suggesting changes in bacterial gene expression during the course of infection. The current study provides fundamental insight into the molecular responses of human neutrophils to infection with H. pylori, and may increase our understanding of why neutrophils fail to effectively kill this common and persistent pathogen.	Co-expression
SRP165652	Homo sapiens Genome sequencing	This study presented the preliminary mechanistic studies of teniposide analogs for toxicity reduction	Co-expression
SRP165679	Atopic Dermatitis, Psoriasis and healthy control RNA-seq cohort	To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply-sequenced RNA-seq samples using long (125b) paired-end reads. By integrating deep sequencing-based skin transcriptome profiling with systems biology analysis, we are able to provide deep characterization for the expression signatures for AD, and by including psoriasis samples in the analysis, we can reveal the distinct molecular features of uninvolved and lesional skin of AD that have not been previously described. Overall design: We performed high-depth sequencing of 147 skin transcriptomes obtained from a carefully matched and tightly defined cohort of 27 AD patients, 28 PSO patients, and 38 healthy controls, whom were recruited within an ongoing investigator-initiated clinical study to identify shared and distinct disease mechanisms of AD and Psoriasis.	Co-expression
SRP165680	Evaluation of cryopreserved primary nasal and bronchial epithelial cells for rhinovirus infection in- vitro studies	There is increasing interest in using primary nasal epithelial cells (PNECs) instead of primary bronchial epithelial cells (PBECs) in order to study epithelial responses in rhinitis and asthma. This study aimed to establish a robust cell culture model appropriate for studying rhinovirus infection and the consequent epithelial responses in asthma and rhinitis. First, a comprehensive comparison of fresh and cryopreserved primary nasal epithelial cells from three donors before and after RV infection was conducted, using high throughput RNA sequencing and transcriptomics.	Co-expression
SRP165725	Calibrated CAR activation potential directs alternative T cell fates and therapeutic potency	CD19-specific CARs that comprise CD28 and CD3z signaling domains program highly performing effector functions that mediate potent tumor elimination, but they impart a relatively limited T cell lifespan. Increasing functional T cell persistence without reducing effector potency is therefore likely to further enhance the therapeutic success of 1928z CAR T cells. We demonstrate that the number and position of ITAMs in 1928z CAR T cells influence functional, phenotypic and transcriptional programs, resulting in profound effects on antitumor efficacy. Improved therapeutic potency of CAR T cells can thus be achieved by calibrating activation strength, thereby retaining memory functions and preventing exhaustion, without compromising effector functions. Our transcriptional analysis underscores the potential of ITAM dosage and position to direct different T cell fates. We were able to identify a novel CAR design, termed 1XX, which programs a favorable balance of effector and memory signatures, inducing increased persistence of highly functional CARs with the replicative capacity of long-lived memory cells and potent effector functions. Overall design: In order to assess the different phenotypic and functional patterns of CARs encoding a single immunoreceptor tyrosine-based activation motif (ITAM), we compared the genome-wide transcriptional profiles of 1928z, 1XX and XX3 after CD19 antigen stimulation of TRAC-edited naïve T cells. Sorted naïve (TN), stem cell memory (TSCM) and effector (TEFF) CD8+ T cells served as controls.	Co-expression
SRP165739	Transciptomic profiling of human fetal lung samples	Fibroblast Growth Factor (FGF) signaling plays an important role in lung organogenesis. Over recent decades, FGF signaling in lung development has been extensively studied in animal models. However, little is known about the expression, localization and functional roles of FGF ligands during human fetal lung development. Therefore, we aimed to determine the expression and function of several FGF ligands and receptors in human lung development. Using in situ hybridization (ISH) and RNA-sequencing, we assessed their expression and distribution in native human fetal lung. Human fetal lung explants were treated with recombinant FGF7, FGF9 or FGF10 in air-liquid interface culture. Explants were analyzed grossly, to observe differences in branching pattern, as well as at the cellular and molecular level. ISH demonstrated that FGF7 is expressed in both the epithelium and mesenchyme; FGF9 is mainly localized in the distal epithelium, whereas FGF10 demonstrated diffuse expression throughout the parenchyma with some expression in the smooth muscle cells (SMCs). FGFR2 expression was high in both proximal and distal epithelial cells as well as the SMCs. FGFR3 was expressed mostly in the epithelial cells, with lower expression in the mesenchyme, while FGFR4 was highly expressed throughout the mesenchyme and in the distal epithelium. Using recombinant FGFs, we demonstrated that FGF7 and FGF9 had similar effects on human fetal lung as on mouse; however, FGF10 caused the human explants to expand and form cysts as opposed to inducing epithelial branching as seen in the mouse. In conjunction with decreased branching, treatment with recombinant FGF7, FGF9 and FGF10 also resulted in decreased double-positive SOX2/SOX9 progenitor cells, which are exclusively present in the distal epithelial tips in early human fetal lung. Although FGF ligand localization may be somewhat comparable between developing mouse and human lungs, their functional roles may differ substantially. Overall design: Excised piece of human fetal lung samples containing proximal and distal compartments	Co-expression
SRP165826	Heart in a dish: A stable in vitro model of continuously beating human myocardium	In vitro models incorporating the complexity and function of adult human tissues are an integral part of efficient translational research. Whilst vital slices of human myocardium approach these demands, the rapid degeneration occurring under current tissue culture conditions preclude long-term experimentation.Here, we report preservation of structure and performance of human myocardium under conditions of physiological preload, contractility and compliance provided by computer-controlled biomimetic culture chambers. Tissue slices were prepared from explanted failing human hearts. Contractile force and continuous beating were monitored and maintained in biomimetic culture for up to 4 months or 2.000.000 beats in vitro. Programmed stimulation was used to repeatedly determine refractory periods thereby permitting sensitive analysis of slowly evolving effects of the hERG-inhibitor pentamidine on cardiac repolarization.Biomimetic tissue culture of cardiac slices is a novel research tool that will provide new opportunities to study drug targets, gene functions, and cellular plasticity in adult human myocardium.	Co-expression
SRP165889	Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways	We examined the transcriptional changes modulated by estrogen receptor beta (ERß) by performing global transcriptome analysis. U87 cells were transduced with lentiviral particles carrying either empty vector or ERß-FLAG expression vector and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that ERß modulated genes were related to homologous recombination, DNA damage response, ATM signaling and cell cycle pathways. Overall design: Total RNA was isolated from U87 cells expressing either empty vector or ERß expression vector. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat2. Genes were annotated and quantified by HTSeq-DESeq pipeline.	Co-expression
SRP165903	A non-canonical GLTSCR1L-containing BAF complex mediates H3K27ac-dependent enhancer activities	H3K27ac is known to associate with regulatory active enhancers, but it's exact role in enhancer function remains elusive. Using mass spectrometry-based interaction proteomics, we identified the Super Elongation Complex (SEC) and GBAF, a non-canonical GLTSCR1L- and BRD9-containing SWI/SNF chromatin remodeling complex, to be major interactors of H3K27ac. Our interaction proteomics analysis refined the composition of GBAF by adding BCL7A/B/C as a new subunit. We further characterized the conserved GLTSCR1/1L-contained “GiBAF”-domain, which we found to be responsible for GBAF complex formation and nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and BRD9 to be H3K27ac dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in a genome-wide downregulation of enhancer transcription. Our results indicate that GBAF is an enhancer-associated chromatin remodeller important for the correct transcriptional and regulatory activity of enhancers. Overall design: CAGE-seq (with 3 replicates) and ATAC-seq profiling of HeLa S3 cells untreated (DMSO) and treated with bromodomain-containing protein 9 inhibitor (I-BRD9) on a EGF-induced time course (0,30,60 and 240 minutes).  ChIP-seq for BRD9 and GLTSCR1L proteins before (DMSO) and after treatment (I-BRD9) for time point 0 and corresponding inputs.	Co-expression
SRP165928	CDC7 inhibition induces a senescence-like state in Hep3B and Huh7 cells	Purpose: to check senescence gene expression signature in XL413 treated liver cancer cells. Methods: Hep3B and Huh7 cells are treated with XL413 for 4 days. For RNA sequencing, the library was prepared using TruSeq RNA sample prep kit according to the manufacturer's protocol (Illumina). Gene set enrichment analysis was performed using gene set enrichment analysis software. The FRIDMAN_SENESCENCE_UP gene set was used to assess the enrichment of senescence-associated genes in the XL413-treated versus control cells. Overall design: RNA seq data of Hep3B-control, Hep3B-XL413, Huh7-control, and Huh7-XL413 cells, to check senescence gene expression signature	Co-expression
SRP165929	RNA seq data of Hep3B-control, Hep3B-sertraline, Hep3B-XL413, Hep3B-XL413-sertraline, Huh7-control, Huh7-sertraline, Huh7-XL413, Huh7-XL413-sertraline cells	Hep3B and Huh7 cells pre-treated with XL413 for 10 days to induce senescence prior to sertraline treatment for 24 hours. For RNA sequencing, the library was prepared using TruSeq RNA sample prep kit according to the manufacturer's protocol (Illumina). Gene set enrichment analysis was performed using gene set enrichment analysis software. Overall design: RNA seq data of Hep3B-control, Hep3B-sertraline, Hep3B-XL413, Hep3B-XL413-sertraline, Huh7-control, Huh7-sertraline, Huh7-XL413, Huh7-XL413-sertraline cells, to check gene expression signatures	Co-expression
SRP165962	Genome-wide transcriptional analysis of human iPSC-derived healthy control vs. schizophrenia cortical interneurons	We report specific changes in schizophrenia developmental interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Fourteen independent iPSC lines per group with two independent differentiations	Co-expression
SRP165983	Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model	Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect in patients. Because ATR governs DNA repair response, the mutation has been considered the cause of an impaired response to DNA replication stress in neuronal progenitor cells (NPCs), which is associated with the pathogenesis of microcephaly. However, the precise mechanism through which the mutation causes SS remains unclear. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone by genome editing. Interestingly, SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs. In SS-NPCs, abnormal mitotic spindles were observed more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that a CLK1 inhibitor, TG003, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Furthermore, treatment with TG003 restored the function of ATR in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model of SS revealed a novel function of the ATR mutation in NPCs and NPC-specific missplicing, proving its usefulness for dissecting the pathophysiology of ATR-SS. Overall design: RNA-sequencing was conducted to identify the transcriptomic profiling of iPSC-derived cells	Co-expression
SRP165984	RNA-Sequencing data of Varicella Zoster Virus (VZV)-infected human dermal fibroblasts (HDF)	RNA profiles of HDF infected with various VZV strains were generated by High-throughput sequencing using Illumina Hi-seq 2500 Overall design: Investigation of host immune response differences in response to infection with clinical VZV and vaccine VZV.	Co-expression
SRP166001	RNAseq over the course of T. gondii infection	Samples from uninfected or T. gondii infected 60 mm dishes of HFFs paired to infected metabolomics dishes were resuspended in TRIzol. RNA was extracted per the manufacturer's protocol, assayed for quality with an Agilent Bioanalyzer and Nano-6000 RNA chip, and synthesized into libraries with a TruSeq RNA Library Preparation Kit v2. Sequencing was performed through the UW Biotechnology Sequencing Center, using Illumina HiSeq2000.	Co-expression
SRP166025	Disruption of the TFAP2A regulatory domain causes Branchio-Oculo-Facial Syndrome (BOFS) and illuminates pathomechanisms for other human neurocristopathies [RNA-seq data set 2]	BOFS is a rare congenital syndrome that arises due to defects during neural crest (NC) development and is thus considered as a human neurocristopathy. All reported BOFS cases are caused by heterozygous mutations within TFAP2A. Here we describe a unique BOFS patient carrying a de novo heterozygous inversion in which one of the breakpoints is located 40 kb downstream of TFAP2A. Using in vitro and in vivo NC developmental models, we uncovered that TFAP2A is located within a large Topologically Associating Domain (TAD) containing enhancers essential for TFAP2A expression in NC cells (NCC). Importantly, using patient-specific hiPSC lines, we showed that the inversion causes a loss of physical interactions between the inverted TFAP2A allele and its cognate enhancers, leading to TFAP2A monoallelic and haploinsufficient expression in human NCC. More generally, our results highlight potential etiological mechanisms for other human neurocristopathies and illustrate how TAD disruption can lead to a loss of enhancer gene-interactions and, consequently, to pathological changes in gene expression. Overall design: Gene expression profiles were investigated in WT d11hNCC and del0.4Mb d11hNCC using RNA-seq.	Co-expression
SRP166055	Human endogenous retrovirus K proviruses-encoded small RNA are active biomarkers in systemic lupus erythematosus by transcriptome wide screening and functional prediction Raw sequence reads	Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. There is an urgent need for development of a potential marker to facilitate diagnosis and prognosis. The association between human endogenous retroviruses-K (HERV-K or HML2) and SLE has been indicated, and thus, the retroviruses are potential candidates for investigation as non-invasive biomarkers in SLE. In this study, we observed the expression and functional prediction of HML2 proviruses-encoded small RNA in peripheral blood mononuclear cells (PBMCs) of SLE patients by bioinformatics analysis and we further assessed their diagnostic values in SLE and lupus nephritis (LN).	Co-expression
SRP166092	O-GlcNAc transferase fine-tunes MYC-dependent transcription to promote cell cycle [RNA-seq]	O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. Here, we employed ChIP-seq to map chromatin-bound O-GlcNAc loci in prostate cancer cells and discovered that these overlap with sites of active transcription and MYC binding. Using RNA-seq, we show that inhibition of OGT promotes MYC-dependent transcriptional repression of mRNAs involved in G1-S transition. O-GlcNAc ChIP-seq regions are highly enriched to transcription start sites and identify the 'GFY'-motif. Proteins binding to this motif have not been established and we use synthetic oligonucleotides as a bait to enrich protein complexes associated with this sequence. By comparing the unbiased proteomic data from oligonucleotide enrichment with proteomic data from O-GlcNAc and MYC ChIP-mass spectrometry, we identified host cell factor 1 (HCF-1) as an interaction partner of MYC. Inhibition of OGT disrupted the interaction between MYC and HCF-1, and compromised MYC's ability to promote proliferation of prostate cancer cells in the absence of androgens. Reverse phase protein arrays identified a set of proteins involved in mitosis that are dependent on MYC and OGT activity for expression. In conclusion, we show that OGT activity regulates MYC-driven proliferation by coordinating transcription and translation of cell cycle genes. Overall design: two biological replicates for prostate cancer cell line (LNCaP) overexpressing MYC gene under the control of Doxycycline. Differential expressed genes were retreaved for these cells treated for 4 and 24 hours with Doxycycline, OSMI2 (a OGT inhibitor), or a cmbination of both (combo) versus the vehicle treated cells (DMSO)	Co-expression
SRP166095	Poly(ADP-ribose) polymerase 1 is necessary for coactivating hypoxia-inducible factor-1-dependent gene expression by Epstein-Barr virus latent membrane protein 1	Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Poly(ADP-ribose) polymerase 1 (PARP1) regulates accessibility of chromatin, alters functions of transcriptional activators and repressors, and has been directly implicated in transcriptional activation. Previously we showed that LMP1 activates PARP1 and increases Poly(ADP-ribos)ylation (PARylation) through PARP1. Therefore, to identify targets of LMP1 that are regulated through PARP1, LMP1 was ectopically expressed in an EBV-negative Burkitt's lymphoma cell line. These LMP1-expressing cells were then treated with the PARP inhibitor olaparib and prepared for RNA sequencing. The LMP1/PARP targets identified through this RNA-seq experiment are largely involved in metabolism and signaling. Interestingly, Ingenuity Pathway Analysis of RNA-seq data suggests that hypoxia-inducible factor 1-alpha (HIF-1a) is an LMP1 target mediated through PARP1. PARP1 is acting as a coactivator of HIF-1a-dependent gene expression in B cells, and this co-activation is enhanced by LMP1-mediated activation of PARP1. HIF-1a forms a PARylated complex with PARP1 and both HIF-1a and PARP1 are present at promoter regions of HIF-1a downstream targets, leading to accumulation of positive histone marks at these regions. Complex formation, PARylation and binding of PARP1 and HIF-1a at promoter regions of HIF-1a downstream targets can all be attenuated by PARP1 inhibition, subsequently leading to a buildup of repressive histone marks and loss of positive histone marks. In addition, LMP1 switches cells to a glycolytic 'Warburg' metabolism, preferentially using aerobic glycolysis over mitochondrial respiration.  Finally, LMP1+ cells are more sensitive to PARP1 inhibition and, therefore, targeting PARP1 activity may be an effective treatment for LMP1+ EBV-associated malignancies. Overall design: Examination of the effect of LMP1 and PARP inhibition on global gene expression in EBV-negative Burkitt's lymphoma DG75 cell line. mRNA profiles of LMP1+ or LMP1- (pBABE empty vector) DG75 cell lines treated with 1 uM olaparib for 72 hrs were generated by deep sequencing, in triplicate, using Illumina GAIIx.	Co-expression
SRP166108	The Power of Resolution: Contextualized Understanding of Chemical-biological Interactions	Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions. However, limited throughput, high-costs and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. We utilized a novel high-throughput transcriptomics platform to explore a broad range of exposures to 24 reference compounds in both differentiated and undifferentiated human HepaRG cultures. Our goals were to 1) explore transcriptomic characteristics distinguishing liver injury compounds, 2) assess impacts of differentiation state on baseline and compound-induced responses (e.g., metabolically-activated), and 3) identify and resolve reference biological-response pathways and their quantitative translation to human exposures. Study data revealed the predictive utility of transcriptomic concentration-response modeling to quantitatively identify human liver injury compounds by their respective benchmark concentrations (BMCs), and model hepatic responses to classical reference compounds yielding plausibly-relevant estimations of human potency.	Co-expression
SRP166109	An environmental code tunes the intracellular signaling network activity to shape cellular responses	Cells constantly survey a complex set of inputs that is processed by the intracellular signaling network, but little is known of how cells integrate input information from more than one cue. We employed a FRET biosensor-based imaging platform to study the effect of combinatorial growth factor levels on the signaling network in human cells. We found that pairwise stimuli caused distinct concentration- and ratio-dependent signaling states through signaling signatures such as antagonism, additivity, and synergy. The unique signaling states correlated with differential gene expression and non-additive transcription patterns. We further elucidated how a signal-rich environment can fine-tune the signaling network and adjust physiological outcomes, by kinase and phosphatase activity profiling. We describe how complex extracellular conditions affect phospho-turnover and the basal phosphorylation status. Thus, we provide mechanistic insights into cellular processing of multiple cues and explain part of the complexity of cellular adaptation to changes in the extracellular environment. Overall design: Examination of mRNA abundance upon individual or combinatorial growth factor treatments (EGF, IGF-1, EGF + IGF-1) at 4 hours after stimulation	Co-expression
SRP166112	Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to ER-directed therapies	Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. Examination of treatment-naïve primary tumors in five patients revealed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. These mutations were mutually exclusive with ER mutations, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that these mutations conferred estrogen independence. In addition, and in contrast to ER mutations, these mutations resulted in resistance to tamoxifen, fulvestrant, and the CDK4/6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib, highlighting an effective treatment strategy in these patients. Overall design: Examination of the transcriptional output (mRNA) of  the HER2 activating mutations compared with controls under various drugs. Specifically, we expressed the activating mutations S653C, L755S, V777L, and L869R  in ER+/HER2- breast cancer cell line (T47D), and controls (GFP, wild-type HER2, kinase-dead HER2, and ESR1 Y537S). Cell were then treated with DMSO, 1µM fulvestrant, 1µM neratinib, 10µM palbociclib, 1µM fulvestrant + 1µM neratinib, or 1µM fulvestrant + 10µM palbociclib for 24 hours. All experimental conditions were done in 6 replicates, sequenced in 3 replicates	Co-expression
SRP166160	RNA sequencing to determine gene expression changes in HMCES knockout cells	The purpose of this study was to deteremine gene expression changes in when HMCES is inactivated. We found very few changes. Overall design: Compare wild type and HMCES knockout U2OS cancer cells using RNA-seq.	Co-expression
SRP166162	Identification of biomarkers for amyotrophic lateral sclerosis by comprehensive analysis of exosomal mRNAs in human cerebrospinal fluid.	In comparison with exosomal mRNAs in CSF from four patients with amyotrophic lateral sclerosis, 543 genes were significantly changed, as represented by CUEDC2. Overall design: Signatures of CSF exosomal mRNAs were then compared between four normal healthy donors and four sporadic amyotrophic lateral sclerosis patients to identify disease-related biomarkers.	Co-expression
SRP166169	Estrogen therapy induces an unfolded protein response to drive cell death in ER+ breast cancer	Estrogens have been shown to elicit anti-cancer effects against estrogen receptor alpha (ER)-positive breast cancer. We sought to determine the underlying mechanism of therapeutic response. Response to estrogen treatment was assessed in ER+ breast cancer models of anti-estrogen resistant disease: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells.	Co-expression
SRP166184	Differentiation enhances Zika virus infection in neuronal brain cells	Zika virus (ZIKV) is an emerging, mosquito-borne pathogen associated with a widespread 2015–2016 epidemic in the Western Hemisphere and a proven cause of microcephaly and other fetal brain defects in infants born to infected mothers. ZIKV infections have been also linked to other neurological illnesses in infected adults and children, including Guillain-Barré syndrome (GBS), acute flaccid paralysis (AFP) and meningoencephalitis, but the viral pathophysiology behind those conditions remains poorly understood. Here we investigated ZIKV infectivity in neuroblastoma SH-SY5Y cells, both undifferentiated and following differentiation with retinoic acid. We perform RNA seq, and global trancriptome analysis to corroborate the effect of retinoic acid in SH-SY5Y cells. Then we analyze the virus infection in differentiated and undifferntiated cells. We found that multiple ZIKV strains, representing both the prototype African and contemporary Asian epidemic lineages, were able to replicate in SH-SY5Y cells. Differentiation with resultant expression of mature neuron markers increased infectivity in these cells, and the extent of infectivity correlated with degree of differentiation.  Enhanced ZIKV infectivity in a neural cell line following differentiation may contribute to viral neuropathogenesis in the developing or mature central nervous system. Overall design: Analysis of Zika virus infection in one neuroblastoma cell line differentiated, or not with retinoic acid.	Co-expression
SRP166200	HLA Class II analysis of human pancreatic beta cells	We interrogated the transcriptome from bulk-sorted T1D donor ß-cells as compared to non-diabetic donors. We found ß-cells also expressed mRNA for HLA Class II and Class II antigen presentation pathway components, but not macrophage markers.	Co-expression
SRP166275	Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-seq of KLF6 KO)	Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: CRISPR-Cas9 mediated knockout of KLF6 was performed in human peripheral blood CD34+ cells (n=4 replicates). RNA-seq was utilized to determine the effect of KLF6 knockout compared to a non-targeting control control.	Co-expression
SRP166282	ALS implicated protein TDP-43 sustains levels of STMN2 a mediator of motor neuron growth and repair	The discovery that TDP-43 mutations cause familial ALS and that many patients display pathological TDP-43 mislocalization has nominated altered RNA metabolism as a potential disease mechanism. Despite its importance, the identity of RNAs regulated by TDP-43 in motor neurons remains poorly understood. Here, we report transcripts whose abundances in human motor neurons are sensitive to TDP-43 depletion. Notably, we found STMN2, which encodes a microtubule regulator, declined after TDP-43 knockdown, in patient-specific motor neurons, following TDP-43 mislocalization, and in the postmortem patient spinal cords. Loss of STMN2 upon reduced TDP-43 function was due to the emergence of a cryptic exon, which is of substantial functional importance, as we further demonstrate that STMN2 is necessary for both axonal outgrowth and repair. Importantly, post-translational stabilization of STMN2 could rescue neurite outgrowth and axon regeneration deficits induced by TDP-43 depletion.  We propose restoring STMN2 expression warrants future examination as an ALS therapeutic strategy. Overall design: Transcriptome differential expression analysis in HUES3 cells with and without siRNA knockdown of TDP-43	Co-expression
SRP166289	Recruiting Endogenous ADARs with Antisense Oligonucleotides to Reprogram the Transcriptome	Huge efforts are made to engineer safe and efficient genome editing tools. An alternative might be the harnessing of ADAR-mediated RNA editing. We now present the engineering of chemically optimized antisense oligonucleotides that recruit endogenous human ADARs to edit endogenous transcripts in a simple and programmable way, an approach we refer to as RESTORE. Notably, RESTORE was markedly precise, and there was no evidence for perturbation of the natural editing homeostasis. We applied RESTORE to a panel of standard human cell lines, but also to several human primary cells including hepatocytes. In contrast to other RNA and DNA editing strategies, this approach requires only the administration of an oligonucleotide, circumvents the ectopic expression of proteins, and thus represents an attractive platform for drug development. In this respect we have shown the repair of the PiZZ mutation causing a1-antitrypsin deficiency and the editing of phosphotyrosine 701 in STAT1. Overall design: Identification of off-target editing events and Interferon-a influence in HeLa cell line transfected with an ASO for RNA editing by RNA-Seq, 2 samples (ASO +/- IFN) , 2 control sample (+/-IFN),  2 biologically independent experiments for each sample, 8 samples in total	Co-expression
SRP166295	Gene expression profiling U87 cells knocking down Glud1 under low glucose treatment	U87 cells (shGlud1 and shNT) were treated with low glucose for 6 hours, then mRNA were extracted for high-throughput sequencing Overall design: shGlud1 v.s. shNT, in duplicate	Co-expression
SRP166302	Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells	RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of steroid receptor coactivator-2/nuclear receptor coactivator 2 (SRC-2/NCOA2) Overall design: Primary human endometrial stromal cells isolated from 3 healthy volunteers. Transfected with nontargeting or SRC-2/NCOA2 siRNA. Treated with estradiol, medroxyprogesterone acetate, and cAMP (EPC) for 0 or 3 days	Co-expression
SRP166328	Global gene expression analysis of human monocyte-derived dendritic cells (DCs) treated with HMGN1 (N1) and R848 alone or in combination.	RNA-seq data demonstrate that N1 plus R848 at the global gene expression level synergistically promotes DC maturation and subsequent upregulation of many genes in DCs that are involved in the polarization of CD4+ T cells into Th1-type effectors. Overall design: DCs sham-treated or treated with N1, R848, or N1 plus R848 for 4 hours.	Co-expression
SRP166457	Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors [Modifications - screen]	Base Editing has been touted the most intelligent and precise application of the CRISPR platform so far, merging the simplicity of RNA-guided nucleases with deaminases that allow for the programmable generation of single base substitutions - without introduction of double-strand breaks. Even though the two-component system has been expected to cause off-target substitutions, studies involving cytosine base editors (CBEs) showed that in most cases, relatively few single base off-targets could be detected on DNA. We introduce the concept of multi-dimensional off-targeting, presenting an extensive amount of RNA cytidines being edited by DNA base editors. Epitranscriptomic off-target effects affected different cell lines and were independent of the guide RNAs used, suggesting Cas9-independent activity of the cytidine deaminase rAPOBEC1 on single-stranded RNA. With the help of protein engineering, we developed CBE variants with massively reduced inadvertent mutation of RNA that preserve and enhance DNA base editing capabilities.  Overall design: HEK293T cells were transfected with pCAG-BE3-P2A-EGFP or variants thereof or control pCAG-nCas9(D10A)-UGI-NLS-P2A-EGFP or control pCAG-P2A-EGFP constructs with various gRNAs as described below. Cells were sorted for top 5% GFP or all GFP + cells based on FITC signal. RNA-seq was performed to measure transcriptional changes associated with different constructs and guides.	Co-expression
SRP166458	Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors [BaseEditors - RNA]	Base Editing has been touted the most intelligent and precise application of the CRISPR platform so far, merging the simplicity of RNA-guided nucleases with deaminases that allow for the programmable generation of single base substitutions - without introduction of double-strand breaks. Even though the two-component system has been expected to cause off-target substitutions, studies involving cytosine base editors (CBEs) showed that in most cases, relatively few single base off-targets could be detected on DNA. We introduce the concept of multi-dimensional off-targeting, presenting an extensive amount of RNA cytidines being edited by DNA base editors. Epitranscriptomic off-target effects affected different cell lines and were independent of the guide RNAs used, suggesting Cas9-independent activity of the cytidine deaminase rAPOBEC1 on single-stranded RNA. With the help of protein engineering, we developed CBE variants with massively reduced inadvertent mutation of RNA that preserve and enhance DNA base editing capabilities.  Overall design: HEK293T and HepG2 cells were transfected with pCAG-BE3-P2A-EGFP or control pCAG-nCas9(D10A)-UGI-NLS-P2A-EGFP or control pCAG-P2A-EGFP constructs with various gRNAs as described below. Cells were sorted for top 5% GFP or all GFP + cells based on FITC signal. RNA-seq was performed to measure transcriptional changes associated with different constructs and guides.	Co-expression
SRP166459	Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors [Modifications - validation]	Base Editing has been touted the most intelligent and precise application of the CRISPR platform so far, merging the simplicity of RNA-guided nucleases with deaminases that allow for the programmable generation of single base substitutions - without introduction of double-strand breaks. Even though the two-component system has been expected to cause off-target substitutions, studies involving cytosine base editors (CBEs) showed that in most cases, relatively few single base off-targets could be detected on DNA. We introduce the concept of multi-dimensional off-targeting, presenting an extensive amount of RNA cytidines being edited by DNA base editors. Epitranscriptomic off-target effects affected different cell lines and were independent of the guide RNAs used, suggesting Cas9-independent activity of the cytidine deaminase rAPOBEC1 on single-stranded RNA. With the help of protein engineering, we developed CBE variants with massively reduced inadvertent mutation of RNA that preserve and enhance DNA base editing capabilities.  Overall design: HEK293T and HepG2 cells were transfected with regular and modified pCAG-BE3-P2A-EGFP or control pCAG-nCas9(D10A)-UGI-NLS-P2A-EGFP or control pCAG-P2A-EGFP constructs with various gRNAs as described below. Cells were sorted for top 5% GFP or all GFP + cells based on FITC signal. RNA-seq was performed to measure transcriptional changes associated with different constructs and guides.	Co-expression
SRP166531	ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing	The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo an MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm. Overall design: Three independent clones for each genotype were generated. ZEB1+/+ and ZEB1+/- (generated using CRISPR-Cas9 gene editing) parental lines were initially generated, then transduced with lentivirus containing ZEB1 cDNA to generate ZEB1 transgenic lines of the parental lines.	Co-expression
SRP166560	Epidermal growth factor activates ß-catenin via integrin-linked kinase to control proliferation of mesenchymal stromal cells.	Mesenchymal stromal cells (MSCs) are located in bone marrow where they help to maintain bone homeostasis and repair through the ability to expand in response to mitotic stimuli and differentiate into skeletal linages. The signalling mechanisms that enable precise control of MSC function remain unclear. Here, we have identified a non-canonical epidermal growth factor (EGF) signalling pathway in MSCs, which acts via integrin-linked kinase (ILK) to activate ß-catenin, a key component of Wnt signalling. EGF induces nuclear translocation of ß-catenin in MSCs but does not drive T cell factor (TCF)-mediated transactivation of Wnt target genes, and we demonstrate by Design of Experiments statistical analysis that the EGF/ß-catenin and Wnt/ß-catenin pathways do not cross-talk following co-stimulation with multiple concentrations of both ligands. By examining EGF-regulated genes in MSCs by RNA-Sequencing, we identified gene sets that were exclusively regulated by the EGF/b-catenin pathway, which were distinct from canonical EGF-regulated genes. In contrast, the expression of subsets of canonical EGF signalling gene targets were significantly influenced by b-catenin activation. These newly-identified EGF signalling pathways cooperate to enable EGF-mediated proliferation of MSCs by alleviating the suppression of cell cycle pathways induced by canonical EGF signalling. Overall design: Examination of expression profiles of 3 samples of untreated MSCs, 3 samples EGF treated, 3 samples EGF + IWR-1 treated MSCs using RNA-seq analysis	Co-expression
SRP166768	Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations [RNA-Seq]	How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer. Overall design: Nuclear RNA profiling in lymphoblastoid TK6 cell line	Co-expression
SRP166796	RNA sequencing for KSHV circular RNAs	The purpose was to detect viral circular RNAs from infected cells. Overall design: Total RNA was harvested from KSHV-infected HUVEC cells. A portion of the RNA was digested with RNase R to enrich for circular RNAs.	Co-expression
SRP166862	Homo sapiens Transcriptome (RNA sequencing)	Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, Infinium MethylationEPIC array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria from fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.	Co-expression
SRP166866	Transcriptomic analysis of the interaction of choriocarcinoma spheroids with receptive vs. non-receptive endometrial epithelium cell lines: an in vitro model for human implantation	The aim of this study was to establish an in vitro model to investigate the initial stages of human implantation based on co-culture of a) immortalized cells representing the receptive (Ishikawa) or non-receptive (HEC-1-A) endometrial epithelium with b) spheroids of a trophoblastic cell line (JEG-3) modified to express green fluorescent protein. After co-culturing Ishikawa cells with trophoblast spheroids, 310 and 298 genes increased or decreased their expression compared to non-co-cultured Ishikawa control cells, respectively; only 9 genes (5 increased and 4 decreased) were differentially expressed in HEC-1-A upon co-culture with trophoblast spheroids. Compared to HEC-1-A, the trophoblast challenge to Ishikawa cells differentially regulated the expression of 495 genes. In summary, upon co-culture with the trophoblast spheroids, non-receptive epithelium is characterized by a muted transcriptional response which in turn fails to activate the full transcriptional response that trophoblast spheroids undergo when co-cultured with receptive epithelium. Overall design: GFP expressing JEG-3 spheroids were co-cultured with confluent monolayers of receptive Ishikawa or non-receptive HEC-1-A epithelia. After 48 hours of co-culture, GFP+ (trophoblast JEG-3 spheroid cells) and GFP- cell fractions (receptive Ishikawa or non-receptive HEC-1-A epithelial cells) were isolated by fluorescence-activated flow cytometry (FACS). The specific transcriptional changes of the isolated cell populations were analyzed by RNA-seq profiling. Statistical significance of gene expression differences was set at an absolute log2 fold change (log2FC) =1 and an adjusted p-value <0.05.	Co-expression
SRP166888	Single-nucleus RNA sequencing of multiple sclerosis lesions	We performed unbiased isolation and single-nucleus RNA sequencing of cortical multiple sclerosis lesions, as well as of cortical tissue from unaffected controls.	Co-expression
SRP166889	Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma	Glioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-?-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with ClinicalTrials.gov under the identifier NCT02852655 (https://clinicaltrials.gov/ct2/show/NCT02852655). Overall design: This dataset contains the transcriptomes of recurrent glioblastoma with either neoadjuvant (1 dose) or adjuvant pembrolizumab treatment	Co-expression
SRP166896	SCAF4 and SCAF8, Transcriptional Anti-Terminator Proteins (mRNA-Seq)	Accurate regulation of RNA Polymerase II (RNAPII) transcriptional termination is a prerequisite for correct gene expression. Here we describe a role for SCAF4 and SCAF8 as anti-terminators, suppressing the use of early, alternative polyadenylation sites (PASs). The SCAF4/8 proteins bind the hyper-phosphorylated RNAPII C-terminal repeat domain (CTD) modified on both Ser2 and Ser5, and are detected at early, alternative PASs. Concomitant knockout of human SCAF4 and SCAF8 results in altered PAS selection, leading to expression of truncated mRNAs and proteins lacking functional domains, and is cell-lethal. While SCAF4 and SCAF8 thus work redundantly to suppress early termination, they also have independent, non-essential functions. SCAF8 is a positive RNAPII elongation factor, whereas SCAF4 is required for correct termination at canonical transcription termination sites in the presence of SCAF8. Together, SCAF4 and SCAF8 coordinate the transition between elongation and termination, directing PAS selection to ensure correct RNAPII transcriptional termination in human cells. Overall design: To study the function of SCAF4 and SCAF8 in human cells, we used CRISPR-Cas9 nickase technology to generate single and double knockouts (KOs) in HEK293 Flp-In TREX cells, which also contained a single copy of a doxycycline (Dox)-inducible SCAF4 or SCAF8 rescue construct, with the encoded GFP-tagged protein expressed at near-normal levels. All cell lines were maintained in the presence of Dox to ensure expression of the CRISPR-resistant rescue gene during and after KO cell line generation. Expression of the rescue protein reaches undetectable levels after 5 days growth in Dox-free media, resulting in effective single of double KOs. Due to the manner in which these cell lines were generated, a total of 12 cell types (6 different cell lines grown with or without Dox) were often analysed together. For example, SCAF4 SCAF8 double KOs were generated either by first knocking out SCAF4 and then SCAF8, or vice versa, and these different cell lines were in turn also derived from cell lines containing either a Dox-inducible SCAF4- or a SCAF8 rescue gene, giving rise to a total of 4 genotypically identical SCAF4 SCAF8 dKO cell lines. Moreover, a SCAF4 SCAF8 double KO that expresses a rescue gene (i.e. grown in the presence of doxycycline) is effectively a single KO; for example, a SCAF4 SCAF8 double KO expressing the SCAF4 rescue gene is genotypically and phenotypically a single SCAF8 KO cell line. For PAR-CLIP experiments, HEK293 Flp-In TREX cells stably expressing FLAG-tagged SCAF4 or SCAF8 were used for FLAG immunoprecipitations from RNA-protein crosslinked extracts.	Co-expression
SRP166945	Small-molecule targeting of brachyury transcription factor addiction in chordoma [rnaseq_sgrna]	Chordoma is a primary bone cancer with no approved therapy. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling. These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. In other cancer types, transcriptional CDK inhibitors have been observed to downregulate highly expressed, enhancer-associated oncogenic transcription factors (TFs). In chordoma, we find that T is associated with a 1.5-Mb region containing “super-enhancers” and is the most highly expressed super-enhancer-associated TF. Strikingly, transcriptional CDK inhibition leads to preferential and concentration-dependent downregulation of cellular brachyury protein levels in all models tested. Together, these data demonstrate small-molecule targeting of brachyury TF addiction in chordoma, identify a mechanism of T gene regulation that underlies this therapeutic strategy and provide a blueprint for applying systematic genetic and chemical screening approaches to discover vulnerabilities in genomically quiet cancers. Overall design: RNA-sequencing of sg-T- and sg-EGFP-treated UM-Chor1 chordoma cells. Two independent sgRNAs targeting T were used. Two biological replicates were generated for each condition.	Co-expression
SRP166966	A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys	Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples. Overall design: Single-nucleus (sn)Drop-seq was used to generate RNA expression estimates across two kidney regions (cortex and medulla), 15 different individuals, 7 different tissue processing methods, and from tissues acquired from two different institutions (Washington University and University of Michigan through KPMP consortium). From the resulting ~18,000 sequenced nuclei passing QC filtering (>400 <5000 non-MT genes detected, >50 post-QC nuclei per library, >30 nuclei per cluster), we identified 30 different cell populations (see supplementary file UCSD-WU_Single_Nuclei_Cluster_Annotations.csv).	Co-expression
SRP166991	Specifying the Anterior Primitive Streak by Modulating YAP1 Levels in Human Pluripotent Stem Cells	Specifying the primitive streak (PS) guides stem cell differentiation in vitro, however much remains to be learned about the transcription networks that direct anterior and posterior PS cells (APS and PPS, respectively) to differentiate to distinct mesendodermal subpopulations. Here, we show that APS genes are predominantly induced in YAP1-/- hESCs in response to ACTIVIN. This finding establishes the Hippo effector YAP1 as a master regulator of PS specification, functioning to repress ACTIVIN-regulated APS genes in hESCs. Moreover, transient exposure of wild-type hESCs to dasatinib, a potent C-SRC/YAP1 inhibitor, enables differentiation to APS-derived endoderm and cardiac mesoderm in response to ACTIVIN. Importantly, these cells can differentiate efficiently to normal beating cardiomyocytes without the cytoskeletal defect seen in YAP1-/- hESC-derived cardiomyocytes. Overall, we uncovered an induction mechanism to generate APS cells using a cocktail of ACTIVIN and YAP1i molecules that holds practical implications for hESC and iPSC differentiation into distinct mesendodermal lineages. Overall design: Our data strongly indicate that combined treatment of ACTIVIN and YAP1i during the first 24h of differentiation in WT hESCs and hiPSCs is sufficient to generate APS cells that efficiently differentiate into cardiac mesoderm. Thus, we reasoned that transient ACTIVIN+YAP1i exposure might provide an alternative strategy to generate cardiomyocytes in WT  hESCs.We then compared the transcriptomes of cardiomyocytes generated from WT H1 hESC by YAPi+ACTIVIN treament to the GiWi protocol at Day 30 of differentiation.	Co-expression
SRP167149	Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing	Methylation of guanosine on position N7 (m7G) on internal RNA positions have been found in all domains of life and have been implicated in human disease, but m7G modifications has so far only been mapped in a limited number of RNA molecules. Here, we present m7G Mutational Profiling sequencing (m7G-MaP-seq), which allows high throughput detection of m7G modifications. In our method, m7G modified positions are converted to abasic sites by mild reduction, recorded as cDNA mutations through reverse transcription, sequenced and subsequently detected by identification of positions with increased mutation rates in the reduced sample compared to the control. We show that m7G-MaP-seq efficiently detects m7G modifications in rRNA, including a previously uncharacterised rRNA modification in Arabidopsis thaliana. Furthermore, we identify m7G tRNA modifications in budding yeast, human and arabidopsis tRNA and show that m7G modification occurs before tRNA splicing. We do not find any evidence for internal m7G modifications being present in other small RNA, such as miRNA, snoRNA and sRNA. Likewise, high coverage m7G-MaP-seq analysis of mRNA from E. coli or yeast cells failed to identify any internal m7G modifications. Overall design: RNA from E. coli (strain BW25113 and RsmG KO), Saccharomyces cerevisiae (BY4741), HeLa, Arabidopsis Thaliana Columbia-0 . The RNA was treated with NaBH4 or mock-treated, then reverse transcribed.	Co-expression
SRP167165	E2F activity effect on gene expression	The activity of different E2F constructs with respect to gene expression was measured. E2F constructs differed in degradability, and were doxycycline inducible. Different samples with the different E2F constructs, and with or without dox inductions were assayed for gene expression.	Co-expression
SRP167203	Comprehensive gene expression analysis of TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs)	Lysine 9 di-methylation and lysine 27 tri-methylation of histone H3 (H3K9me2 and H3K27me3) are mostly linked to gene repression. However, functions of repressive histone methylation dynamics during inflammatory responses remain poorly understood. Here, we show that lysine demethylase 7A (KDM7A) and 6A (UTX) are rapidly transported to nuclear factor kappa-B (NF-?B) related elements in human endothelial cells in response to tumor necrosis factor (TNF)-a. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and cooperatively activate NF-?B dependent inflammatory genes. Furthermore, using both in situ Hi-C and other 3C based technology, loops between super enhancers (SEs) are newly formed following TNF-a-stimuli at NF-?B-dependent inflammatory loci where KDM7A- and UTX-recruitment coincide. Collectively, these findings suggest that erasing of repressive histone marks by KDM7A and UTX within NF-?B-related elements might functionally associate with formation of SE-SE three-dimensional interactions and could be a cue signal during inflammatory responses in human endothelial cells. Overall design: Total 29 samples were derived from [1] HUVECs in the absence or presence of TNF-alpha (0, 4, and 24 hrs) to determine TNF-alpha-responsive genes during inflammation, [2] si control, siKDM7A, siUTX, or siKDM7A+siUTX transfected HUVECs under TNF-alpha-stimuli (4 hrs) to understand molecular function of KDM7A and UTX during inflammation.	Co-expression
SRP167214	Transcriptome analysis of NPC xenographs and tumors that develop in mice following injection of NPC cell lines	RNA-Seq study of tumors that develop in mice after injection of nasopharyngeal carcinoma (NPC) cell line C666.1 and the xenograph tumors C15 and C17	Co-expression
SRP167217	Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells	Long RNA-seq analysis on cellular and extracellular samples from a KRAS mutant colorectal cancer cell model, in association with Hinger et al 2018 Overall design: Biological triplicates of 3 exosome RNA samples with biological triplicates of 6 cellular RNA samples. Cellular samples are submitted as biological triplicates of 3 RNA samples, with either no treatment or treatment with ionomycin. All samples are derived from 3 distinct colorectal cancer cell lines dependent of KRAS status of the cells. These include WT/- (DKs8), WT/MUT (DLD1), and -/MUT (DKO1).	Co-expression
SRP167265	H1609088 Human RNA-Sequencing	Transcriptome profiling of KYSE30 cells after intracellular invasion by Porphyromonas gingivalis  Purpose: Overabundance of Porphyromonas gingivalis (P. gingivalis) plays oncogenic roles in development and progression of esophageal squamous cell carcinoma (ESCC). To unveil the molecular mechanisms underlying the tumor-promoting role, RNAseq was used to identify differentially expressed genes in response to P. gingivalis in KYSE30 cells.  Methods: mRNA profiles were generated by deep sequencing for P. gingivalis-treated KYSE30 cells and PBS-treated control cells in triplicate. RNAseq data were mapped to human genome (hg19) using Hisat2. Differentially expressed genes were identified using StringTiel and Ballgown.  Results: A total of 10 239 genes and a total of 10 297 genes were identified in KYSE30 cells treated with P. gingivalis and PBS, respectively. After expression quantification using Ballgown, 124 up-regulated genes and 122 down-regulated genes were identified in P. gingivalis-treated KYSE30 cells compared with PBS-treated cells. Enrichment analysis of GO and KEGG pathway showed response to virus, innate immune response, Herpes simplex infection, metabolism of xenobiotics by cytochrome P450 and tyrosine metabolism were enriched in P. gingivalis-treated KYSE30 cells.  Conclusions: This study reveals that P. gingivalis infection in ESCC triggers immune response and may cause deregulation of signal transduction through tyrosine metabolism. Overall design: mRNA profiles were generated by deep sequencing for P. gingivalis-treated KYSE30 cells and PBS-treated control cells in triplicate. RNAseq data were mapped to human genome (hg19) using Hisat2. Differentially expressed genes were identified using StringTiel and Ballgown.	Co-expression
SRP167336	Transcriptome analysis of tumors that develop in mice following injection of AGS cell lines	RNA-seq study of tumors that develop in mice after injection of gastric carcinoma cell line, AGS, with or without Epstein-Barr virus infection	Co-expression
SRP167389	Gene expression profiles of isogenic single-cell derived clones of BRAF-mutated SK-MEL-5 melanoma cell lines	We recently reported that single-cell derived isogenic subclones of SKMEL5 cells have differential initial sensitivity to BRAF-inhibitors. In order to probe differences among these subclones, we selected three subclones with unique drug responses: progressing (SK-MEL-5 SC10), stationary (SK-MEL-5 SC07), and regressing (SK-MEL-5 SC01) and performed RNASeq. This study examines differentially expressed genes (DEGs) among the subclones to identify the molecular basis for initial differences in drug sensitivity. Overall design: Transcriptomics analysis between single-cell derived isogenic subclones of BRAF-mutated melanoma cell line, SK-MEL-5	Co-expression
SRP167434	Prediction of bacterial infection outcome using single cell RNA-seq analysis of human immune cells [WT/TLR10 bulk RNA-seq]	During host-pathogen encounters, the complex interactions between different immune cell-types can determine the outcome of infection. Advances in single cell RNA-seq (scRNA-seq) allow to probe this complexity of immunity, and afforded the basis for deconvolution algorithms that infer cell-type compositions from bulk RNA-seq measurements. However, immune activation, an important aspect of immune surveillance, is not represented in current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we developed a novel deconvolution algorithm to infer dynamic immune states from bulk measurements. We applied our dynamic deconvolution algorithm both to cohorts of healthy individuals challenged ex vivo with Salmonella and to cohorts of tuberculosis patients during different stages of disease. We revealed cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and can be applied to comprehensively study human infection outcome. Overall design: PBMCs were isolated from 8 individuals bearing or not TLR10 polymorphism and were infected ex vivo with Salmonella enterica serovar Typhimurium. RNA was extracted before infection, 4 hours post infection and 8 hours post infection.	Co-expression
SRP167647	Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the Hippo pathway	Loss of FAT1 promotes resistance to CDK4/6 inhibitors. This study was to compare the differential mRNA expression of FAT1 crispr cells with parental cells, to identify the underlying mechanisms of resistance. Overall design: Examnination of differential RNA expression in FAT1 loss cells compared to MCF-7 parental cells.	Co-expression
SRP167686	Spatial clustering and common regulatory elements lead to TGF-ß induced concerted gene expression	Cellular responses require temporally concerted transcriptional regulation of multiple genes. A single-input-module motif with one transcription factor regulating multiple target genes can generate the coordinated gene expression. In eukaryotic cells, the local environment of a gene characterized by histone modifications, DNA methylations, and the three-dimensional chromosome structure also regulates its transcriptional activity. To examine how the local environment and transcriptional factor regulation is coupled, we performed combined analysis of time-course RNA-seq data of TGF-ß treated MCF10A cells and corresponding epigenome and Hi-C data. We discovered, genes co-regulated by a common transcription factor has tendency to be close both in the linear DNA sequence and spatially. Specifically, we identified local spatial organization of over a hundred of AP1-regulated genes, and competition between hetero- and homo-dimeric AP1 fine-tunes the complex structure leading to differential expression of downstream genes sharing similar local environment. We suggest this spatial organization as a general regulation principle. Overall design: Gene expression profiling of MCF10A cells with 7 different duration of TGF-beta inducing as well as one control group without inducing, each time point with 3 biological replicates.	Co-expression
SRP167690	Prediction of bacterial infection outcome using single cell RNA-seq analysis of human immune cells [scRNA-seq ind.1]	During host-pathogen encounters, the complex interactions between different immune cell-types can determine the outcome of infection. Advances in single cell RNA-seq (scRNA-seq) allow to probe this complexity of immunity, and afforded the basis for deconvolution algorithms that infer cell-type compositions from bulk RNA-seq measurements. However, immune activation, an important aspect of immune surveillance, is not represented in current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we developed a novel deconvolution algorithm to infer dynamic immune states from bulk measurements. We applied our dynamic deconvolution algorithm both to cohorts of healthy individuals challenged ex vivo with Salmonella and to cohorts of tuberculosis patients during different stages of disease. We revealed cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and can be applied to comprehensively study human infection outcome. Overall design: Frozen PBMCs from healthy individual were defrosted and infected ex vivo with Salmonella enterica serovar Typhimurium.	Co-expression
SRP167719	Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency	It is important to understand how cells can maintain and exit human pluripotency. We exploited the metabolic and epigenetic differences between naïve and primed pluripotent cells to design a CRISPR-Cas9 screen for identifying genes that promote the exit from naïve pluripotency. Among the known and novel regulators of this early step of human development, we identified the tumor suppressor folliculin (FLCN). Flcn is important for implantation of the mouse embryo into the uterus and has been shown to regulate the exit of pluripotency in mouse through activation of Esrrb. However, the function of FLCN is unknown in human embryonic stem cells (hESC). Knock-out (KO) of FLCN revealed that it is not essential to maintain the naïve pluripotent state but is required for the exit of that state, in part by controlling the localization of the transcription factor TFE3. While mainly found in the cytoplasm of cells exiting the naïve state, FLCN KO resulted in TFE3 nuclear localization. TFE3 targets up-regulated in FLCN KO exit assay were members of Wnt pathway and ESRRB. Treatment of FLCN KO hESC with a Wnt inhibitor rescued the phenotype and allowed the cells to exit the naïve state. In contrast, the lack of rescue in ESRRB/FLCN double KO lines suggested that ESRRB was not responsible for the FLCN mutant phenotype. Using co-immunoprecipitation and mass spectrometry analysis we identified unique FLCN binding partners, in addition to known FLCN interactors, at various stages of pluripotency. The interactions of FLCN with components of the mTOR pathway (mTORC1 and mTORC2) revealed a mechanism of FLCN function during exit from naïve pluripotency. Overall design: RNA-seq of 2 biological replicates in 6 conditions: Elf 2iLIF, Elf 2iLIF FLCN KO, Elf 2iLIF FLCN AAVS1-FLCN-GFP no Dox, Elf 2iLIF FLCN KO AAVS1-FLCN-GFP with Dox, Elf FLCN KO in TeSR 7 day, and Elf in TeSR 7 day; RNA-seq of Elf FLCN KO treated with IWP2 and DMOS; ChIP-seq of H3K27me3 for NNMT CRISPR mutant 6.2.4	Co-expression
SRP167746	Merkel Cell Carcinoma Cell Lines - RNA-seq	Studies on the efficacy of small molecule inhibitors in Merkel Cell Carcinoma (MCC) have been limited and largely inconclusive. In this study, we investigated the therapeutic potential of a potent BET degrader, BETd-246 in the treatment of MCC. We found that MCC cell lines were significantly more sensitive to BETd-246 than to BET inhibitor treatment. Therapeutic targeting of BET proteins resulted in a loss of MCC “lineage-specifying” genes but not MYC expression as previously described irrespective of Merkel cell polyomavirus (MCPyV) status. In MCPyV+ MCC cells, BETd-246 alone suppressed downstream targets in the MCPyV-LT Ag axis. We also found enrichment of HOX and cell cycle genes in MCPyV- MCC cell lines that were intrinsically resistant to BETd-246. Our findings uncover a requirement for BET proteins in maintaining MCC lineage identity and point to the potential utility of BET degraders for treating MCC. We generated RNA-seq data for untreated MCC cell lines.	Co-expression
SRP167845	Genome wide expression profiles (RNAseq) of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) at diferent time points	Background: Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion of activated T cells. Blockade of the PD 1 pathway is widely used for cancer treatment, yet the inhibitory signals transduced by PD-1 in T cells remain elusive. Methods: Expression profiles of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) conditions were evaluated by RNA-seq. Bioinformatic analyses were used to identify signaling pathways differentially regulated in PD 1-stimulated cells. Overall design: Total RNA was isolated from T control (IgG1-coated beads were used as control , N=3), T activadas (N=3) and Tactivadas+PD1 (N=3) at 6, 24 and 48 h post-stimulation.	Co-expression
SRP167870	Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells	Using RNA-seq to identify gene expression changes after genetic deletion of ADAR Overall design: RNA-seq of A549, HCC366, NCI-H1650, and NCI-H196 cells after CRISPR-Cas9-mediated deletion of ADAR as compared to a control gene. A549 cells were also treated with vehicle or interferon-ß for 24 hours prior to collection for RNA-seq.	Co-expression
SRP167893	Insights into the role of immunomodulation of ZIKV-infected UCMSC by using transcriptomic analysis.	RNA profiles of UCMSC infected with various ZIKV strains were generated by High-throughput sequencing using Illumina Hi-seq 2500 Overall design: Investigation of host immunesuppression effect differences in response to infection with ZIKV two strains.	Co-expression
SRP167965	RNA sequencing of GLO1-depleted MDA-MB-231 breast cancer cells	We reported the expression of a pro-metastatic signature in GLO1-depleted MDA-MB-231 cells compared to control. Overall design: RNA sequencing was performed on 3 biological replicates of 2 clones of GLO1-silenced (shGLO1) cells and 1 control (shNT) clone	Co-expression
SRP167977	Gene expression profile in FTSEC cells (FT190 and FT194 cell lines) transduced with shRNA to knockdown RNF20 or with control shRNA using RNA-seq.	We identified that downregulation of RNF20/H2Bub1 is involved in HGSOC progression through altering key immune signaling pathways. The goal of this RNA-seq is to analyze gene expression profile in FTSEC cells (FT190 and FT194 cell lines) with RNF20 knockdown (shRNF20) or control shRNA. Integrating the data from ATAC-seq for same samples, we observed that expression of immune signaling pathways have significantly changed by RNF20/H2Bub1 downregulation. Overall design: mRNA profiles of FT190 and FT194 shRNF20 (RNF20 knockdown) or control shRNA cells were generated by deep sequencing using Illumina HiSeq 2500, in triplicate.	Co-expression
SRP168038	Bacterial sepsis triggers an antiviral response that causes translation shutdown	In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the Eif2ak2-Eif2a axis is the key mediator of translation initiation block in late phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings implicate that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis. Overall design: Bulk 20 um thickness specimens from cross-sectional human kidney biopsies embedded in OCT underwent RNA sequencing. All subjects had ATN, AIN, or a mix of both conditions.	Co-expression
SRP168172	PolyA-sequencing in Kelly and Kelly E9R neuroblastoma cells treated with THZ531 or DMSO	We performed RNA-seq analsysis of polA transcripts in Kelly and Kelly E9 resistant (E9R) cells treated with THZ531 for 6h and DMSO as a control Overall design: Expression of  polA transcripts in Kelly and Kelly E9R cells treated with THZ531 using  the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen)  in duplicate, for a total of 8 indyvidual samples Please note that the bigWig processed data was generated from both replicates and is linked to the corresponding rep1 (*_1) sample records.	Co-expression
SRP168173	PolyA-sequencing in IMR-32 neuroblastoma cells with shRNA mediated depletion of CDK12, CDK13 or GFP.	We performed RNA-seq analysis of polA transcripts in IMR-32 cells with shRNA-mediated depletion of CDK12 and CDK13 and GFP as a control Overall design: Expression of polA transcripts in IMR-32 cells with shRNA-mediated depletion of CDK12 and CDK13 using  the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen)  using 2 different shRNA constructs for each target in duplicate, for a total of 10 individual samples Please note that processed data files were generated from the merged replicates, as indicated in the corresponding sample description field.	Co-expression
SRP168212	Aging-associated patterns in the expression of human endogenous retroviruses	Human endogenous retroviruses (HERV) are relics of ancient retroviral infections in our genome. Most of them have lost their coding capacity, but proviral RNA or protein have been observed in several disease states (e.g. in inflammatory and autoimmune diseases and malignancies). However, their clinical significance as well as their mechanisms of action have still remained elusive. As human aging is associated with several biological characteristics of these diseases, we now analyzed the aging-associated expression of the individual proviruses of two HERV families, HERV-K (91 proviruses) and HERV-W (213 proviruses) using genome-wide RNA-sequencing (RNA-seq). RNA was purified from blood cells derived from healthy young individuals (n=7) and from nonagenarians (n=7). The data indicated that in the case of HERV-K (HML-2) 33 proviruses had a detectable expression but in only 3 of those the expression levels were significantly different between the young and old individuals. In the HERV-W family expression was observed in 45 loci and only in one case the young/old difference was significant. However, applying the hierarchical clustering on the HERV expression data resulted in the formation of two distinct clusters, one containing the young individuals and another the nonagenarians. This suggests, that even though the aging-associated differences in the expression levels of individual proviruses are minor, there seems to be some underlying aging-related pattern. These data indicate that aging does not have a strong effect on the expression of individual HERV proviruses, but instead several proviruses are affected moderately, leading to age-dependent expression profiles. Overall design: Seven peripheral blood mononuclear cell (PBMC) samples from healthy nonagenarians, aged 94, all female. Seven PBMC samples from healthy young laboratory personnel, aged 26 to 32 median age 28, all female. RNA-sequencing of the samples was done. Expression of genes and human endogenous retroviruses (HERVs) was quantified.	Co-expression
SRP168232	Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (RNA-Seq)	HIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable. Overall design: RNA-seq was performed to identify up- or down-regulated genes associated with in vitro resistance to R5-tropic viruses in activated CD4+ T cells from HIV+ Elite Controllers and family members	Co-expression
SRP168244	SPI1/PU.1 controls fibroblast polarization and tissue fibrosis	Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix which lead to scaring and organ failure. In sharp contrast, the hallmark feature of fibroblasts in arthritis is matrix degradation by the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms driving these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts are enigmatic. We have compared resting, fibrotic, and inflammatory fibroblasts; PU.1 was overexpressed in dermal fibroblasts and compared to scr-transfected controls. Fibrotic fibroblasts isolated from the skin of patients with systemic sclerosis were treated with PU.1 inhibitor and compared to untreated fibrotic fibroblasts and respective healthy controls. Through this, we identified the transcription factor PU.1 as an essential orchestrator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms which normally control PU.1 expression is perturbed in fibrotic diseases such as pulmonary fibrosis, systemic sclerosis, liver cirrhosis, kidney fibrosis and chronic graft-versus-host disease, resulting in upregulation of PU.1, the induction of fibrosis-associated gene sets, and a phenotypic switch in matrix-producing pro-fibrotic fibroblasts. In contrast, inactivation of PU.1 disrupts the fibrotic network and enables re-programming of fibrotic fibroblasts into resting fibroblasts with regression of fibrosis in different organs. Targeting of PU.1 may thus represent a novel therapeutic approach for the treatment of a wide range of fibrotic diseases. Overall design: The 21 analyzed samples belong to 6 different groups with 3 to 4 biological replicates per group. Two of the groups consisted of control samples.	Co-expression
SRP168371	Epigenome regulation during epidermal lineage commitment [RNA-seq]	Recent advances in human pluripotent stem cell (hPSC) technology provide a unique resource for skin tissue replacement, but the detailed understanding of regulatory  mechanisms limits standardization and broad clinical application. Here, we interrogate chromatin accessibility and transcriptome dynamics during hPSC-derived epidermal  differentiation, and discover two critical transition periods: surface ectoderm initiation and keratinocyte maturation. Using inference network modeling, we develop a computational  framework for each transition, and identify TFAP2 and TP63 and their cofactors as key regulators. Surprisingly, functional studies demonstrate the sufficiency of TFAP2C to  initiate surface ectoderm differentiation by activating the early TF network and its chromatin landscape changes, while loss of TFAP2C inhibits early commitment. TFAP2Cinitiated  cells are competent to further differentiate into functional keratinocytes in selective media, accompanied by activation of the keratinocyte maturation network and  decline of the early network. Mechanistically, TFAP2C activates the expression and increases binding site accessibility and positive autoregulation of the master regulator  P63, while loss of P63 results in failure to close TFAP2-initiated early program and leads to maturation and survival defects, revealing a positive-negative feedback loop that  ensures complete transition from progenitor to maturation tissue. Our work reveals the logic underlying dynamic epigenome-transcription factor interactions during human  epidermal lineage commitment that will facilitate improved tissue engineering and regenerative medicine. Overall design: chromatin accessibility and gene expression profile in epidermal differention from normal hESC, and hESCs containing inducible expression of TFAP2C or p63 KO  were generated by ATAC-seq and RNA-seq, in two replicates at each stage, using illunia Hiseq 2000 and Nextseq 500.	Co-expression
SRP168405	Effects of NSUN2 deficiency on the mRNA 5-methylcytosine modification and gene expression profile in HEK293 cells (RNA-Seq)	Aim: To study the biological function of NSUN2 in regulating gene expression and cell proliferation. Materials & methods: The NSUN2 gene was knocked down in HEK293 cells via CRISPR/Cas9 system. Gene expression were assessed using RNA-Seq. Results: A total of 790 differentially expressed genes (DEGs) were identified. Overall design: mRNA profiles of wild type (WT) and NSUN2-/- HEK293 cells were generated by deep sequencing, in triplicate.	Co-expression
SRP168409	ISL1 predicts poor outcomes for patients with gastric cancer and drives tumor progression through binding to the ZEB1 promoter together with SETD7	The goals of this study are to analyze the transcriptome profiling (RNA-seq) after ISL1 overexpression in SGC7901. Overall design: SGC7901cells were transfected by ISL1 expression lentivirus and blank lentivirus as control.Total RNA was extraced by Qiagen kit and the RNA profiles were generated by deep sequencing, in duplicate, using Illumina Hiseq 2500.	Co-expression
SRP168421	SLE PBMC RNA-seq	RNA sequencing of systemic lupus erythematosus (SLE) and healthy PBMCs to measure transcriptional changes in gene and endogenous retrovirus expression Overall design: RNA sequencing using RNA obtained from PBMCs of SLE patients and healthy controls	Co-expression
SRP168620	Transcriptomic analysis to functionally map the intrinsically disordered domain of EWS/FLI [Experiment 2]	The purpose of this study was to define unique classes of EWS/FLI target genes and the distinct set of structural features present in the EWS domain required for target gene regulation at different EWS/FLI response elements. This study reports the first genome-wide transcriptomic description of a partially-functional EWS/FLI mutant . We report new structure-function dependencies across different classes of response element and tie these dependencies to the ability of EWS/FLI to transform cells. Overall design: For knockdown of wildtype EWS/FLI and rescue with differing cDNAs in A673 Ewing sarcoma cell lines, shRNAs were retrovirally delivered on day 1. Selection in 2 µg/mL puromycin (Sigma P8833) occurred on days 2-5. Cells were infected with retrovirus containing the cDNA in the pMSCV-hygro backbone on day 5. Double selection in puromycin and 400 µg/mL hygromycin B (Thermo Fisher 10687010) began on day 6 and continued until day 16. Cells were subsequently harvested for RNA, protein, and seeded for soft agar assays.	Co-expression
SRP168621	Transcriptomic analysis to functionally map the intrinsically disordered domain of EWS/FLI [Experiment 1]	The purpose of this study was to define unique classes of EWS/FLI target genes and the distinct set of structural features present in the EWS domain required for target gene regulation at different EWS/FLI response elements. This study reports the first genome-wide transcriptomic description of a partially-functional EWS/FLI mutant . We report new structure-function dependencies across different classes of response element and tie these dependencies to the ability of EWS/FLI to transform cells. Overall design: For knockdown of wildtype EWS/FLI and rescue with differing cDNAs in A673 Ewing sarcoma cell lines, shRNAs were retrovirally delivered on day 1. Selection in 2 µg/mL puromycin (Sigma P8833) occurred on days 2-5. Cells were infected with retrovirus containing the cDNA in the pMSCV-hygro backbone on day 5. Double selection in puromycin and 400 µg/mL hygromycin B (Thermo Fisher 10687010) began on day 6 and continued until day 16. Cells were subsequently harvested for RNA, protein, and seeded for soft agar assays.	Co-expression
SRP168639	SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons	Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). To investigate their effect on synaptic connectivity, we generated cortical neurons from induced pluripotent stem cells (iPSC) derived from neurotypic and ASD-affected donors. We developed Sparse coculture for Connectivity (SparCon) assays where SHANK2 and control neurons were differentially labeled and sparsely seeded together on a lawn of unlabeled control neurons. We observed striking increases in total synapse number and dendrite complexity. Dendrite length increases were exacerbated by IGF1 or BDNF treatment. Increased excitatory synapse function in haploinsufficient SHANK2 neurons was phenocopied in gene-edited knockout SHANK2 neurons. Gene correction of an ASD SHANK2 mutation rescued excitatory synapse function supporting a role for SHANK2 as a negative regulator of connectivity in developing human neurons. The transcriptome in these isogenic SHANK2 neurons was deeply perturbed in synaptic and plasticity gene sets and ASD gene modules, and activity dependent dendrite extension was defective. Our unexpected findings provide evidence for hyperconnectivity and profoundly altered transcriptome in SHANK2 neurons derived from ASD subjects. Overall design: RNA-Seq comparison of isogenic pairs of human induced pluripotent stem cell derived neurons at 4- and 9-weeks of age, with 4 replicates at each time point	Co-expression
SRP168642	Neutrophil gene expression in systemic juvenile idiopathic arthritis	Systemic juvenile idiopathic arthritis (SJIA) is a chronic childhood arthropathy with features of autoinflammation. Early inflammatory SJIA is associated with expansion and activation of neutrophils with a sepsis-like phenotype, but neutrophil phenotypes present in longstanding and clinically inactive disease (CID) are unknown. The objective of this study was to examine activated neutrophil subsets, S100 alarmin release, and gene expression signatures in children with a spectrum of SJIA disease activity.  Methods: Highly-purified neutrophils were isolated using a two-step procedure of density-gradient centrifugation followed by magnetic-bead based negative selection prior to flow cytometry or cell culture to quantify S100 protein release. Whole transcriptome gene expression profiles were compared in neutrophils from children with both active SJIA and CID.  Results: Patients with SJIA and active systemic features demonstrated a higher number of CD16+CD62Llo neutrophil population compared to controls. This neutrophil subset was not seen in patients with CID or patients with active arthritis not exhibiting systemic features. Using imaging flow cytometry, CD16+CD62Llo neutrophils from patients with active SJIA and features of macrophage activation syndrome (MAS) had increased nuclear hypersegmentation compared to CD16+CD62L+ neutrophils. Serum levels of S100A8/A9 and S100A12 were strongly correlated with peripheral blood neutrophil counts. Neutrophils from active SJIA patients did not show enhanced resting S100 protein release; however, regardless of disease activity, neutrophils from SJIA patients did show enhanced S100A8/A9 release upon PMA stimulation compared to control neutrophils. Furthermore, whole transcriptome analysis of highly purified neutrophils from children with active SJIA identified 214 differentially expressed genes compared to neutrophils from healthy controls. The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4. Interestingly, this gene set showed intermediate levels of expression in neutrophils from patients with long-standing CID yet persistent serum IL-18 elevation. Indeed, all patient samples regardless of disease activity demonstrated elevated inflammatory gene expression, including inflammasome components and S100A8.  Conclusion: We identify features of neutrophil activation in SJIA patients with active disease and CID, including a proinflammatory gene expression signature, reflecting persistent innate immune activation. Taken together, these studies expand understanding of neutrophil function in chronic autoinflammatory disorders such as SJIA. Overall design: Highly purified neutrophils isolated from patients with SJIA and healthy controls	Co-expression
SRP168742	Paired Related Homeobox Protein 1 Regulates Quiescence in Human Oligodendrocyte Progenitors	Human oligodendrocyte progenitor cells (hOPCs) persist into adulthood as an abundant precursor population of capable of division and differentiation. The transcriptional mechanisms that regulate hOPC homeostasis remain poorly defined. Herein, we identified paired related homeobox protein 1 (PRRX1) in primary PDGFaR+ hOPCs. We show that enforced PRRX1 expression resulted in reversible G0/1 arrest. While both PRRX1 splice variants reduced hOPC proliferation, only PRRX1a abrogated migration. hOPCs engraftment into hypomyelinated shiverer/rag2 mouse brain was severely impaired by PRRX1a, characterized by reduced cell proliferation and migration. PRRX1 induced a gene expression signature characteristic of stem cell quiescence. Both IFN-g and BMP signaling up-regulated PRRX1 and induced quiescence. Importantly, PRRX1 knockdown modulated IFN-g induced quiescence. In mouse brain, PRRX1 mRNA was detected in non-dividing OPCs and was up-regulated in OPCs following demyelination. Together, these data identify PRRX1 as a regulator of quiescence in hOPCs and as a potential regulator of pathological quiescence. Overall design: Effect of PRRX1a or PRRX1b over-expression on hOPCs, 3 mCherry control, 3 PRRX1a, 3 PRRX1b	Co-expression
SRP168821	Human lineage tracing enabled by mitochondrial mutations and single cell genomics [CRC_scRNA]	Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease. Overall design: Primary cells from a patient with colorectal adenocarcinoma were sorted based on EPCAM+ surface marker expression and forwarded to a combination of 1) ATAC-seq and single cell RNA-seq. The single-cell RNA-seq data are listed here.	Co-expression
SRP169065	Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance	To Study the role of mutant Braf V600E and ERK dependent phosphorylation of TFEB in regulation of autophagy and lysosome biogenesis in the context of melanoma growth and metastasis, we used whole geneome RNA-seq to study role TFEB mediated  BRAFV600E autophagy regulation. Overall design: For subcutaneous xenografts, A375 cells stably expressing WT TFEB or TFEB mutants (5 x 10^6) were injected subcutaneously into the lower flank of 5-6 six-week-old female NOD/SCID mice. After a three-weeks of post-inoculation, mice were sacrificed, and tumors were dissected and processed for RNA isolation.	Co-expression
SRP169094	On-Treatment Biomarkers Improve Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer	Background: Neoadjuvant chemotherapy is increasingly being used to preoperatively shrink breast tumours prior to surgery. This approach also provides the opportunity to study the molecular changes associated with treatment and evaluate whether on-treatment sequential samples can improve response and outcome predictions over diagnostic or excision samples alone. Methods: A total of 95 samples from a cohort of 50 neoadjuvant chemotherapy-treated primary breast cancer patients (aged 29-76, 48% ER+, 20% HER2+) enrolled in the NEO trial taken before, at 2 weeks on-treatment, mid-therapy and at resection were sequenced with Ion Ampliseq transcriptome yielding expression values for 12,635 genes. Differential expression analysis was performed across 16 responders and 34 non-responders defined by pathological complete response and over treatment time to identify significantly differentially expressed genes, pathways and markers indicative of response status. Prediction accuracy was compared with estimations of established gene signatures, for this dataset and validated using data from the I-SPY1 trial. Results: AAGAB was identified as a novel on-treatment biomarker for pathological complete response, with an accuracy of 100% in the NEO training dataset and 78% accuracy in the I-SPY1 Trial. AAGAB levels on treatment were also significantly predictive of term survival (p = 0.048, p = 0.031) in the two cohorts. This single gene on-treatment biomarker, had greater predictive accuracy than established prognostic tests, Mammaprint and Pam50 risk of recurrence score, although interesting both of these tests performed better in the on-treatment rather than the accepted pre-treatment setting (accuracy improving consistently by 2-8%). Conclusion: Changes in gene expression measured in sequential samples from breast cancer patients receiving neoadjuvant chemotherapy resulted in the identification of a novel on-treatment biomarker and suggest that established prognostic tests may have greater prediction accuracy on- than before treatment. These results support the potential use and further evaluation of on- treatment testing in breast cancer to improve the accuracy of tumour response prediction. Overall design: A cohort of 95 paired sequentially sampled breast cancer patients with known treatment response were pooled. Samples were taken via needle aspiration at T1 (Pre-treatment), T2 (2 weeks on treatment), T3 (mid chemo, usually 6 weeks), and T4 at surgical resection. Samples were fresh frozen after collection. Samples were sequenced on the Ampliseq platform and differential analysis and processing were performed in R.	Co-expression
SRP169509	A platform for generation of chamber specific cardiac tissues and disease modelling	We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells. Overall design: hiPSC-CMs from 3 affected (Left Ventricular Hypertrophy [LVH]) and 3 non-affected donors were sequenced using ThermoFisher's whole transcriptome targeted AmpliSeq assay	Co-expression
SRP169561	Next Generation Sequencing of Wild Type IFNG versus partial agonists in A549 cell line human transcriptomes	Purpose: Next-generation sequencing (NGS) of human transcriptome of over 20,000 genes to compare gene expression of wild-type versus designed IFNG partial agonsits Methods: A549 cells were treated with either wild-type IFNG or partial agonists for 48 hours. RNA was extracted and prepared for NGS on using Thermo Ampliseq human transriptome kit on an Ion S5 XL system (Thermo). Relative expression was determined from the data. Results: Over 20,000 transcripts were matched to the human transcriptome to compare expression between protein treatments. We find genes that are stably expressed regardless of protein agonist treatment and other genes that have altered expression levels compared to wild-type. Conclusions: Our study represents a comprehensive list of genes along with their sensitivity to IFNG induced signaling. Overall design: RNA was extracted from two biological replicates in A549 cells after 48 hours of protein treatment, libraries prepared for and read on an Ion S5 XL system using the AmpliSeq human transcriptome kit.	Co-expression
SRP169574	Receptor tyrosine kinase signaling promotes post-embryonic morphogenesis and survival of glia and neural progenitor cells	Glioblastomas (GBMs), which are the most deadly malignant brain tumors of children and adults, infiltrate the brain and grow rapidly, and are resistant to current therapies. Glioblastomas (GBMs) frequently display mutations that activate receptor tyrosine kinases (RTKs), such as EGFR, which are thought to cooperate with additional factors to drive tumorigenesis. To identify and characterize genetic pathways that cooperate with RTKs to drive GBM progression, we performed RNA sequencing on several cell cultures created from surgical specimens from tumors with alterations in RTKs, and these cultures were grown as neurospheres in serum-free media used for normal neural stem/progenitor cell cultures. Under these conditions, GBM cells retain many defining features and mutations found in primary tumors. For comparison, we profiled commercially available human normal neural stem cells (HNPCs), which were grown under the same conditions. Data from these cell cultures was analyzed for transcripts differentially expressed between GBM cells and HNPCs, which showed that GBM cells that show RTK alterations strongly overexpressed the PDGFA and IGF2 secreted factors, which likely cooperate with EGFR to drive tumor progression. Overall design: Transcriptomic profiling of human glioblastoma neurospheres	Co-expression
SRP169582	Genome-wide co-localization of RNA-DNA interactions and fusion RNA pairs (RNAseq)	Despite the ever-increasing speed of detecting fusion transcripts in cancer, it remains formidable to predict what unreported RNA pairs can form new fusion transcripts. By systematic mapping of chromatin-associated RNAs (caRNAs) and their respective genomic interaction loci, we obtained genome-wide RNA-DNA interaction maps from two non-cancerous cell types. The gene pairs involved in RNA-DNA interactions in these normal cells exhibited strong overlap with those with cancer-derived fusion transcripts. These data suggest an RNA-poise model, where the spatial proximity of one gene's transcripts and the other gene's genomic sequence poises for the creation of fusion transcripts. We validated this model with 96 additional lung cancer samples. One of these additional samples exhibited fusion transcripts without a corresponding fusion gene, suggesting that genome-recombination is not a required step of the RNA-poise model. Overall design: Targeted RNA-seq on lung cancer patient biopsy and H2228 cell line	Co-expression
SRP169608	RNA-seq approach to study the specific effects of SREBF1-depleting antisense oligonucleotide (ASO) reagent in human melanoma cells.	Purpose: Detailed exploration of de novo Fatty Acid Synthesis (DNFA) transcription regulation and clinical relevance in melanomas. This study was designed to achieve the following goals: 1) determine the impact of SREBP1 depletion on gene expression in metastatic melanoma cells; 2) determine the specificity of ASO and other reagents inhibiting SREBF1 mRNA.  Method: RNA-Seq was performed after culture with control and various SREBF1-depleting agents, including pooled siRNAs and individual ASOs, in HT-144 cells.  Results: using STAR, we mapped about 2 X 4 million pair-end sequence reads per sample to the human genome (build GRCh38.94) and identified around 2 million annotated transcripts per sample. Overall design: 6 RNA samples (4 technical replicates for each biological sample) were sequenced (paired-end) on a NextSeq® 500 sequencer (Illumina). RNA sequence alignment was performed on the 24 pairs of FASTQ files from the sequence results.	Co-expression
SRP169609	Selective roles of vertebrate PCF11 in premature and full-length transcript termination (chromatin-bound RNA-seq)	The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: Semi-nascent transcriptome measured by chromatin-bound RNA-seq in HeLa cells. Control and PCF11 knock-down (2 biological replicates) and control and PCF11 PAS1 deletion (4 biological replicates).	Co-expression
SRP169611	Next generation sequencing of human hepatic stellate cell line, LX-2 treated with recombinant human TGF-ß1, with DMSO or ML290 (5 µM) for 72h.	The overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.	Co-expression
SRP169618	Transcriptomic analysis of different human cardiac cell types produced in vitro from human pluripotent stem cells or derived from patients.	The epicardium, an epithelium covering the heart, is essential for cardiac development. During embryogenesis, the epicardium provides instructive signals for the growth and maturation of cardiomyocytes and for coronary angiogenesis. We generated an in vitro model of human embryonic epicardium derived from human pluripotent stem cells (hPSC-epi). These cells were able to differentiate into cardiac fibroblasts (cf) and smooth muscle cells (smc) in vitro (hPSC-epi-cf and hPSC-epi-smc respectively). Furthermore, we showed that they improved maturation of hPSC-derived cardiomyocytes (hPSC-cardio) in vitro while neural crest cells derived from hPSC (hPSC-NC) could not. Furthermore, they improved survival of hPSC-cardio and stimulated angiogenesis when injected in a rat model of myocardium infarction. We performed mRNA sequencing of the hPSC-epi, hPSC-epi-cf, hPSC-smc and hPSC-NC in order to identify the secreted molecules specifically produced by the hPSC-epi and/or its derivatives in comparison with the hPSC-NC. Vascular smooth muscle cells have different embryonic origins and different properties depending on their location in the body. The coronary smooth muscle cells come from the epicardium while the aortic ones come from the mesoderm or the neural crest. We performed mRNA sequencing of human coronary artery smc and human aortic smc to identify a specific signature of the coronary smc. We also compared the genes expressed in the hPSC-epi-smc and the smc derived from hPSC-derived lateral plate mesoderm. Overall design: For hPSC-derived samples the three replicates are coming from three different in vitro differentiations from H9. For the human primary cells, the triplicates are technical replicates (three different wells from the same culture at the same passage)	Co-expression
SRP169851	RNA-seq of resting and activated CD4+ T cells +-JQ1	HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection. Overall design: Triplicates of: resting JQ1 treated CD4 T cells, activated JQ1 treated CD4 T cells, resting control CD4 T cells, activated control CD4 T cells	Co-expression
SRP169937	RNA sequencing data in AGS-BX1 cells treated with C7	C7 is a novel lytic cycle inducer of Epstein-Barr virus (EBV) in EBV-positive epithelial cells. To analyze the potential signaling pathways that are activated by C7 for induction of EBV lytic cycle, we performed a RNA sequencing to analyze the RNA expression profiles in AGS-BX1 gastric carcinoma cells before and after treatment with C7. Overall design: AGS-BX1 cells are either untreated or treated with C7 with 8 or 24h. RNA was extracted for RNA-sequencing.	Co-expression
SRP169950	Acetylation of spliceosome protein PHF5A modulates stress responses and colorectal carcinogenesis through alternative splicing mediated upregulation of KDM3A	The process utilized by cancer cells for adapting to cellular stress is a key point for carcinogenesis. Alternative pre-mRNA splicing induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. However, the protein post-translational modification, especially protein acetylation on pre-mRNA splicing processes under stress is unknown. Here, we uncovered a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHD finger-like domain-containing protein 5A (PHF5A/SF3b14b), a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses. P300 and HDAC6 regulate PHF5A acetylation levels. PHF5A acetylation strengthens the interaction among U2 snRNPs, and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of colon cancer patients. Our findings uncovered a novel mechanism of anti-stress pathway that acetylation on PHF5A promotes the cancer cells capacity for stress resistance and consequently contributes to colon carcinogenesis. Overall design: 6 samples. HCT116 colon cancer cells were stable expression PHF5A WT or PHF5A K29Q, Cells' RNA was harvested using Trizol reagent. 3 ug of total RNA is used for the construction of sequencing libraries by Hiseq 4000 PE150.	Co-expression
SRP170018	Robust generation of honemogeneous midbrain organoids with in vivo–like cellular composition facilitates neurotoxin-based Parkinson's disease modeling	We could establish the advanced protocol for generating homogeneous and mature midbrain organoids by manipulating SMAD inhibitor combination and in vitro WNT gradient elaborately. Overall design: Here we perform RNA-Seq experiment in different stage of midbrain organoids generated  by various conditions. hESCs was used as a starting source of midbrain organoids.	Co-expression
SRP170025	RNA Sequencing of three pairs of gastric cancer	The prognosis after curative resection of gastric cancer (GC) remains unsatisfactory, and thus, the development of treatments involving alternative molecular and genetic targets is critical. Circular RNAs (circRNAs), new stars of the non-coding RNA network, have been identified as critical regulators in various cancers. Here, we aimed to determine the circRNA expression profile and investigate the functional and prognostic significance of circRNA in GC. Using next-generation sequencing profiling, we first characterized an abundant circRNA, hsa_circ_0008549, derived from the OSBPL10 gene, and named it circOSBPL10. The expression of circOSBPL10 was found via quantitative real-time RT-PCR (qRT-PCR) to be upregulated in GC tissues, and silencing of circOSBPL10 significantly inhibited gastric cancer cell growth, migration and invasion in multiple experiments. We further confirmed that miR-136-5p is a downstream target of circOSBPL10 using RNA pull-down and luciferase reporter assays. Rescue experiments confirmed that circOSBPL10 regulates biological functions in GC cells via a circOSBPL10-miR-136-5p-WNT2 axis. In vivo experiments showed that circOSBPL10 promotes tumor growth and metastasis in mice. Furthermore, the level of circOSBPL10 was observed to be a prognostic marker of the overall survival and disease-free survival of patients with GC. Taken together, our findings reveal that circOSBPL10 may serve as a new proliferation factor and prognostic marker in gastric cancer. Overall design: RNA profiles of three gastric cancer and normal tissues adjacent to gastric cancer were generated by deep sequencing, using Illumina HiSeq 2000.	Co-expression
SRP170055	Expression profiling of pancreatic adenocarcinoma and ductal adenocarcinoma cell lines.	We characterized baseline gene expression profiles for eleven human pancreatic adenocarcinoma and ductal adenocarcinoma cell lines. Overall design: Eleven human pancreatic adenocarcinoma (Hs 766T, Panc 03.27, SU.86.86 and SW1990) and pancreatic ductal adenocarcinoma (AsPC-1, BxPC-3, Capan-2, CFPAC-1, HPAF-II, MIA PaCa-2 and PANC-1) cell lines were grown under standard conditions. RNA expression profiling was performed on total cell extracts using Illumina HiSeq 2000 paired-end sequencing to determine baseline gene expression.	Co-expression
SRP170102	Homo sapiens Genome sequencing	Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1, a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /MET markers after knockdown of SETDB1. Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis. Therefore, development of SETDB1 inhibitors and functional studies may help develop more effective clinical guidelines for BRC treatment	Co-expression
SRP170332	Genes regulated in HT-1080 cells after 24 hours of treatment with IRAK4 inhibitor	Analysis of HT-1080 fibrosarcoma cells transcriptome following  24 hours treatment with IRAK4 inhibitor was performed.  Results provide insight into mode of action of IRAK4 inhibitor under study. Project co-financed from European Regional Development Fund under The Operational Program Innovative Economy, 2007-2013, measure 1.4 (UDA-POIG.01.04.00-12-049/11-00) Overall design: Samples from HT-1080 cells treated for 24 hours with IRAK4 inhibitor and control samples were subjected to RNA sequencing using Ion Torrent Proton. Three biological replicates for a given condition were studied.	Co-expression
SRP170342	Genes regulated in HT-1080 cells after 4 hours of treatment with IRAK4 inhibitor	Analysis of HT-1080 fibrosarcoma cells transcriptome following 4 hours treatment with IRAK4 inhibitor was performed.  Results provide insight into mode of action of IRAK4 inhibitor under study. Project co-financed from European Regional Development Fund under The Operational Program Innovative Economy, 2007-2013, measure 1.4 (UDA-POIG.01.04.00-12-049/11-00) Overall design: Samples from HT-1080 cells treated for 4 hours with IRAK4 inhibitor and control samples were subjected to RNA sequencing using Ion Torrent Proton. Three biological replicates for a given condition were studied.	Co-expression
SRP170415	Cistromic re-programming by truncating GATA3 mutations promotes mesenchymal transformation in vitro, but not mammary tumour formation in mice [RNA-seq]	Heterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice. Overall design: RNAseq data of T47D cells expressing HA-tagged wild-type GATA3 (HA_GATA3_wt) or one of two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2).	Co-expression
SRP170544	single-cell RNA sequencing in patient-derived primary myocytes for facioscapulohumeral muscular dystrophy	Facioscapulohumeral muscular dystrophy (FSHD) is characterized by sporadic de-repression of the transcription factor DUX4 in skeletal muscle. We employed single-cell RNA-sequencing, combined with pseudotime trajectory modeling, to study FSHD disease etiology and cellular progression in human primary myocytes. We identified a small FSHD-specific cell population in all tested patient-derived cultures and detected new genes associated with DUX4 de-repression. We furthermore generated an FSHD cellular progression model, reflecting both the early burst-like DUX4 expression as well as the downstream activation of various FSHD-associated pathways, which allowed us to correlate DUX4 expression signature dynamics with that of regulatory complexes, thereby facilitating the prioritization of epigenetic targets for DUX4 silencing. Overall design: This dataset includes data from muscle biopsy-derived myocyte cultures from 2 FSHD1 patients, 2 FSHD2 patients and 2 healthy control individuals	Co-expression
SRP170619	Pentoxifylline-induced differentially-expressed genes in hypertrophic scar fibroblasts	Pentoxifylline attenuated hypertrophic scars by influencing the cell cycles Overall design: mRNA profiles of control hypertrophic scar fibroblasts and pentoxifylline treated cells were generated by deep sequencing, in triplicate, using Ion  Proton.	Co-expression
SRP170629	RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture	Background and Purpose—Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. Methods—We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. Results—We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions—For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture. Overall design: RNA sequencing of 44 intracranial aneurysm samples (including 21 unruptured, 22 ruptured and 1 undetermined) and 16 control samples of the intracranial cortical artery	Co-expression
SRP170684	Spontaneously slow-cycling subpopulations of human cells originate from activation of stress response pathways	Slow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a non-cycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA-sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses – the p53 transcriptional response and the integrated stress response – are the most salient causes of spontaneous entry into the slow-cycling state. Overall design: mRNA profiling of spontaneously quiescent human cells and cells forced into quiescence by four different methods	Co-expression
SRP170956	Differential requirement for centriolar satellites in cilium formation and ciliary signaling among different vertebrate cells	Centriolar satellites are an array of membrane-less granules that localize and  move around the vertebrate centrosome/cilium complex. They have recently  emerged as key regulators of the biogenesis and function of the  centrosome/cilium-complex and their mutations are linked to ciliopathies.  Although centriolar satellites are ubiquitous structures of the vertebrate cells,  their precise function and molecular mechanism of action in different cell types  remain poorly understood. Here, we generated kidney and retinal epithelial cells  that lack centriolar satellites by genetically ablating their scaffolding protein  PCM1 and investigated the cellular and molecular consequences of satellite loss  in cells. We showed that centriolar satellites are required for cilium assembly,  regulation of ciliary content, timely response to Hedgehog signals and three-  dimensional epithelial cell organization, but not for cell proliferation, cell cycle  progression and centriole duplication. Importantly, the requirement for centriolar  satellites in cilium assembly varied between retinal and kidney epithelial cells and  we identified the differences in the efficiency of targeting key ciliogenesis factors  to the centrosome including Mib1 and Talpid3 as the likely molecular basis for  this phenotypic variability. Quantitative global transcriptomic and proteomic  profiling of satellite-less cells showed that loss of centriolar satellites does not  lead to a major transcriptional response, but leads to a significant rearrangement  of the global proteome. Together, our findings identify important roles for  centriolar satellites in key cilium-related cellular processes through regulating the  proteostasis and centrosomal/ciliary targeting of proteins and provide insight into  the disease mechanisms of ciliopathies. Overall design: We performed global transcriptome analysis of wild type (WT) and PCM1 knock-out cells by using two different cells: human RPE1, and mouse IMCD3 cells. Deep sequencing technique was utilized via  illumina HiSeq4000 platfrom in two biological replicates for each condition.	Co-expression
SRP170967	Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts	X-chromosome inactivation (XCI) provides a dosage compensation mechanism where, in each female cell, one of the two X chromosomes is randomly silenced. However, some genes on the inactive X  chromosome and outside the pseudoautosomal regions escape from XCI and are expressed from both alleles (escapees). We investigated XCI at single-cell resolution combining deep single cellRNA sequencing with whole-genome sequencing to examine allelic-specific expression in 935 primary fibroblast and 48 lymphoblastoid single cells from five female individuals. In this framework we integrated an original method to identify and exclude doublets of cells. In fibroblast cells, we have identified 55 genes as escapees including five novel escapee genes. Moreover, we observed that all genes exhibit a variable propensity to escape XCI in each cell and cell type and that each cell displays a distinct expression profile of the escapee genes. A metric, the Inactivation Score—defined as the mean of the allelic expression profiles of the escapees per cell—enables us to discover a heterogeneous and continuous degree of cellular XCI with extremes represented by “inactive” cells, i.e., cells exclusively expressing the escaping genes from the active X chromosome and “escaping” cells expressing the escapees from both alleles. We found that this effect is associated with cell-cycle phases and, independently, with the XIST expression level, which is higher in the quiescent phase (G0). Single-cell allele-specific expression is a powerful tool to identify novel escapees in different tissues and provide evidence of an unexpected cellular heterogeneity of XCI. Overall design: Single-cell RNA seq study on 935 human fibroblasts and 48 lymphoblastoid cells from 5 female individuals, in order to investigate the X chromosome nactivation mechanism on a single cell level and to identify escapee genes	Co-expression
SRP170971	mRNA sequencing of oropharyngeal cancer cell lines	mRNA sequencing was performed on oropharyngeal cancer cell lines including 4 HPV-positive and 4 HPV-negative lines. Two lines  (CUOP2 and CUOP3) were newly derived from HPV-positive tonsil cancers (derivation is described in "Sensitivity to inhibition of DNA repair by Olaparib in novel oropharyngeal cancer cell lines infected with Human Papillomavirus" by Pirotte et al. This work was undertaken with the aims of quantifying levels of HPV gene transcription and identifying human:viral fusion transcripts arising from integrated viral sequences. We also wished to compare expression of genes involved in DNA damage responses between HPV positive and negative cell lines. The published analyses showed expression of HPV encoded genes in all of the HPV-positive cell lines, and the presence of fusion transcripts derived from integrated virus. We did not identify any obvious correlation between expression of DNA repair genes and HPV status. Overall design: mRNA sequencing was performed in the 8 cell lines. Cells were grown in standard conditions, mRNA was extracted, and a single sequencing run was undertaken for each line.	Co-expression
SRP171015	2-5A-Mediated mRNA Decay and Transcription Act in Concert to Reprogram Protein Synthesis during dsRNA Response	RNA degradation by RNase L during 2-5A-mediated decay (2-5AMD) is a conserved mammalian stress response to viral and endogenous double-stranded RNA (dsRNA). To understand this mechanism we examined 2-5AMD in human cells by spike-in RNA-seq. Overall design: Poly-IC transfection for 0-4 h followed by poly-A pulldown and RNAseq	Co-expression
SRP171024	mRNA expression profile in MHCC-97H-SH-NC And MHCC-97H-SH-UCK2 liver cancer cells	To study the mRNA modulating network and different expressed mRNA lists in MHCC-97H-SH-UCK2 cells, we use high-throughout method to genomically detect the expression profile of mRNA Overall design: mRNA expression profile in MHCC-97H-SH-NC And MHCC-97H-SH-UCK2 liver cancer cells.  Illumina PE150 for mRNA expression profile were chosen. The high-throughout experiment service are supplied by novogene (Beijing, China).	Co-expression
SRP171042	Formative transition of human naïve pluripotent stem cells	Human naïve pluripotent stem cells (PSC) share features with pre-implantation epiblast. They thus provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens. Here we confirm that naïve PSC do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole transcriptome profiling during this formative transition highlights dynamic changes in gene expression, affecting many cellular properties, including metabolism and epithelialisation. Notably, naïve pluripotency factors are exchanged for post-implantation factors, but competent cells remain devoid of lineage primed transcription. The gradual pace of transition for human naïve PSC is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human naïve cells tracks the progression of epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus the formative transition of naïve PSC in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis. Overall design: 2 lines of human naïve pluripotent stem cells (embryo-derived HNES1 and chemically reset cR-H9-EOS) were cultured in N2B27 and 2uM XAV939 for 10 days. After that the cells were split into two conditions: N2B27 + 2uM XAV939 + 3ng/ml Activin A + 10ng/ml FGF2 (XAF), or E8 medium, for extended maintenance. The experiment was performed in biological triplicates for each cell line. RNAseq was performed with the cells on day 0, 1, 2, 3, 7, 10, when the cells were cultured in XAV939; and one time point after transfer to maintenance conditions, at not less than 22 days of culture from the start of the experiment. Conventional hES cell line H9-EOS, which was a parental line for the chemically reset cR-H9-EOS was used as a control (in biological triplicate).	Co-expression
SRP171051	Small Sample-Big Data: Integrative Indexed Systems Biology Reveals Dramatic Molecular Ontogeny over the First Week of Human Life in Papua New Guinea	This study examines the global transcriptomic profiles in peripheral blood of Papua New Guinea newborns at birth (D0) comparing with follow up at day 1 (D1), day 3 (D3), or day 7 (D7) post birth. Overall design: Systems biology provides a powerful approach to unravel complex biological processes yet it has not been applied systematically to samples from newborns, a group highly vulnerable to a wide range of diseases. Published methods rely on blood volumes that are not feasible to obtain from newborns. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1ml of blood, a volume readily obtained from newborns. Furthermore, indexing to baseline and applying innovative integrative computational methods that address the challenge of few data points with many features enabled identification of robust findings within a readily achievable sample size. This approach uncovered dramatic changes along a stable developmental trajectory over the first week of life. The ability to extract information from 'big data' and draw key insights from such small sample volumes will enable and accelerate characterization of the molecular ontogeny driving this crucial developmental period.	Co-expression
SRP171053	Neural cell adhesion molecule 1 (NCAM1; CD56) promotes leukemogenesis and confers drug resistance in acute myeloid leukemia.	Neural cell adhesion molecule 1 (NCAM1; also known as CD56) is expressed in up to 20% of acute myeloid leukemia (AML) patients. Expression of NCAM1 is widely used as a marker of minimal residual disease; however, the biological function of this cell surface protein in AML remains elusive. In this study we investigated the impact of aberrant NCAM1 expression on leukemogenesis, drug resistance and its role as a biomarker to guide therapy.Gene expression profiling was performed with RNA-seq in three cell lines (SKM-1, NOMO-1, MOLM-14) after doxycycline-mediated induction of scrambled shRNA or shNCAM1 at timepoint 72 hours. Overall design: mRNA profiles of cell lines SKM-1, NOMO-1, MOLM-14 transfected either with scrambled shRNA or shRNA-NCAM1 were generated using TruSeq RNA Library Prep Kit v2 (Illumina) followed by sequencing with 100 bp paired-end reads on HiSeq 2000.	Co-expression
SRP171066	A chemical probe for Tudor domain protein SPIN1 to investigate chromatin functions	Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails and in combination with other modifications provide the basis for a combinatorial 'chromatin or histone code'. Recognition of modified histone residues is accomplished in a specific manner by 'reader' domains that recognize chromatin modifications allowing to associate with specific effector complexes mediating chromatin functions. The methyl-lysine and methyl-arginine reader domain protein SPINDLIN1 (SPIN1) belongs to a family of 5 human genes, and has been identified as a putative oncogene and  transcriptional co-activator containing three Tudor domains, able to mediate chromatin binding. Here we report on the discovery of the potent and selective bivalent Tudor domain inhibitor VinSPINIn, which simultaneously engages Tudor domains 1 and 2 and effectively competes with chromatin binding. Inhibitor, chemoproteomic and knockdown studies in squamous cell carcinoma suggest an un-anticipated complexity of SPIN isoform mediated interactions in regulating cellular phenotypes. Overall design: Triplicates for 2 compounds, 1 siRNA, DMSO and scrambled siRNA control at 2 time points are examined by RNA-Seq	Co-expression
SRP171119	Aberrant enhancer reprogramming drives hepatic carcinogenesis through global transcriptional reprogramming [RNA-seq]	?Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- and bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated enhancer of CCAAT/enhancer-binding protein-beta (C/EBPß) which correlates with C/EBPß over-expression and poorer prognosis of patients. Demethylation of C/EBPß enhancer reactivates a self-reinforcing enhancer-target loop via direct transcriptional up-regulation of enhancer RNA. Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPß expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers, leading to drastic suppression of driver oncogenes and abrogation of HCC tumorigenicity. Hepatitis B X protein transgenic mouse model of HCC recapitulates this paradigm, as C/ebpß enhancer hypomethylation associates with oncogenic activation in early tumorigenesis. These results support a causal link between aberrant enhancer hypomethylation and C/EBPß over-expression, thereby driving hepatocarcinogenesis through global transcriptional reprogramming. Overall design: Examination of RNA profiles in WT and C/EBPB enh- HepG2 cells	Co-expression
SRP171137	RNA-Seq of human Schneiderian papillomas and associated carcinomas	Transcriptome analysis and comparisons of human Schneiderian papillomas and associated carcinoma versus sinonasal mucosa was performed to characterize tumor subtypes on molecular level, and find candidates for disease biomarkers and drivers. Improving the understanding of the development and recurrence of this disease.	Co-expression
SRP171145	Effects of losmapimod on non-specific inflammatory response in aged skin.	We have previously demonstrated older skin exhibits increased sterile inflammation 6 hours after saline-injection. In this work, we examined whether p38MAPK inhibitor in vivo would attenuate this non-specific inflammatory response towards saline in elder individuals (=65 years). Overall design: Skin mRNA profiles 6 hours after saline injection were studied before and after losmapimod treatment.	Co-expression
SRP171611	Discovery and Characterization of Small Molecule Inhibitors of SWI/SNF ATPase Activity in BRG1/SMARCA4-Deficient Non-Small Cell Lung Cancers	Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among the most frequently mutated genes across various cancers informing critical roles of their dysregulation towards the malignant state. While elucidating the mechanisms of SWI/SNF mutations remains a significant area of investigation, recent studies have also revealed an important role for the remaining SWI/SNF activity in supporting the growth of SWI/SNF-mutant cancers. In particular, the discovery of synthetic lethality between BRM/SMARCA2 and BRG1/SMARCA4, the highly homologous and mutually exclusive catalytic subunits of SWI/SNF complexes, has driven great interest in pursuing the therapeutic targeting of BRM in BRG1-mutant/deficient cancers. We report for the first time the discovery and functional characterization of allosteric small molecule dual inhibitors of BRM and BRG1 ATPase activity. BRM011 and its structurally related analogs display cellular activity in modulating BRM-dependent gene expression and inducing growth inhibition in BRG1-mutant lung cancer models. Genome wide assessments show that BRM011 treatment induces specific changes in chromatin accessibility and gene expression profiles similar to genetic depletion of BRM. Overall, these studies not only elucidate the previously unexplored feasibility of chemically modulating the enzymatic activity of such a complex and unprecedented target, but also provide fundamental tools for further dissecting SWI/SNF function in cancers, normal tissues and other disease contexts.	Co-expression
SRP172096	RNA-sequencing and CRISPR/Cas9 Screen of PEO1 cells grown in suspension.	RNA-sequencing of PEO1 cells grown in suspension (SUS1 and SUS3) was performed to evaluate transcriptional reprogramming during anokis escape. CRISPR/Cas9 screen of PEO1 cells grown in adherent and suspension culture settings for 5 days or 10 days. GeCKO v2 library transduced in PEO1 cell line and cells were selected with puromycin. PEO1 line was authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Overall design: PEO1 cells grown in suspension (SUS1 and SUS3) compared to PEO1 cells grown in adherent conditions (PEO1_Adherent_1  and PEO1_Adherent_2). PEO1 cells transduced with GeCKO v2 library were cultured in adherent or suspension settings for 5 or 10 days. Please note that the two PEO1_Adherent sample records are duplicated sample record of GSM3308399, GSM3308400 for the convenient retrieval of the complete raw data from SRA	Co-expression
SRP172099	Targeting Transcriptional Addiction by a Novel Highly Selective CDK9 Kinase Inhibitor for AML.	we reported a novel CDK9 high selective inhibitor JSH-009, it displayed high potency against CDK9 (IC50=1nM) and achieved high selectivity over CDKs family kinases (range from 200-10000 fold). JSH-009 showed high potent anti-proliferation effect in a range of AML cells and primary patient cells through downregulation of a number of transcriptional, apoptotic genes and related signaling pathways. In addition, this compound exhibited great anti-leukemic efficacy in the MV4-11 mediated xenograft, engraftment and AML PDX preclinical models. Currently, JSH-009 is under extensive preclinical development and We believe the work presented here would be of great interest to readers of Leukemia. Overall design: AML cell HL60's mRNA profiles of  JSH-009 treatment and DMSO treatment were generated by deep sequencing, in two replicates, using Illumina HiSeq2000.	Co-expression
SRP172461	The cytokine environment influence on human skin-derived T cells	Illumina RNA sequencing to study DEGs between freshly isolated and emigrated skin T cells Overall design: skin T cell RNA profile of freshly isolated T cells and emigrated T cells under IL-2, IL-4, TGF-beta and IL-2, IL-15 cytokine condition	Co-expression
SRP172499	Proteogenomic characterization of human early-onset gastric cancer	We report proteogenomic analysis of diffuse gastric cancers (GCs) in young population. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs. Overall design: Transcripome profiling of tumor tissues and adjacent normal tissues from 80 patients in the  early-onset gastric cancer(EOGC) cohort.	Co-expression
SRP172519	A reference collection of cell line and xenograft models of proneural, classical and mesenchymal GBM	RNA Seq data of primary glioblastoma cell line models.	Co-expression
SRP172570	NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells	Prostate cancer is the second leading cause of cancer death among men in the United States. The Androgen receptor (AR) antagonist Enzalutamide is a FDA approved therapy for treatment of late stage prostate cancer patients and is currently under clinical study for early stage prostate cancer treatment. After a short positive response period, patients will develop drug resistance. In this study we used RNA-sequencing and bioinformatics analysis to identify Notch signaling pathway as a deregulated pathway in Enzalutamide-resistant cells. NOTCH2 and c-MYC positively correlated with AR expression in patients' samples mimicking cells with Enzalutamide-resistance. In Enzalutamide-resistant cells, MR49F and C4-2R, we found that cleaved-NOTCH1, HES1 and c-MYC protein expression are significantly elevated indicating an activated NOTCH1 pathway in those cells. In addition, ADAM10 and ADAM17 had a higher expression in Enzalutamide-resistant cells, suggesting a role for S2 cleavage in the increased cleaved NOTCH1 expression. Furthermore, treatment of Enzalutamide-resistant cells with PF-03084014 in combination with Enzalutamide increased cell death, decreased colony formation ability and re-sensitized Enzalutamide-resistant cells to Enzalutamide. Knockdown of NOTCH1 in C4-2R increases Enzalutamide sensitivity by decreasing cell proliferation and increasing cell death. In a 22RV1 xenograft model, PF-03084014 and Enzalutamide induced a decrease in tumor growth through a reduced cell proliferation and increased apoptosis. These results indicate that Notch1 signaling can contribute to Enzalutamide-resistance in Prostate cancer and inhibition of this pathway can re-sensitize resistant cells to Enzalutamide. Overall design: Method: polyA selection of mRNA from enzalutamide sensitive and resistant cells (n=3 biological replicates) and sequenced on a HiSeq2500	Co-expression
SRP172671	Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner	RNA-seq analysis of BJ cells overexpressing RasV12 and escaping senescence Overall design: Immortalized BJ-hTERT cells expressing an oncogenic version of Ras under the control of a doxycyclin-inducible promoter were grown for 60 days in the presence of Dox to induce oncogene-induced senescence (OIS). Three individual clones escaping senescence were isolated and were analyzed by RNA-seq.	Co-expression
SRP172786	Polymyxin nephrotoxicity in kidney chip	Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive, and thus, novel techniques, including human microphysiological systems, or “organs on chips,” are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; yet clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.2 ×10–16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)–like 2 pathway despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and  NAB741 and reveal cholesterol biosynthesis as the novel (to our knowledge) pathway for PMB- induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used  for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule. Overall design: Cells from six donors were seeded into a total of 74 kidney chips, and effluents of kidney MPS were exposed for 48 hours of treatments	Co-expression
SRP172788	RNA-seq of FSHD and control immortalised myoblasts II	FSHD myoblasts show a suppression of ESRRA and PPARGC1A during myogenesis Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent, then induced to differentiate for 3.5 days, samples were taken at 8 time points during differentation for 54-6 and 54-12 and at confluency and terminal differentiation in the remaining lines. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.	Co-expression
SRP172794	EGR1-controlled transcriptome of T HESCs	Sequencing of mRNA isolated from a human endometrial stromal cell line (T HESCs) following control or EGR1 siRNA-mediated knockdown. Overall design: RNA isolated from THESCs following 48h transfection with nontargeting or EGR1 siRNA. Triplicate samples for each siRNA are derived 3 from independent experiments.	Co-expression
SRP172805	Single Cell RNA sequence data from a human ovarian cancer sample	Purpose: Investigate cellular heterogeneity in a fresh human ovarian cancer tissue sample Methods: Enzymatic digestion of fresh tissue sample collected from the operating room to produce single cell suspension. Cells were labelled with fluorescent antibodies to CD3, CD14, CD19, CD20, CD56 and FACS sorted to remove immune cells.  The negative population was used for sequencing. Single cells were processed using the Fluidigm C1 Chip to generate barcoded cDNA for each cell.  Amplifed cDNA was sequenced using an Illumina HiSeq 2500 machine. Results: Single cell RNA sequence data was obtained for 92 cells and a "bulk" sample of 1000 cells. 26 cells were removed from analysis due to quality control standards. The remaining 66 cells and the bulk sample were analyzed. Conclusion: Single cell RNA sequence analysis reveals heterogeneity in gene expression in cells harvested from a high grade ovarian serous cancer Overall design: A single cell suspension generated from a fresh high grade serous ovarian cancer sample was run through two Fluidigm C1 chips to isolate single cells and produce barcoded cDNA. Sequencing was performed in a single lane of an Illumina HiSeq 2500 machine. 92 single cells were sequenced and 1 bulk sample was sequenced, for a total of 93 samples.	Co-expression
SRP172814	Homo sapiens isolate:Lung carcinoma epithelium cells Genome sequencing	This cell was used for measuring cytotoxicity of 3D8 scFv protein	Co-expression
SRP172824	RNA-seq of WT and Nocturnin knockout A549 cells	mRNA regulation by the circadian protein Nocturnin in A549 cells. Overall design: Total RNA from WT and NOCT KO A549 cells were subject to poly-A pulldown and RNA-seq.	Co-expression
SRP172904	Disruption of PRPF31 leads to deregulated expression and altered splicing of genes involved in phototransduction	Purpose: PRPF31 as a general mRNA splicing factor has important roles in every cell of each organ in the body. But, there is not enough evidence to clarify how PRPF31 deficiency is associated with retina specific disease as Retinitis Pigmentosa (RP). In this study, we investigated the functional effects of PRPF31 downregulation in a model of Human Organotypic Retinal Culture (HORC) using RNA sequencing technique.Methods: Human eyes from young donors (20-40 years old) were obtained within the 24 hours post mortem from Iranian eye bank. The retinas were isolated and transfected using PRPF31 and scramble siRNA. PRPF31 downregulation was confirmed by quantitative real time PCR (q-RTPCR). The mRNA libraries were sequenced on Illumina HiSeq 4000 and analyzed using bioinformatics approaches. Then, q-RTPCR for some downregulated genes was performed for additional confirmation.Results: PRPF31 reduction in siRNA treated samples led to downregulation of 1040 of genes and upregulation of 858 of genes, as a whole. The differentially downregulated genes were enriched in phototransduction (RHO, ROM1, FSCN, GNAT, CRX, NR2E3) and rhodopsin mediated visual cycle. RNA sequencing analysis confirmed q-RTPCR results of selected genes involved in phototransduction. In addition, genes with increased expression were mainly associated with immune and inflammatory responses, particularly innate immune system. Also, we examined the effects of PRPF31 deficiency on splicing by analysis of differential exon usage (DEU) of the retina. Pathway analysis of DEU genes indicated that the most affected pathways are the phototransduction, cortical actin cytoskeleton organization and photoreceptor cell development .Conclusion: Our data reveals that PRPF31 deficiency has a crucial role in retina specific pathology by affecting the expression and exon usage of wide range of genes implicated in phototransduction and rhodopsin mediated signaling pathway. In addition, there was an evidence of upregulation of some genes which bioinformatics approach showed their important role in activation of inflammatory response. Together these findings not only confirm our model of RP11 but also unravel some mysteries in pathophysiology of this disease in human retina	Co-expression
SRP173049	Sensitivity to Splicing Modulation of BCL2 Family Genes Defines Cancer Therapeutic Strategies for Splicing Modulators	Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark of cancer. Small molecule splicing modulators have been introduced into clinical trials to treat solid tumors or leukemia bearing recurrent spliceosome mutations. Nevertheless, further investigation of the molecular mechanisms that may enlighten therapeutic strategies for splicing modulators is highly desired. Here, using unbiased functional approaches, we report that the sensitivity to splicing modulation of the anti-apoptotic BCL2 family genes is a key mechanism underlying preferential cytotoxicity induced by the SF3b-targeting splicing modulator E7107. While BCL2A1, BCL2L2 and MCL1 are prone to splicing perturbation, BCL2L1 exhibits resistance to E7107-induced splicing modulation. Consequently, E7107 selectively induces apoptosis in BCL2A1-dependent melanoma cells and MCL1-dependent NSCLC cells. Furthermore, combination of BCLxL (BCL2L1-encoded) inhibitors and E7107 remarkably enhances cytotoxicity in cancer cells. These findings inform mechanism-based approaches to the future clinical development of splicing modulators in cancer treatment.	Co-expression
SRP173163	RNA sequence of UC-012-DA	To compare the global RNA expression level between UC-012-DA and HU treated	Co-expression
SRP173199	Integrated epigenomic and transcriptomic profiling of terminal human erythropoiesis [TMCC2]	HUDEP-2 cells were lentivirally infected with CRISPRi constructs using a nontargeting guide or guides targeting an enhancer in the TMCC2 locus Overall design: Whole transcriptome libraries were sequenced for three replicates of non-targeting gRNA and two replicates each for two different gRNA targeting a regulatory region upstream of the TMCC2 erythroid-specific isoform	Co-expression
SRP173268	Codon usage optimization in pluripotent embryonic stem cells [tRNA sequencing]	The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias on regulating cell state-specific expression programs is currently debated. Here, we asked whether the gene expression program in the well-defined cell states of self-renewal and differentiation in embryonic stem cells is driven by optimized codon usage. Using ribosome and transcriptome profiling, we identified distinct codon signatures for human self-renewing and differentiating embryonic stem cells. One driver for the cell state-specific codon bias was the genomic GC-content of the differentially expressed genes and thus, determined by transcription rather than translation. However, by measuring the codon frequencies at the ribosome's active sites interacting with transfer RNAs (tRNA), we discovered that the wobble position tRNA modification inosine strongly influenced the codon optimization in self-renewing embryonic stem cells. This effect was conserved in mice and independent of the differentiation stimulus. In summary, we newly reveal how translational mechanisms based on RNA modifications can shape optimized codon usage in embryonic stem cells.  Overall design: tRNA sequencing of self-renewing and differentiating human H9 cells, 4 biological replicates per condition	Co-expression
SRP173277	Distinct structural classes of activating FOXA1 alterations in prostate cancer progression [RNA-Seq]	Expression profiles of 22RV1 prostate cancer cells following FOXA1 genetic engineering and or TLE3 knock-down Overall design: treatment control design with biological replicates (n=2)	Co-expression
SRP173279	BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors	Heterozygous germline mutations in BRCA2 predispose to breast and ovarian cancer. Contrary to non-cancerous cells, where BRCA2 deletion causes cell cycle arrest or cell death, BRCA2 inactivation in tumors is associated with uncontrolled cell proliferation. We set out to investigate this conundrum by exploring modalities of cell adaptation to loss of BRCA2 and focused on genome-wide transcriptome alterations. Human cells in which BRCA2 expression was inhibited using a doxycycline (DOX)-inducible shRNA for 4 or 28 days were subjected to RNA-seq analyses. Gene sets differentially expressed in BRCA2-deficient versus -proficient cells revealed a biphasic response to BRCA2 abrogation. The early, acute response consisted of downregulation of genes involved in cell cycle progression, DNA replication and repair and was associated with cell cycle arrest in G1. Surprisingly, the late, chronic response consisted exclusively of upregulation of innate immune response genes controlled by interferon. Activation of the cGAS-STING pathway detected in these cells further substantiated the concept that long-term BRCA2 abrogation triggers cell-intrinsic immune signaling. Importantly, we found that treatment with PARP inhibitors stimulated the interferon response in cells and tumors lacking BRCA2. We propose that PARP inhibitors suppress growth of BRCA2-deficient cells and tumors, in part, by activating interferon signaling. Overall design: RNA-seq data in BRCA2-/- and BRCA2+/+ human non-small cell lung carcinoma H1299 and invasive ductal breast cancer MDA-MB-231 cells.	Co-expression
SRP173282	Expression profile of MM.1S tumors folloiwing treatment with bortezomib	MM.1S orthotopic tumors were analyzed fro their gene expression upon tumor outgrowth. In contorl/bortezomib/elesclmol and combo treatments. Overall design: examination of three tumors for each condition.	Co-expression
SRP173284	Expression profile of Lo19S state cells in the presence and absence of bortezomib treatment	We transiently induce the Lo19S state with a dox inducible shRNa targeting PSMD2 and explore the gene expression in the presence and absence of bortezomib Overall design: one cell type (T47D), two states (Control and Lo19S) with and without treatment with 20nM bortezomib , all in triplicates	Co-expression
SRP173313	Thymine DNA Glycosylase as a novel target for melanoma: effect of TDG silencing on gene expression in SK-mel-28 melanoma cells	Melanoma is an aggressive neoplasm with increasing incidence that is classified by the NCI as a recalcitrant cancer, i.e., a cancer with poor prognosis, lacking progress in diagnosis and treatment. In addition to conventional therapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints. As drug resistance remains a major obstacle to treatment success, advanced therapeutic approaches based on novel targets are still urgently needed. We reasoned that the base excision repair enzyme Thymine DNA Glycosylase (TDG) could be such a target for its dual role in safeguarding the genome and the epigenome, by performing the last of the multiple steps in DNA demethylation. Overall design: Six samples : cells treated with shTDG and cells treated with shControl both in triplicates.	Co-expression
SRP173314	Transcriptome analysis upon C6orf203 silencing	In our studies we were searching for the new factors engaged in mitochondrial nucleic acids metabolism under stress conditions in humans. Quantitative proteomic approach revealed C6orf203 protein as a potential new factor engaged in response to perturbed mitochondrial gene expression. We showed that C6orf203 is a mitochondrial RNA binding protein which is able to rescue diminished mitochondrial transcription in stress conditions. Overall design: The dataset corresponds to RNAseq studies and comprises experiment performed in triplicate. The aim of this study was to examine the influence of C6orf203 silencing on mitochondrial transcriptome. To this end we engineered two stable cell lines with the use of human 293 Flp-In T-Rex cells as parental. First cell line inducible expressed miRNAs silencing endogenous copy of C6orf203 gene while second one expressed additionally transgenic version of FLAG-tagged C6orf203 which contained silent mutations causing insensitivity to miRNA. We also analyzed RNA isolated from parental 293 Flp-In T-Rex cells. RNAseq libraries were prepared with the use of strand-specific library preparation procedures. RNAs were random fragmented and reverse transcribed using random oligomers as primers (dUTP-based protocol, see PMID: 29590189, PMID: 22609201; this pipeline enables analysis of RNAs (> ~100 nucleotides)). RNA was isolated from unfractionated cells using TRI-Reagent. Before preparation of the libraries total RNA was subjected to depletion of nuclear-encoded rRNAs (Ribo-Zero rRNA Removal Kit (Human/Mouse/Rat), Epicenter). Libraries were sequenced with the help of Illumina sequencing platform.	Co-expression
SRP173343	Ultracentifugation and nanoscale deterministic lateral displacement (nanoDLD) of samples for exRNA analysis	An integrative analysis of human biofluid data in the exRNA Atlas revealed the existence of distinct extracellular RNA cargo types. To gain further insight on the biological nature of these cargo types, we correlated exRNA Atlas cargo profiles with a variety of other RNA-seq profiles. This study focuses on those samples obtained via ultracentrifugation and nanoscale deterministic lateral displacement (nanoDLD). Overall design: Whole blood samples (2 to 5 ml) were collected by the team of Dr. Ashutosh Tewari at the Icahn School of Medicine at Mount Sinai, New York, Department of Urology by venipuncture from 9 consenting adult male Prostate Cancer patients under Institute Review Board approved protocols (GCO # 06-0996, 14-0318, and surgical consent) in purple capped tubes.  After blood collection, serum was isolated using BD Vacutainer blood collection tubes, serum separation tubes (Fisher Scientific, Cat # 368016) and kept at -80°C until further steps were taken for exosome isolation. Serum was rapidly thawed prior to EV isolation with both nanoDLD and UC.	Co-expression
SRP173362	Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by the TBX2 Subfamily of Tumor Suppressor Genes	T-box (TBX) transcription factors are evolutionary conserved genes and master transcriptional regulators. In mammals, TBX2 subfamily (TBX2, TBX3, TBX4, and TBX5) genes are expressed in the developing lung bud and tracheae. Our group previously showed that the expression of TBX2 subfamily was significantly high in human normal lungs, but markedly suppressed in lung adenocarcinoma (LUAD). To further elucidate their role in LUAD pathogenesis, we first confirmed abundant expression of protein products of the four members by immunostaining in adult human normal lung tissues. We also found overall suppressed expression of these genes and their corresponding proteins in a panel of human LUAD cell lines. Transient over-expression of each of the genes in human (NCI-H1299), and mouse (MDA-F471) derived lung cancer cells was found to significantly inhibit growth and proliferation as well as induce apoptosis. Genome-wide transcriptomic analyses on NCI-H1299 cells, overexpressing TBX2 gene subfamily, unraveled novel regulatory pathways. These included, among others, inhibition of cell cycle progression but more importantly activation of the histone demethylase pathway. When using a pattern-matching algorithm, we showed that TBX's overexpression mimic molecular signatures from azacitidine treated NCI-H1299 cells which in turn are inversely correlated to expression profiles of both human and murine lung tumors relative to matched normal lung. In conclusion, we showed that the TBX2 subfamily genes play a critical tumor suppressor role in lung cancer pathogenesis through regulating its methylating pattern, making them putative candidates for epigenetic therapy in LUAD. Overall design: Genetic profiling of the transient overexpression of TBX2-5 in NCI-H1299 cells	Co-expression
SRP173378	Whole blood RNAseq from Generalised Pustular Psoriasis patients and healthy individuals	Whole blood RNAseq Overall design: 9 affected individuals and 7 controls	Co-expression
SRP173383	Combined MEKi (GDC-0973) and WNT (G007-LK) treatment in APC and KRAS mutant HCT-15 cell line	We report RNAseq data from HCT-15 cells were treated wih control(DMSO), GDC-0973, G007-LK and combined GDC-0973 and G007-LK treatmetn for 24 hours. Overall design: Three biological replicates of cultured HCT-15 cells treated with DMSO (0.02%), G007-LK (1µM), GDC-0973 (1µM) or G007-LK and GDC-0973 for 24 hours before Rna extraction	Co-expression
SRP173388	Single-cell RNA-sequencing of Herpes simplex virus 1-infected cells identifies NRF2 activation as an antiviral program	We describe the viral gene expression cascade at the single-cell level, showing bifurcations and bottleneck states. Host gene expression changes are related to viral transcription. The role of cellular signaling pathways in infection is studied using trajectory analysis and the importance of the Nrf2 transcription factor studied in follow-up experiments. Overall design: Human primary fibroblasts were infected with HSV-1 and single-cell RNA-sequencing was performed at different early time points after infection.	Co-expression
SRP173389	Clonal replacement of tumor-specific T cells following PD-1 blockade [single cells]	Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: Dissociated tumor samples were sorted as either CD45+ CD3+ tumor-infiltrating T cells, other CD45+ CD3- tumor-infiltrating lymphocytes and CD45- CD3- tumor/stromal cells. Sorted cells were subjected to paired single cell RNA- and TCR-sequencing on the droplet based 10X Genomics platform.	Co-expression
SRP173390	Clonal replacement of tumor-specific T cells following PD-1 blockade [bulk RNA]	Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: CD4+ T helper cells were sorted as naive T cells (CD4+CD25-CD45RA+), Treg (CD4+CD25+IL7Rlo), Th1 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6-), Th2 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6-), Th17 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6+), Th1-17 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6+), and Tfh subsets (CXCR5+ counterparts of each). RNA-seq cDNA library construction was performed using the SMART-Seq v4 Ultra Low Input RNA Kit (Clontech) with 2?ng of input RNA. Sequencing libraries were prepared using the Nextera XT DNA Library Prep Kit (Illumina).	Co-expression
SRP173395	RNA-seq data for non-targeting siRNA and lncRNA LOL siRNA transfection in MCF-7 cells	To  elucidate which portions of signaling pathways LOL influences in luminal breast cancer, RNA-seq analysis was performed in siLOL MCF-7 cell lines. Eight hundred eighty-three downregulated genes and 1182 upregulated genes (fold change =1.5) were detected after LOL knockdown. Gene set enrichment analysis (GSEA) of hallmarks indicated that the gene sets related to DNA_Repair, G2M_Checkpoint, E2F_Targets and MYC_Targets were positively correlated with LOL downregulation. Overall design: Examine the gene expression pattern in NC and LOL KD MCF-7 cells, and compare the gene expression to find out the differentially expressed genes.	Co-expression
SRP173428	Zika virus antagonizes interferon response in patients and disrupts RIG-I-MAVS interaction through its CARD-TM domains	The emerging threat to global health associated with the Zika virus (ZIKV) epidemics and its link to severe complications highlights a growing need to better understand the pathogenic mechanisms of ZIKV.  Accumulating evidence for a critical role of type I interferon (IFN-I) in protecting hosts from ZIKV infection lies in the findings that ZIKV has evolved various strategies to subvert the host defense line by counteracting the early IFN induction or subsequent IFN signaling.  Yet, mechanisms underlying the counter-IFN capability of ZIKV and its proteins, which might contribute to the well-recognized broad cellular tropisms and persistence of ZIKV, remain to be fully understood.  In our current study, using RNA sequencing-based transcriptional profiling from the whole blood cells isolated from patients acutely infected by ZIKV, we found that transcriptional signatures of antiviral interferon-stimulated genes and innate immune sensors was absent in ZIKV-infected patients presents inactive as compared to healthy donors, suggesting that ZIKV might suppress the induction of IFN-I during the natural infection process in human.  Furthermore, utilizing cellular or extracellular analysis of molecular interaction in a ZIKV NS4A-overexpression system, or in the context of actual ZIKV infection, we have identified that ZIKV NS4A directly binds MAVS and thereby interrupts RIG-I/MAVS interaction through its CARD-TM domains, leading to attenuated production of IFN-I.  Taken together, these findings originated from patient studies have added new knowledge and molecular details to our understanding regarding how ZIKV mediates suppression of the IFN-I system and may provide new basis for future development of anti-ZIKV strategies. Overall design: Peripheral blood were collected from three patients during the onset period and also from three healthy donors by using the anticoagulant vacuum blood collection tubes (BD Franklin Lakes, NJ), and subsequently whole blood cells were collected by centrifugation at 800 x g for 20 min at room temperature.  Total RNA was extracted from the collected blood cells with the TRIzol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer's instruction.   Host cell transcriptional profiling was performed using RNA deep sequencing by employing the Annoroad Gene Technology Co., Ltd (Beijing, China).	Co-expression
SRP173431	Transcriptomes of CD31+CD34+HEPs with different expression of CD105 derived from human early hematopoietic differentiation by RNA Sequencing	Purpose: The goals of this study are to dessect the molecular signature of CD31+CD34+HEPs with different expression of CD105 ,and to explore the regulators such as signaling and transcription factors of CD105+ cells' generation. Methods: mRNA profiles of HEPs samples collected at day4 of  hematopoietic differentiation were generated by deep sequencing using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Conclusions: The CD31+CD34+CD105-HEPs possess hematopoietic potential whereas the CD31+CD34+CD105+HEPs possess endothelial potential. In addition, the generation of CD105+cells were regulated by TGFbeta signaling and ETS1. Overall design: mRNA profiles of HEPs samples collected at day4 of  hematopoietic differentiation were generated by deep sequencing using Illumina HiSeq 2000	Co-expression
SRP173554	In vivo RNA editing of point mutations via RNA-guided adenosine deaminases	We investigated the specificity profiles of a variety of RNA guided adenosine deaminases while exploring roles of NLS/NES and hyperactive mutants via analysis of the transcriptome-wide off-target A->G editing effected by these tools. To this end, HEK 293T cells were transfected with each construct and analyzed by RNA-seq. Untransfected cells were included as controls. From each sample, we collected ~40 million uniquely aligned sequencing reads. We then used Fisher's exact test to quantify significant changes in A->G editing yields, relative to untransfected cells, at each reference adenosine site having sufficient read coverage. The number of sites with at least one A->G editing event detected in any of the samples was computed. Overall design: Study of transcriptome wide A->G off-targets arising due to the overexpression of a variety of RNA guided adenosine deaminases.	Co-expression
SRP173593	Single cell RNA-seq of 25 thousand epithelial cells from xenografts of triple-negative breast cancers	Patient derived xenografts (PDX) were created from two triple-negative breast cancers (PDX-110 and PDX-332) taken at the time of surgery from drug-naive patients. Freshly sorted epithelial cells were profiled by single-cell RNA-seq (scRNA-seq) using a 10X Genomics Chromium System. Overall design: Transcriptional profiling was completed for 10,060 total epithelial cells from PDX-110 and 14,681 total epithelial cells from PDX-322.	Co-expression
SRP173650	Metabolism as an early predictor of DPSCs aging	Pluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs).  The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-ß) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs.  This metabolic signature can be used to predict the onset of replicative senescence phenotypes.  Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging. Overall design: We did RNA-seq of dental pulp stem cells (DPSC) using our own approach (ID# 29, 43, 44, 45), as well as commercial DPSC and mesenchymal stem cells (MCS) from Lonza.	Co-expression
SRP173653	single cell analysis of human embryonic and fetal heart-derived cardiac cells	We collected human aborted embryonic and fetal hearts from authorized resources with appropriate informed consents. Collected hearts were micro-dissected into 3 parts (atria, ventricle, and outflow tract), which were further digested into single cardiac cells and subject to single-cell RNA-seq analyses.	Co-expression
SRP173814	Fatty Acids Promote the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells	Although human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the metabolic substrate switch from glucose to fatty acids. We hypothesized that fatty acid supplementation would enhance hPSC-CM maturation. Fatty acid treatment induces cardiomyocyte hypertrophy and significantly increases cardiomyocyte force production. The improvement in force generation is accompanied by enhanced calcium transient peak height and kinetics, and by increased action potential upstroke velocity. Fatty acids enhance mitochondrial respiratory reserve capacity. RNA sequencing showed fatty acid treatment upregulates genes involved in fatty acid ß-oxidation and downregulates genes in lipid synthesis. Signal pathway analyses reveal that fatty acid treatment results in phosphorylation of multiple intracellular kinases. Thus, fatty acids increase human cardiomyocyte hypertrophy, force generation, calcium dynamics, action potential upstroke velocity, and oxidative capacity.  This enhanced maturation should facilitate hPSC-CMs usage for cell therapy, disease modeling, and drug/toxicity screens. Overall design: We did RNA-seq of hPSC-CM culture in control and fatty acid media, with two biological replicates per condition	Co-expression
SRP173817	Cataract transcriptome reveals gene changes leading to rare genetic disease diagnosis	The genetic diagnosis for a pediatric female patient with bilateral congenital total cataracts, poikiloderma, alopecia, and microdontia was obtained by a combination of RNA-seq analyses performed on the patient cataract lens (CLe), against an age-matched normal donor lens (Le), together with further analysis of the whole exome sequence (WES) raw data.	Co-expression
SRP173821	RNA Sequencing Facilitates Quantitative Analysis of Transcriptomes of human ESCs early hematopoietic differentiation	Purpose:hESCs hematopoietic differentiation recapitulates embryonic hematopoiesis in vivo and occurs through three main stages: mesoderm commitment, hemogenic endothelium (HE) formation and hematopoietic specification. The goal of this study are to increase the understanding of hESCs hematopoietic differentiation process and its regulatory mechanism. Methods: hESC samples were collected through flow cytometry sorting.mRNA profiles of  this samples were generated by deep sequencing using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Conclusions: Compared with other three populations, 57 cell surface markers were highly enriched in CD31+CD34+ endothelial cells. Overall design: hESCs hematopoietic differentiation	Co-expression
SRP173998	Low-dose pesticide mixture induces accelerated mesenchymal stem cells aging.	The general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSC) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis. We thus hypothesized that common combination of pesticides may induce a premature aging of adult MSC.Our goal was to evaluate if the prolonged exposure to pesticide mixture could accelerate aging-related markers and in particular deteriorate the immunosuppressive properties of MSCs.MSC exposed to pesticide mixture, under long-term culture and obtained from aging donor were compared by bulk RNA sequencing analysis. Aging, senescence and immunomodulatory markers were compared. A functional profile modified were found with similarities with aging process.	Co-expression
SRP174033	CNS metastasis-associated stromal cells	Metastasis to the central nervous system (CNS) remains a clinically vexing complication and a major cause of mortality and morbidity in patients with systemic cancer. However, the mechanistic interactions of the neural niche with disseminated tumors cells in CNS metastases (CM) are still poorly understood. In this study, aimed at better understanding the pathophysiologic cross-talk between the neural niche and secondary metastatic tumors, we generated five different patient-derived cell lines (PDCs) originating from surgically resected CM: two lung adenocarcinomas to brain (CM03, CM08), one lung adenocarcinoma to spine (CM02), one small cell lung carcinoma (SCLC) to brain (CM04), and one breast carcinoma to brain (CM01). To assess the genetic and epigenetic characteristics of each PDC, DNA and RNA sequencing, and DNA methylation analysis was performed. CM01, CM02, CM03, and CM08-PDCs revealed normal copy number profiles and retention of germline mutations with the same allelic ratios as seen in patient-matched germline DNA from blood. In contrast, CM04-PDC resembled its patient tumor, showing numerous copy number and somatic alterations. RNA-seq and DNA methylation analysis demonstrated that non-tumor PDCs highly resembled each other, suggesting a common cell of origin for these cells. In addition, non-tumor PDCs revealed gene expression signatures associated with cancer associated fibroblasts, epithelial to mesenchymal transition, and mesenchymal stem cells. Further in vivo studies demonstrated that CM04 cells were tumorigenic, whereas CM08 cells were unable to form tumors in mice. However, CM04:CM08 mixed tumors were significantly smaller than CM04 only tumors. Immunohistochemistry revealed induction of a fibrotic response in CM04:CM08 mixed tumors only; this was also seen in vitro, where only CM01, CM02, CM03, CM08-PDCs displayed evidence of extensive collagen and fibronectin deposition. These data offer the first evidence that CNS metastasis-associated stromal cells (cMASCs) produce a collagen and fibronectin-rich extracellular matrix to constitute a protective barrier by the host, impeding growth of tumor cells, suggesting that the therapeutic potential of these cells need to be further explored	Co-expression
SRP174040	Effects of a novel TNIK inhibitor for osteosarcoma cell lines	We found the feasibility of targeting TNIK in osteosarcoma. Here, we describe the effects of pharmacological inhibition of TNIK in osteosarcoma cell lines.	Co-expression
SRP174053	Comprehensive analysis of RNA-seq kits for standard, low and ultra-low quantity samples	High-throughput RNA-sequencing has now become the gold standard method for whole-transcriptome gene expression analysis. It is widely used in a number of applications studying various transcriptomes of cells and tissues. It is also being increasingly considered for a number of clinical applications, including expression profiling for diagnostics or alternative transcripts detection. However, RNA sequencing can be challenging in some situations, for instance due to low input quantities or degraded RNA samples. Several protocols have been proposed to overcome some of these challenges, and many are available as commercial kits. Here we perform a comprehensive testing of three recent commercial technologies for RNA-seq library preparation (Truseq, Smarter and Smarter Ultra-Low) on human reference tissue preparations, for standard (1ug), low (100 and 10 ng) and ultra-low (< 1 ng) input quantities, and for mRNA and total RNA, stranded or unstranded. We analyze the results using read quality and alignments metrics, gene detection and differential gene expression metrics. Overall, we show that the Truseq kit performs well at 100 ng input quantity, while the Smarter kit shows degraded performances for 100 and 10 ng input quantities, and that the Smarter Ultra-Low kit performs quite well for input quantities < 1 ng. All the results are discussed in details, and we provide guidelines for the selection of a RNA-seq library preparation kits by biologists. Overall design: RNA-seq profiles of Human Universal Reference Total RNA (Clontech) and Human Brain reference RNA (Ambion) were generated by deep sequencing, in duplicate, using Illumina HiSeq2000 or 2500 sequencers.	Co-expression
SRP174055	Wnt1 silences CC/CXC motif chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma	Lung adenocarcinoma (LUAD)-derived oncogenic Wnts increase cancer cell proliferative/stemness potential, but whether they also impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. Wnt1 correlated strongly with tolerogenic genes on the TCGA expression data. In another cohort, Wnt1 was inversely associated with T cell abundance. Altering Wnt1 expression profoundly affected growth of murine lung adenocarcinomas  and this was strongly dependent on conventional dendritic cells and T cells. Mechanistically, Wnt1 lead to transcriptional silencing of CC/CXC chemokines in dendritic cells and T cell cross-tolerance. Wnt-target genes were up-regulated in human intratumoral dendritic cells and decreased upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-loaded nanoparticles as single therapy or part of combinatorial immunotherapies acted at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 enhances adaptive immune rejection of lung adenocarcinomas and highlight its potential targeting as a novel therapeutic strategy  Overall design: RNAseq data of two DC subsets of 4 patients with lung adenocarcinomas (LUADs).	Co-expression
SRP174204	Neonatal and adult human testis defined at the single-cell level	Spermatogenesis has been well studied in rodents and invertebrates, but remains poorly understood in humans. As a step towards illuminating human spermatogenesis, we used single-cell RNA-sequencing (scRNAseq) analysis to analyze neonatal and adult human testes. Clustering analysis of neonatal testes revealed 3 germ subsets, including cells with characteristics of primordial germ cells (PGCs), and more differentiated cells with gene expression profiles similar with adult spermatogonial stem cells (SSCs). We identified markers for these neonatal subsets, including protein markers for the PGC-like (PGCL) subset. Clustering analysis of the adult testis revealed 9 germ and 3 somatic cell subsets. Among the germ cell clusters are 4 undifferentiated spermatogonia (SPG) states, each marked by specific genes. One of the SPG states has characteristics suggesting it is enriched for SSCs. We identified protein markers specific for this state, including cell-surface proteins that we used to enrich for these cells. We mapped the timeline of male germ cell development from PGCs through fetal germ cells to differentiating adult SPG stages. We also defined somatic cell subsets in the human testis and traced their developmental trajectories.  Together, our data provides a blueprint for understanding the development of the male germline and supporting somatic cells in humans. The germ cell subset markers we identified are candidates to be used for clinical applications, including SSC therapy for treating infertility.  Overall design: Single cell sequencing from two neonatal and two adult testicular cells was performed. Cells were either enriched for ITGA6 expression or unfractionated before GEM capture	Co-expression
SRP174367	Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons	Purpose: The transcriptional differences between iPSC-derived cortical neurons from patients with idiopathic ASD and unaffected controls was examined over a 135-day course of neuronal differentiation using RNAseq analysis Methods: Induced pluripotent stem cells (5 control iPSC and 6 ASD-specific iPSC) were differentiated into cortical neurons and RNA samples were obtained at two different time points day 35 post differentiation and day 135 post differentiation. RNAseq was performed from the RNA isolated at the different time points and the differentially expressed genes identified. Pathway analysis for gene ontology and biological processes, as well as, weighted gene co-expression network analysis was performed. Results: The results of this analysis show ASD-specific misregulation of genes involved in neuronal differentiation, axon guidance, cell migration, DNA and RNA metabolism, and neural region patterning. Furthermore, functional analysis revealed defects in neuronal migration and electrophysiological activity, providing compelling support for the transcriptome analysis data. Conclusions: Transcriptional analyses of the ASD and control neurons showed ASD-specific molecular phenotypes affecting networks involved in neuronal differentiation, the cytoskeletal matrix structure formation, patterning, DNA and RNA metabolism. Overall design: Transcriptome analysis was performed on cortical neurons derived from induced pluripotent stem cells from individuals with autism and cognitively normal control individuals. Transcriptome analysis was performed by next generation sequencing (RNAseq) and the genes that were differentially expressed between the control iPSC-derived neurons and the Autism-specific iPSC-derived neurons. Transcriptome analysis was performed at day 35 post differentiation and day 135 post differentiation.	Co-expression
SRP174368	Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted hearts	Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here, we engineer perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design. Overall design: Three groups of constructs (SA only, µV only, and µV + SA) are made and cultured for three days (the same conditions as that prior to graft implantation). These constructs were then lysed for RNA collection for transcript profiling using RNAseq analysis. The microvessels in the µV only and µV + SA constructs are made from a large grid pattern (13 x 13) with lumen diameter of 125 µm to maximize the vascular surface and RNA yield. Each group had duplicate samples.	Co-expression
SRP174405	Single cell RNA-sequencing of 75-day old human H1 and H9 embryonic stem cell-derived cerebral organoids	The scRNA-seq analysis of 75 day old human cerebral organoids grown at the air-liquid interface (ALI-COs) reveals six well-defined major clusters. Cell-type and maturity markers define a (1) distinct population of deep layer subcortical projection neurons, (2) upper layer intracortical (callosal) projection neurons and intermediate progenitors, (3) ventricular and subventricular zone radial glial cells, (4) more mature upper and deep layer neurons, (5) interneurons and (6) actively dividing cells with intermediate progenitor and radial glia markers. In addition, the gene expression profile of these clusters corresponds with their expected functional characteristics appropriate to their maturity. Altogether, our data reflect a full repertoire of cortical neuronal and progenitor identities corresponding with the stages of cortical development in age-matched fetal brains. Overall design: Single cell RNA-sequencing data was generated using the 10X Genomics Chromium Single Cell 3' Chip and workflow.	Co-expression
SRP174409	Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution	Microglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses, which were transcriptionally different from perivascular macrophages, in up to six different CNS regions during development and diseases. Single-cell analysis revealed specific time- and region-dependent microglia subtypes during homeostasis. In contrast, demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Finally, diverse microglia subsets were also identified in normal and diseased human brains. Our data provide new insights into the CNS endogenous immune system during development, health and perturbations. Overall design: CD45+ cells isolated from healthy and MS-affected human brains were FACS-sorted in 384-well plates and used for scRNAseq. The patients were aged between 22 and 25 years. Data comprises 5 healthy and 5 MS patients. CEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016).	Co-expression
SRP174467	Transcriptome of human keratinocytes with or without HPV16 oncogene expression	We used freshly established immortalized human keratinocytes with a well-defined HPV16 E6 E7 expression cassette to get a more complete and less biased overview about global changes induced by HPV16 using RNA-seq. We identified novel factors regulated by HPV oncogenes that could serve an essential role in cancer development. Overall design: mRNA profiles of human Keratinocytes transduced with HPV16-E6/E7 constructs and empty vectors in triplicates, sequenced with Illumina Hiseq 2000.	Co-expression
SRP174497	Acne flare-up in treatment process: investigating the difference of gene expression in peripheral blood	Objectives: To identify gene expression changes in acne flare-up patients, thereby exploring the mechanisms of acne flare-up after treatment. Methods: 11 acne patients and 3 healthy people were divided into 4 groups (group1: 4 with flare-up, group2: 4 with improvement, group3: 3 without obvious changes, group4: healthy control). Peripheral blood of patients before and after isotretinoin or minocycline were collected. RNA-seq were used to detect the gene expression. We applied data in self-contrast and intergroup comparisons. Results: In the self-contrast of group1, 22 upregulated genes were involved in Toll-like receptor signaling pathway and inflammatory response. Comparing group1 and group3 before treatment, 1778 upregulated genes enriched in Th17 cell differentiation, while 57 downregulated genes enriched in defensive response to organism. Conclusions: The gene expression profiles of acne flare-up patients changed. Inflammatory, immune responses played a prominent role in acne flare-up process and relatively weak defensive response to microbes, comedogenesis might be risk factors. Overall design: RNA-seq were used to detect the gene expressions in acne flare-up patients and healthy controls.	Co-expression
SRP174498	LARP7 is a substrate of BRCA1 that regulats genome instability and tumorigenesis	Impaired DNA repair leads to cancer, aging and many genetic diseases. However, understanding of the complexity of DNA is far from complete, resulting in the failure of therapies using genotoxic reagents. Here, we found that LARP7, an RNA-binding protein known to stabilize 7SK RNA, was degraded after DNA injury caused by ionizing radiation and chemotherapy. The LARP7 degradation was catalyzed by an E3 ligase complex of BRCA1 and BARD1 that was triggered by ATM-mediated phosphorylation. LARP7 depletion caused transcriptional repression of the cell cycle regulators CCNB1, CCNB2 and CDK1; this repression arrested cells before the G2/M DNA damage checkpoint and reduced BRCA2 phosphorylation, therefore enhancing Rad51 recruitment and ultimately ensuring the homologous repair of damaged DNA. Importantly, the increased DNA damage repair capacity induced by LARP7 depletion caused resistance to ionizing radiation and CDDP treatment in both wild-type and BRCA1-mutant breast cancer cells and in mouse xenografts. Such resistance also contributed to reduced relapse-free survival rates in breast cancer patients with low levels of LARP7 after chemotherapy. Taken together, the results of this study show that LARP7 coordinates cell cycle progression and faithful DNA repair. We suggest that this mechanism could be exploited to prevent tumorigenesis and improve the effectiveness of cancer therapies. Overall design: RNA-seq on wild-type MEFs, LARP7-/- MEFs, and two breast cancer cell lines (MDA-MB-231 and HCC1937) with or without siLARP7 treatment.	Co-expression
SRP174499	In vivo developmental trajectories of human podocyte development inform in vitro differentiation of pluripotent stem-cell derived podocytes	To assess in vitro derived podocytes, we examined the transcriptional changes during human podocyte development and applied that knowledge to pinpoint strengths and limitations of hESC-derived podocytes. Overall design: We performed transcriptionaling profiling of kidney organoids and organoid-derived MAFB-eGFP+ podocytes at various differentiation time points.	Co-expression
SRP174502	A Human Liver Cell Atlas reveals Heterogeneity and Epithelial Progenitors	We perfomed single-cell RNA-sequnecing of around 10,000 cells from normal human liver tissue to construct a human liver cell atlas. We reveal previously unknown subtypes in different cell type compartments. We also use our normal liver cell atlas to infer perturbed phenoytpes of cells from HCC samples, human cells engrafted into a mouse liver and liver organoids. Overall design: Single cells were isolated from human liver resection specimens and then sorted by FACS into 384 well plates in a unbiased way and on the basis of cell surface markers for distinct cell types. ScRNA-seq was done using the mCelSeq2 protocol cellbarcodes_cellid.csv Supplemetary file contains cellds and one of the 192  unique cellbarcode associated with the cellid.	Co-expression
SRP174505	RNA-sequencing in irradiated and normal A549 cells.	The aim of this study is to investigate the role of circRNAs/miRNAs/lncRNAs in radioresistance in A549 cells. For irradiation, A549 cells were exposed to a single fraction 2 GY or 4GY X-ray dose using an X-RAD 160-225 instrument (Precision X-Ray, Inc., Branford, CT, USA; filter: 2 mm AI; 42 cm, 225 kV/s, 12.4 mA, 2.0 Gy/min). The irradiated A549 cells (after a single dose of irradiation) and normal A549 cells  were cultured for further 48h and then collected its total RNA for high-throughput sequencing. Overall design: Examing 3 conditions, each with 3 replicates. The three groups were 0GY group (control),  2GY group (treatment-1) and  4GY group (treatment-2).	Co-expression
SRP174508	SRSF1 role in cellular gene expression and splicing	SRSF1 is an abundant RNA-binding protein with functions in mRNA splicing, stability, translation and transcription of cellular and viral genes. We analyzed the role that SRSF1 plays in cellular gene transcription and splicing by transfecting HEK293 cells with a SRSF1 expression plasmid and by analyzing the transcriptome of the transiently transfected cells 15 hrs and 48 hrs post transfection. We also explored the role of the SRSF1 domains by transfecting a deletion clone of SRSF1 carrying only the RNA Recognition Motifs 1 and 2 (RRM1,2) but not the Arg-Ser rich (SR) domain. Overall design: Comparison of the transcriptome of HEK293 cells transfected with SRSF1,SRSF1  RRM12 and control expression vector at 15 and 48 hours post transfection	Co-expression
SRP174549	Cell-specific expression and function patterns of microRNA-150-5p in liver fibrogenesis	MicroRNAs (miRNAs) are endogenous and small non-coding RNA molecules that mediate post-transcriptional gene suppression by incomplete matches with their host mRNAs. Recent studies have highlighted that miRNAs are involved in the pathology of liver lipid metabolism, metabolic inflammation, oxidative stress, chronic liver injury, regeneration and fibrogenesis. During liver fibrosis, miRNAs are simply categorized into pro-fibrotic or anti-fibrotic miRNAs according to their expression alterations in one liver cell type especially hepatic stellate cells (HSCs). Our current study observed a miRNA, termed miR-150-5p, exhibited cell-specific expression pattern in liver fibrosis. Although the expression level of miR-150-5p in fibrotic liver tissues or hepatocytes was significantly enhanced, it was notably down-regulated in HSCs in the context of liver fibrosis. Perturbation of miR-150-5p evidently affected the cell viability of HSCs but had no obvious effect on hepatocytes. While overexpression of miR-150-5p could sensitize the apoptosis of hepatocytes in the presence of pro-apoptotic factors. Further investigations revealed that miR-150-5p mimic treatment had a larger influence on the transcriptomic stability of HSCs but a minor effect on hepatocytes. The genes related to anti-apoptosis or pro-proliferation were decreased and genes associated with pro-apoptosis or anti-proliferation were increased after miR-150-5p overexpression, which might be the potential targets of miR-150-5p overexpressed in HSCs. Collectively, our study provide a strong supporting evidence that some miRNAs may express or function in a cell-specific pattern in the backdrop of liver fibrosis. Overall design: MiR-150-5p mimics or controls were transfected into LX-2 and QSG cells (n=2 for each group) for 48 hours. Total RNA was isolated using Trizol reagent (Invitrogen, USA). Agilent 2100 Bioanalyzer (Agilent Technologies, USA) was used to evaluate the RNA quality. One µg RNA was used to generate cDNA library based on TruSeq RNA Sample Prep Kit v2 (Illumina, USA) according to the manufacturer's instructions. Then the cDNA libraries were sequenced on the Illumina HiSeq 2500 System (Illumina, USA) with 100 nucleotide paired-end reads, per the standard manufacturer's protocol. The RNA-Seq reads were aligned to human reference genome (hg38) using Tophat (version 2.0.10) with default parameters. Read counts were scaled to reads per kilo-base of exon model per million mapped reads (RPKM).	Co-expression
SRP174604	A runaway PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma (RNA-Seq)	PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma Overall design: 16 samples total. 3 experiments: (i) PRH shRNA knockdown vs scrambled control. 2 independent clones expressing each shRNA (4 samples total). (ii) PRH overexpression using myc-PRH adenovirus vs empty adenovirus. 2 independent infections with each virus (4 samples total). (iii) Overexpression of PRH in Notch3 KD and control shRNA cell lines using myc-PRH adenovirus. (8 samples total - 2 independent infections each for all combinations of Notch3/control shRNA and myc-PRH/empty adenovirus)	Co-expression
SRP174609	Transcriptomic Profiling of Circulating Tumor Cells in Multiple Myeloma: A New Model to Understand Disease Dissemination III	The number of peripheral blood (PB) circulating tumor cells (CTCs) predicts risk of transformation in smoldering multiple myeloma (MM) and survival in active MM. Growing evidence suggests that as the tumor progresses and the microenvironment becomes hypoxic, clonal plasma cells (PCs) constantly invade new regions of the bone marrow (BM) through induced systemic recirculation. Of note, the frequency of CTCs is typically low and thus, it could be hypothesized that the dissemination of MM is made by few tumor cells with unique features that induce them to egress the BM and spread the disease through PB. This hypothesis has not been demonstrated because the molecular profile of CTCs in MM has not been investigated. Overall design: We used index sorting single-cell RNA sequencing (Precise Assay, Becton Dickinson) to identify genes and cell clusters related to disease dissemination by comparing the molecular profile of CTCs with patient-matched BM clonal PCs.	Co-expression
SRP174620	Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes (ALK)	Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genes MYCN, ALK and PHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAs MIAT and MEG3 and MYCN and PHOX2B activity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs. Overall design: CLB-GA cells were treated with 500nM of crizotinib (3 samples) or with a control (3 samples) for 24 hours.	Co-expression
SRP174621	Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes (PHOX2B)	Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genes MYCN, ALK and PHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAs MIAT and MEG3 and MYCN and PHOX2B activity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs. Overall design: CLB-GA was transduced with control or inducible shPHOX2B. The cells were treated with doxycycline for 5 days.	Co-expression
SRP174625	Genome-wide identification of cancer-specific alternative splicing in circRNA	Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is hard to be determined since of the alternative splicing happened in exons and introns of circRNA and the cancer-specific alternative splicing of circRNA is less to be identified. Here we proposed a custom tool CircSplice, which could identify internal alternative splicing of circRNA and compare the differential splicing between samples. By applying CircSplice in ccRCC, we identified cancer-specific alternative splicing (AS) events belong to circRNAs in ccRCC. We further confirmed the existence of alternative splicing events in circRNAs by RT-PCR. This study is the first exploration of cancer-specific alternative splicing in circRNAs, which helps researchers to better understand potential functions of splicing of circRNAs in cancers. Overall design: Circular RNAs profiles of three pairs of Clear Cell Renal cell carcinoma tissues and adjacent normal tissues were generated by RNA deep-sequencing, using HiSeq2500, Illumina.	Co-expression
SRP174638	Cell type-specific immune phenotypes predict loss of insulin secretion in new-onset type 1 diabetes	Peripheral blood samples were collected from control-arm subjects enrolled in 6 clinical trials conducted by the Immune Tolerance Network and Type 1 Diabetes TrialNet. The included trials evaluated immune-modifying therapy in new-onset T1D, with similar trial timecourses, primary outcomes, and data and sample collection. Total RNA was isolated from whole blood samples and then globin-reduced. RNAseq libraries were prepared from the globin-reduced RNA. Overall design: Subjects from the control arms of 6 clinical trials in new-onset T1D were aggregated to evaluate variation in disease course in the immediate post-diagnostic period.  All trials used serum C-peptide concentration after a mixed-meal tolerance test as the primary outcome, with an initial trial duration of approximately two years, with longer-term follow-up in some cases. We obtained RNA-seq data from all available subject visits (N = 138 subjects), ranging from the time of study entry to three years, for a total of 496 samples (mean 3.6 samples per subject). Three samples were removed due to SNP-based kinship values indicating sample contamination or mis-identification; these samples are excluded from the submitted dataset. Of the remaining 493 samples, 471 yielded high-quality RNA-seq data from unique visits consistent with subject annotation, and were used in downstream analyses.	Co-expression
SRP174653	Single Cell RNA-Seq profiling of human embryonic kidney outer and inner cortical cells and kidney organoid cells	To study the developmental process of human podocytes and compare to the in vitro counterpart, we dissociated cells from the inner and outer kidney cortex as well as kidney organoids, and performed 10X Genomics single-cell RNA sequencing. Overall design: Identifying cell types and studying human podocyte developmental process in human kidney and in organoids	Co-expression
SRP174659	Characterization of human ILC2 subsets	To characterize a novel human ILC2 subset found in peripheral blood, RNAseq was performed. Other ILC subsets from blood and tonsil were also included. Overall design: ILC subsets were sort purified, and immediately lysed for RNA extraction. RNAseq was performed using SmartSeq technology.	Co-expression
SRP174668	NASH	Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity and type 2 diabetes. Transcriptomic Profiling of Obesity-Related Nonalcoholic Steatohepatitis Reveals a Core Set of Fibrosis-Specific Genes	Co-expression
SRP174910	MDM2 and MDM4 are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors	Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers.  We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer. Overall design: RNA-seq in TTC642 MRT cells treated with idasanutlin compared to DMSO	Co-expression
SRP174924	Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma	Resistance to proteasome inhibitors (PIs) is a ubiquitous clinical concern in multiple myeloma (MM).  We proposed that signaling-level responses after PI would reveal new means to enhance efficacy.  Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on spliceosome components.  Spliceosome modulation was invisible to RNA or protein abundance alone.  Transcriptome analysis demonstrated broad-scale intron retention suggestive of PI-specific splicing interference.  Direct spliceosome inhibition synergized with carfilzomib and showed potent anti-myeloma activity.  Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerabilityin myeloma.  Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma. Overall design: We examine 1) gene expression of MM cells in response to PI and 2)alternative splicing in response to PI and comparator chemotherapeutic compound.  We further investigate splice factor mechanism in MM cells, by examining alternative splicing in MM with overexpression of wild type and mutant splice factor, SRSF1	Co-expression
SRP174927	Reversing Abnormal Neural Development by Inhibiting OLIG2 in Down Syndrome Human iPSC Brain Organoids and Neuronal Mouse Chimeras	Down syndrome (DS), caused by triplication of human chromosome 21 (HSA21), is the most common genetic origin of intellectual disability. Despite the limited success of current pharmacological interventions, little has been achieved to reverse the abnormal brain developmental in DS. Here, using human induced pluripotent stem cell (hiPSC)-based brain organoid and in vivo human neuronal chimeric mouse brain models, we demonstrate that the HSA21 genes OLIG1 and OLIG2 exhibit distinct temporal expression patterns during neuronal differentiation. The population of OLIG2-expressing ventral forebrain neural progenitors is overabundant in DS, which results in excessive production of calretinin- and somatostatin-expressing GABAergic interneurons and causes impaired recognition memory in DS chimeric mice. Furthermore, we find that overexpression of OLIG2 in DS alters the expression of GABAergic neuron lineage-determining transcription factors such as DLX1 and LHX8. We further show that OLIG2 can directly bind to promoter regions of DLX1 and LHX8 to increase their expression, leading to lineage specification of interneurons. Importantly, knockdown of OLIG2 largely reverses the abnormal global gene expression profile of early stage DS neural progenitors, reduces inhibitory neuronal population in DS organoids and chimeric mouse brains, as well as improves behavioral performance of DS chimeric mice. Therefore, OLIG2 potentially is a target for developing prenatal personalized therapeutics for intellectual disability in subjects with DS Overall design: Organoids (5-week old) generated from hiPSC lines derived from two DS patients (patient DS1 and DS3 and corresponding cell lines include DS1, control1, isogenic Tri-DS3 and Di-DS3, Tri-DS3+ContshRNA, and Tri-DS3+OLIG2shRNA hiPSCs) were used for RNA-sequencing. For each cell line, total 40-60 organoids collected from three batches of organoid cultures were pool together for RNA extraction and sample preparation. By pooling organoids, we increased the chances of identifying genes that were commonly up- or down-regulated in the three batches of cultures, whereas on the other hand, we decreased the chances of identifying genes that had varied expression levels in the three batches of cultures.	Co-expression
SRP174935	lncRNA-PCAT1 knockdown effect on the gene expression of androgen independent LNCaP (LNCaP-AI) cell line	We generated and characterized an androgen-independent LNCaP-AI cell line by long-term culture of androgen-dependent LNCaP cells in RPMI-1640 medium containing charcoal-stripped serum. This approach used to generate the line mimics the castration resistant condition for treating prostate cancer, supporting the relevance of the LNCAP-AI cell line to Castration Resistant Prostate Cancer. Overall design: LNCaP-AI cells transfected with lncRNA PCAT1 shRNA and the scramble shRNA were used for the RNA-seq.	Co-expression
SRP174970	Altered migratory trajectories in cerebral organoids derived from individuals with neuronal heterotopia	Malformations of the human cortex represent a major cause of disability. Mouse models  with mutations in known causal genes only partially recapitulate the phenotypes and are  therefore not unlimitedly suited for understanding the molecular and cellular mechanisms  responsible for these conditions. Here we study periventricular heterotopia (PH) by analyzing  cerebral organoids derived from induced pluripotent stem cells of patients with mutations in  the cadherin receptor-ligand pair DCHS1 and FAT4 or from isogenic knock-out lines. Our  results show that human cerebral organoids reproduce the cortical heterotopia associated with  PH. Mutations in DCHS1 and FAT4 or knock-down of their expression cause changes in the  morphology of neural progenitor cells and result in defective neuronal migration dynamics  only in a subset of neurons. Single-cell RNA-sequencing data reveal a subpopulation of  mutant neurons with dysregulated genes involved in axon guidance, neuronal migration and  patterning. We suggest that defective neural progenitor cell (NPC) morphology and an altered  navigation system in a subset of neurons underlie this form of periventricular heterotopia. Overall design: Single cell transcriptomes from human control and mutant organoids were analyzed in this study. Mutant organoids were generated from patient-derived iPSCs and carry mutations in the cadherin receptor-ligand pair DCHS1 and FAT4. Data were generated from dissected regions of 3 organoids per condition and processed using the SmartSeq2 approach. Additionally, 2d cultured neurons differentiated from control and mutant iPS cells were profiled using 10X Genomics 3' single cell transcriptome technology.	Co-expression
SRP174971	Gene expression analysis of immortalized human liver progenitor-like cells in culture	We described a highly efficient method to establish the immortalized HepLPC cell, these cell lines could efficiently expand and able to readily differentiate back into metabolically functional hepatocytes. To further characterize them, we compare the global expression profiles among immortalized human liver progenitor-like cells (iHepLPCs), hepatocyte-like cells differentiated from iHepLPCs (iHepLPCs-Hep) and 3D cell spheroids of the iHepLPCs-Hep (iHepLPCs-Hep-3D). Overall design: Immortalized human liver progenitor-like cells (iHepLPCs)  were cultured in the transition and expansion medium or in the modified hepatic maturation medium for 9 days. 3D cell spheroids of the iHepLPCs-Hep was aggregated by iHepLPCs and then  cultured in the modified hepatic maturation medium for another 9 days. Sample was assayed in double.	Co-expression
SRP174994	Induction and Therapeutic Targeting of Human NPM1c+ Myeloid Leukemia in the Presence of Autologous Immune System in Mice	Purpose: To understand the molecular mechanisms underlying NPM1c-mediated tumorigenesis by comparing the transcriptome of de novo generated bulk human leukemic cells and leukemic stem cells Overall design: Human hematopoietic stem/progenitor cells (HSPC) are transduced with lentiviruses expressing a mutated form of Nucleophosmin (NPM1c). Following engraftment into immunodeficient mice, transduced HSPCs give rise to human myeloid leukemia whereas untransduced HSPCs give rise to human immune cells in the same mice. The de novo AML, with CD123+ leukemic stem cells (LSC), resembles NPM1c+ AML from patients.	Co-expression
SRP175005	Transcriptomic Responses to Lumacaftor/Ivacaftor Therapy in Cystic Fibrosis	Cystic fibrosis (CF) remains a life-shortening disease without a definitive cure. Novel therapeutics targeting the causative defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are now in clinical use.  Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR mutation p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. We aimed to determine changes in gene expression related to treatment initiation and response. Whole-blood transcriptomics was performed using RNA-Seq in 20 patients with CF pre- and 6 months post-lumacaftor/ivacaftor (drug) initiation and 20 non-CF healthy controls.  Correlation with clinical variables was performed by stratification via clinical responses.  We identified 491 genes that were differentially expressed in CF patients (pre-drug) compared with non-CF controls. In addition, 36 genes were differentially expressed when comparing pre-drug to post-drug profiles within CF patients. Transcriptomics revealed novel pathways in CF patients at baseline compared to non-CF, and in clinical responders to lumacaftor/ivacaftor. Overall changes in gene expression post-lumacaftor/ivacaftor were modest compared to pre-drug CF profiles. Overall design: 20 control non-CF samples,  20 CF samples pre-drug,  20 samples from the same CF patients 6 months-post drug	Co-expression
SRP175016	Selective roles of vertebrate PCF11 in premature and full-length transcript termination (human 3' mRNA-seq)	The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in HeLa cells. Control and PCF11 knock-down (4 biological replicates); control and PCF11 PAS1 deletion clones muA and muB (3 biological replicates); control and additional PCF11 PAS1 deletion clones muC and muD (1 replicate).	Co-expression
SRP175046	Bromodomain inhibition of the co-activators CBP/EP300 facilitates reprogramming (RNA-seq fibroblasts)	Silencing of the somatic cell-type specific gene expression programs is a critical yet poorly understood step in nuclear reprogramming. To uncover chromatin-related pathways important for maintaining cell identity, we carried out a reprogramming screen using inhibitors of chromatin factors. Here we identify two independent acetyl-lysine competitive inhibitors targeting the bromodomains of coactivators EP300 and CBP as potent enhancers of reprogramming. EP300/CBP bromodomain inhibition is critical during early stages of reprogramming, significantly accelerates the emergence of iPSCs and, when combined with Dot1L inhibition, enables efficient derivation of human iPSCs with Oct4 and Sox2 alone. In contrast, complete inhibition of catalytic acetyl-transferase activity of EP300/CBP prevents reprogramming. Genome-wide expression analyses indicate that EP300/CBP bromodomain inhibition diminishes the expression of somatic-specific genes without affecting the induction of pluripotency regulators. Through expression analyses, we identify the master mesenchymal transcription factor PRRX1 as a functionally important target in reprogramming that is downregulated upon EP300/CBP bromodomain inhibition. Collectively, our data uncover a role for bromodomain-mediated interactions of EP300/CBP in sustaining cell type specific gene expression programs and maintaining somatic cell identity Overall design: RNA-seq of OSKM-infected or uninfected fibroblasts treated with DMSO, CBP-30, ICBP112, or A485.	Co-expression
SRP175072	Safety profiling of genetically engineered Pim-1 kinase overexpression for oncogenicity risk in human c-kit+ cardiac interstitial cells	Bulk RNA-seq to profile of c-kit+ cardiac interstitial cells, comparing the transcriptomes of Pim-1 enhanced cardiac progenitor cells and transfection control Overall design: Transcriptional profiling of Pim-1 enhanced human derived cardiac interstitial cells by bulk RNA-Seq	Co-expression
SRP175164	Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy	Improvements in cancer immunotherapy are needed. The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune sytem. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy. Overall design: For B16 mouse tumor studies, B16 tumors in OT-1 chimeras were treated with relevant or irrelevant viral peptide. 9 hours after peptide delivery, B16 tumors were harvested from 3 mice per group. RNA was isolated from tumor homogenate for sequencing. For Braf/Pten tumor studies, murine melanoma tumors in OT-1 chimeras were isolated, sliced into thin sections, and incubated with relevant or irrelevant peptide ex vivo. RNA was isolated from tumor culture homogenate for sequencing. For human tumor samples, tumors were sliced into thin sections, and incubated with relevant or irrelevant viral peptides ex vivo. RNA was isolated from tumor culture homogenate for sequencing.	Co-expression
SRP175270	Identification of altered developmental pathways in human juvenile HD iPSC with 71Q and 109Q using transcriptome profiling	Purpose: In Huntington disease (HD) subtle symptoms in patients may occur years or even decades prior to diagnosis. HD changes at a molecular level may begin as early as in cells that are non-lineage committed such as stem cells or HD patients induced pluripotent stem cells (iPSCs) offering opportunity to enhance the understanding of the HD pathogenesis. In addition, juvenile HD non-linage committed cells were previously not directly investigated in detail by RNA-seq. Methods: Strand-specific RNA-seq of the whole transcriptome was performed using 3 clonal lines from each of 2 HD patients  (6 HD iPSC lines) with 71 or 109 CAG repeats in exon 1 of the HTT gene, and 2 healthy individuals, with 17/18 (2 clonal iPSC lines) and 21 CAG repeats (one iPSC line), to comprehensively identify mRNAs related to HD. A DESeq2 pipeline for transcripts of HD was developed to identify significantly dysregulated mRNAs. During the RNA-seq data analysis, we compared 6 HD iPSC lines vs control lines and also compared separately each set of 3 HD lines from one patient vs 3 control lines. As a result of such an approach, we generated statistical values for three comparison groups, HD vs WT, HD71Q vs WT and HD109Q vs WT Methods: 9 pM-indexed libraries were sequenced with the use of Illumina HiSeq2000, rapid run with paired-end 75 bp reads. On average, 65 mln reads were collected per library Results: We identified 107 (6 HD lines), 198 (3 HD71Q lines) and 217 (3 HD109Q lines) significantly dysregulated mRNAs in each comparison group. Conclusion: The analyses showed that many of dysregulated transcripts in HD109Q iPSC lines are involved in DNA damage response and apoptosis, such as CCND1, CDKN1A, TP53, BAX, TNFRSF10B, TNFRSF10C, TNFRSF10D, DDB2, PLCB1, PRKCQ, HSH2D, ZMAT3, PLK2, and RPS27L. Most of them were identified as downregulated and their proteins are direct interactors with TP53. HTT probably alters the level of several TP53 interactors influencing apoptosis.This may lead to accumulation of an excessive number of progenitor cells and potential disruption of cell differentiation and production of mature neurons. In addition, HTT effects on cell polarization also demonstrated in the analysis may result in a generation of incorrect progenitors. Overall design: Total RNA from 9 samples were isolated for RNA-seq analysis, including 3 from control iPSC lines, 3 from clonal iPSC lines with 71 CAG repeats and 3 from clonal iPSC lines with 109 CAG repeats.	Co-expression
SRP175293	Generation and persistence of human tissue-resident memory T cells in lung transplantation	Tissue resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, while their establishment and role in human tissues has been difficult to assess.  Here, we investigated human lung TRM generation, maintenance and function in airway samples obtained longitudinally from HLA-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, while lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes while recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared to recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide novel spatial and temporal insights into how human TRM develop, function, persist, and impact tissue integrity within the complexities of lung transplantation. Overall design: Pooled Single-cell RNA-seq of FAC-sorted T cells in 96-well plates	Co-expression
SRP176423	Quantitative Analysis of negative control and overexpression-TRIB1 in PC3 and DU145 Transcriptomes	The goals of this study is to find effect of overexpression-TRIB1 to prostate cancer cell (PC3 and DU145). Overall design: Overexpressing-TRIB1 DU145 and PC3 cell lines were constructed. Detection of transcriptional changes in 2 cell lines.Repeat 2 times for each cell.Differently expressed genes (DEGs) were identified by cutoff with Ilog2(FoldChange)I> 1 and padj (Corrected Pvalue) < 0.05. KEGG\GO and PPIs analysis should be done.	Co-expression
SRP176458	Phosphatase inhibitor PPP1R11 modulates resistance of human T cells towards Treg-mediated suppression of TCR signaling	We have performed RNAseq analysis of human T cells upon PPP1R11 siRNA silencing. We have explored the role of PPP1R11 for the first time in primary human T cells and discovered that PPP1R11 is a novel negative mediator of T cell activation. Overall design: CD4+ T cells from 3 donors were treated with either control or PPP1R11 siRNA for 4.5 days and either stimulated with cross linked CD3/CD28 for 6h or left unstimulated for RNAseq analysis	Co-expression
SRP177950	Epigenetic modulation of ß-cells by interferon-a via PNPT11-miR-26a-TET2 triggers autoimmune diabetes [RNA-seq]	Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic ß cells. Mounting evidence supports a central role for ß-cell alterations in triggering the activation of self-reactive T-cells in T1D. However, the early deleterious events that occur in ß cells, underpinning islet autoimmunity are not known. We hypothesized that epigenetic modifications induced in ß cells by inflammatory mediators play a key role in initiating the autoimmune response. We analyzed DNA methylation (DNAm) patterns and gene expression in human islets exposed to IFNa, a cytokine associated with T1D development. We found that IFNa triggers DNA demethylation and increases expression of genes controlling inflammatory and immune pathways. We then demonstrated that DNA demethylation was caused by up-regulation of the exoribonuclease, PNPase Old-35 (PNPT1), which caused degradation of miR-26a. This in turn promoted the up-regulation of ten-eleven translocation TET2 enzyme and increased 5-hydoxymethylcytosine levels in human islets and pancreatic ß-cells. Moreover, we showed that specific IFNa expression in the ß cells of IFNa-INS1CreERT2 transgenic mice, led to development of T1D that was preceded by increased islet DNA hydroxymethylation through a PNPT1/TET2-dependent mechanism. Our results suggest a new mechanism through which IFNa regulates DNAm in ß cells, leading to changes in expression of genes in inflammatory and immune pathways that can initiate islet autoimmunity in T1D. Overall design: We exposed human pancreatic islets from three donors to 2000 IU IFNa and assessed gene expression by RNAseq. The cDNA library was prepared using Illumina TruSeq RNA Sample Prep Kits. Next generation sequencing was performed on Illumina HiSeq2000 using the Single-Read Cluster Generation kit v2 and SBS Sequencing kit v3. Image analysis and base calling were conducted using the SDS 2.5/RTA1.5 software.	Co-expression
SRP178052	Integrative transcriptomic analysis reveals mechanisms controlling the reciprocity of epithelial and mesenchymal genes during epithelial-to-mesenchymal transition	Epithelial-to-mesenchymal transition (EMT) is an important developmental process that is also activated during disease progressions. Many genes involved in EMT have been identified to date, but the key molecules governing the coupling between the dynamics of epithelial genes and that of the mesenchymal genes are unclear. In addition, it has been shown that there is a remarkable diversity of EMT phenotypes in different pathological conditions or microenvironments, but its mechanistic basis remains elusive. In this study, we used transcriptomic analysis to identify the roles of an EMT-inducing transcription factor ZEB1 in controlling epithelial and mesenchymal genes. We found that the mesenchymal genes exhibit a significant diversity in terms of their responsiveness to ZEB1. We applied machine learning approaches to the transcriptome data and identified three groups of M-genes that are controlled by EMT promoting factors via different types of regulatory circuits. We inferred the functional differences among the M-gene clusters in motility regulation of cultured cells and in survival of breast cancer patients. We characterized the roles of ZEB1 in controlling the reciprocity and reversibility of EMT using mathematical modeling. Our integrative analysis reveals the key roles of ZEB1 in coordinating the dynamics of a large number of genes during EMT, and it provides new insights into the mechanisms for the diversity of EMT phenotypes. Overall design: MCF10A cells were treated by combinations of perturbations as follows: recombinant TGF-beta (200 nM) for 4 weeks, CRISPR/Cas9-mediated ZEB1 knockout, doxycycline-inducible expression of exogenous ZEB1, and TGF-beta type1 receptor inhibiotr (SB-431542, 10microM) treatment	Co-expression
SRP178053	lncRNA n384546 promotes thyroid papillary cancer proliferation and migration by targeting miR-145-5p to regulate AKT3	we document a novel lncRNA, n384546, which may exert its oncogenic property in PTC tumorigenesis by sponging miR-145-5p and then regulating its target AKT3.This study reveals that n384546 is an oncogenic lncRNA in human thyroid cancer. Overall design: RNA-seq was performed in human papillary thyroid cancer tissue sample and adjacent normal tissue sample	Co-expression
SRP178112	Single Cell Sequencing Reveals Gene Expression Signatures Associated with Bone Marrow Stromal Cell Subpopulations and Time in Culture [NGS_bulk cell RNA-seq]	Background Bone marrow stromal cells (BMSCs) are a heterogeneous population that participates in wound healing, immune modulation and tissue regeneration. Next generation sequencing was used to analyze transcripts from single BMSCs in order to better characterize BMSC subpopulations. Methods Cryopreserved passage 2 BMSCs from one healthy subject were cultured through passage 10. The transcriptomes of bulk BMSCs from designated passages were analyzed with microarrays and RNA sequencing (RNA-Seq). For some passages, single BMSCs were separated using microfluidics and their transcriptomes were analyzed by RNA-Seq. Results Transcriptome analysis microarray and RNA-Seq of unseparated BMSCs from passages 2, 4, 6, 8, 9 and 10 yielded similar results; both data sets grouped passages 4 and 6 and passages 9 and 10 together and genes differentially expressed among these early and late passage BMSCs were similar. 3D Diffusion map visualization of single BMSCs from passages 3, 4, 6, 8 and 9 clustered passage 3 and 9 into two distinct groups, but there was considerable overlap for passage 4, 6 and 8 cells. Markers for early passage, FGFR2, and late passage BMSCs, PLAT, were able to identify three subpopulations within passage 3 BMSCs; one that expressed high levels of FGFR2 and low levels of PLAT; one that expressed low levels of FGFR2 and high levels of PLAT and one that expressed intermediate levels of FGFR2 and low levels of PLAT. Conclusions Single BMSCs can be separated by microfluidics and their transcriptome analyzed by next generation sequencing. Single cell analysis of early passage BMSCs identified a subpopulation of cells expressing high levels of FGFR2 that might include skeletal stem cells. Overall design: Cryopreserved passage 2 BMSCs from one healthy subject were cultured through passage 10. The transcriptomes of bulk BMSCs from designated passages were analyzed with microarrays and RNA sequencing (RNA-Seq). For some passages, single BMSCs were separated using microfluidics and their transcriptomes were analyzed by RNA-Seq.	Co-expression
SRP178124	Single Cell Sequencing Reveals Gene Expression Signatures Associated with Bone Marrow Stromal Cell Subpopulations and Time in Culture [scRNA-seq]	Background Bone marrow stromal cells (BMSCs) are a heterogeneous population that participates in wound healing, immune modulation and tissue regeneration. Next generation sequencing was used to analyze transcripts from single BMSCs in order to better characterize BMSC subpopulations. Methods Cryopreserved passage 2 BMSCs from one healthy subject were cultured through passage 10. The transcriptomes of bulk BMSCs from designated passages were analyzed with microarrays and RNA sequencing (RNA-Seq). For some passages, single BMSCs were separated using microfluidics and their transcriptomes were analyzed by RNA-Seq. Results Transcriptome analysis microarray and RNA-Seq of unseparated BMSCs from passages 2, 4, 6, 8, 9 and 10 yielded similar results; both data sets grouped passages 4 and 6 and passages 9 and 10 together and genes differentially expressed among these early and late passage BMSCs were similar. 3D Diffusion map visualization of single BMSCs from passages 3, 4, 6, 8 and 9 clustered passage 3 and 9 into two distinct groups, but there was considerable overlap for passage 4, 6 and 8 cells. Markers for early passage, FGFR2, and late passage BMSCs, PLAT, were able to identify three subpopulations within passage 3 BMSCs; one that expressed high levels of FGFR2 and low levels of PLAT; one that expressed low levels of FGFR2 and high levels of PLAT and one that expressed intermediate levels of FGFR2 and low levels of PLAT. Conclusions Single BMSCs can be separated by microfluidics and their transcriptome analyzed by next generation sequencing. Single cell analysis of early passage BMSCs identified a subpopulation of cells expressing high levels of FGFR2 that might include skeletal stem cells. Overall design: Cryopreserved passage 2 BMSCs from one healthy subject were cultured through passage 10. The transcriptomes of bulk BMSCs from designated passages were analyzed with microarrays and RNA sequencing (RNA-Seq). For some passages, single BMSCs were separated using microfluidics and their transcriptomes were analyzed by RNA-Seq.	Co-expression
SRP178255	Gene expression altered by HOTAIR knockdown in MCF-7-TNR	The human HOTAIR-specific siRNA and control siRNA were transfected into MCF-7-TNR cells. RNA was collected at 72 hrs after transfection. RNA-SEQ was carried out to profile the gene expression altered by HOTAIR knockdown. Overall design: The goal of this experiment was to profile the genes that are regulated by HOTAIR in a human breast cancer cell line. HOTAIR was knockdown by siRNA. Gene expression was probed globally using RNA-SEQ.	Co-expression
SRP178271	Hypersensitive interferon responses in lupus keratinocytes reveal key mechanistic determinants in cutaneous lupus	SLE patients exhibit increased interferon signatures in their skin secondary to increased production and a robust, skewed IFN response that is regulated by PITX1. Targeting of these exaggerated pathways may prove to be beneficial to prevent and treat hyperinflammatory responses in SLE skin. Overall design: A cohort of 72 RNA-sequencing samples from 14 individuals (7 SLE and 7 healthy controls) was analyzed to study the transcriptomic effects of type I and type II IFNs on SLE vs. control keratinocytes.	Co-expression
SRP178454	Epithelial control of colonisation by Streptococcus pneumoniae at the human mucosal surface	Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive disease, interrupting onward transmission, and in achieving herd protection. We hypothesised that the pattern of pneumococcal-epithelial engagement dictates the inflammatory response to colonisation, and that this epithelial sensing is linked to bacterial clearance. Here we have used nasal curette biopsies from a serotype 6B Experimental Human Pneumococcal Carriage Model (EHPC) to visualize S. pneumoniae colonisation and relate these interactions to epithelial surface marker expression and transcriptomic profile upregulation. We have used a Detroit 562 cell co-culture model to further understand these processes and develop an integrated epithelial transcriptomic module to interrogate gene expression in the EHPC model. We have shown for the first time that pneumococcal colonisation in humans is characterised by microcolony formation at the epithelial surface, microinvasion, cell junction protein association, epithelial sensing, and both epithelial endocytosis and paracellular transmigration. Comparisons with other clinical strains in vitro has revealed that the degree of pneumococcal epithelial surface adherence and microinvasion determines the host cell surface marker expression (ICAM-1 and CD107), cytokine production (IL-6, IL-8 and ICAM-1) and the transcriptomic response. In the context of retained barrier function, epithelial microinvasion is associated with the upregulation of a wide range of epithelial innate signalling and regulatory pathways, inflammatory mediators, adhesion molecules, cellular metabolism and stress response genes. The prominence of epithelial TLR4R signalling pathways implicates pneumolysin, a key virulence factor, but although pneumolysin gene deletion partially ameliorates the inflammatory transcriptional response in vitro, critical inflammatory pathways persist in association with enhanced epithelial adhesion and microinvasion. Importantly, the pattern of the host-bacterial interaction seen with the 6B strain in vitro is also reflected in the EHPC model, with evidence of microinvasion and a relatively silent epithelial transcriptomic profile that becomes most prominent around the time of bacterial clearance. Together these data suggest that epithelial sensing of the pneumococcus during colonisation in humans is enhanced by microinvasion, resulting in innate epithelial responses that are associated with bacterial clearance. Overall design: 27 nasal samples coming from 20 healthy adults volunteers around experimental human pneumococcal challenge were analysed (samples were collected 5 days prior or 2 days post experimental challenge). Nasal cells were collected using curettes, after which RNA was extracted and sequenced	Co-expression
SRP178543	Single-cell RNA sequencing on breast cancer cells enriched for cancer stem cell properties using functional assays	We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing Overall design: Single cells from three different populations: 30 cells from G1 cell cycle phase cultured in adherent conditions, 46 cells with low proliferation cultured in non-adherent conditions (mammosphere assasy), 45 cells with high proliferation cultured in non-adherent conditions (mammosphere assay)	Co-expression
SRP179030	Differetially expressed genes after hTR overexpression in U2OS cells	lncRNA is reported to regulate gene transcription in variety of ways. hTR is a lncRNA with 451 nt. It is classical role is serving as template for telomere lengthening. However, it involves in some other biology processes as a lncRNA. To screen for genes regulated by hTR, we performed RNAseq with hTR expressed U2OS cells, using pBabe-U2OS as control. Overall design: Total RNA was extract from HTR-U2OS and pBabe-U2OS stable cell lines in triplicate. RNAseq was performed using Illumina Hiseq 2000 platform.	Co-expression
SRP179061	Alzheimer's gene expression by cell type - SFG	AD patients all had Braak stages V or VI, and were also pathologically confirmed to have amyloid plaque. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0018621 Overall design: RNA from purified cell types from AD and control post-mortem frozen superior frontal gyrus of AD and control patients.	Co-expression
SRP179078	Effect of Toxoplasma gondii efector TgIST on global transcriptome of human foreskin fibroblasts (HFFs) upon type I IFN activation	TgIST is an effector secreted by Toxoplasma gondii into the host cell that translocates to the nucleus and block STAT1 mediated transcription. STAT1 is involved in type I and II interferon (IFN) mediated upregulation of range of anti-parasitic molecules.  A total of 544,234,059 read sequences generated from 3 independent biological replicates were mapped to human hg19 reference genome. Type I IFN activation of HFFs infected with TgIST knockout parasites showed upregulation of genes involved in interferon signaling compared to wild type parasites. Overall design: HFFs were infected with wild type (RH) or TgIST knockout (RH KO) T. gondii parasites for 12 hours, followed by stimulation with or without human IFN-ß for 6 hours. Uninfected cells with or without IFN-ß treatment were used as controls. RNA samples isolated from 3 independent replicates were used for next-generation mRNA sequencing to analyze the ability of TgIST to regulate type I IFN responses in host cells.	Co-expression
SRP179613	Lysine specific demethylase 1 inactivation enhances differentiation and promotes cytotoxic response when combined  with all-trans retinoic acid in acute myeloid leukemia across   subtypes	Combined treatment with all-trans retinoic acid and GSK2879552 results in synergistic effects on gene expression, cell proliferation, markers   of differentiation, and, most importantly, cytotoxicity. Overall design: Gene expression analysis of DMSO, single and combination treatment (ATRA and GSK2879552) on 6 AML cell lines at two time-points with two replicates (paired end RNA-seq on 96 samples in total)	Co-expression
SRP179641	SREBP1 drives Keratin 80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERa breast cancer	Approximately 30% of women diagnosed with ERa breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD) undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse in vivo while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of tumors from prospectively recruited patients shows that KRT80 levels correlate with stiffer tumors in vivo. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment. Overall design: Total RNA profiling of MCF7 breast adenocarcinoma cell line and MCF7 overexpressing KRT80. Experiments were carried out in four replicates in both cell lines.	Co-expression
SRP179648	Phytochrome-based extracellular matrix with reversibly tunable mechanical properties	Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength-specific, and dose- and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a polyethylene glycol matrix, hydrogel materials responsive to light in the cell-compatible red/far-red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechano-signaling pathways respond to changing mechanical environments, and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows addressing fundamental questions of how cells react to dynamic mechanical environments. Further, remote control of such matrices could create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. Overall design: Analysis of global gene expression changes due to differences in the mechanical properties of the phytochrome-based hydrogels	Co-expression
SRP179668	RNA-seq of human iPS derived  macrophages with or without KLF1- transcription factor Activation	Red blood cells (RBCs) mature within a specialized niche (the erythroblastic island (EI)), which consists of a central  macrophage surrounded by differentiating erythroblasts. Human Induced Pluripotent Stem Cell derived macrophages (iPSC-DMs) enhance proliferation and terminal maturation of Umbilical Cord Blood (UCB) CD34+ derived erythroid cells and iPSC derived erythroid cells. These effects are further increased when an inducible KLF1-ERT2 fusion protein is activated in iPSC-DMs.  To assess the mechanism of action, we sought to compare the transcriptome of iPSC-DMs with and without KLF1 activation. For this, we used an inducible IPSC line (iKLF1.2) in which upon tamoxifen addition, the KLF1 transcription factor is translocated to nucleus and consequently KLF1 downstream targets are expressed. The identification and characterisation of could identify factors involved in erythroid maturation and thus helpful to improve current protocols to manufacture RBCs  in vitro. Overall design: iKLF1.2 iPSCs were differentiated to macrophages and then split into 2 groups, one was treated with tamoxifen for the last 4 days of culture to activate KLF1. The other group was not treated with tamoxifen. Four biologically independent differentiation experiments were carried out and so 8 samples were generated: 4 samples of untreated iKLF1.2 iPSCs-derived macrophages and 4 samples of tamoxifen treated iKLF1.2 iPSC-derived macrophages. Total RNA was extracted from each sample and RNA integrity was of a high enough quality for library preparation, as all RIN values were above 9 for every sample.	Co-expression
SRP179696	RNA sequencing of oocyte from ovarian endometriosis	Oocytes from endometriosis patients, independently of whether the ovary was affected, exhibited a differential transcriptomic profile compared to oocytes from healthy donors.	Co-expression
SRP179743	PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells (RNA-seq)	The PLZF transcription factor is essential for osteogenic differentiation of hMSCs, however, its regulation and molecular function during this process is not fully understood. Here we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naïve hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation. Overall design: Effect of PLZF knockdown on osteogenic differentiation of hMSC (RNAseq)	Co-expression
SRP179749	Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids	RNA sequencing technology was applied to determine the transcriptional changes due to palmitate treatment, RNF213 knockdown, and GPAT4 knockdown. Overall design: Total RNA was isolated from K562 cells using an RNeasy Kit. The library construction and sequencing were performed by the TUFTS sequencing core (tucf-genomics.tufts.edu/). Briefly, the RNA was run on a Bioanlayzer (Agilent) to assess RNA quality and quantification. The biological triplicates were pooled at this point. The library preparation was performed using the TruSeq Stranded mRNA Library Prep Kit (Illumina). The samples were sequenced by HiSeq 2500, Rapid Paired-End 100 (RL-PE100) or HiSeq 2500, High Output v4 Paired-End 100 (HI-PE100, Illumina). All reads were mapped to the UCSC hg19 human reference genome using Tophat2 with multi-read correction, followed by normalization, quantification and differential expression analysis using Cuffdiff.	Co-expression
SRP179781	Digital gene expression (DGE) based transcript profiling of CDK inhibitors	We compare differences in gene expression induced after 6 hours of exposure to one of three CDK4/6 inhibitors or a pan-CDK inhibitor Overall design: mRNA levels for 7 breast cancer cell lines or PDX models treated with one of three CDK4/6 inhibitors (abemaciclib, palbociclib, or ribociclib)  at 4 concentrations (0.1, 0.3, 1, 3 um) or the pan-CDK inhibitor alvocidib at 2 concentrations (0.1, 1 um) in triplicate.	Co-expression
SRP179954	Autophagy impairments in directly reprogrammed neurons in patients with idiopathic Parkinson's disease	Protein degradation impairment is strongly suspected to play a role in idiopathic Parkinson's disease (PD). However, current tools and models are lacking to study such disease associated phenotypes across the PD patient population. Here, we generate functional induced dopaminergic neurons (iDANs) directly reprogrammed from adult dermal fibroblasts of patients with PD to investigate intra-neuronal autophagy alterations. Overall design: RNA sequencing of fibroblasts and induced neuronal cells from persons with and without Parkinsons Disease	Co-expression
SRP179978	Compare of gene expression between p16INK4A positive and negative Colon cancer [2018HC173]	To evaluate gene expression in an in colon cancer, we analyzed the gene expression profile of p16INK4A positive or negative expressed colon cancer region by RNA sequencing. Overall design: Examination of p16INK4A positive expressed colon cancer (I) region each compared with  p16INK4A negative expressed colon cancer (C).	Co-expression
SRP179980	Compare of gene expression between p16INK4A positive and negative Colon cancer [2018HC100]	To evaluate gene expression in an in colon cancer, we analyzed the gene expression profile of p16INK4A positive or negative expressed colon cancer region by RNA sequencing. Overall design: Examination of p16INK4A positive expressed colon cancer (I) region each compared with  p16INK4A negative expressed colon cancer (C).	Co-expression
SRP179981	Compare of gene expression between p16INK4A positive and negative Colon cancer [2018HC067]	To evaluate gene expression in an in colon cancer, we analyzed the gene expression profile of p16INK4A positive or negative expressed colon cancer region by RNA sequencing. Overall design: Examination of p16INK4A positive expressed colon cancer (I) region each compared with  p16INK4A negative expressed colon cancer (C).	Co-expression
SRP179984	Compare of gene expression between p16INK4A positive and negative Colon cancer [2017HC070]	To evaluate gene expression in an in colon cancer, we analyzed the gene expression profile of p16INK4A positive or negative expressed colon cancer region by RNA sequencing. Overall design: Examination of p16INK4A positive expressed colon cancer (I) region each compared with  p16INK4A negative expressed colon cancer (C).	Co-expression
SRP180007	TMED9-gated CNIH4 and TGFa signaling promotes pro-metastatic states in human primary colon cancer cells	How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of WNT signaling upon knock-down (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFa as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the membrane localization, and thus function, of TGFa. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFa exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFa ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFa and GLI1 that enhances metastases. We suggest that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities. Overall design: CC14 and CC36, two primary colon cancer cells, were treated with control or shTMED9 expressing lentivirus. In addition, CC14 cells were also treated with shTMED3 expressing lentivirus. All the experiments were run in triplicates totaling 15 Samples.	Co-expression
SRP180012	Identify novel TGF-ß-regulated genes by RNA-sequencing from MCF10A cells	TGF-ß signaling and its induced EMT (Epithelial to mesenchymal transition) play fundamental roles in development and disease including cancers. Although, TGF-ß-regulated genes have been extensively studied, with RNA-sequencing (RNA-seq) analysis, new TGF-ß-regulated genes are still been identified. Moreover, many significantly regulated genes by TGF-ß are not emphasized. This study employs RNA-seq on MCF10A cells treated by TGF-ß for 1.5 (this GEO), 24, 48, and 72 (GSE74377) hours and aims to identify novel TGF-ß-regulated genes. With 1.5 fold gene expression change (log2 0.58) and p<0.05 at any length of the treatment, 1166 and 861 genes were found to be upregulated and downregulated by TGF-ß, respectively. These genes were analyzed for their enrichments in KEGG pathways and prognostic markers of cancers. Several genes of interest were further analyzed for their regulation by TGF-ß across cell lines and their functions in context of TGF-ß were further studied. This study systematically analyzed TGF-ß-regulated genes and revealed novel factors mediating the pro-migratory role of TGF-ß signaling, hence, sheds a light on the understanding of the mechanisms underlying the role of TGF-ß signaling in cancer development. Overall design: mRNA profiles of MCF10A cells stably expressing a scramble shRNA with TGF-ß1 treatment for 0, 1.5 hours were generated by RNA-seq, in duplicate, using HiSeq2500 instrument.	Co-expression
SRP180190	Novel mutations segregating with Complete Androgen Insensitivity Syndrome and their molecular characteristics.	We analysed three interesting, rare cases of CAIS (Complete Androgen Insensitivity Syndrome) and report three hitherto undisclosed causes of the disease. Comparative RNA-Seq analysis of CAIS and control samples (3 testicular oligobiopsies from men with normal spermatogenesis) revealed 4,293 significantly deregulated genes. Overall design: The comparative analysis of gene expression profiles by RNA-Seq between individuals with CAIS (n=3) and control (men with normal spermatogenesis) (n=3)	Co-expression
SRP180281	Interferon-beta-inducible genes in human monocyte-derived macrophages (MDMs)	Transcriptome analysis of human macrophages stimulated with Interferon Beta at different time points. Control Media data for all different time points can be found at Series GSE82227. Overall design: RNA sequencing of human monocyte differentiated macrophages stimulated with Interferon Beta at 2, 6 and 24h (285u/ml). Control media data for each time point is available at Series GSE82227.	Co-expression
SRP180324	Time course of TGFbeta induced epithelial mesenchymal transition (EMT) in H358 NSCLC cells.	The capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival. Overall design: RNA was harvested 0, 1, 2, 4, 6, 8, 18, 24, 72, 168, ~500 and ~4500 hours after TGFbeta addition and subjected to 50bp paired-end Illumina RNAseq analysis. Haley, J.A., Haughney, E., Ullman, E., Bean, J., Haley, J.D.* and Fink, M.Y. (2014) 'Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant KRas NSCLC Models' Front. Oncology, doi/10.3389/fonc.2014.00344.	Co-expression
SRP180337	Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution	Direct comparisons of human and non-human primate brain tissue have the potential to reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is largely inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. First, we systematically evaluated the fidelity of organoid models to primary human and macaque cortex, finding organoid models preserve gene regulatory networks related to cell types and developmental processes but exhibit increased metabolic stress. Second, we identified 261 genes differentially expressed in human compared to chimpanzee organoids and macaque cortex. Many of these genes overlap with human-specific segmental duplications and a subset suggest increased PI3K/AKT/mTOR activation in human outer radial glia. Together, our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution. Overall design: Single cell mRNA sequencing of iPS-derived neural and glial progenitor cells using the Fluidigm C1 system This series includes re-analysis of publicly available data in accessions: phs000989.v3, GSE99951, GSE86207, GSE75140. Sample metadata and accession IDs for the re-analyzed samples are included in the file "GSE124299_metadata_on_processed_samples.xlsx" available on the foot of this record. The following samples have no raw data due to data loss: GSM3569728, GSM3569738, GSM3571601, GSM3571606, GSM3571615, GSM3571621, GSM3571625, and GSM3571631	Co-expression
SRP180340	Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells	Embryonic stem cells can self-renew and differentiate, holding great promise for regenerative medicine. They also employ multiple mechanisms to preserve the integrity of their genomes. Nucleotide excision repair, a versatile repair mechanism, removes bulky DNA adducts from the genome. However, the dynamics of the capacity of nucleotide excision repair during stem cell differentiation remain unclear. Here, using immunoslot blot assay, we measured repair rates of UV-induced DNA damage during differentiation of human embryonic carcinoma (NTERA-2) cells into neurons and muscle cells. Our results revealed that the capacity of nucleotide excision repair increases as cell differentiation progresses. We also found that inhibition of the apoptotic signaling pathway has no effect on nucleotide excision repair capacity. Furthermore, RNA-seq-based transcriptomic analysis indicated that expression levels of four core repair factors, xeroderma pigmentosum (XP) complementation group A (XPA), XPC, XPG, and XPF-ERCC1, are progressively up-regulated during differentiation, but not those of replication protein A (RPA) and transcription factor IIH (TFIIH). Together, our findings reveal that increase of nucleotide excision repair capacity accompanies cell differentiation, supported by the up-regulated transcription of genes encoding DNA repair enzymes during differentiation of two distinct cell lineages. Overall design: Determination of nucleotide excision repair capacity during multi-lineage differentiation of NT2 cells.	Co-expression
SRP180359	Epithelial mesenchymal transition (EMT) in A549 NSCLC cells. TGFbeta was used to induce EMT, RNA isolated and subjected to RNAseq on Illumina HiSeq	The capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival. Overall design: Haley, J.A., Haughney, E., Ullman, E., Bean, J., Haley, J.D.* and Fink, M.Y. (2014) 'Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant KRas NSCLC Models' Front. Oncology, doi/10.3389/fonc.2014.00344.	Co-expression
SRP180885	Next Generation Sequencing Quantitative Analysis of Wild Type and AML1-ETO Related Fusion Circular RNA (F-CircAE) Knockdown Kasumi-1 Cells Transcriptomes	The goal of this study is to determine the difference in transcriptome expression profils between wild type and AML1-ETO related fusion circular RNA knockdown Kasumi-1 cells Overall design: Kasumi-1 mRNA profiles of wild type and  AML1-ETO related fusion circular RNA knockdown were generated by deep sequencing, in triplicate, using Illumina.	Co-expression
SRP180975	Therapeutic rescue of Spinal Muscular Atrophy mouse models by AAV9-Exon Specific U1 snRNA part2	Exon-Specific U1 snRNAs (ExSpeU1) are modified U1 snRNAs that promotedefinition of defective exons. In Spinal Muscular Atrophy (SMA), their transgenicgermline expression rescued the severe pathology in a mouse model. Here, weevaluate the therapeutic levels, the activity and safety profile of ExSpeU1 deliveredby AAV9 vectors. AAV9-ExSpeU1 systemic treatment increases SMN2 exon 7inclusion and SMN protein mainly in peripheral organs and rescues the phenotype inmild and severe SMA mice. In the severe mouse, the treatment improves theneuromuscular function and significantly increases the life span (from 10 to 219days). The rescued adult mice showed normal morphology of the neuromuscularjunction, normal number of motoneurons in spinal cord and a significant persistenceafter one month of the ExSpeU1 expression in the AAV9 transduced tissues. A lowtherapeutic level of ExSpeU1 RNA relative to the endogenous U1snRNA (~ 0.1-0.3%/U1wt) is required for efficacy. RNA-SEQ analysis on two representative tissuesshowed a parallel recover of the SMA-induced expression and splicing profilesmostly related to DNA damage, cell cycle control and acute phase response. Offtarget analysis by RNA-SEQ in a human model cell line that overexpress highamount of ExSpeU1 (~20- 40%/U1wt) did not identify significant differentiallyexpressed genes or splicing events. These results indicate that AAV-mediateddelivery of a modified U1 snRNP particle is a safe and valid therapeutic option inSMA to improve SMN2 defective splicing.	Co-expression
SRP181044	Global transcriptional changes in the JJN3 myeloma cell line that occur as a result of treatment with 2 pyrrolobenzodiazepine (PBD) monomers	Background: This study characterises a group of Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomeric hybrids to investigate the global transcriptional changes that occur as a result of treatment in these cells. It was also of interest to determine whether compounds show a selective inhibitory effect on the NF-kB consenus sequence and hence NF-kB signalling. Methods: NF-kB is often overexpressed and over-active in multiple myeloma. Therefore, JJN3 myeloma cells were selected for this investigation. These cells were treated with 2 PBD monomers - DC-1-170 and DC-1-192 - at a concentration of 30nM, in triplicate alongside untreated controls. They were lysed in Trizol reagent (Thermo Fisher) and RNA was extracted using an RNeasy mini-prep kit (Qiagen). Isolated RNA was then taken forward for RNA-seq. Downstream analysis was performed using GenView2 software (in-house analysis tool developed by Peter Giles) and Ingenuity Pathway Analysis (Qiagen). Results: RNA-seq analysis revealed an overall inhibitory effect on gene transcription as a result of treatment with both PBD monomers, with a small proportion of genes experiencing increased transcription. Approximately 80% of genes that were altered were common to both PBD compounds tested. Both PBD compounds also showed significant inhibition of NF-kB signalling. Conclusions: RNA-sequencing confirmed gene set enrichment for NF-?B pathway genes although as expected, other canonical pathways were also affected. This could be linked with the toxicity that these cells experience as a result of treatment with PBD monomer hybrids. Overall design: JJN3 cells were treated with 30nM of DC-1-170 and DC-1-192 for 4 hours alongside untreated controls in triplicate.	Co-expression
SRP181198	Human colon organoids reveal distinct physiologic and oncogenic Wnt responses	Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.	Co-expression
SRP181265	A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes	Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture HiC and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and TAD analysis based on HiC data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.	Co-expression
SRP181468	Comparative gene expression profiles in parathyroid adenoma and normal parathyroid tissue	Transcriptome analysis to compare parathyroid adenomas and normal parathyroid glands with the aim of identifying differentially expressed genes	Co-expression
SRP181649	Targeting HuH7 cells with JumonjiC Lysine Demethylase Inhibitors (RNA-Seq)	Characterization of gene expression changes in HuH7 HCC cells upon treatment with the Jumonji KDM inhibitor, JIB-04, GSK-J4 and SD-70. Overall design: Comparison of gene expression changes between HuH7 cells treated with JIB-04, GSK-J4 or SD-70 vs. DMSO	Co-expression
SRP181663	Next Generation Sequencing Quantitative Analysis of HepG2, hyper-glycolytic model cell, oxamate treated cells	To determine the genes potentially responsible for the lactate-mediated gene expression regulation in hepatocellular carcinoma, we performed RNA-seq analyses on parental HepG2, HepG2/metR and oxamate-treated HepG2/metR cells. To gain mechanistic insights into the lactate-induced pro-migratory phenotypes, we established a cell model that acquired a resistance to metformin while producing lactate at a high level by selecting HepG2 cells that survived a chronic exposure to metformin for more than 5 months (HepG2/metR). In HepG2/metR cells, glycolysis rates were increased by more than 3 folds compared with parental cells, and consequently, lactate production was also highly enhanced. To clarify the gene expression regulation between the lactate level in the HepG2/metR model, we treated the cells with oxamate, an inhibitor of lactate dehydrogenase, and found that it significantly. Using a 2-fold change cut-off value in transcriptome, we selected 1,757 genes significantly up-regulated in HepG2/metR vs parental HepG2 cells. 690 genes were down-regulated by oxamate treatment in HepG2/metR cells. Eventually, we selected 136 genes that are common in the two gene sets, which may directly respond to lactate signaling Overall design: mRNA profiles of HepG2 cells, HepG2/metR (hyper-glycolytic cell model), oxamate treated HepG2/metR (decreased lactate concentration cell) were generated by deep sequencing using Illumina Nextseq 500	Co-expression
SRP181756	mRNA sequencing for normal BEAS-2B and cigarette smoke-induced malignant transformed cell	To idendentify some smoking-related genes, the in vitro model for malignant transformation was established by exposing BEAS-2B cells to cigarette smoke continuously for 30 passages (S30).	Co-expression
SRP181858	Global Gene Expression Changes in Cholangiocytes Treated with TGF-beta	The growth factor, TGF-beta can have profound effect on global gene expression changes. Since TGF-beta signaling is not well studied in liver epithelia, RNA-seq analysis was performed to evaluate TGF-beta signaling in cholangiocytes. Overall design: Cholangiocyte cell line, HIBEC,  were treated with Vehicle or TGF-beta for 48 hours to look at the gene expresson changes induced by TGF-beta	Co-expression
SRP181859	Human colon organoids reveal distinct physiologic and oncogenic Wnt responses II	Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed comprehensive transcriptome and proteome profiling in human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal colon stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC. Overall design: Culturing normal and CRISPR/Cas9 engineered APC mutant isogenic organoid lines in the presence or absence of Wnt-stimulation, followed by transcriptome and proteome profiling allowed for the stratification of physiologic and oncogenic Wnt responses.	Co-expression
SRP181871	Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes	The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. We use a microvasculature-on-a-chip system as a PVN model to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs were found to preferentially localize in the perivascular zone, where they exhibited either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. The degree of co-localization between tumor cells and microvessels varied significantly across patients. To validate these results from the microvasculature-on-a-chip system, single-cell transcriptome sequencing (10 patients and 21,750 single cells in total) was performed to identify tumor cell subtypes. The co-localization coefficient was found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlated strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that our BTSC-on-a-chip model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions. Overall design: Single cell RNA-seq of human glioblastoma cells from 10 patients.	Co-expression
SRP181907	RNA-sequencing of fibrolamellar carcinoma (FLC) cell line treated with miR-375 mimic	Fibrolamellar carcinoma (FLC) is a rare liver cancer. Expression of miR-375 is significantly lost in primary FLC tumors compared to non-malignant liver. Here, we treated a FLC cell line with miR-375 mimic or scramble control to determine the function of miR-375 in FLC. Overall design: RNA expression profiles were generated by high throughput sequencing using the Illumina NextSeq500 platform	Co-expression
SRP182093	RNA Sequencing	No description.	Co-expression
SRP182096	Transcriptomic profiling of peripheral blood NK cells of chronic HBV, HCV and HIV patients	Background: NK cells during chronic viral infection have been well studied over the last decade. We performed an unbiased next-generation RNA-sequencing approach to identify commonalities or differences of the effect of HIV, HCV and HBV viremia on NK cell transcriptomes. Methods: Using cell sorting, we obtained CD3-CD56+ NK cells from blood of 6 HIV, 11 HCV, and 32 HBV infected and untreated patients. Library preparation and sequencing were done using Illumina mRNA-Seq Sample Prep Kit and the HiSeq 2000, HiSeq2500 or NextSeq 500, and further analysis by an in-house analytic pipeline. Results: In NK cells from HIV, HCV and HBV patients, transcriptome analysis identified 272, 53, and 56 differentially expressed genes, respectively (fold change >1.5, q-value 0.2). Interferon stimulated genes were induced in NK cells from HIV/HCV patients, but not during HBV infection. HIV viremia downregulated ribosome assembly genes in NK cells. In HBV, viral load and ALT variation had little effect on genes related to NK effector function. Conclusion: We compare, for the first time, NK cell transcripts of viremic HIV, HCV and HBV patients. We clearly demonstrate distinctive NK cell gene signatures in 3 different populations, suggestive for a different degree of functional alterations of the NK cell compartment as compared to healthy individuals. Overall design: We analyzed NK cell transcripts collected from the blood of well-characterized chronic HBV patients (n=32), chronic HCV patients (n=8), and HIV patients (n=6). Differential gene expression analysis, global module analysis, and unsupervised clustering analysis were performed by employing RNA-sequencing on blood NK cell transcriptomes.	Co-expression
SRP182599	Transcriptome of medulloblastoma cell line DAOY	RNA-seq data for CLIC1 and EAG2 knockdown in DAOY cell line.	Co-expression
SRP182649	Transcriptomic analysis of frontal fibrosing alopecia	We undertook transcriptome profiling with RNA-sequencing of scalp skin from seven cases of European ancestry and seven matched controls. Overall design: Transcriptomic analysis was undertaken in 7 cases vs 7 matched controls with the objective to identify significantly differentially expressed genes and perform pathway analysis thereof.	Co-expression
SRP182665	The contribution of adenosine receptor 3-mediated signaling to TLR4-induced responses by human dendritic cells	Human dendritic cells were exposed to LPS, in the absence and presence of adenosine receptor 3 inhibitor Overall design: 4 donors, 4 experimental conditions. VUF concentration used was 5 µM, LPS was 500 ng/ml. Exposure times were 6 hours	Co-expression
SRP182694	Point mutations in the PDX1 transactivation domain impair human ß-cell development and function (RNA-Seq)	Missense mutations in coding region of PDX1 predispose to type-2 diabetes mellitus as well as cause MODY through largely unexplored mechanisms. Here, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying heterozygous missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1P33T/+, PDX1C18R/+ mutations and engineered isogenic cell lines carrying homozygous PDX1P33T/P33T, PDX1C18R/C18R mutations and a heterozygous PDX1 loss-of-function mutation (PDX1+/-). Using an in vitro ß-cell differentiation protocol, we demonstrated that both PDX1P33T/+, PDX1C18R/+ and PDX1P33T/P33T, PDX1C18R/C18R mutations impair ß-cell differentiation and function. Furthermore, PDX1+/- and PDX1P33T/P33T mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1P33T/+ and PDX1P33T/P33T mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NEURONATIN, both involved in insulin synthesis and secretion. Our results reveal mechanistic details of how diabetes-associated PDX1 point mutations impair human pancreatic endocrine lineage formation and ß-cell function and contribute to pre-disposition for diabetes. Overall design: We performed RNA-seq of control and isogenic PDX1 mutant cell lines at PP stage	Co-expression
SRP182708	Differential expression of mRNAs in IFN-gamma treated HTR-8/SVneo versus untreated control by next generation sequencing	The goal of this study is to compare genes expressed by IFN-gamma treated HTR-8/SVneo cells to genes expressed in untreated control HTR-8/SVneo cells to identify genes which play a role during IFN-gamma-mediated HTR-8/SVneo cells invasion Overall design: cDNA libraries were made from total RNA of untreated control and 24 h IFN-gamma treated samples by TruSeq RNA Library Prep Kit v2. Deep sequencing of cDNA libraries were performed with the help of Illumina Genome Analyzer IIx. Raw sequence data was imported into the CLC Genomics Workbench 6.5.1. software. The sequence reads were trimmed for adapter sequences and low quality base. The trimmed raw sequences were subjected to mRNA-sequence analysis, by mapping them to Human Genome GRCH37.p.13  .	Co-expression
SRP182776	Pilot transcriptome analysis of human iPSC-derived healthy control vs. schizophrenia cortical interneurons	We report specific changes in schizophrenia developmental interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Nine independent iPSC lines per group.	Co-expression
SRP182832	Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice (human RNA-Seq)	ARID1A is a component of the mammalian SWI/SNF complex involved in chromatin remodeling. A functional SWI/SNF complex is required for diverse physiological processes including hematopoiesis, however, the precise role played by ARID1A in hematopoietic development is unclear. Here we utilize hematopoietic cell-specific deletion of Arid1a in mice to uncover its role during adult hematopoiesis. We demonstrate that ARID1A is essential for maintaining the frequency and function of hematopoietic stem cells and its loss impaired the differentiation of both myeloid and lymphoid lineages. ARID1A deficiency led to a global reduction in open chromatin and ensuing transcriptional changes affected key genes involved in hematopoietic development. We also observed that silencing of ARID1A affected ATRA-induced differentiation of NB4 cells, suggesting its role in granulocytic differentiation of human leukemic cells. Overall, our study provides a comprehensive elucidation of its function in hematopoiesis and establishes ARID1A as a major regulator of chromatin dynamics in hematopoietic cells. Overall design: RNA-sequencing of control (LacZ sg) and ARID1A-deficient (sg1 and sg5) NB4 cells. Cells were treated with doxycycline for 7 days.	Co-expression
SRP182839	Human Megakaryocytes Possess  Intrinsic Anti-Viral Immunity through Regulated Induction of IFITM3	Evolving evidence indicates that platelets and megakaryocytes (MKs) have unexpected activities in inflammation and infection; but whether viral infections upregulate biologically active, anti-viral immune genes in platelets and MKs is unknown. We examined anti-viral immune genes in these cells in dengue and influenza infections, viruses that are global public health threats. Using complementary biochemical, pharmacological, and genetic approaches, we examined the regulation and function of interferon induced transmembrane protein 3 (IFITM3), an anti-viral immune effector gene not previously studied in human platelets and MKs. IFITM3 was markedly upregulated in platelets isolated from patients during clinical influenza and dengue (DENV) infections. Lower IFITM3 expression in platelets correlated with illness severity and mortality in patients. Administering a live, attenuated DENV vaccine to healthy donors significantly increased platelet IFITM3 expression. Infecting human MKs with DENV selectively increased type I interferons (IFNs) and IFITM3. Overexpression of IFITM3 in MKs was sufficient to prevent DENV infection. In naturally-occurring, genetic loss-of-function studies MKs from healthy donors harboring a homozygous mutation in IFITM3 (rs12252-C, a common SNP in areas of the world where DENV is endemic) were significantly more susceptible to DENV infection. DENV-induced MK secretion of IFNs prevented infection of bystander MKs and hematopoietic stem cells (HSCs). Thus, viral infections upregulate IFITM3 in human platelets and MKs, and IFITM3 expression is associated with adverse clinical outcomes. These observations establish, for the first time, that human MKs possess anti-viral functions, preventing DENV infection of MKs and HSCs following local immune signaling.	Co-expression
SRP182842	UCP1-expression associated gene signatures of human epicardial adipose tissue.	The primary objective of the study was to investigate the uncoupling protein-1 (UCP1) associated features of human epicardial adipose tissue (eAT) using next generation deep sequencing.  In addition, paired mediastinal adipose tissue (mAT) and subcutaneous adipose tissue (sAT) samples colleced from patients undergoing cardic surgeries at our center were included in the study. Overall design: Paired biopsies of eAT, mAT and sAT obtained from cardiac surgery patients (n=10), with specific criteria of high- and low- expression of UCP1 in eAT, were subjected to RNA sequencing. While the primary objective was to compare high- vs. low UCP1 expression in eAT, our study design further allowed us to investigate depot- and disease specific transcriptomic shifts in these patients. Specifically, 10 patients provided 30 samples (n = 10 each for eAT, mAT and sAT) that could be compared based on depot specificity (n = 10), obesity (n = 5 lean, n = 5 obese) and coronary artery disease (CAD) (n = 6 CAD, 4 = Non-CAD).	Co-expression
SRP182844	Gene expression profile in response to HIF-1a inhibition together with PPARa activation and the postnatal factors (T3, IGF-1 and dexamethasone) in hiPSC-CMs	Methods: RNA-seq libraries were prepared using the Illumina TruSeq technology. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq2500 system. Reads were mapped on the Human Genome Reference (GRCh38) and normalized expression table was generated. Results: Among differentially expressed genes, compared with DMSO-treated hiPSC-CMs, 505 genes were upregulated in FM+WY+TID-treated hiPSC-CMs, with 72 genes commonly upregulated in both FM+WY+TID-treated hiPSC-CMs and LV groups and 949 genes were downregulated in FM+WY+TID-treated hiPSC-CMs and 2137 genes were downregulated in LV, with 437 genes downregulated in both FM+WY+TID-treated hiPSC-CMs and LV compared with DMSO-treated hiPSC-CMs . Conclusions: Data demonstrate increased expression of genes associated with many metabolic processes which are also highly enriched in human pediatric heart samples including many interconnected metabolic processes that are upstream of lipid metabolism and FAO, agreeing with the shift to FAO for energy utilization in more mature CMs, and decreased expression of genes involved in developmental processes, adhesion and signaling in both FM+WY+TID-treated hiPSC-CMs and LV. The overlap in both upregulated and downregulated genes in both groups confirmed an advanced degree of cardiomyocyte maturation in response to FM+WY+TID. Overall design: RNA-sequencing analysis was performed to compare global gene expression profiles of hiPSC-CMs at differentiation day 28 with maturation factors (FM+WY+TID) treatment (Treat)  vs. DMSO treatment (DMSO) vs. left ventricle tissue sample (LV).	Co-expression
SRP182916	Transcriptomic profiling of human peripheral blood-derived mast cells	Here, we characterized the transcriptome of MCs under steady state, immunoglobulin E (IgE)-sensitized and anti-IgE-treated conditions. Overall design: MCs were left untreated or sensitized overnight with myeloma-IgE (0.5 µg/ml) and treated with anti-IgE (1 µg/ml) for 2h. RNA was isolated with Trizol and RNeasy columns and RNA-seq was performed.	Co-expression
SRP182935	Non-coding and coding transcriptional profiles are significantly altered in pediatric Retinoblastoma tumors	To find out the transcriptomic signature of Retinoblastoma compared to adult Retina. The methadology used was RNA sequencing using Illumina Platform. Overall design: This is the first transcriptomic report on RB tumours from patients compared to retina. This experiment gives valuable information about gene expression fusions and Long Non-coding RNAs and RNA mutations	Co-expression
SRP182965	Global gene expression profiles of cardiomyocytes differentiated from human pluripotent stem cells (hiPSC-CMs) in 3D culture exposed to ethanol	Methods: RNA-seq libraries were prepared using the Illumina TruSeq RNA kit and the TrueSeq method was employed for mRNA enrichment. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq2500 system. Reads were mapped on the Human Genome Reference and normalized expression table was generated. Results: RNA-seq results reveal gene expression of cardiac toxicity in hiPSC-CMs that are consistent with alcohol-induced pathophysiology observed in animal models.  For example MMP9 is among the top 5 upregulated genes in ethanol-treated hiPSC-CMs,  MMP9 concentrations are significantly higher in human sera of chronic alcohol abusers and MMP9 mRNA and protein levels are increased in the myocardium of rats following acute ethanol exposure. Conclusions: Data demonstrate significant alteration in gene expression, among the top 60 genes significantly altered by ethanol exposure, 8 genes are involved in ion channels, which may be in part contributing to the abnormal intracellular Ca2+ transients. Ethanol up-regulated the expression of genes associated with collagen metabolism and extracellular matrix (MMP9, EMID1, COL14A1), most of the downregulated genes are involved in cardiovascular system development (NPPB, DNAAF3), actin filament-based process (LMOD2, MYH4) and muscle contraction (MYL2).  These findings are consistent with previous studies showing a correlation between alcohol exposure and defects in heart and circulatory system development. Overall design: RNA-sequencing analysis was performed to compare global gene expression profiles of cardiomyocytes under ethanol treatment vs. control.	Co-expression
SRP183013	Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program	Expression analysis of mouse sinoatrial nodes and working cardiomyocytes Overall design: RNA-seq on human and mouse sinoatrial node and working myocardial tissue	Co-expression
SRP183071	GOYA DLBCL clinical trial - RNASeq dataset	This dataset contains collected RNASeq data of 552 samples from the GOYA clinical trial. Overall design: The GOYA trial tested the efficacy of Gazyva (GA101) compared with Rituxan (Rituximab) in first line, untreated DLBCL patients. Patients were randomized 1:1 to either G or R combined with a CHOP chemotherapy backbone. Tumor samples were collected at baseline, RNA was isolated using RNA-Access, and RNASeq was run with TruSeq (Illumina) RNASeq.	Co-expression
SRP183146	Genome-wide transcriptional analysis of human iPSC-derived healthy control vs. schizophrenia cortical interneurons.	We report specific changes in schizophrenia developmental interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Fourteen independent iPSC lines per group with two independent differentiations	Co-expression
SRP183186	Subjects acutely Infected with Chikungunya Virus	A systems biology approach was used to analyze the blood transcriptomes of adults acutely infected with Chikungunya Virus. There were identified gene signatures and pathways that were associated to viral RNA amounts and to the onset of symptoms that characterize the adults' acute infection.	Co-expression
SRP183188	Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity	Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies. Overall design: Bone marrow aspirates of five healthy control donors, 16 AML patients at diagnosis, and 19 matched samples during treatment were analyzed using Seq-Well single-cell RNA-sequencing (scRNA-seq). Acute myeloid leukemia (AML) patients in this study underwent standard induction chemotherapy between diagnosis (D0) and later time points (D14 and later). The only exception is AML328, who was treated with azacitidine + venetoclax. All 35 AML patient samples were also subjected to targeted amplification of known mutations in AML driver genes. One AML patient (AML921A) was analyzed in technical duplicate.	Co-expression
SRP183218	Single-cell transcription profiling in KS1 patient iPSCs and NPCs	We conducted single-cell RNA-seq (scRNA-seq) in human-derived induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) generated from Kabuki syndrome 1 (KS1) patients and healthy controls Overall design: scRNA-seq of iPSCs and differentiating NPCs induced by synergistic inhibition of GSK3, TGF-B, and Notch	Co-expression
SRP183453	Single cell analysis of HSV-1 infection reveals anti-viral and developmental programs are activated in distinct sub-populations with opposite outcomes	Viral infection is usually studied at the population level by averaging over millions of cells. However, infection at the single-cell level is highly heterogeneous, where most infected cells give rise to none or few viral progeny while some cells produce thousands. Analysis of HSV-1 infection by population averaged measurements has taught us a lot about the course of viral infection, but has also produced contradictory results, such as the concurrent activation and inhibition of type I interferon signaling during infection. Here, we combine live-cell imaging and single-cell RNA sequencing to characterize viral and host transcriptional heterogeneity during HSV-1 infection of primary human cells. We find extreme variability in the level of viral gene expression among individually infected cells and show that they cluster into transcriptionally distinct sub-populations. We find that anti-viral signaling is initiated in a rare group of abortively infected cells, while highly infected cells undergo cellular reprogramming to an embryonic-like transcriptional state. This reprogramming includes the re-localization of b-catenin into the host nucleus and viral replication compartments and is required for late viral gene expression and progeny production. These findings uncover the transcriptional differences in cells with variable infection outcomes and shed new light on the manipulation of host pathways by HSV-1. Overall design: HDFn cells mock-infeted, infected with wt HSV-1 or dICP0 HSV-1 for 5 hours. drop-seq data for single-cell RNA-sequncing as well as bulk RNA-seq of sorted cell population (ICP4 positive or negative in each experimet, in duplicates)	Co-expression
SRP183468	Phospho-small RNA-seq reveals circulating, extracellular mRNA/lncRNAs as potential biomarkers in human plasma: Hematopoietic Stem Cell Transplant [HSCT]	Extracellular RNAs (exRNAs) in blood and other biofluids have attracted great interest as potential biomarkers in liquid biopsy applications, as well as for their potential biological functions. Whereas it is well-established that extracellular microRNAs are present in human blood circulation, the degree to which messenger RNAs (mRNA) and long noncoding RNAs (lncRNA) are represented in plasma is less clear. Here we report that mRNA and lncRNA species are present as small fragments in plasma that are not detected by standard small RNA-seq methods, because they lack 5'-phosphorylation or carry 3'-phosphorylation. We developed a modified sequencing protocol (termed "phospho-sRNA-seq") that incorporates upfront RNA treatment with T4 polynucleotide kinase (which also has 3' phosphatase activity) and compared it to a standard small RNA-seq protocol, using as input both a pool of synthetic RNAs with diverse 5' and 3' end chemistries, as well exRNA isolated from human blood plasma. Using a custom, high-stringency pipeline for data analysis we identified mRNA and lncRNA transcriptome fingerprints in plasma, including multiple tissue-specific gene sets. In a longitudinal study of hematopoietic stem cell transplant (HSCT) patients, we found different sets corresponding to bone marrow- and liver- enriched genes, which tracked with bone marrow recovery or liver injury, providing proof-of-concept validation of this method as a biomarker approach. By accessing a previously unexplored realm of mRNA and lncRNA fragments in blood plasma, phospho-sRNA-seq opens up a new space for plasma transcriptome-based biomarker development in diverse clinical settings. Overall design: ExRNA-seq libraries were prepared from platelet-poor plasma obtained from serial blood draws collected from two individuals undergoing bone marrow transplantation. A total of 11 samples were collected from each individual, starting prior to chemotherapy/ratiation treatment (approximately 7 days pre-HSCT) the day of transplant, and then weekly up to approximately Day 63.	Co-expression
SRP183475	Human pluripotency is initiated and preserved by a unique subset of founder cells [single-cell RNA-sequencing]	The assembly of organized colonies is the earliest manifestation in the derivation or induction of pluripotency in vitro. However, the necessity and origin of this assemblance is unknown. Here, we identify human pluripotent founder cells (hPFCs) that initiate as well as preserve and establish pluripotent stem cell (PSC) cultures. PFCs are marked by N-cadherin expression (NCAD+) and reside exclusively at the colony boundary of primate PSCs. Functional analysis demonstrated hPFCs harbor the clonogenic capacity of PSC cultures, and emerge prior to commitment events or phenotypes associated with pluripotent reprogramming. Comparative single cell analysis with pre- and post-implantation primate embryos revealed hPFCs share hallmark properties with primitive endoderm (PrE) and can be regulated by non-canonical Wnt signaling. Uniquely informed by primate embryo organization in vivo, our study defines a subset of founder cells uniquely involved in the establishment pluripotent state. Overall design: Droplet-based single-cell RNA-sequencing of bulk- and NCAD-positive hESCs. Two lines of hESCs (H1 and H9) were loaded to the Chromium Controller as mixtures and then computationally segregated based on coverage of the sex chromosomes after sequencing and alignment.	Co-expression
SRP183528	RNA-sequencing of formalin fixed human primary melanoma tissue	We identify the differences in nervous system related genes and pathways inside melanoma and in the tissure adjacent to melanoma tumor. Overall design: Formalin fixed primary human melanoma tissue sections from a single tumor were microdissected into samples containing tumor center, tumor border or tissue adjacent to the tumor. Three separate areas of the tumor were used to generate nine samples, which were analyzed by RNA sequencing.	Co-expression
SRP183682	Single-cell RNA-sequencing of CD14+ monocyte differentiation with M-CSF stimulus	We obtained single-cell RNA-sequencing (scRNA-seq) profiles of CD14+ monocytes isolated from human peripheral blood at 0, 3 and 6 days after M-CSF stimulation (to differentiate the cells into macrophages) across multiple donors. Integration of single-cell RNA sequencing (scRNA-seq) data from multiple experiments, laboratories, and technologies can uncover biological insights, but current methods for scRNA-seq data integration are limited by a requirement for datasets to derive from functionally similar cells. We use a novel algorithm, Scanorama, to identify and merge the shared cell types among all pairs of datasets and to accurately integrate heterogeneous scRNA-seq datasets. Scanorama is sensitive to subtle temporal changes within the same cell lineage, successfully integrating functionally similar cells across time series data of CD14+ monocytes at different stages of differentiation into macrophages. Scanorama is not only able to differentiate between completely disparate cell types but is also sensitive to subtler transcriptional changes within a cell type due to processes like stimulation. Overall design: scRNA-seq of human CD14+ monocytes at 0, 3, and 6 days after M-CSF stimulation in multiple donors	Co-expression
SRP183700	Homo sapiens Genome sequencing	We examined skin biopsies from a diverse cohort of 23 SSc patients (including lesional forearm and non-lesional back samples) by RNA-seq. Metagenomic filtering and annotation was performed using the Integrated Metagenomic Sequencing Analysis (IMSA). Associations between microbiome composition and gene expression were analyzed using single-sample gene set enrichment analysis (ssGSEA).	Co-expression
SRP183811	Spatial and Temporal Mapping of Human Innate  Lymphoid Cells Reveals Elements of Tissue  Specificity	We provide a map of human ILC heterogeneity across multiple  anatomical sites. Tissue-specific distinctions    are particularly apparent for ILC1 populations, whose  distribution was markedly altered in obesity or aging.    Furthermore, the degree of ILC1 population hetero-  geneity differed substantially in lymphoid versus    mucosal sites. Together, these analyses comprise a  comprehensive characterization of the spatial and    temporal dynamics regulating the anatomical distri-  bution, subset heterogeneity, and functional poten-  tial of ILCs in non-diseased human tissues. Overall design: We present a quantitative analysis of ILC distribution and  heterogeneity in lymphoid, mucosal, and metabolic tissues  obtained from a diverse cohort of 44 previously non-diseased  organ donors over a wide range of ages and body mass indexes  (BMIs).	Co-expression
SRP184220	ELP1 splicing correction reverses proprioceptive sensory loss in familial dysautonomia	Familial dysautonomia (FD) is a recessive neurodegenerative disease caused by a splice mutation in Elongator complex protein 1 (ELP1, also known as IKBKAP) which leads to variable skipping of exon 20 and to a drastic reduction of ELP1 levels in the nervous system. Clinically, many of the debilitating aspects of the disease are related to a progressive loss of proprioception, which leads to severe gait ataxia, spinal deformities and respiratory insufficiency due to neuromuscular incoordination. There is currently no effective treatment for FD and the disease is ultimately fatal. Development of a drug that targets the underlying molecular defect provides hope that the drastic peripheral neurodegeneration characteristic of FD can be halted. We demonstrate herein that the FD mouse, TgFD9; Ikbkap?20/flox, recapitulates the proprioceptive impairment observed in individuals with FD, and we provide the in vivo evidence that postnatal correction of mutant ELP1 splicing promoted by the small molecule kinetin can rescue neurological phenotypes in FD. Daily administration of kinetin starting at birth improves sensory-motor coordination and prevents the onset of spinal abnormalities by stopping the loss of proprioceptive neurons. These phenotypic improvements correlate with increased levels of full length ELP1 mRNA and protein in multiple tissues including the peripheral nervous system (PNS). Our results show that postnatal correction of the underlying ELP1 splicing defect can rescue devastating disease phenotypes and is therefore a viable therapeutic approach for persons with FD. Overall design: Both placebo and kinetin treatments were applied on six human FD fibroblast lines. Paired-end RNASeq was performed on these twelve fibroblast lines.	Co-expression
SRP184221	COX-2 mediates tumor-stromal Prolactin signaling to initiate tumorigenesis [DF]	Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: We performed RNA-seq on the human dermal fibroblast cell line DF treated for six hours with PGE-2 or untreated.	Co-expression
SRP184297	Integrative vascular endothelial cell genomics identify AIDA as a coronary artery disease candidate gene (RNAseq)	Genome-wide association studies (GWAS) have identified 100s of loci associated with coronary artery disease (CAD) and blood pressure (BP)/hypertension. Many of these loci are not associated with traditional risk factors, nor include obvious candidate genes, complicating their functional characterization. We hypothesized that many GWAS loci associated with vascular diseases modulate endothelial functions. Endothelial cells play critical roles in regulating vascular homeostasis (e.g. selective barrier, inflammation, hemostasis, vascular tone) and endothelial dysfunction is a hallmark of atherosclerosis and hypertension. We generated an integrated map of gene expression (RNA-sequencing), open chromatin regions (ATAC-sequencing), and 3D interactions (Hi-C) in resting and TNFa-treated human endothelial cells. We showed that genetic variants associated with CAD and BP are enriched in open chromatin regions identified in endothelial cells. We used physical loops identified by Hi-C to link open chromatin peaks that include CAD or BP SNPs with the promoter of genes expressed in endothelial cells. This analysis highlighted 4,548 combinations of regulatory elements-promoters, including 108 pairs that involve a differentially open chromatin site and a differentially expressed gene following TNFa treatment. At a CAD locus, we validated one of these pairs by engineering a deletion of the TNFa-sensitive regulatory element using CRISPR/Cas9 and measuring an effect on the expression of the novel CAD candidate gene AIDA. Our data support an important role played by genetic variants acting in the vascular endothelium to modulate inter-individual risk in CAD or hypertension Overall design: RNAseq of TNF-alpha treated endothelial cells (teloHAEC and HCAEC) for 0, 4h or 24h	Co-expression
SRP184505	Transcriptional cofactors display core promoter class-specificity in human	Transcriptional cofactors communicate regulatory cues from enhancers to promoters and are central effectors of transcription activation and gene expression, which is a hallmark of all multicellular organisms. However, the extent to which different cofactors display intrinsic specificity for distinct promoters is unclear. Testing intrinsic COF – core promoter (CP) compatibilities requires the systematic assessment of transcriptional activation for many CPs in the presence or absence of a given COF in an otherwise constant standardized reporter system. We therefore combined a plasmid-based high-throughput reporter assay, Self-Transcribing Active Core Promoter-sequencing (STAP-seq), with the specific recruitment of individual COFs to create a high-throughput activator bypass-like assay. Using this assay, we tested whether 5 different individually tethered human COFs (MED15, BRD4, EP300, MLL3 and EMSY) activate transcription from a selection of 12,000 candidate sequences encompassing different types of gene core promoters, enhancers and control sequences. In addition, we used the strong transcriptional activator P65 as a positive control and GFP as a negative control. We found that different COFs preferentially activate different CPs. For instance, MED15 prefers TATA-box containing CPs, while MLL3 preferentially activates CpG island promoters. The observed compatibilities between cofactors and promoters can explain how different enhancers specifically activate distinct sets of genes or alternative promoters within the same gene, and may underlie distinct transcriptional programs in human cells. Overall design: STAP-seq upon recruitment of individual transcriptional cofactor in HCT116 cells with 5 different cofactors and 2 controls, each in biological triplicate.	Co-expression
SRP184517	Single-cell RNA sequencing of inflammatory tissue T cells in eosinophilic esophagitis	T cell heterogeneity is highly relevant to allergic disorders. We resolve the heterogeneity of human tissue CD3+ T cells during allergic inflammation, focusing on a tissue-specific allergic disease, eosinophilic esophagitis (EoE). We investigated 1,088 single T cell derived from patients with a spectrum of disease activity. Eight disparate tissue T cell subtypes (designated T1-T8) were identified, with T7 and T8 enriched in the diseased tissue. The phenotypes of T7 and T8 resemble putative TREG (FOXP3+) and effector Th2 (GATA3+)-like cells, respectively. Prodigious levels of IL-5 and IL-13 were confined to HPGDS+ CRTH2+ IL-17RB+ FFAR3+CD4+ T8 effector Th2 cells. EoE severity closely paralleled a lipid/fatty acid–induced activation node highlighted by the expression of the short-chain fatty acid receptor FFAR3. Ligands for FFAR3 induced Th2 cytokine production from human and murine T cells including in an in vivo allergy model. Therefore, we have elucidated the defining characteristics of tissue-residing CD3+ T cells in EoE, a specific enrichment of CD4+ TREG and effector Th2 cells, confinement of type 2 cytokine production to the CD4+ effector population, a highly likely role for FFAR3 in amplifying local Th2 responses in EoE, and a resource to further dissect tissue lymphocytes and allergic responses. Overall design: Single-cell transcriptome profililng of esophagus biopsies from patients with active eosinophilic esophagitis (EoE, n=11), in remission (n=6), and without disease (n=5)	Co-expression
SRP184530	A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity	We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities.  Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation.  Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins.  Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant.  Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes.  Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls.  Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts.  Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes. Overall design: Total RNA samples were isolated from 3 different cultures of HTB17 cells that overexpressed CtBP1 wt or the pathogenic mutant, W342 and analyzed by high- throughput RNA sequencing.	Co-expression
SRP184538	Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors	Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFß1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs.  Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties (EP) of the cardiomyocytes compared to co-culture with dermal fibroblasts (DFs). The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration. Overall design: We performed RNA-seq for hPSC-CFs, primary CFs and DFs to compare the gene expression for each type of fibroblasts. We also added the hPSC-CMs and hPSCs as the positive and negativ controls in the RNA-seq to compare the gene expression for cardaic factors. Five cell types (hPSC-CFs, human adult CFs and DFs, hPSC-CMs and hPSCs) with 2 biological replicates for each cell type of a total 10 samples were sequenced.	Co-expression
SRP184695	A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.	Development of a novel CRISPR-derived cell line which is a derivative of CWR22Rv1 cells, called CWR22Rv1-AR-EK, that has lost expression of FL-AR, but retains all endogenous AR-Vs. AR-Vs act unhindered by loss of FL-AR to drive cell growth and expression of androgenic genes. Global transcriptomics demonstrate that AR-Vs drive expression of a cohort of DNA damage response genes and depletion of AR-Vs sensitizes cells to ionizing radiation. Overall design: Transcriptomic profile (mRNA) of AR splice variants in CWR22Rv1 AR-EK cells was generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.	Co-expression
SRP185454	Gene expression profiling of human  CD19+ B cells and EBV transformed lymphoblastoid cell lines (LCLs)	Genome wide association studies have identified >200 susceptibility loci accounting for much of the heritability of Multiple Sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been identified as necessary but not sufficient for development of MS. The molecular and immunological basis for this has not been established. Infected B cell proliferation is driven by signalling through the EBV produced cell surface protein LMP1, a homologue of the MS risk gene CD40.  Methods: We have investigated transcriptomes of B cells and EBV infected B cells at Latency III (LCLs) and identified MS risk genes with altered expression on infection Overall design: 5 individuals with paired CD19+ B cells and LCLs	Co-expression
SRP185514	Expression profiling of converted and control dermal BJ fibroblasts	We report transcriptional changes following ectopic expression of wildtype or mutant p63+/- KLF4 for 72 hours in dermal BJ fibroblasts. Overall design: RNA-seq of dermal BJ fibroblasts following ectopic expression of a control empty vector or wild type/mutant p63 +/- KLF4  for 72 hours in biological duplicates (NextSeq500)	Co-expression
SRP185693	Gene expression analysis of a subcutaneous MV4;11 tumor treated with curaxin CBL0137.	The aim of this experiment was to identify how CBL0137 decreased tumor growth in a subcutaneous MV4;11 xenograft model by investigating the gene expression changes induced upon treatment. Overall design: > 1 million MV4;11 cells were inoculated subcutaneously in the flank of NOD/SCID (NOD/SCID NOD.CB17-Prkdcscid/SzJ) mice. When tumors measured around 100 mm3, mice were treated with CBL0137 (70 mg/kg CBL0137 intravenously) on day 0 and day 8. Tumors were harvested 24h post last injection on day 8. Tumors were also harvested from untreated mice. Tumors were flash frozen in liquid nitrogen and RNA was isolated.	Co-expression
SRP185707	Transcriptomic analysis of the effect of histone H4 K31R mutation in U2OS cells	To explore the genome-wide gene expression changes induced by the K31R mutation in the histone H4 protein, we performed RNA-sequencing analysis in U2OS cells expressing either wildtype H4 or K31R mutant H4. We found that the lysine (K) to arginine (R) mutation mainly affected oxidative phosphorylation, mtiochondria dysfunction and et al, but not DNA damage signaling pathways. Overall design: Total RNAs were extracted from 3 wild-type (WT) H4 and 3 K31R mutant H4 expressing U2OS cells and profiled by RNA-sequencing.	Co-expression
SRP185716	Gene expression and chromatin organization changes in lamin A/C haploinsufficient human induced pluripotent stem cell-derived cardiomyocytes [RNA-seq]	Pathogenic mutations in A-type nuclear lamins may dysregulate gene expression due to changes in chromatin organization into active (A) and inactive (B) compartments. To test this, we performed genome-wide chromosome conformation analyses (Hi-C) and transcriptome profiling (RNA-seq) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a haploinsufficient mutation for Lamin A/C that causes cardiac laminopathy. Mutant hiPSC-CM have marked electrophysiological, contractile, and gene expression alterations. While large-scale changes in chromatin topology are evident, differences in chromatin compartmentalization are limited to a few hotspots. These regions normally transition from A to B during cardiogenesis, but remain in A in mutant hiPSC-CM. Non-cardiac genes located within such aberrant domains are ectopically expressed, including the neuronal P/Q-type calcium channel CACNA1A. Pharmacological inhibition of the resulting currents partially mitigates elongation of field potential duration in mutant hiPSC-CM. On the other hand, A/B compartment changes do not explain most gene expression alterations observed in mutant hiPSC-CM, putting in perspective the role of chromatin organization dysregulation in cardiac laminopathy. Overall design: RNA-seq analyses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a heterozygous R225X mutation (mutant), and hiPSC-CM from two isogenic control lines where such  mutation was reverted to the wild-type allele using CRISPR/Cas9 (corrected); three biological replicates from independent differentiations per cell line.	Co-expression
SRP185739	Exploring ILF2 regulatory genes by next-generation sequencing	We knocked down the expression of ILF2 in the A549 cell line and sequenced the RNA genes with the untreated A549 cells to find the regulatory gene of ILF2. Overall design: Examination of ILF2 regulatory genes in A549 cell line.	Co-expression
SRP185789	Loss of Nuclear TDP-43 Is Associated with Decondensation of LINE Retrotransposons [RNA-Seq]	Loss of the nuclear RNA binding protein TAR DNA binding protein-43 (TDP-43) into cytoplasmic aggregates is the strongest correlate to neurodegeneration in amyotrophic lateral sclerosis and frontotemporal degeneration. The molecular changes associated with the loss of nuclear TDP-43 in human tissues are not entirely known. Using a novel subcellular fractionation and fluorescent activated cell sorting method to enrich for diseased neuronal nuclei without TDP-43 from post-mortem FTD-ALS human brain, we characterized the effects of TDP-43 loss on the transcriptome and chromatin accessibility. Nuclear TDP-43 loss is associated with gene expression changes that affect RNA processing, nucleocytoplasmic transport, histone processing and DNA damage. Loss of nuclear TDP-43 was also associated with chromatin decondensation around long interspersed nuclear elements (LINEs) and increased LINE1 DNA content. Moreover, loss of TDP-43 leads to increased retrotransposition that can be inhibited with antiretroviral drugs, suggesting that TDP-43 neuropathology is associated with altered chromatin structure including decondensation of LINEs. Overall design: Examination of gene expression profiles and chromatin accessibility in neuronal nuclei, which have either retained or lossed TDP-43, extracted from FTD/ALS patient post-mortem frontal cortex	Co-expression
SRP185812	Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors [ABE-max]	CRISPR-Cas base editor technology enables targeted nucleotide alterations and is being rapidly deployed for research and potential therapeutic applications. The most widely used base editors induce DNA cytosine (C) deamination with rat APOBEC1 (rAPOBEC1) enzyme, which is targeted by a linked Cas protein-guide RNA (gRNA) complex. Previous studies of cytosine base editor (CBE) specificity have identified off-target DNA edits in human cells. Here we show that a CBE with rAPOBEC1 can cause extensive transcriptome-wide RNA cytosine deamination in human cells, inducing tens of thousands of C-to-uracil (U) edits with frequencies ranging from 0.07% to 100% in 38% - 58% of expressed genes. CBE-induced RNA edits occur in both protein-coding and non-protein-coding sequences and generate missense, nonsense, splice site, 5' UTR, and 3' UTR mutations. We engineered two CBE variants bearing rAPOBEC1 mutations that substantially decrease the numbers of RNA edits (reductions of >390-fold and >3,800-fold) in human cells. These variants also showed more precise on-target DNA editing and, with the majority of gRNAs tested, editing efficiencies comparable to those observed with wild-type CBE. Finally, we show that recently described adenine base editors (ABEs) can also induce transcriptome-wide RNA edits. These results have important implications for the research and therapeutic uses of base editors, illustrate the feasibility of engineering improved variants with reduced RNA editing activities, and suggest the need to more fully define and characterize the RNA off-target effects of deaminase enzymes in base editor platforms. Overall design: HEK293T cells were transfected with pCMV-ABEmax-P2A-EGFP or control pCMV-bpNLS-32AAlinker-nCas9(D10A)-bpNLS constructs with HEK site 2 gRNA as described below. Cells were sorted for top 5% GFP based on FITC signal. RNA-seq was performed to measure transcriptional changes associated with different constructs.	Co-expression
SRP185818	Next Generation Sequencing Facilitates Quantitative Analysis of SW480 cells and HPSE-knockdown SW480 cells Transcriptomes	Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. The goals of this study are to compare the mRNA transcriptome differences between SW480 cells and HPSE-knockdown SW480 cells. Methods: mRNA profiles of SW480 cells and HPSE-knockdown SW480 cells were generated by deep sequencing, in triplicate, using Illumina. Overall design: mRNA profiles of SW480 cells and HPSE-knockdown SW480 cells were generated by deep sequencing, in triplicate, using Illumina.	Co-expression
SRP185827	PR attentuation of interferon signaling	Why some tumors remain indolent and others progress to clinical relevance remains a major unanswered question in cancer biology. Interferon signaling in nascent tumors, mediated by STAT1, is a critical step through which the surveilling immune system can recognize and destroy developing tumors. Herein, we have identified an interaction between the progesterone receptor (PR) and STAT1 in breast cancer cells. This interaction inhibited efficient interferon-induced STAT1 phosphorylation, as we observed a decrease in phospho-STAT1 in response to interferon treatment in PR-positive breast cancer cell lines. This phenotype was further potentiated in the presence of PR ligand. In human breast cancer samples, PR-positive tumors exhibited lower levels of phospho-STAT1 as compared to their PR-negative counterparts, indicating that this phenotype translates to human tumors. Breast cancer cells lacking PR exhibited higher levels of interferon-stimulated gene (ISG) RNA, the transcriptional endpoint of interferon activation, indicating that unliganded PR alone could decrease transcription of ISGs. Moreover, the absence of PR led to increased recruitment of STAT1, STAT2 and IRF9 (key transcription factors necessary for ISG transcription) to ISG promoters. These data indicate that PR, both in the presence and absence of ligand, attenuates interferon-induced STAT1 signaling, culminating in significantly abrogated activation of genes transcribed in response to interferons. PR-positive tumors may use downregulation of STAT1-mediated interferon signaling to escape immune surveillance, leading to the development of clinically relevant tumors. Selective immune evasion of PR-positive tumors may be one explanation as to why over 65% of breast cancers are PR-positive at the time of diagnosis. Overall design: 2 different cell lines (T47D-Y [PR null] and T47D-co [PR-positive]) were treated +/- interferon and R5020 (PR ligand), in biologic triplicate. There are a total of 8 groups, 3 replicates each, making for 24 samples total	Co-expression
SRP185842	Transient stabilization, rather than inhibition of MYC amplifies extrinsic apoptosis and therapeutic responses in refractory B-cell lymphoma	Identification of gene expression changes following inhibition of GSK-3 in Burkitt lymphoma Overall design: We profiled cells treated for 0, 3, and 6 hours with the GSK-3 inhibitor CHIR99021 in biological triplicates	Co-expression
SRP185844	Next Generation Sequencing of isolated EGFR+ and HLA-G+ first trimester human trophoblasts	The aim of this study was to identify differentially expressed signatures of non-invasive (EGFR+) and invasive (HLA-G+) human trophoblast subtypes. These populations were isolated from single first trimester placentas from 10-12 weeks of gestation. Overall design: We performed RNAseq to analyze the global expression profile of two different trophoblastic subtypes.	Co-expression
SRP185848	A NIK-SIX signaling axis controls inflammation by targeted silencing of noncanonical NF-?B	The non-canonical NF-?B signaling cascade is essential for lymphoid organogenesis, B-cell maturation, osteoclast differentiation, and inflammation in mammals, whereas dysfunction of this system is associated with human diseases, including immunological disorders and cancer. While controlled expression of NF-?B Inducing Kinase (NIK) is the rate-limiting step in non-canonical NF-?B activation, mechanisms of inhibition remain largely unknown. Here, we report the identification of the sine oculis homeobox homolog family transcription factors SIX1 and SIX2 as essential inhibitory components of the non-canonical NF-?B signaling pathway. The developmentally silenced SIX-proteins are reactivated in differentiated macrophages by NIK-mediated suppression of the ubiquitin proteasome pathway. Consequently, SIX1 and SIX2 target a subset of inflammatory gene promoters and directly inhibit RelA and RelB trans-activation function in a negative feedback circuit. In support of a physiologically pivotal role for SIX-proteins in host immunity, human SIX1 transgene suppressed inflammation and promoted the recovery of mice from endotoxic shock. In addition, SIX1 and SIX2 protected RAS/p53-driven lung adenocarcinoma cells from inflammatory cell death induced by SMAC-mimetic chemotherapeutic agents, small-molecule activators of the non-canonical NF-?B pathway. Collectively, our study reveals a NIK-SIX signaling axis that fine-tunes inflammatory gene expression programs under both physiological and pathological conditions. Overall design: In this data set, we first analyzed NIK-stimulated genes by expressing NIK and Fluc (control experiment) in STAT1-deficient fibroblasts. Each group has 2 independent experiments. Second, we analyzed the SIX2-downregulated NIK-stimulated genes, FlucRFP/FlucBFP, NIKRFP/FlucBFP, NIKRFP/SIX2BFP, or FlucRFP/SIX2BFP lentivirus was transduced into WT fibroblasts. We then analyzed the whole genome transcription prfiles. Each group has 2 independent experiments. Third, WT and SIX1-/- SIX2-/- H1792 treated with mock or BV6/TNF for 24 hours. we analyzed the whole genome transcription profiles. Each group has 2 independent experiments.	Co-expression
SRP185902	Genome-wide fetalization of enhancer architecture in heart disease [RNA-Seq]	Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart.  However, the impact of this reactivation on the genome-wide regulatory landscape in heart disease has remained obscure.  Here we show that pervasive epigenomic changes occur in heart disease, with thousands of regulatory sequences reacquiring fetal-like chromatin signatures.  We used RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from 18 healthy controls and 18 individuals with idiopathic dilated cardiomyopathy (DCM).  Healthy individuals had a highly reproducible epigenomic landscape, consisting of more than 31,000 predicted heart enhancers.  In contrast, we observed reproducible disease-associated gains or losses of activity at more than 7,500 predicted heart enhancers.  Next, we profiled human fetal heart tissue by ChIP-seq and RNA-seq.  Comparison with adult tissues revealed that the heart disease epigenome and transcriptome both shift toward a fetal-like state, with more than 3,400 individual enhancers sharing fetal regulatory properties.  Our results demonstrate widespread epigenomic changes in DCM, and we provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of heart disease etiology. Overall design: Total RNA-seq of adult left ventricle tissue from healthy hearts, adult explanted hearts with ideopathic dilated cardiomyopathy, and embryonic/fetal hearts	Co-expression
SRP185927	RNA-seq of APMAP knockdown PC-3 cells	This study goal is to obtain the different expression genes induced by APMAP knockdown.	Co-expression
SRP185955	RNA editing with CRISPR-Cas13	No description.	Co-expression
SRP185956	Circular RNA profile of steroid-induced osteonecrosis of the femoral head	Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs, which drew little attention in the past. Recently, limited data showed their promising future to act as biomarkers in human diseases, but the characteristics and functions remain largely unknown in steroid-induced osteonecrosis of the femoral head. In this study, with the help of circRNA sequecing, we demonstrated the expression profile of circRNAs in steroid-induced osteonecrosis of the femoral head patients, and identified a large number of circRNAs. We also described a circRNA signature related to steroid-induced osteonecrosis of the femoral head based on the bioinformatics prediction.	Co-expression
SRP185979	A novel fate-mapping approach allows intratumoral profiling of hypoxic cells	We designed a novel approach to fate-map hypoxic cells in order to determine their cellular response to physiological O2 gradients. Our system causes a change in the expressing fluorescent protein upon hypoxic exposure (DsRed -> GFP). We generated hypoxia fate-mapping tumors using MDA-MB-231 cells expressing our system. Tumors were resected 2 weeks post-implantation, mechanically disrupted and digested with collagenase to obtain a cell suspension. The cell suspension was enriched using magnetic-activated cell sorting (MACS) and DsRed+ cells were isolated from GFP+ cells by fluorescence-activated cell sorting (FACS) directly into Tris Reagent (Zymo Research). Total RNA was extracted from cells using TRIzol (Invitrogen) and purified using Direct-zol RNA mini kit (Zymo Research) with DNase I treatment. After RNA purification, samples were confirmed to have a RIN value > 9.0 when measured on an Agilent Bioanalyzer. Libraries for RNA-Seq were prepared with KAPA Stranded RNA-Seq Kit. The workflow consisted of mRNA enrichment, cDNA generation, end repair to generate blunt ends, A-tailing, adaptor ligation and 12 cycles of PCR amplification. Unique adaptors were used for each sample in order to multiplex samples into several lanes. Sequencing was performed on Illumina Hiseq 4000 with a 150bp pair-end run. A data quality check was done on Illumina SAV. Demultiplexing was performed with Illumina Bcl2fastq2 v 2.17 program. Overall design: In order to permanently mark hypoxic cells upon exposure to hypoxia, we generated a dual-vector hypoxia fate-mapping system delivered by a lentiviral approcah. Vector 1 expresses a red fluorescent reporter protein (DsRed) with a stop codon flanked by tandem loxP sites (“floxed”) and located in front of a gene encoding a green fluorescent protein (GFP). Vector 2 contains an altered Cre gene modified by the addition of an oxygen-dependent degradation domain (ODD) that is under the transcriptional control of a synthetic HIF-DNA binding sequence (HRE). HIF stabilization causes the activation of vector 2 by binding to hypoxia-dependent DNA response elements (HREs). Vector 2 activation causes the production of a genetically modified Cre protein that is only stable under hypoxia, leading to the cleavage of DsRed and permanent GFP expression. DsRed+ and GFP+ cells were sorted from MDA-MB-231 hypoxia fate-mapping tumors.	Co-expression
SRP185999	RNA sequencing analysis to identify gene targets of Kaposi's sarcoma herpesvirus (KSHV) ORF24	ORF24 is the core component of a virally encoded transcription complex in KSHV that is active during later stages of infection. ORF24 makes interactions with both promoter DNA and host RNA polymerase II. The aim of this study was to identify the targets of the virally encoded transcription complex by sequencing total RNA from cells that express a mutant ORF24 that does not interact with RNA polymerase II and compare it to RNA from a mutant rescue cell line (WT). We observed that most viral genes were down regulated in the absence of the ORF24-Pol II interaction and as expected, majority of them were late genes. Overall design: iSLK cells latently infected with the mutant KSHV ORF24 (RAAAG) or the mutant rescue (MR) were reactivated in to the lytic cycle using doxycycline and sodium butyrate. 24 or 48 hours post reactivation, the total RNA was extracted from the cells and subject to library preparation for RNA sequencing.	Co-expression
SRP186009	RNA-sequencing uncovers transcriptomes of human diseased, healthy, and disease-modeled retinal pigment epithelial cells.	Human donor derived retinal pigment epithelial cells from healthy, diseased, and disease-modeled sources underwent RNA-sequencing to identify unique, gene signatures. Overall design: Retinal pigment epithelial cell transcriptomes of human healthy, diseased, and disease-modeled cells were uncovered using Illumina RNA-sequencing, in triplicate.	Co-expression
SRP186016	Investigation of transcriptional changes in cells expressing different levels of MeCP2	MeCP2 is transcriptional regulator, however the mechanism is not fully understood. This study uses various levels of MeCP2 in human neurons to discover mechanism of MeCP2 action. The transcriptional data are used to correlate with methylation status of genes. Overall design: LUHMES-derived neurons have been modified to express seven levels of MeCP2 and RNA-seq was performed for all the cell lines.	Co-expression
SRP186168	Capture RNA Sequencing  for a Panel of Human Cell Lines	Capture RNA Sequencing for a Panel of Human Cell Lines using Agilent SureSelect Human All Exon V4 and V5+lncRNA kits.	Co-expression
SRP186185	Potential signaling pathways and gene signatures associated with brain metastases in NSCLC patients	RNA-Seq analyses of various cancers have identified thousands of target genes that help guide clinical treatment. By using RNA-Seq analysis, we examined primary lung tumors from NSCLC patients with and without BM to identify differentially-expressed genes and potential signaling pathways in two groups. A total of 6 patients with histopathologically confirmed NSCLC (against AJCC criteria) were enrolled in the RNA-Seq study, 3 patients with BM and other 3 without BM. All the cancer tissues used in this study were taken from surgical specimens and biopsies, and preserved immediately in liquid nitrogen after surgery. Totally, 566 differentially-expressed genes between BM+ and BM- samples were identified by DESeq2 with log2Fold Change being more than 2 and P value of statistical test less than 0.05, 326 genes were significantly down-regulated and 240 genes were up-regulated in BM+ group. Overall design: RNA isolation and RNA sequencing were performed in 6 NSCLC patients, 3 patients with BM and other 3 without BM. All libraries were sequenced on the Illumina Hiseq 2500 Sequencer.	Co-expression
SRP186200	Spatially Resolved RNA Sequencing in Micropatterned Tumor Models	MCF-7 breast cancer cells were micropatterned in circular regions surrounded by Bone Marrow Stromal Cells (BMSCs) in a micropatterned tumor-stromal assay (uTSA). After four days of culture, cancer cells from the edge and center of the micropattern were extracted with Laser Capture Microdissection (LCM), and their RNA was isolated and sequenced.Relevance: The goal of this project is to understand the heterogeneity of cell signaling in association with tumor architecture and tumor-stromal interactions in the tumor microenvironment (TME).	Co-expression
SRP186205	Weighted gene co-expression network analysis for RNA-Sequencing data of the varicose veins transcriptome	Our study aims to elucidate transcriptomic regulations of varicose veins bydetecting differentially expressed genes, pathways and regulator genes.	Co-expression
SRP186290	CAR T cell trogocytosis and cooperative killing   regulate tumour antigen escape	Chimeric antigen receptors (CARs) are synthetic receptors for antigen that reprogram T cell specificity, function and persistence. Patient-derived CAR T cells have demonstrated remarkable efficacy against a range of B-cell malignancies, and early trial results suggest activity in multiple myeloma. Despite high complete response rates, relapses occur in a large fraction of patients, some of which are antigen-negative and others antigen-low. Unlike mechanisms resulting in complete and permanent antigen loss, those leading to antigen-low tumour escape remain obscure. In murine leukaemia models, we show that CARs provoke reversible antigen loss through trogocytosis, an active process whereby target antigen is transferred to T cells, thereby decreasing target density on tumour cells and abating T cell activity by promoting fratricide killing and exhaustion. These mechanisms affect both CD28 and 4-1BB-based CARs, albeit differentially, depending on antigen density. They can be offset by cooperative killing and combinatorial targeting. Overall design: Examination of mRNA CD19 expression in  NALM6 retrieved from relapsed mice treated with 19-BB? CAR T cells (D0),  retrieved NALM6 after ex-vivo culture (D6), and  NALM6 culture in vitro (ctrl).	Co-expression
SRP186314	RNA sequencing of isogenic BRCA2 haploinsufficient vs. wild-type T-ALL cells	We found a high frequency of heterozygous Fanconi-BRCA pathway mutations in pediatric T-ALL.  BRCA2 was the most commonly mutated gene.  We transduced Cas9-expressing Jurkat cells, which lacked an identifiable BRCA2 mutation, with an integration-defective lentiviral guide RNA expression construct targeting exon 11 of BRCA2 (NM_000059).  Single-cell cloning and sequencing analysis revealed two distinct clones harboring monoallelic BRCA2 frameshift mutations, termed clones W4 and W5.  Each of these clones was subjected to RNA sequencing analysis. Overall design: RNA sequencing was performed on 2 independent BRCA2 haploinsufficient Jurkat clones and 2 controls (parental and Cas9-transduced) Jurkat clones, using paired end 75 bp reads on an Illumina NextSeq 500 instrument.	Co-expression
SRP186327	Transcriptomic analysis of iPSC and ESC challenged with atmospheric or physiological oxygen	Modulation of metabolism by 5% (physiological) oxygen during reprogramming has been shown to improve reprogramming efficiency, yet it is not known how it may affect the transcriptome and physiology of iPSC. RNA-seq analysis highlighted that iPSC derived under 20% oxygen displayed transcriptomic instability. Consequently, inappropriate modulation of metabolism by atmospheric oxygen during reprogramming significantly impacts the resultant iPSC transcriptional landscape. Overall design: RNA-Seq analysis of two iPSC lines, and one ESC line, each sub-cultured under 20% and 5% oxygen.	Co-expression
SRP186329	Human pluripotent stem cell-derived 2D neural tissue samples for predictive neurotoxicity screening	There is a growing need for fast and accurate methods for testing developmental neurotoxicity across industrial, pharmaceutical, and environmental chemical exposures. Current approaches, such as in vivo animal studies, and assays of animal and human primary cell cultures, suffer from challenges related to time, cost, and applicability to human physiology. Prior research demonstrated success employing machine learning to predict developmental neurotoxicity using gene expression data collected from complex human 3D tissue models exposed to various compounds, but the complexity of 3D tissue models require extensive expertise and effort to employ. While a 3D tissue model is more physiologically accurate, by focusing only on the goal of constructing an assay of developmental neurotoxicity, we propose that a simpler 2D tissue model may prove sufficient. We thus compared the accuracy of predictive models trained on data from a 2D tissue model with those trained on prior dataset from a more complex 3D tissue model, and found the accuracy of the 2D model to be substantially better than the 3D model. Furthermore, we found that the 2D tissue model is more robust and consistent under stringent gene set selection, whereas the 3D tissue model suffers substantial degradation of accuracy. While both approaches have advantages and disadvantages, we propose that our described 2D tissue model has the potential to serve as a valuable tool for decision makers when prioritizing neurotoxicity screening. Overall design: H1-NPC cells were thawed and expanded in DF3S+N2B27+5ng/ml FGF2 for 5 days before they were harvested by Accutase treatment. Roughly 1x10e5 cells were then seeded into one well of a 48 well plate in DF3S+N2B27. Chemical treatment started on the same day (day 0). Samples are collected at indicated time points by lysing cells directly on plate with 150ul RLT buffer. Chemical information can be found a separate sheet.	Co-expression
SRP186331	Cell cycle dynamics of human pluripotent stem cells primed for differentiation	Understanding the molecular properties of the cell cycle of human pluripotent stem cells (hPSCs) is critical for effectively promoting differentiation. Here, we use the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) system adapted into hPSCs and perform RNA-sequencing on cell cycle sorted hPSCs primed and unprimed for differentiation. Gene expression patterns of signaling factors and developmental regulators change in a cell cycle-specific manner in cells primed for differentiation without altering genes associated with pluripotency. Furthermore, we identify an important role for PI3K signaling in regulating the early transitory states of hPSCs towards differentiation. Overall design: H9 FUCCI hPSCs were cell-cycle sorted into the early G1, late G1, and SG2M phases. For each phase, cells were treated with 2% DMSO for a 24 hour time course. RNA-seq was performed on the DMSO-treated samples and corresponding controls (2 technical replicates for each cell-cycle phase x DMSO status combination).	Co-expression
SRP186375	Reducing the structure bias of RNA-Seq reveals a large number of non-annotated non-coding RNA	The study of RNA expression is the fastest growing area of genomic research. However, despite the dramatic increase in the number of sequenced transcriptomes, we still do not have accurate estimates of the number and expression levels of non-coding RNA genes. Non-coding transcripts are often overlooked due to incomplete genome annotation. In this study, we use annotation-independent detection of RNA reads generated using a reverse transcriptase with low structure bias to identify non-coding RNA. Transcripts between 20 and 500 nucleotides were filtered and crosschecked with non-coding RNA annotations revealing 115 non-annotated non-coding RNAs expressed in different cell lines and tissues. Inspecting the sequence and structural features of these transcripts indicated that 60% of these transcripts correspond to new tRNA and snoRNA genes. The identified genes exhibited features of their respective families in terms of structure, expression, conservation and response to depletion of interacting proteins. Together, our data reveal a new group of RNA that are difficult to detect using standard gene prediction and RNA sequencing techniques, suggesting that reliance on actual gene annotation and sequencing techniques distort the perceived architecture of the human transcriptome. Overall design: RNA was isolated from SKOV3ip1 human cell lines and various normal human tissues from which fragmented ribo-depleted TGIRT-Seq libraries were made. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.	Co-expression
SRP186383	Transcriptional trajectories of human kidney injury progression	RNAseq analysis on protocol biopsies obtained from 42 kidney transplant recipients at 4 time points after kidney transplantation. Overall design: Protocol biopsies obtained before reperfusion, after reperfusion, 3 months and 12 months after kidney transplantation.	Co-expression
SRP186406	A temporal proteogenomic atlas of HCV-host interactions unravels cell circuits driving viral and metabolic liver disease.	Background and aims: Hepatitis C virus (HCV) infection is a major cause of liver disease including steatosis, fibrosis and liver cancer. Viral cure cannot fully eliminate the risk of disease progression and hepatocellular carcinoma (HCC) in advanced liver disease. The mechanisms for establishment of infection, liver disease progression and hepatocarcinogenesis are only partially understood. To address these questions, we probed the functional proteogenomic architecture of HCV infection within a hepatocyte-model. Methods: Time-resolved HCV infection of hepatocyte-like cells was analyzed by RNA sequencing, proteomics, metabolomics, and leveraged by integrative genomic analyses. Using differential expression, gene set enrichment analyses, and protein-protein interaction mapping we identified pathways relevant for liver disease pathogenesis that we validated in livers of 216 cirrhotic patients with HCV. Results: We uncovered marked changes in the protein expression of gene sets involved in innate immunity, metabolism and hepatocarcinogenesis. In infected cells, HCV enhances glucose metabolism and creates a Warburg-like shift of the lactate flux. HCV infection impaired the formation of peroxisomes -organelles required for long-chain fatty acid oxidation- causing intracellular fatty acid accumulation, which is a hallmark of non-alcoholic fatty liver disease (NAFLD). Ex vivo studies confirmed perturbed peroxisomes and revealed an association of hepatic catalase expression with clinical outcomes and phenotypes in HCV-associated cirrhosis, NAFLD and HCC cohorts. Conclusion: Our integrative analyses uncover how HCV perturbs the hepatocyte cell circuits to drive chronic liver disease and hepatocarcinogenesis. This proteogenomic atlas of HCV infection provides a model for the discovery of novel drivers for viral- and non-viral induced liver disease. Overall design: mRNA profiles of either mock or HCV-infected Huh7.5.1dif cells, performed in triplicates and collected every day between days 0 and 10 post infection. HCV infection reached plateau at day 7 post infection (pi). After day 7 pi unspecific effects cannot be excluded.	Co-expression
SRP186416	RNA-sequencing of Wnt-dependent and Wnt-independent of Glioblastoma stem cell cultures	Four Wnt-dependent and four Wnt-independent GSC cultures were grown in stem cell media and RNA expression between the two subsets evaluated Overall design: Four biological replicates each of Wnt-dependent and Wnt-independent GSC cultures	Co-expression
SRP186433	The alternative splicing regulator Nova2 constrains vascular Erk signalling to limit specification of the lymphatic lineage	The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors, however the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signalling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signalling and Prox1 expression is dynamically controlled by Erk signalling. We identify a mechanism whereby Nova2 regulated splicing constrains Erk signalling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.	Co-expression
SRP186455	Disparate anticancer activity of structurally similar multi-kinase inhibitors through cumulative differential effects on individual targets	Despite recent improvements many cancer patients do not respond to immune or targeted drugs and require new therapies. Through a systems pharmacology approach including phenotypic screening, chemical and phosphoproteomics and RNA-Seq, we elucidated the mechanism of action underlying the differential anticancer activity of two structurally related multi-kinase inhibitors, foretinib and cabozantinib, in lung cancer cells. Biochemical and cellular target validation using probe molecules and RNA interference revealed a polypharmacology mechanism of foretinib involving MEK1/2, FER and AURKB, which were each more potently inhibited by foretinib than cabozantinib. Based on this, we rationally developed a synergistic combination of foretinib with barasertib, a more potent AURKB inhibitor, for MYC-amplified small cell lung cancer. This systems pharmacology approach showed that small structural changes of drugs can cumulatively through multiple targets result in pronounced anticancer activity differences and that detailed mechanistic understanding can lead to new repurposing opportunities for cancers with unmet medical need. Overall design: The H1155 cell line was profiled under three conditions: treated with DMSO (control), treated with 1um foretinib or treated with 1um cabozantinib. Each condition was profiled in triplicate.	Co-expression
SRP186516	Designing a single cell RNA sequencing benchmark dataset to compare protocols and analysis methods [5 Cell Lines Cel-seq]	Single cell RNA sequencing (scRNA-seq) technology has undergone rapid development in recent years and brings new challenges in data processing and analysis. This has led to an explosion of tailored analysis methods for scRNA-seq to address various biological questions. However, the current lack of gold-standard benchmarking datasets makes it difficult for researchers to evaluate the performance of the many methods available in a systematic manner. Here, we designed and generated a cross-platform benchmark dataset that has in-built truth in various forms and varying levels of biological noise. We used this dataset to compare different protocols and data analysis methods.  We found that different protocols have different data quality and ERCC spike-in works independently to endogenous RNA. We found significant differences in the results from the methods compared and we associated the results with data characteristics to identify methods that perform well in different situations. Our dataset and analysis provide a valuable resource for algorithm selection in different biological settings. Overall design: our experiment utilized the 5 human lung adenocarcinoma cell lines H2228, H1975, A549, H838 and HCC827. For the single cell designs, the five cell lines were mixed equally and processed by 10X chromium and CEL-seq2, referred to as sc_10X_5cl, and sc_CEL-seq2_5cl respectively in analysis that follows. For CEL-seq2, three plates were sorted and processed.	Co-expression
SRP186520	mTOR hyperactivation in Down Syndrome mediates deficits in autophagy induction, autophagosome formation, and mitophagy	Down syndrome (DS), a complex genetic disorder caused by chromosome 21 trisomy, is associated with mitochondrial dysfunction leading to the accumulation of damaged mitochondria. Here we report that mitophagy, a form of selective autophagy activated to clear damaged mitochondria is deficient in primary human fibroblasts derived from individuals with DS leading to accumulation of damaged mitochondria with consequent increases in oxidative stress.  We identified two molecular bases for this mitophagy deficiency: PINK1/PARKIN impairment and abnormal suppression of macroautophagy.  First, strongly downregulated PARKIN and the mitophagic adaptor protein SQSTM1/p62 delays PINK1 activation to impair mitophagy induction after mitochondrial depolarization by CCCP or antimycin A plus oligomycin. Secondly, mTOR is strongly hyper-activated, which globally suppresses macroautophagy induction and the transcriptional expression of proteins critical for autophagosome formation such as ATG7, ATG3 and FOXO1. Notably, inhibition of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) using AZD8055 (AZD) restores autophagy flux, PARKIN/PINK initiation of mitophagy, and the clearance of damaged mitochondria by mitophagy. These results recommend mTORC1-mTORC2 inhibition as a promising candidate therapeutic strategy for Down Syndrome. Overall design: mRNA-Seq profiling of 9 2N and 8 DS human fibroblasts samples of age 5 months (< 1 year) and 2 years. These samples come from 5 unrelated 2N individuals (of which 2 individuals, one each of 5 months and 2 years, have 3 replicates each) and 3 unrelated DS individuals (of which 2 individuals, one each of 5 months and 2 years, have 3 replicates each). Five samples were reanalyzed from GSE55504.	Co-expression
SRP186685	Transcriptomic profiling of head and neck squamous cell carcinoma cell lines	Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer world wide, and survival rates range from 40-80% depending on subsite.  As novel treatment strategies are investigated, comprehensively characterized cell lines representative of the diversity seen in patients will be crucial to correlating genetic and phenotypic features with therapeutic response.  The University of Michigan has generated a large panel of HNSCC cell lines that are utilized in laboratories worldwide.  Here, we provide transcriptome sequencing of 36 of these cell lines in addition to 5 HNSCC lines derived elsewhere to inform selection of model systems for future studies. Overall design: Analysis of 41 HNSCC cell lines by 75 nucleotide paired end sequencing to >100x depth on an Illumina HiSEQ4000.	Co-expression
SRP186787	Inferring dynamic regulatory programs in non-stationary expression time courses with applications to early human neural development	We generated RNA-seq data to measure transcriptional profiles of twenty hPSC-derived NSC populations, representing distinct regions of the developing human hindbrain and rostral cervical spinal cord. These cells are differentiated using a protocol that induces collinear activation of region-specific HOX genes during exposure to FGF8 and Wnt signaling (Lippmann et al, 2015 PMID:25843047). By transitioning to media containing retinoic acid after varying durations of Wnt signaling, NSCs are generated with unique rostrocaudal identities that uniformly express the neuroectodermal marker Pax6 and form N-cadherin+ rosette structures in vitro. Overall design: The data consist of RNA-seq measurements taken from hPSC-derived NSCs that were exposed to CHIR99021 for differents amount of time (2-72hr) prior to retinoic acid treatment. Each time point is represented in triplicate, with the exception of 48 hours, for which one replicate (48_B1) was filtered due to excessive zero-count genes.	Co-expression
SRP186789	Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells	A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA-E in tumor cells, which suppresses natural killer (NK) cell activity via ligation of the NK inhibitory receptor CD94/NKG2A. To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. Constructs containing a single-chain variable fragment derived from an anti-NKG2A antibody were linked to endoplasmic reticulum-retention domains. After retroviral transduction in human peripheral blood NK cells, these NKG2A Protein Expression Blockers (PEBLs) abrogated NKG2A expression. The resulting NKG2Anull NK cells had higher cytotoxicity against HLA-E-expressing tumor cells. Overall design: We examined the expression of NK cell receptor in NKG2A-prified NK cells after transduction with PEBL or green fluorescent protein by using RNA-seq.	Co-expression
SRP186796	Gene regulation by TLR2 and TLR10 in oncogene-induced senescence	In the present study, we analyse the effect of knocking down TLR2 and TLR10 during oncogene induced senescence in IMR90 cells expressing a inducible version of oncogenic RAS (ER:RAS) in the transcriptome using Ampliseq RNA sequencig. We observed that TLR2 and TLR10 regulate the expression of many pro-inflammatory cytokines and chemokines that constitute the senescence associated secretory phenotype. There is also significant regulation of genes of the acute phase response. Overall design: IMR90 expressing ER:RAS fusion protein induced to senescence with activated oncogenic RAS by addition of 4 hydroxy-tamoxifen (4OHT), were transfected with siRNA to knockdown of TLR2 and TLR10. Total mRNA was extracted and expression profiles were analysed.	Co-expression
SRP186820	Alternative polyadenylation dependent function of splicing factor SRSF3 contributes to cellular senescence	Down-regulated splicing factor SRSF3 is known to modulate cellular senescence via its alternative splicing dependent function in human cells. Here we discovered alternative polyadenylation (APA) dependent function of SRSF3 as a novel mechanism explaining SRSF3 downregulation induced cellular senescence. Knockdown of SRSF3 (SRSF3-KD) resulted in preference of proximal poly(A) (pA) sites and thus global shortening of 3' untranslated regions (3' UTRs) of mRNAs. SRSF3-KD also induced senescence-related phenotypes in both human and mouse cells. These 3' UTR shortened genes were enriched in senescence-associated pathways. Shortened 3' UTRs tended to produce more proteins than the longer ones. Simulating the effects of 3' UTR shortening by overexpression of three candidate genes (PTEN, PIAS1 and DNMT3A) all led to senescence-associated phenotypes. Mechanistically, SRSF3 has higher binding density near proximal pA site than distal one in 3' UTR shortened genes. Further, upregulation of PTEN by either ectopic overexpression or SRSF3-KD induction both led to reduced phosphorylation of AKT and ultimately senescence-associated phenotypes.	Co-expression
SRP186861	Fetal ovary expression profile	We sequenced RNA extracted from a 21-weeks gestation human ovary, at the time when dynamic developmental changes occur in human ovarian development and include primordial follicle formation. We examined genes comprised by copy number variants in fertile and POI women for their expression level in ovarian tissue. Overall design: analysis of genes expreesion in fetal ovaries	Co-expression
SRP186868	CANVAS RNAseq	RNA sequencing from fibroblasts, lymphoblastoid cell lines and brain (frontal cortex and vermis) from CANVAS cases	Co-expression
SRP186882	Corneal endothelium transcriptome profiling of patients with Fuchs endothelial corneal dystrophy	At present, there is no etiotropic treatment of Fuchs endothelial corneal dystrophy (FECD). Corneal transplantation is the only option for patients with advanced FECD. Recently the expansion of CTG18.1 trinucleotide repeat in TCF4 gene was associated with the development of FECD. However, the mechanism of disease pathogenesis has not been elucidated yet. Transcriptome profiling of corneal endothelium from patients with FECD may help identify the metabolic and signaling pathways involved in the pathological process and provide a basis for the development of specific non-surgical therapy. In this study, we used RNA-Seq to obtain the gene expression profile of corneal endothelium of 12 patients with FECD (8 with TCF4 expansion and 4 without it) and 6 control samples of donor corneal endothelium (without TCF4 expansion) obtained from the eye bank.	Co-expression
SRP186896	Single-cell RNA sequencing-based CRISPRi screening resolves molecular drivers of early human endoderm development [set 1]	Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. Yet, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human pluripotent stem cells (hPSCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of hPSCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR-perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFß signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic endoderm specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development. Overall design: CRISPRi screen of endodermal differentiation with a single-cell RNA readout. This submission contains the chromatin data.	Co-expression
SRP186903	Profiling the transcriptome of human thymic epithelial cell subsets	RNA-seq libraries were generated on thymic epithelial cell (TEC) subsets from thymic samples (11 days to 3 months of age). Cells were sorted to isolate cortical TEC (cTEC), MHC low medullary TEC (mTEClo) and MHC high medullary TEC (mTEChi). Between 7,575 and 50,000 cells were isolated for each sample. TEC were isolated using CD45 MACS depletion followed by the sorting protocol described in Stoeckler et al. J Vis Exp 2013 (PMID 24084687; doi: 10.3791/50951). The study has been granted ethical approval and is publicly listed (IRAS ID 156910, CPMS 19587). Overall design: 1 sample for each of cTEC, mTEClo and mTEChi were generated on a total of 3 individuals (~50,000 cells per sample) and 3 replicates for each of cTEC, mTEClo and mTEChi were generated on 1 individual (7,575 cells per sample)	Co-expression
SRP186906	Comparing two approaches of miR-34a target identification, biotinylated-miRNA pulldown vs miRNA overexpression	Here we show that biotin-labelled miR-34a can be loaded to AGO2, and AGO2 immunoprecipitation can pulldown biotinylated miR-34a (Bio-miR pulldown). RNA-sequencing (RNA-seq) of the Bio-miR pulldown RNAs efficiently identified miR-34a mRNA targets, which could be verified with luciferase assays. In contrast to the approach of Bio-miR pulldown, RNA-seq of miR-34a overexpression samples had limited value in identifying direct targets of miR-34a. It seems that pulldown of 30 -Biotin-tagged miRNA can identify bona fide microRNA targets at least for miR34a. Overall design: biotin-labelled miR-34a pulldown and RNA sequencing of miR-34a overexpression samples	Co-expression
SRP186927	AmpliSeq transcriptome profiling of human adipose tissue progenitor cell types	Three different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).	Co-expression
SRP187053	A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia	Inhibition of the Menin (encoded by MEN1) and MLL1 (KMT2A) protein-protein interaction has been proposed as a potential targeted therapeutic strategy for MLL-rearranged (MLL-r) leukemia. We sought to develop more potent and selective Menin-MLL1 interaction inhibitors that are effective in vitro and in vivo to directly assess potential therapeutic opportunities. Structure-based design yielded the potent, highly selective and orally-bioavailable small molecule inhibitor VTP-50469. Human cell lines carrying MLL-rearrangements were highly sensitive and selectively responsive to treatment with VTP-50469. VTP-50469 displaced Menin from high molecular weight protein complexes and inhibited chromatin occupancy of MLL1 at select target genes. Loss of MLL1 binding led to specific changes in gene expression, cellular differentiation, and apoptosis. Mice engrafted with leukemia cells isolated from patients with either MLL-r AML or MLL-r ALL showed dramatic reductions of leukemia burden and prolonged survival when treated with VTP-50469. Remarkably, multiple mice engrafted with MLL-r ALL remained disease free greater than 1 year following cessation of treatment. Therefore, inhibition of the Menin-MLL1 interaction with VTP-50469 is highly effective in patient-derived xenograft (PDX) models of human MLL-r AML and MLL-r ALL which supports rapid translation of this approach to clinical trials. This submission represents the scRNAseq component of the study. Overall design: Single cell sequencing of full-length transcripts (scRNA-seq) was used to investigate molecular profiles of ALL PDX cells in response to VTP-50469 treatments for 28 days.	Co-expression
SRP187054	Transcriptomic analysis of cultured isogenic myotonic dystrophy type 1 myoblasts with and without the DMPK CTG repeat	RNA-seq on proliferating myoblasts of the DM11 line carrying 13 and 2600 CTG repeats in the DMPK gene, compared to their genome-edited counterparts without both the 13 and 2600 CTG repeat or just lacking the 2600 CTG repeat. Overall design: DM1 patient-derived and immortalized myoblasts (DM11) were genome-edited using CRISPR-Cas9 to excise the CTG repeat from the DMPK gene, thereby creating isogenic healthy controls for the DM1 cell line. After the CRISPR procedure, cells were clonally expanded and genetically characterized. We performed RNAseq on polyA selected RNA of one myoblast clone of which exclusively the expanded CTG repeat was excised (1E6), three clones of which the CTG repeat of both alleles was excised (3E3, 3B11 and 4A3) and three clones of which the repeat was still present after this procedure (4F9, EA11 and EA7), along with the DM11 source cell line (DM11 parental). This procedure and initial characterisation is described in Van Agtmaal et al. (2017) Molecular Therapy vol. 25 issue 1 p24-43	Co-expression
SRP187064	Transcriptomic profile of human embryonic renal corpuscles	In order to characterize and benchmark the podocytes-like cells generated through human ES cell differentiation, we generated transcriptional profiles of renal corpuscles from embryonic human kidneys using RNA-Seq.  To compare, we also performed RNA-Seq of human immortalized podocyte cell lines before and after thermoswitch. Overall design: We performed RNA-Seq of poly-A selected RNA from hESC-derived kidney organoids, organoid-derived MAFB-eGFP+ podocytes at different time points, and human immortalized podocytes.	Co-expression
SRP187088	FLT3-N676K drives acute myeloid leukemia in a xenograft model of KMT2A-MLLT3 leukemogenesis	Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements. Herein, we show that co-expression of FLT3-N676K and KMT2A-MLLT3 in human CD34+ cord blood cells primarily cause acute myeloid leukemia (AML) and rarely acute lymphoblastic leukemia (ALL) in immunodeficient mice. By contrast, expression of KMT2A-MLLT3 alone cause ALL, double-positive leukemia (DPL, expressing both CD33 and CD19), or bilineal leukemia (BLL, comprised of distinct myeloid and lymphoid leukemia cells), and rarely AML. Further, AML could only be serially propagated with maintained immunophenotype in secondary recipients when cells co-expressed KMT2A-MLLT3 and FLT3-N676K. Consistent with the idea that activated signaling would allow myeloid cells to engraft and maintain their self-renewal capacity, in a secondary recipient, a de novo KRAS-G13D was identified in myeloid cells previously expressing only KMT2A-MLLT3. Gene expression profiling revealed that KMT2A-MLLT3 DPL had a highly similar gene expression profile to ALL, with both expressing key lymphoid transcription factors and ALL cell surface markers, in line with the DPL cells being ALL cells with aberrant expression of CD33. Taken together, our results highlight the need for constitutive active signaling mutations for driving myeloid leukemia in a human xenograft model of KMT2A-R acute leukemia. Overall design: mRNA sequencing of various immunophenotypic populations from KMT2A-MLLT3 xenograft leukemias with or without FLT3-N676K generated using Illumina NextSeq 500.	Co-expression
SRP187105	NCBI GEO Submission of human whole blood transcriptomes in response to a high-fat meal	Modern humans spend most of their time having eaten recently. The purpose of the current project is to understand how the blood, which contains immune cells, responds in the hours after eating a meal that is moderately high in fat. We used a sequencing method to observe the expression of all the genes in blood cells in five participants who were each fed a high fat meal on three separate days. The results are reported in the manuscript, “Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal." Overall design: We used a sequencing method to observe the expression of all the genes in blood cells in five participants who were each fed a high fat meal on three separate days, resulting in 45 whole blood transcriptomes. For each sample, 3 mL of venous whole blood was drawn into a Tempus Blood RNA tube, shaken vigorously, and then frozen at -80°C until use. Total RNA was purified with the Tempus Spin RNA Isolation Kit with minor modifications to the manufacturer's protocol. To remove residual genomic DNA, RNA samples were treated on-column with RNase-Free DNase per manufacturer's instructions. RNA quantity, quality, and integrity were assessed with NanoDrop 1000 and 2100 Bioanalyzer. All isolated RNA had A260/A280 ratios greater than 2 and RNA integrity numbers higher than 7.3. RNA-Seq libraries were constructed at the DNA Technologies and Expression Core at the University of California, Davis, using the Ovation Human Blood RNA-Seq Library System (NuGEN Technologies). Sequencing was performed in a 2x100bp format with 45 samples multiplexed on 3 lanes on an Illumina HiSeq 4000. Analysis of the data is reported in the manuscript, “Temporal changes in postprandial blood transcriptomes reveal subject-specific pattern of expression of innate immunity genes after a high-fat meal.”	Co-expression
SRP187181	RNA-seq experiment performed on activated human CD4+ T cells	Analysis perfomed on four paired samples with two treatments and paired untreated sample Overall design: We purified naïve CD45RA+CD4+ T cells from PBMCs collected from SLE patients. These cells were maintained for two days in culture medium supplementd with 20 IU of IL-2. Thereafter cells were harvetd and total RNA was purified using the kit from InVitroen. The sequencing was perfomed using Ion Torrent Kit. The RNA-seq was perfomed on Ion Torrent Sequncer.	Co-expression
SRP187300	Disruption of the exocyst induces podocyte loss and dysfunction	In this study we plan to compare the profiles of control sample (cultured podocytes) with the Exoc5 knock down in cutured podocytes to examine the differentially expressed genes. Overall design: We hope to identify the genes that are downregulated on knocking down Exoc5 in cultured human podocytes cells	Co-expression
SRP187496	Comprehensive Gene Expression Analysis in NMIBC	This study was designed to explore the molecular mechanism of bladder cancer through an RNA-seq	Co-expression
SRP187530	Transcriptional Profiling of CENPA-Depleted Prostate Cancer Cell Lines	Overexpression of centromeric proteins has been identified in a number of human malignancies, though their functional and mechanistic contributions to disease progression have not been characterized. CENPA, the centromeric histone H3 variant, is the epigenetic mark that determines centromere identity. Here, we demonstrate that CENPA is highly overexpressed in prostate cancer in both tissue and cell lines, and the level of CENPA expression correlates with the stage of disease. Gain-of- and loss-of-function experimentation confirms that CENPA promotes prostate cancer cell line growth. Integrated sequencing studies further reveal a previously unidentified function of CENPA as a transcriptional regulator that modulates expression of critical proliferation, cell-cycle, and centromere/kinetochore genes. Our findings, therefore, suggest a previously undescribed biological function for CENPA, a protein normally thought to be solely and importantly involved in centromere identity. Overall design: Examination of transcriptional profile of prostate cancer cells under CENPA-depleted condtions	Co-expression
SRP187565	Altered expression of signaling pathways regulating neuronal excitability in hippocampal tissue of temporal lobe epilepsy patients with low and high seizure frequency	Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean= 4 seizure/month) versus high (HSF, mean= 60 seizures/month) seizure frequency identified 979 genes with =2-fold change in transcript abundance (FDR-adjusted p-value <0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1,676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE. Overall design: Investigation of alterations in hippocampal gene expression in temporal lobe epilepsy	Co-expression
SRP187586	Lysosomal dysfunction in Down syndrome is APP-dependent and mediated by APP-ßCTF (C99)	Lysosomal failure underlies pathogenesis of numerous congenital neurodegenerative disorders and is an early and progressive feature of Alzheimer's disease (AD) pathogenesis. Here, we report that lysosomal dysfunction in Down Syndrome (Trisomy 21) requires the extra gene copy of amyloid precursor protein (APP) and is mediated by the beta cleaved carboxy terminal fragment of APP (APP-ßCTF, C99).  In primary fibroblasts from individuals with Down Syndrome (DS), lysosomal degradation of autophagic and endocytic substrates is selectively impaired causing them to accumulate in enlarged autolysosomes/lysosomes.  Direct measurements of lysosomal pH uncovered a significant elevation (0.6 units) associated with slowed LC3 turnover and the inactivation of cathepsin D (CTSD) and other lysosomal hydrolases known to be unstable or less active when lysosomal pH is persistently elevated.  RNA sequencing analysis excluded a transcriptional contribution to hydrolase declines.  Normalizing lysosome pH by delivering acidic nanoparticles to lysosomes ameliorated lysosomal deficits, implicating pH elevation as their primary basis.  Cortical neurons cultured from the Ts2 mouse model of DS exhibited lysosomal deficits similar to those in DS cells.  Lowering APP expression with siRNA or BACE1 inhibition reversed cathepsin deficits in both fibroblasts and neurons.  Deleting one BACE1 allele from adult Ts2 mice had similar rescue effects in vivo.  The modest elevation of endogenous APP-ßCTF needed to disrupt lysosomal function in DS is relevant to sporadic AD where APP-ßCTF, but not APP, is also elevated.  Our results extend evidence that impaired lysosomal acidification drives progressive lysosomal failure in multiple forms of AD. Overall design: (1) mRNA-Seq profiling of six Trisomic and six Disomic human fibroblasts samples (3 replicates from 2 individuals in each group) from 5 months (3 replicates) and 2 years (3 replicates) old unrelated inviduals treated with either siRNA against human APP (siAPP) or a negative control DsiRNA (siNC). (2) A separate Differential Gene Expression (DGE) analysis was also carried out to compare transcriptomic profile of human Disomic and Trisomic fibroblasts using Disomic samples treated with siNC (3 replicates each of 5 months and 2 years individuals; Total = 6) in conjunction with age matched untreated human Disomic fibroblasts samples already deposited by Letourneau et al. (GSM1338333, GSM1338336) and Sullivan et al. (GSM2105075, GSM2105077); and Trisomic samples treated with siNC (3 replicates each of 5 months and 2 years individuals; Total = 6) in conjunction with age matched untreated human Trisomic fibroblasts samples from Letourneau et al. (GSM1338325, GSM1338326, GSM1338327) and Sullivan et al. (GSM2105044, GSM2105047). The final count of samples for the Disomic and Trisomic group is 11 and 10 respectively.	Co-expression
SRP187597	Intrinsic Resistance to MEK Inhibition Through BET Protein Mediated Kinome	Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC.  Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.	Co-expression
SRP187599	mRNA sequencing of single-cell and 20-cell pools of CD103+CD8+ and CD103-CD8+ T lymphocytes sorted from human ovarian cancer	Cytotoxic T cells confer a prognostic benefit in many tumors, including ovarian cancer. We and others have previously identified a subset of CD8+ T cells, namely CD103+CD8+ T cells, that seems to have a better prognostic effect. The aim of this study is to identify how these CD103+ T cells differ from CD103-CD8+ T cells on mRNA level in human samples of ovarian cancer. Overall design: mRNA profiles of 10 pools of 20 cells CD103+CD8+, 10 pools of 20 cells CD103-CD8+, 20 single-cells CD103+CD8+, 20 single-cells CD103-CD8+ were generated from TILs of 3 ovarian cancers (high-grade serous ovarian cancer) by SMARTseq2	Co-expression
SRP187753	HDAC inhibition enhances the in vivo efficacy of MEK inhibitor therapy in uveal melanoma	Purpose: The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. The current study has used unbiased multi-omics and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance. Overall design: Examination of 92.1 uveal melanoma cell lines treates with two different single agent inhibitors and their combination compared to the vehicle control.	Co-expression
SRP187772	RNA sequencing to compare gene expession in control and PF228-treated hepatic stellate cells	Primary human hepatic stellate cells (HSCs) isolated from healthy donors were purchased from Sciencell.  They were preincubated with or without PF228 and stimulated with TGFbeta1 (5 ng/ml) for 24 hours.  Cells were collected for RNA isolation and RNA sequencing.  The goal of this study is to identify genes transcriptionally regulated by TGF-beta1 and FAK. There were 4 cell groups in the experiments:  DMSO, DMSO+TGFbeta1, PF228, PF228+TGFbeta1. Overall design: There were 4 cell groups in the experiments:  DMSO, DMSO+TGFbeta1, PF228, PF228+TGFbeta1, and each group had 3 repeats. So 12 RNA samples were sent to UMN genomic Center for RNA sequencing.  12 RNA samples were converted to Illumina sequencing libraries using Illumina's Truseq Stranded mRNA Sample Preparation Kit.  Truseq libraries were then subjected to cluster using Illumina cBot instrument and sequencing using HiSeq2500	Co-expression
SRP187955	Gene expression profile during senescence induced by LSG1 knockdown	In the present study, we analyze the effect of knocking down LSG1 and KRas(V12D) overexpression in MRC5 cells  in the transcriptome using Ampliseq RNA sequencig. We observed that shLSG1 induced a potent senescence response that is characterized by the activation of ER-Stress and cholesterol biosynthetic pathway Overall design: MRC5  were transfected with siRNA to knockdown the small GTPase LSG1. Total mRNA was extracted and expression profiles were analyzed.	Co-expression
SRP187984	Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing	Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n=14) and matched sedentary controls (n=11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing oxygen consumption (V?O2) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P=0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes. Overall design: RNAseq of whole blood samples from ME/CFS patients and controls following exercise.	Co-expression
SRP188079	Transcriptome analyses of trophoblast upon ALKBH5 knockdown	ALKBH5 play important role in regulation of trophoblast invasion, we examined the downstream genes of ALKBH5 via transcriptome sequencing Overall design: Transcriptome analyses of mRNAs from trophoblast cells upon ALKBH5 knockdown	Co-expression
SRP188088	Stage-specific regulation of the WNT/ß-catenin pathway enhances differentiation of hESCs into hepatocytes	Background & Aims Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize that the functionality of hPSC-derived hepatocytes might be improved by making the differentiation method more similar to normal in vivo hepatic development. Methods We tested combinations of growth factors and small molecules targeting candidate signaling pathways culled from the literature to identify optimal conditions for differentiation of hESCs to hepatocytes, using qRT-PCR for stage-specific markers to identify the best conditions. Immunocytochemistry was then used to validate the selected conditions. Finally, induction of expression of metabolic enzymes in terminally differentiated cells was used to assess the functionality of the hESC-derived hepatocytes. Results Optimal differentiation of hESCs was attained using a 5-stage protocol. After initial induction of definitive endoderm (stage 1), we showed that inhibition of the WNT/ß-catenin pathway during the 2nd and 3rd stages of differentiation was required to specify first posterior foregut, and then hepatic gut cells. In contrast, during the 4th stage of differentiation, we found that activation of the WNT/ß-catenin pathway allowed generation of proliferative bipotent hepatoblasts, which then were efficiently differentiated into hepatocytes in the 5th stage by dual inhibition of TGF-ß and NOTCH signaling. Conclusion Here, we show that stage-specific regulation of the WNT/ß-catenin pathway results in improved differentiation of hESCs to functional hepatocytes. Overall design: mRNA profiles of undifferentiated, definitive endoderm, stage 2-5 cell ines were generated by deep sequencing, in duplicate, as well as five liver samples.	Co-expression
SRP188099	Transcription profile analysis of wild type and Irf9-/- human monocytic THP1 cells in response to type I interferons	Host defense by the innate immune system requires the establishment of antimicrobial states allowing cells to cope with microorganisms before the onset of the adaptive immune response. Interferons (IFN) are of vital importance in the establishment of cell-autonomous antimicrobial immunity.   Speed is therefore an important attribute of the cellular response to IFN. With much of the antimicrobial response being installed de novo, this pertains foremost to gene expression, the rapid switch between resting-state and active-state transcription of host defense genes. Our results show how mRNA expression changes upon IFNb treatment in wild type and Irf9-/- THP1 cells. Overall design: Methods: mRNA of untreated and IFNb treated wild-type (WT) and Irf9 knock out (IRF9-/-) human monocytic THP1 cells were analyzed by deep sequencing, in triplicate, using Illumina sequencing.	Co-expression
SRP188141	Functional Enrichment and Analysis of Antigen-Specific Memory B Cell Antibody Repertoires in PBMCs, transcriptome data	Phenotypic screening of antigen-specific antibodies in human blood is a common diagnostic test for infectious agents and a correlate of protection after vaccination. In addition to long-lived antibody secreting plasma cells residing in the bone marrow, memory B cells are a latent source of antigen-experienced, long-term immunity that can be found at low frequencies in circulating PBMCs. Assessing the genotype, clonal frequency, quality, and function of antibodies resulting from an individual's persistent memory B cell repertoire can help inform the success or failure of immune protection. We have applied ELISPOT cell culture methods to functionally expand the memory repertoire from PBMCs and clonally map monoclonal antibodies from this population. We show that combining deep sequencing of stimulated memory B cell repertoires with retrieving single antigen-specific cells is a promising approach in evaluating the latent, functional B cell memory in PBMCs.	Co-expression
SRP188142	Single-Cell Transcriptome Analysis Of CD8+ T-cell Memory Inflation	We sought to define the nature of the transcriptional mechanisms underpinning memory inflation at different sites. We used single-cell RNA sequencing of M38-tetramer+-sorted cells from a single MCMV-infected mice, analyzing transcriptional networks in virus-specific populations in the spleen and gut intra-epithelial lymphocytes (IEL). Overall design: Illumina sequencing of single cells from murine M38 tetramer+ T cells from gut intraepithelium in comparison with murine M38 tetramer+ T cells from spleen.  Lymphocytes were extracted from the spleen and gut intraepithelium by mechanical and enzymatic digestion. CD8+ T-cells were enriched by negative selection using the Miltenyi Biotec GmbH CD8a+ T-cell isolation kit (Bergisch Gladbach, Germany) . After M38-tetramer and surface staining, tetramer+ CD3+ CD8+ single-cells were sorted in two 96-well plates using a SH800S cell sorter (Sony, Tokyo, Japan).  Sequencing libraries were prepared using the TruSeq dual-index sequencing primers (Illumina, San Diego, California) and paired-end sequencing was performed on the Illumina HiSeq4000 platform.	Co-expression
SRP188219	Differentially Expressed Genes for Atrial Fibrillation Identified using RNA Sequencing from Paired Human Left and Right Atrial Appendages.	Next Generation RNA Sequencing was carried out  on human paired left and right atrial appendages from patients with and without Atrial Fibrillation. EdgeR software was used to show a total of 247 genes were found to have significant differential expression between left and right atria. Overall design: Left and Right atrial appendages from 5 patients in Sinus Rhythm and 5 patients in atrial fibrillation were subjected to RNA sequencing and differential gene expression using EdgeR.	Co-expression
SRP188222	Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders	Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate. culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small-intestinal microbial diversity and small-intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment. Overall design: A host duodenal RNA sequencing study in conjuction with a microbial analysis of small bowel aspirates following dietary intervention to reduce fiber intake for 1 week.   Aspirates were collected during research endoscopy and submtttied for for 16S microbial identification (european	Co-expression
SRP188242	RNA-seq analyses of human prostate cancer cells	To study the transcriptome of human prostate cancer cells, RNA-seq experiments were performed. Overall design: RNA was harvested after 72h of steroid deprivation to study the basal transcriptome of LNCaP and 22rv1 cells, two human AR-positive prostate cancer cell lines,	Co-expression
SRP188245	CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq) (HEK293T MCF7)	The CDKN2A/B locus at 9p21.3 contains crucial tumor suppressors (P16, P14, and P15) and oncogenic lncRNA ANRIL genes. This locus is most frequently inactivated in cancer genomes by deletion and DNA methylation. However, the mechanisms coordinately regulating their expression level are far from clear. In the present study, a novel lncRNA, P14AS, was characterized in the antisense strand of the fragment near CDKN2A in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq). Overall design: RNAs were characterized in the antisense strand of the fragment near CDKN2A in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq).	Co-expression
SRP188296	IHEC_RNA-seq	RNA-seq involves purification of RNA, followed by either selection of poly-A(+) RNA or depletion of ribosomal RNA. RNA is then converted into cDNA by one of two methods; 1) random priming, followed by cDNA fragmentation, end-repair and Illumina/SOLiD linker ligation or, 2) Enzymatic or chemical RNA fragmentation followed by linker ligation and cDNA generation. Following PCR amplification of tailed cDNA fragments with primers suitable for solid phase (Illumina) or emPCR (SOLiD) clonal amplification RNA-seq libraries are subjected to sequencing. Sequence alignment software is then used to compare the short sequence reads to reference genome and transcriptome databases, and exon-exon junction databases. From this analysis paradigm emerges data that is used for a variety of purposes, including the measurement of gene- level and exon-level expression abundance; detection of base changes (mutations and polymorphisms) relative to reference datasets; measurement of alternative splicing events; identification of gene fusion events; and identification of RNA editing events.	Co-expression
SRP188300	Single cell RNAseq of human TCRVdelta 1 and TCRVdelta 2 gammadelta T lymphocytes purified from healthy adults blood	?d T lymphocytes represent ~1% of human PBMC and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current scRNA-Seq studies do not identify ?d T lymphocytes since their transcriptomes at the single cell level are unknown. Here we show that high resolution clustering of large scRNA-Seq data sets and a combination of gene signatures allow the specific detection of human ?d T lymphocytes and identification of their TCRVd1 and TCRVd2 subsets in large data sets from complex cell mixtures. In t-SNE plots from blood and tumor samples, the few ?d T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVd1 and TCRVd2 subsets form close yet distinct sub-clusters respectively neighbouring NK and CD8 T cells owing to expression of shared and distinct cytotoxic maturation genes. Similar pseudo-time maturation trajectories of TCRVd1 and TCRVd2 ?d T lymphocytes were discovered, unveiling in both subsets an unattended pool of TEMRA cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single cell transcriptomes of thousands of individual gd T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping and deep characterization of human ?d T lymphocytes in further scRNA-Seq studies of complex tissues in physiological and disease conditions. Overall design: 6 samples of purified human gd T cells from 3 donors (CMV+ and CMV-). Cell-sorted TCRVdelta1 and TCRVdelta2 T lymphocytes from each donor PBMC.	Co-expression
SRP188301	Whole blood RNAseq following live attenuated influenza vaccine in Gambian children	The goal of this study was to identify differentially expressed genes between pre-vaccination and day 2 post-vaccination with LAIV in children aged 2 - 4 years old who seroconvert to LAIV. Seroconversion was defined as a 4-fold rise in haemagglutination inhibition titre between baseline and day 21 following vaccination. Overall design: Open label cohort study	Co-expression
SRP188357	RNA-seq of RKO cells with cTAZ KO or putback	RKO cells with cTAZ KO or putback were subjected to RNA isolation and RNA-seq analyses were generated by deep sequencing using Illumina Hiseq. Overall design: RNA-seq analyses of RKO cells with cTAZ KO or putback by deep sequencing using Illumina Hiseq.	Co-expression
SRP188416	Transcriptome analysis of cultured human alveolar epithelial type 2 cells	We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector. Overall design: Cultured human alveolar epithelial type II cells were transfected with retroviral vector containing mutant surfactant protein C or control retroviral vector. The retroviral vector contained LNGFR as a marker. After gene transduction, transduced cells were purified by magnetic-activated cell sorting. The transcriptome of the cells was generated by 5'Tag-seq using Ion Genestudio S5 Sequencer.	Co-expression
SRP188447	Highly-motile versus unsorted MDA-MB-231 breast cancer cells	The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of the aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferation of migratory cells in breast-cancer specimens, for the assessment of their metastatic propensity and for the rapid screening of potential antimetastatic therapeutics. On the basis of the key roles of cell motility and proliferation in cancer metastasis, the device accurately predicts the metastatic potential of breast-cancer cell lines and of patient-derived xenografts. Compared to unsorted cancer cells, highly motile cells isolated by the device exhibited similar tumourigenic potential but markedly increased metastatic propensity in vivo. RNA sequencing of the highly motile cells revealed an enrichment of motility-related and survival-related genes. The approach might be developed into a companion assay for the prediction of metastasis in patients and for the selection of effective therapeutic regimens. Overall design: RNA was isolated from samples of 1000 migratory or unsorted cells in triplicate	Co-expression
SRP188498	Inhibition of DOT1L and PRMT5 promote synergistic anti-tumor activity in a human MLL leukemia model induced by CRISPR/Cas9	Previous studies have identified frequent MLL-AF4 chromosomal translocation breakpoints in patients. Using CRISPRscan, we designed different sgRNAs recognizing patient-specific sequences in intron 11 of the MLL and exon 3 of the AF4 genes, respectively. Using plasmid- and virus-free delivery of sgRNAs with Cas9 protein, we nucleofected CD34+ target cells derived from human umbilical cord blood. Following nucleofection, the cells were maintained in liquid culture supplemented with cytokines and chemokines optimized for growth of MLLr cells. On day 30 (MLL-AF4)  of liquid culture,  MLL translocations were detcted in 100% of cells by FISH analysis allowing for further analysis of pure MLLr cells. MLL-AF4 translocated cells and the respective control cells from the two different donors were maintained in similar culture conditions. After reaching 100% purity of the MLLr cells, they were subjected to RNA-seq. Overall design: huCB CD34+ cells were engineered to bear endogenous MLL-AF4 translocations. RNA sequencing was performed using TruSeq mRNA Stranded Sequencing (Illumina) of two donors comparing engineered and non-treated cells, respectively.	Co-expression
SRP188516	Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination	The SWI/SNF complex is a critical regulator of pluripotency in human embryonic stem cells (hESCs), and individual subunits have varied and specific roles during development and in diseases. The core subunit SMARCB1 is required for early embryonic survival, and mutations can give rise to atypical teratoid/rhabdoid tumors (AT/RTs) in the pediatric central nervous system. We report that in contrast to other studied systems, SMARCB1 KD relieves bivalent gene repression in hESCs and promotes chromatin accessibility at super-enhancers. Moreover, and consistent with its established role as a CNS tumor suppressor, we find that SMARCB1 is essential for neural induction but dispensable for mesodermal or endodermal differentiation. Mechanistically, we demonstrate that SMARCB1 KD cells are robustly resistant to hESC super-enhancer silencing in neural differentiation conditions. This genomic assessment of hESC chromatin regulation by SMARCB1 reveals a novel positive regulatory function at super-enhancers and a unique lineage-specific role in regulating hESC differentiation. Overall design: Examination of effects of SMARCB1 KD on transcription and accessibility in hESCs and differentiating neural stem cells	Co-expression
SRP188526	Small non-coding RNA profiling in human biofluids from healthy individuals	The role of non-coding RNAs in different biological processes and diseases is continuously expanding. Next-generation sequencing together with the parallel improvement of bioinformatics analyses allows the accurate detection and quantification of an increasing number of RNA species. With the aim of exploring new potential biomarkers for disease classification, a clear overview of the expression levels of common/unique small RNA species among different biospecimens is necessary. However, except for miRNAs in plasma, there are no substantial indications about the pattern of expression of various small RNAs in multiple specimens among healthy humans. Overall, the data reported hereby provide an insight of the constitution of the human miRNome and other small non-coding RNAs in various specimens of healthy individuals. This dataset was submitted by the Extracellular RNA Atlas (http://exrna-atlas.org/exat/datasets/EXR-ANACC1S6lJ1C-AN), and the selected raw and processed data for this dataset corresponds to what is available in that resource. Submitter indicates: "The publication associated with the citation below refers to a slightly larger set of samples (includes cervical scrape samples) and contains an alternative analysis to the processed data files provided here." Overall design: Small RNA-Seq data of RNA extracted from exosomes from 123 plasma samples of healthy donors derived from three different studies. Additionally, sequencing was performed on RNA from 39 faecal samples and 47 urine samples.	Co-expression
SRP188555	Transcriptome data of temporal and cingulate cortex in the Rett syndrome brain	Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation in the methyl-CpG-binding protein 2 gene in the majority of cases. We describe an RNA sequencing dataset of postmortem brain tissue samples from four females clinically diagnosed with Rett syndrome and four age-matched female donors. The dataset contains transcriptomes from two brain regions, temporal and cingulate cortex, for each individual, providing a valuable resource to explore the biology of the human brain in Rett syndrome. Overall design: Transcriptional profiles for postmortem temporal and cingulate cortex from four females with Rett syndrome and four age-matched controls.	Co-expression
SRP188564	CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy	CD8+ T cells activated by cancer immunotherapy execute tumor clearance mainly by inducing cell death through perforin-granzyme- and Fas/Fas ligand-pathways. Ferroptosis is a form of cell death that differs from apoptosis and results from iron-dependent lipid peroxide accumulation. Although it was mechanistically illuminated in vitro, emerging evidence has shown that ferroptosis may be implicated in a variety of pathological scenarios. However, the involvement of ferroptosis in T cell immunity and cancer immunotherapy is unknown. Here, we find that immunotherapy-activated CD8+ T cells enhance ferroptosis-specific lipid peroxidation in tumor cells, and in turn, increased ferroptosis contributes to the anti-tumor efficacy of immunotherapy. Mechanistically, IFNg released from CD8+ T cells downregulates expression of SLC3A2 and SLC7A11, two subunits of glutamate-cystine antiporter system xc-, restrains tumor cell cystine uptake, and as a consequence, promotes tumor cell lipid peroxidation and ferroptosis. In preclinical models, depletion of cyst(e)ine by cyst(e)inase in combination with checkpoint blockade synergistically enhances T cell-mediated anti-tumor immunity and induces tumor cell ferroptosis. Thus, T cell-promoted tumor ferroptosis is a novel anti-tumor mechanism. Targeting tumor ferroptosis pathway constitutes a therapeutic approach in combination with checkpoint blockade. Overall design: Human HT-1080 mRNA profiles treated by IFNg for 8 hours was determined by RNA-Seq.	Co-expression
SRP188627	Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues	The goal of this study is to compare gene expression profiles in quiescent RPE1 hTert cells treated with microtubule-stabilizing (paclitaxel) and microtubule-destabilizing poisons (combretastatin A4) Overall design: RPE 1 hTert cells were grown to full confluency, and maintained as such for 5 days to induce quiescence. Quiescent cells were treated with microtubule poisons combretastatin A4 and paclitaxel for 6 or 24 hours. Total RNA was collected and purified using the PureLink RNA Mini Kit (Invitrogen, Thermo Fisher Scientific, USA). RNA concentration and quality were determined using NanoDrop and Bioanalyzer respectively, and 500 ng of purified RNA was used as input for the Illumina TruSeq Stranded mRNA Library Prep Kit (Illumina, USA). Barcoded libraries were pooled and quantitated using KAPA, and single-end sequenced on an Illumina NextSeq (Illumina, USA). RNA-seq reads were mapped using STAR (version 2.1.0j) and processed using HTSeq-count (version 0.6.1). GRCh38 reference genome and transcript annotations were used for gene mapping; Entrez Gene identifiers and org.Hs.eg.db database were used for genome wide annotation. Differential gene expression and statistical analysis were performed using edgeR package. Genes with >50 reads per million and a fold change significantly different from zero in Wilcoxon signed-rank test (p< 0.05), were marked as differentially expressed genes, based on three biological replicates.	Co-expression
SRP188713	HNF1A deficiency impairs ß-cell fate, granule maturation and function	Mutations in HNF1A cause Maturity Onset Diabetes of the Young type 3, the second most frequent form of diabetes caused by single gene mutation. We generated human pancreatic stem cell-derived endocrine cells with mutations in HNF1A and show that HNF1A deficiency impairs scß-cell fate, insulin granule maturation and the secretion of insulin in a glucose responsive manner. Single-cell RNA sequencing reveals that HNF1A orchestrates a network of genes involved in glucose metabolism, zinc transport, calcium ion binding and hormone exocytosis. Furthermore, in both patients and stem cell-derived ß-cells, HNF1A deficiency altered the stoichiometry of secreted c-peptide to insulin. Sulfonylurea, used in the treatment of these patients, restored both insulin secretion and stoichiometry. Significantly, uncoupling of c-peptide and insulin secretion as described here questions the common practice in using c-peptide as a proxy to evaluate ß-cell function. We also demonstrate that correction of the HNF1A locus restores function, providing a path to cell therapy. Overall design: Human embryonic stem cells with different HNF1A genotypes (WT, KO1, KO2, R200Q homozygous) were differentiated into islet-like clusters of endocrine cells for 27-28 days in vitro. First set of 6 samples, clusters of islet-like cells were dissociated into single cells and analyzed by single cell RNA sequencing. There are two WT, two KO and two R200Q samples. Second set of 5 samples, clusters of islet-like cells were dissociated into single cells and insulin producing cells were purified by FACS sorting for INS-GFP. Cells were analyzed by bulk RNA sequencing. There are three WT and two KO.	Co-expression
SRP188837	Azithromycin induces epidermal differentiation and   multivesicular bodies in airway epithelia	Azm affects the integrity of the bronchial epithelial barrier. To better understand these unexpected effects of Azm on bronchial epithelium we have now investigated global changes in gene expression in VA10 cells Overall design: VA10 cells were cultivated in air-liquid interphase (ALI) conditions for 22 days with and without Azm. RNA was isolated at days 4, 10 and 22 and run through high-throughput RNA sequencing.	Co-expression
SRP188861	impact of TIFIA and UBF depletion on genome wide responses to dsDNA	Cells were transfected with control, TIF-IA, or UBF siRNAs prior to transfection of no DNA or dsDNA. The impact of TIF-IA depletion on gene expression and the impact of TIF-IA and UBF depletion on dsDNA-induced gene expression were assayed.	Co-expression
SRP188921	Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells	Analysis of PIWIL1 function in COLO205 [ATCC® CCL-222] colon adenocarcinoma cancer cell culture model. Overall design: Total Small RNAs and small RNAs co-immunoprecipitated with PIWIL1 from COLO205 cells were analyzed for piRNA signatures. Total RNA sequencing from PIWIL1 short hairpin knock-downs and CRISPR-generated knockouts were used for differential gene and transposon expression.	Co-expression
SRP188942	Global gene expression of SLC35F2 Knock-out (KO) H9 with control hESCs	Analysis of SLC35F2 KO hESCs compared with control hESCs. In order to investigate whether SLC35F2 KO affect pluripotency in hESCs, we performed RNA-Seq with SLC35F2 KO and control H9 cells. After establishing SLC35F2 KO hESCs, total RNA was extracted from each cell lines and RNA-Seq was performed after Quality control. Overall design: Total RNA obtained from hESCs of SLC35F2 KO and control H9 cells	Co-expression
SRP188959	Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation (RNA-seq data set)	Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To further characterize the genetic composition of NPM1 mutated (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes (FLT3, DNMT3A, IDH1, IDH2, NRAS) in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n=11). To gain further insight into these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut loss patients (pts) feature distinct mutational patterns that shared almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways including loss of characteristic NPM1mut associated gene expression patterns. In contrast, profiles of pts with persistent NPM1mut at relapse are reflected by a high overlap of mutations between diagnosis and relapse. Thus, our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of “relapse" in a subgroup of cases. Overall design: RNA-Seq was performed on paired (diagnosis and relapse) samples of NPM1mut loss and NPM1mut persistent patients using an Illumina HiSeq2000.	Co-expression
SRP188982	Prediction of bacterial infection outcome using single cell RNA-seq analysis of human immune cells [sorted population Bulk RNA-seq]	During host-pathogen encounters, the complex interactions between different immune cell-types can determine the outcome of infection. Advances in single cell RNA-seq (scRNA-seq) allow to probe this complexity of immunity, and afforded the basis for deconvolution algorithms that infer cell-type compositions from bulk RNA-seq measurements. However, immune activation, an important aspect of immune surveillance, is not represented in current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we developed a novel deconvolution algorithm to infer dynamic immune states from bulk measurements. We applied our dynamic deconvolution algorithm both to cohorts of healthy individuals challenged ex vivo with Salmonella and to cohorts of tuberculosis patients during different stages of disease. We revealed cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and can be applied to comprehensively study human infection outcome. Overall design: PBMCs were isolated from a healthy individual and were infected ex vivo with Salmonella enterica serovar Typhimurium or with PBS as control. Monocytes and NKT cells were sorted from naïve and infected PBMCs. RNA was extracted 4 hours post infection.	Co-expression
SRP188983	Prediction of bacterial infection outcome using single cell RNA-seq analysis of human immune cells [WB/PBMCs bulk RNA-seq]	During host-pathogen encounters, the complex interactions between different immune cell-types can determine the outcome of infection. Advances in single cell RNA-seq (scRNA-seq) allow to probe this complexity of immunity, and afforded the basis for deconvolution algorithms that infer cell-type compositions from bulk RNA-seq measurements. However, immune activation, an important aspect of immune surveillance, is not represented in current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we developed a novel deconvolution algorithm to infer dynamic immune states from bulk measurements. We applied our dynamic deconvolution algorithm both to cohorts of healthy individuals challenged ex vivo with Salmonella and to cohorts of tuberculosis patients during different stages of disease. We revealed cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and can be applied to comprehensively study human infection outcome. Overall design: Whole-blood (WB) cells and PBMCs were isolated from 4 healthy individuals and were infected ex vivo with Salmonella enterica serovar Typhimurium or with PBS as control. RNA was extracted 4 hours later.	Co-expression
SRP188994	TNF-induced Inflammatory Genes Escape Repression in Fibroblast-like Synoviocytes: Transcriptomic and Epigenomic Analysis [RNA-seq]	Investigated genome-wide changes in gene-expression and chromatin remodeling induced by tumour necrosis factor (TNF) in fibroblast-like synovioctyes (FLS) and macrophages to understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA). Overall design: Analysis of transcriptional changes in human RA fibroblast-like synoviocytes (FLS) and macrophages stimulated with or without TNF and I-BET	Co-expression
SRP188999	TM3'seq	Tagmentation-mediated 3'-enriched RNAseq library preparation protocol	Co-expression
SRP189080	Total RNA-Seq data from leukemic patients with complex structural variants	Structural variants can lead to an alteration of gene expression which may be associated with disease worsening. In our study we attempted to describe expression changes associated with the presence of extensive genomic rearrangements in chronic lymphocytic leukemia. Overall design: Peripheral blood samples from leukemic patients were used for RNA extraction. Gene expression profiles were correlated to chromosomal abnormalities identified in the cohort.	Co-expression
SRP189099	Effects on gene expression of ibrutinib treatment in human stem cells-derived atrial- and ventricular-like cardiomyocytes	To gain further insight into the mechanisms underlying the different response of atrial- and ventricular-like cardiomyocytes to ibrutinib, we performed RNA-seq in ibrutinib- or vehicle-treated atrial and ventricular cardiomyocytes and investigate the differential expression genes as well as enriched molecular pathways. Overall design: hESC-derived atrial- and ventricular-like cardiomyocytes were treated with 1uM ibrutinib in experiment group and vehicle (DMSO) in control group in 12-well plates for 24 hours with 3 replicates in each condition.	Co-expression
SRP189165	Modeling and characterization of the dynamic gene regulatory networks underlying cancer drug resistance based on time-course RNA-seq data	Drug resistance is a major cause for the failure of cancer chemotherapy or targeted therapy. However, the molecular regulatory mechanisms controlling the dynamic evolvement of drug resistance remain poorly understood. Thus, it is important to develop methods for unraveling gene regulatory mechanisms underlying the resistance to specific drugs. We used glioma differentiation therapy as a realistic case and time-course RNA-seq to investigate the temporal gene expression changes in sensitive and resistant cells. A computational method was developed to model and characterize the dynamic gene regulatory networks underlying cancer drug resistance based on time-course RNA-seq data. Overall design: DBTRG-05MG/U87/LN18 tumor cells were treated with 1 mol/L dbcAMP for 3 days,respectively.And we used RNA-seq to detail the drug resistance network based on time-course RNA-seq data.	Co-expression
SRP189194	BET bromodomain inhibitor iBET151 impedes human ILC2 activation and prevents experimental allergic lung inflammation	Group 2 innate lymphoid cells (ILC2) increase in frequency in eczema and allergic asthma patients, and thus represent a new therapeutic target cell for type-2 immune-mediated disease. The bromodomain and extra-terminal (BET) protein family of epigenetic regulators are known to support the expression of cell cycle and pro-inflammatory genes during type-1 inflammation, but have not been evaluated in type-2 immune responses.  We isolated human ILC2 and examined the capacity of the BET protein inhibitor, iBET151, to modulate human ILC2 activation following IL-33 stimulation. iBET151 profoundly blocked expression of genes critical for type-2 immunity, including type-2 cytokines, cell surface receptors and transcriptional regulators of ILC2 differentiation and activation.  Furthermore, in vivo administration of iBET151 during experimental mouse models of allergic lung inflammation potently inhibited lung inflammation and airways resistance in response to cytokine or allergen exposure.  Thus, iBET151 effectively prevents human ILC2 activation and dampens type-2 immune responses. Overall design: Lymphocytes were enriched from 150 ml human peripheral blood using lymphoprep (Axis-Shield) according to the manufacturer's instructions. The collected PBMC fraction was washed with PBS/2% FCS followed by red blood cell lysis with ACK solution for 5 min at room temperature. To pre-enrich ILCs, cells were stained with biotinylated anti-CD3, CD14 and B220 in the presence of TruStain FcX (anti-CD16/CD32) followed by depletion with M280 streptavidin beads (Invitrogen). Subsequently, the enriched fraction was stained with CD45-AF488, CD127-PE-Cy7, CD117-PE, CRTH2-BV421, a lineage cocktail (APC-streptavidin, CD8a, CD11b, CD11c, FceRIa, CD123, CD20, CD56, CD71) and Draq7-viability dye, followed by sorting of ILCs as indicated on an Influx FACS. ILC2s designated as Draq7–(live cells)CD45+Lin–(streptavidin-APC, CD8a, CD11b, CD11c, FceRIa, CD123, CD20, CD56, CD71)CD127+CRTH2+ cells, were purified by flow cytometry from the peripheral blood of 3 individual donors and cultured separately. Purified human ILC2s were grown in media containing IL-2 and IL-7 (both at 10 ng/ml) with IL-33 (10 ng/ml) added to the cultures every alternate week.  ILC2s were then rested for 3 days in IL-2 and IL-7-containing media (no IL-33) before being divided and added to the following culture conditions: IL-2/IL-7, +/-IL33 (all at 10 ng/ml), +/- 125 nM iBET151 for 24 hours. Cells were pelleted and RNA prepared for RNAseq analysis.	Co-expression
SRP189204	Alterations of the MEK/ERK, BMP, and Wnt/b-catenin pathways detected in the blood of individuals with lymphatic malformations	Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects	Co-expression
SRP189239	RNA Sequencing Of Intestinal Mucosa in Celiac patients	RNA sequencing of duodenal biopsies in patients with active Celiac Disease(CD), CD in remission, and non-CD controls.	Co-expression
SRP189243	RNA sequencing data of human prostate cancer cells treated with androgen	To analyse and understand the differentially expressed genes following treatment with synthetic androgen (R1881) Overall design: LNCaP or LAPC4 cells were plated in RPMI 1640 media with no phenol red and with 5% charcoal stripped serum, sodium pyruvate, penicillin and streptomycin. After 48h (to allow adnrogen deprivation), fresh media was added, with 96% ethanol or the synthetic androgen R1881 (10nM concentration). 24h later, cells were harvested for RNA purification using the QIAGEN RNeasy plus purification kit. RNA was then enriched for mRNA and then sequenced.	Co-expression
SRP189259	Transcriptome of circANKRD12 knockdown cancer cells and control	Molecular phenotyping of circularANKRD12 RNA in breast, ovarian, lung cancer cell lines. RNAseq analysis was performed on circANKRD12 silenced MDA-MB-231, SKOV3, OVCAR3, NCI-H226 cell lines. The data provide functional and molecular characterization of circANKRD12 in the human cancer cell.	Co-expression
SRP189335	Chemotherapeutic drugs inhibiting Topoisomerase 1 activity inhibit TNF-induced inflammatory gene expression	Inhibitors of DNA topoisomerase I (TOP1), an enzyme relieving torsional stress of DNA by generating transient single-strand breaks, are clinically used to treat ovarian cancer, small cell lung cancer and cervical cancer. As torsional stress is generated by replication and transcription we tested the effects of clinically used TOP1 inhibitors Topotecan and SN-38 on TNF-induced gene expression. RNA-seq experiments showed that inhibition of TOP1 activity interfered with the vast majority of TNF-triggered genes, while interference with TOP2 activity had only a minor impact. TOP1 inhibition affected the expression of early and late induced genes and the relative strength of gene induction played no role in the sensitivity to TOP1 interfering drugs. These data raise the possibility that the inhibition of inflammatory gene expression contributes to the increased risk of infection seen in some patients treated with TOP1 inhibtors. Overall design: The effect of the various toposomerase I inhibitors on inflammatory NF-kB target genes were examined using qPCR and RNA-Seq	Co-expression
SRP189418	Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioural and myelin alterations rescuable by a remyelinating drug [human]	Williams syndrome (WS), caused by a heterozygous microdeletion in 7q11.23, is a neurodevelopmental disorder characterized by hypersociability and neurocognitive abnormalities. Of the deleted genes, general transcription factor II-i (Gtf2i) has been linked to hypersociability in WS, though the underlying mechanisms are poorly understood. We show that selective deletion of Gtf2i in forebrain excitatory neurons caused neuroanatomical defects, fine motor deficits, increased sociability and anxiety. Unexpectedly, 70% of the genes with significantly decreased mRNA levels in the mutant mouse cortex are involved in myelination, and mutant mice had reduced mature oligodendrocyte cell numbers, reduced myelin thickness and impaired axonal conductivity. Restoring myelination properties with clemastine or increasing axonal conductivity rescued the behavioural deficits. Frontal cortex from WS patients similarly showed reduced myelin thickness, mature oligodendrocyte cell numbers and mRNA levels of myelination-related genes. Our study provides molecular and cellular evidence for myelination deficits in WS linked to neuronal deletion of Gtf2i. Overall design: Frontal cortex (BA9) human tissue samples.	Co-expression
SRP189490	RNA sequencing of human macrophages treated with iron chelator deferiprone (DEF), with and without lipopolysaccharide (LPS)	In order to identify transcript changes in response to DEF , we used human macrophages with or without DEF treatment.  In order to study the effect of iron chelation on LPS-polarized macrophage transcriptome, we exposed DEF-treated or control macrophages to short time exposure to LPS. We then performed whole-genome transcriptome sequencing by RNA-sequencing  (RNA-seq). Overall design: Macrophages from 3 healthy donors were either treated with DEF (500 µM - designated as DEF) or left unstimulated (CONTROL). LPS treatment (100 ng/ml, 3 hours) was performed in cells with DEF (designated as LPS+DEF) or without  (LPS). RNA-seq was performed on Illumina Hiseq 2500	Co-expression
SRP189576	Proteomics identifies a marker signature of MAPKi resistance in melanoma	Combined proteomic and RNAseq analysis on 6 melanoma cell cultures reveals a signature for resistance to MAPKi resistance. Overall design: 2 sensitive and 4 resistant melanoma cell cultures were RNAseqed	Co-expression
SRP189607	IL-11 neutralising therapies for the treatment of nonalcoholic steatohepatitis	Background and aims: Here we investigate the role of IL-11 signalling in the pathogenesis of nonalcoholic steatohepatitis (NASH). Methods: HSCs or hepatocytes were stimulated with IL-11 and effects assessed using cellular and high content imaging, immunoblotting, ELISA and invasion assays. Genetic and pharmacological IL-11 gain- or loss-of-function experiments were performed in vitro and in vivo. IL-11 signaling was studied using ERK inhibitors. The effects of anti-IL-11 or anti-IL11RA therapy were assessed in three preclinical NASH models using methionine/choline deficient diets or a Western diet with liquid fructose. Phenotyping was performed using hydroxyproline assay, qPCR, RNA-seq, Western blotting, histology, CyTOF, lipid and metabolic biomarkers. Results: When stimulated with NASH factors HSCs secrete IL-11, which drives an autocrine, ERK-dependent signaling loop required for the HSC-to-myofibroblast transformation. IL-11 is upregulated in human and murine NASH, Il-11 injection causes liver damage, inflammation and fibrosis in mice and Il11ra1 deleted mice are protected from NASH in two preclinical models. Therapeutic antibodies against IL11RA or IL-11 consistently inhibit and reverse fibrosis and steatosis in three murine NASH models. Unexpectedly, IL-11 causes hepatocyte damage and promotes stromal-mediated inflammation and anti-IL-11 therapies reverse NASH-associated hepatotoxicity and hepatitis. Genetic or pharmacologic inhibition of IL-11 signaling in NASH is associated with lower serum triglyceride, cholesterol and glucose. Conclusion: We show an unappreciated and central role for IL-11 in liver pathobiology. Targeting IL-11 signalling with neutralizing antibodies reverses fibrosis, steatosis, hepatocyte death and inflammation across the spectrum of NASH. This novel therapeutic approach is associated with a favorable cardiometabolic profile. Overall design: Mouse liver samples (each category in triplicate): 3 weeks of normal chow diet (NCD),  6 weeks of NCD, 3 weeks of High Fat Methionine- and Choline-deficient Deficient (HFMCD) diet with IgG treatment, 6 weeks HFMCD with IgG treatment, 3 weeks of HFMCD with X203 treatment, 6 weeks of HFMCD with X203 treatment, 3 weeks of HFMCD with X209 treatment, 6 weeks of HFMCD with X209 treatment. Human hepatic stellate cells (HSCs), each category in triplicate: HSCs with no stimulation and HSCs with 24h stimulation with TGFB1 + IgG	Co-expression
SRP189703	circRNA sequence of HeLa S3 nucleus	No description.	Co-expression
SRP189713	The Wnt/ß-catenin and RAS-ERK Pathways were Activated  in Tissues of Chemotherapy-Resistant Gastric Cancer PDX Tumor	Chemotherapy resistance and disease recurrence remains major causes of gastric cancer patient mortality. We describe possible relationship between Wnt/b-catenin and RAS/ERK pathways in GC patients and acquired-resistant GC PDX tumors against FOLFOX, 5-fluorouracil-based chemotherapy. RNA sequencing analysis also demonstrates that Wnt/b-catenin pathway is an actionable target pathway for overcoming the chemotherapy resistance. These provide that an approach targeting both Wnt/b-catenin and RAS/ERK pathways could be novel therapeutic strategy in GC resistant to standard chemotherapy. Overall design: Examination of vehicle- and FOLFOX-treated gastric cancer PDX tumors	Co-expression
SRP189721	The Transcriptome Analysis of THP-1 Macrophage Infected with ?M5447 or Wt Mycobacterium smegmatis by Next Generation Sequencing	Purpose: The goals of this study are systematic analysis of cellular pathway in THP-1 Macrophage which infected with wild type mycobacterium smegmatis (Wt) or MSMEG_5447 gene defected Mycobacterium smegmatis( ?M5447) at 24h postinfection. Method: THP-1 Macrophages mRNA profiles infected with Wt or?M5447 at 24h postinfection  were generated by deep sequencing, in duplicate, using Illumina HiSeq platform and human transcriptome (RefSeq transcriptome index hg19) is a reference sequence. Results: In total, 497 differentially expressed genes (DEGs) was identified in ?M5447-infected macrophages relative to the Wt-infected macrophages which including 173 up-regulated genes and 324 down-regulated genes using adjusted p-value<0.05 as the threthold criteria. The DEGs of THP-1  macrophages infected with ?M5447 strain was enriched in inflammatory related pathway. Conclusion: Our study find that the THP-1  macrophages infected with ?M5447 strain display decreased inflammatory response, MSMEG_5447 may play an essential role in inflammatory response. Overall design: THP-1 Macrophages mRNA profiles infected with Wt or?M5447 at 24h postinfection  were generated by deep sequencing, in duplicate, using Illumina HiSeq,  platform, Wt as control sample.	Co-expression
SRP189743	scRNA sequencing of 2 leukemia patients in remission after T cell therapy	peripheral blood samples of two leukemia patients in remission were profiled by single cell RNA sequencing approximately 1 year after receiving WT1 specific transgenic T cell therapy, at a time when patients were in clinical remission Overall design: single cell RNA sequencing of peripheral blood mononuclear cells	Co-expression
SRP189762	Identification of renal resident macrophages across species [C1]	We use single cell RNA sequencing to identify an evolutionarily conserved gene expression signature in resident macrophages. Based on our single cell data, we show the presence of a core gene expression signature in a cluster of innate immune cells in mouse, rat, pig, and human kidney tissue. Further, using this gene expression signature, we identify novel candidate markers for resident macrophages that span all 4 species tested. Overall design: We performed 10x genomics and fluidigm C1 single cell sequencing on innate immune cells isolated from the kidney of mouse, rat, pig, and human kidney tissue. This series includes mouse and human samples.	Co-expression
SRP189872	Gene expression profiles of primary human NK cells before and after expansion on CSTX002 feeder cells, with and without IL-21 stimulation	NK cell development, maturation, and activation by cytokines is driven by alterations in gene expression mediated by activation and repression or transcriptional programs. In particular, we have extensively studied the role of STAT3 in human NK cells. This was based in part on a method we developed for in vitro expansion of large numbers of highly active NK cells using a genetically-modified feeder cell expressing 4-1BBL and membrane-bound IL-21. To dissect the various gene expression profiles induced by IL-21 from the various other signals received from the feeder cell, we purified peripheral NK cells from 4 healthy subjects (naïve, N), expanded NK cells for 14 days using CSTX002 feeder cells (expanded, E), and extracted RNA from the cells without (Neg) or after (Pos) the cells were activated with IL-21. We then performed RNA sequencing on each sample. Overall design: NK cells were purified from buffy coats obtained from 4 normal healthy blood-bank donors using RosetteSep NK for negative depletion of other cell subsets. NK cells were expanded by weekly stimulation with irradiated CSTX002 feeder cells. Naïve or expanded NK cells were stimulated for 30 minutes with 20 ng/ml recombinant human IL-21. Total RNA was prepared using the Total RNA Purification Plus Kit (Norgen Biotek, Ontario, ON, Canada). Libraries were prepared using the TruSeq RNA Sample Preparation Kit (Illumina Inc., San Diego, CA). 60–80 million paired-end 150 bp sequence reads per library were generated using the Illumina HiSeq4000 platform.	Co-expression
SRP189885	Phenotypic variation between stromal cells differentially impacts engineered cardiac tissue function	Understanding the relationship between parenchymal and supporting cell populations is paramount to recapitulate the multicellular complexity of native tissues. Incorporation of stromal cells is widely recognized to be necessary for the stable formation of stem cell-derived cardiac tissues, yet the types of stromal cells used has varied widely. This study systematically characterized several stromal populations and found that stromal phenotype and morphology was highly variable depending on cell source and exerted differential impacts on cardiac tissue function and iPSC-CM phenotype. Therefore, the choice of supporting stromal population can differentially impact the phenotypic or functional performance of engineered cardiac tissues. Overall design: RNA-sequencing experiment to compare transcriptomes of multiple stromal cell populations commonly used in cardiac tissue engineering studies	Co-expression
SRP189898	Functional Comparison of the HGF/Met and MSP/Ron Systems in a Pancreatic Cancer Model	Pancreatic cancer is an aggressive disease with a poor prognosis for which current standard chemotherapeutic treatment options offer little survival benefit. In recent years, receptor tyrosine kinases (RTK)s have garnered interest as therapeutic targets to augment or replace standard chemotherapeutic therapies because of their high expression levels in various cancers and their ability to promote cell growth, migration, and survival. Met and Ron, which are homologous RTKs activated by the ligands hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), respectively, are over-activated in many of the least treatable cancers. In pancreatic adenocarcinoma, Met expression is linked to poor patient survival and Ron expression is generally higher in tumor samples relative to normal tissue, although its prognostic significance in pancreatic cancer remains unclear. Despite the structural homology between Met and Ron, studies that have directly compared the functional outcomes of these systems in any context are limited. To address this, we sought to determine if the HGF/Met and MSP/Ron systems produce overlapping or divergent contributions towards a malignant phenotype by performing a characterization of MSP and HGF driven signaling, behavioral, and transcriptomic responses in pancreatic cancer cells in vitro. We found HGF and MSP both encouraged cell migration and activated the MAPK/Erk pathway both at the transcript and protein level. HGF uniquely increased proliferation in addition to regulating a wider variety of transcripts compared to MSP. Although HGF and MSP produced a differing breadth of responses, overlapping pro-cancer signaling, behavioral, and transcriptional effects suggest dual inhibition of the MSP/Ron and HGF/Met systems in pancreatic cancer may provide a more complete anti-cancer effect compared to individually targeting either system. Overall design: BxPC-3 cells were treated with vehicle control (PBS), HGF (80 ng/ml), or MSP (100 ng/ml) in triplicate. Total RNA was collected at 1 and 4 hours post-treatment. Libraries were prepped with a KAPA mRNA HyperPrep Kit. Libraries were sequenced on an Illumina HiSeq 4000. All samples were sequenced in duplicate across two lanes.	Co-expression
SRP189956	IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus	Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital- and community-acquired pathogen, but the mechanisms underlying host-defense to MRSA remain poorly understood. Here, we investigated the role of IL-21 in this process. When administered intra-tracheally into wild-type mice, IL-21 induced granzymes and augmented clearance of pulmonary MRSA but not when neutrophils were depleted or a granzyme B inhibitor was added. Correspondingly, IL-21 induced MRSA killing by human peripheral blood neutrophils. Unexpectedly, however, basal MRSA clearance was enhanced when IL-21 signaling was blocked, both in Il21r KO mice and in wild-type mice injected with IL-21R-Fc fusion-protein. This correlated with increased type I interferon and an IFN-related gene signature, and indeed anti-IFNAR1 treatment diminished MRSA clearance in these animals. Moreover, we found that IFNß induced granzyme B and promoted MRSA clearance in a granzyme B-dependent fashion. These results reveal an interplay between IL-21 and type-I IFN in the innate immune response to MRSA. Overall design: RNA-Seq analysis using total RNA either from total lung tissues isolated from mouse or from peripheral blood purified from normal donors or AD-HIES patients.	Co-expression
SRP189980	Systematic comparison of single-cell and single-nucleus transcriptomes during cardiomyocyte differentiation	Purpose:To systematically assess the differences between high-throughput single-cell and single-nuclei RNA-seq approaches, we compared Drop-seq and DroNc-seq, two microfluidic-based 3' RNA capture technologies that profile total cellular and nuclear RNA, respectively, during a time course experiment of human induced pluripotent stem cells (iPSCs) differentiating into cardiomyocytes Conclusions: Clustering of time-series transcriptomes from Drop-seq and DroNc-seq revealed six distinct cell types, five of which were found in both techniques. Furthermore, single-cell trajectories reconstructed from both techniques reproduced expected differentiation dynamics. Overall design: Drop-seq and DroNc-seq each on 2 hiPSC cell lines differentiating into cardiomyocytes across 5 time points. DroNc-seq on post-mortem primary heart tissue.	Co-expression
SRP189993	Identification of renal resident macrophages across species [10X]	We use single cell RNA sequencing to identify an evolutionarily conserved gene expression signature in resident macrophages. Based on our single cell data, we show the presence of a core gene expression signature in a cluster of innate immune cells in mouse, rat, pig, and human kidney tissue. Further, using this gene expression signature, we identify novel candidate markers for resident macrophages that span all 4 species tested. Overall design: We performed 10x genomics and fluidigm C1 single cell sequencing on innate immune cells isolated from the kidney of mouse, rat, pig, and human kidney tissue.	Co-expression
SRP189994	Spatial control of oxygen delivery to 3D cultures alters cancer cell growth and gene expression	Commonly used monolayer cell cultures lack the capacity to provide a physiologically relevant environment for cell culture in terms of cell-cell architecture, extracellular matrix composition, and spatiotemporal delivery of key growth factors and small molecules, such as oxygen. Here, we describe a three-dimensional (3D) approach to cell culture in vitro, utilizing a bioreactor system designed to control oxygenation of 3D cancer cell cultures, in order to better mimic tumor microenvironments observed in vivo. We found transcriptomic differences in breast and ovarian cancer cell cultures grown in traditional monolayer cultures as compared to cultures grown in a Matrigel three-dimensional matrix. We also investigated the transcriptomes of 3D cultures grown in 21% O2, 3% O2, and a gradient of 3% O2 to 0% O2 using our bioreactor system. By controlling oxygen delivery, we observed differences in cell growth morphology and transcriptome regulation under the three conditions. Overall design: Examination of the effects of oxygenation gradients on 3D cancer cell cultures grown in a bioreactor. 3D cell cultures grown in 3% oxygen, 21% oxygen, and gradient oxygen are examined and compared to cells grown in 2D 21% oxygen. MCF-7 and OVCAR-8 cell lines are investigated.	Co-expression
SRP189995	scRNA-seq analysis of the dual expressors, B cells and T cells of a diabetes patient	We identified a rare subset of autoreactive lymphocytes with a hybrid phenotype of T and B cells including coexpression of TCR and BCR and key lineage markers of both cell types (hereafter referred to as dual expressers or DEs).  To investigate the dual phenotype of DEs at single cell resolution, we examined their transcriptomes using single cell RNA sequencing (scRNA-seq). We sorted individual DEs, Bcon and Tcon cells from PBMCs of one type I diabetes patient and analyzed the transcriptomes  of 34 DEs,  20 Bcon , and 23 Tcon  using the plate-based SMART-seq2 protocol (Tirosh and Suva, 2018; Tirosh et al., 2016).  Our results show that DEs have uniquely expressed genes along with genes encoding lineage markers of T and B cells. Overall design: Examination of the transcriptomes of three cell types, Des (Dual Expressors), Bcon (Conventional B) and Tcon (Conventional T) cells from the  PBMCs of one type I diabetes patient	Co-expression
SRP190024	Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors [P2A-EGFP control]	Base Editing has been touted the most intelligent and precise application of the CRISPR platform so far, merging the simplicity of RNA-guided nucleases with deaminases that allow for the programmable generation of single base substitutions - without introduction of double-strand breaks. Even though the two-component system has been expected to cause off-target substitutions, studies involving cytosine base editors (CBEs) showed that in most cases, relatively few single base off-targets could be detected on DNA. We introduce the concept of multi-dimensional off-targeting, presenting an extensive amount of RNA cytidines being edited by DNA base editors. Epitranscriptomic off-target effects affected different cell lines and were independent of the guide RNAs used, suggesting Cas9-independent activity of the cytidine deaminase rAPOBEC1 on single-stranded RNA. With the help of protein engineering, we developed CBE variants with massively reduced inadvertent mutation of RNA that preserve and enhance DNA base editing capabilities.  Overall design: HEK293T or HepG2 cells were transfected with P2A-EGFP. Cells were sorted for top 5% GFP based on FITC signal. RNA-seq was performed to measure transcriptional changes associated with different constructs.	Co-expression
SRP190037	Identification of elevated A-to-I editing sites due to expression of an active ADAR3 mutant in human glioblastoma cells	We have analyzed RNA-seq data to identify A-to-I editing sites in two groups of samples: one group isolated from human U87 cell line expressing an active ADAR3 mutant while the other isolated from U87 cell line expressing the inactive counterpart of the ADAR3 mutant. We compared these two groups of samples and identified sites whose editing levels are higher in the first group than in the second group. Overall design: Examine A-to-I editing sites in two group of samples.	Co-expression
SRP190129	ZIKV infection strongly induces antiviral immune responses in human NPCs	To investigate the cellular pathologies in human NPCs after ZIKV infection, we performed global transcriptome profiling of the FD, FV, and H&S organoids at 3 and 6 dpi.  We found 105 upregulated genes in the FD NPCs, 60 genes in the FV NPCs, and 168 genes in the H&S NPCs, with at least 1.5-fold differences found between ZIKV-infected groups and the control groups at 6 dpi. Among them, 28 genes overlapped in all three regional NPCs. These 28 common genes exclusively referred to the pathways associated with immune responses to viral infection, which could be clustered to the ISG family. Overall design: Three regional organoids were infected with ZIKV at MOI=0.5 or mock infection, and total RNAs were extracted at 3 dpi or 6 dpi and used for global transcriptome analysis. RNA-seq libraries were generated from duplicated samples per condition using the Next Illumina Ultra RNA library prep kit (NEB) following manufacturer's protocols. RNA concentration of library was measured using Qubit RNA Assay Kit in Qubit 2.0. The insert size was assessed using the Agilent Bioanalyzer 2100 system (Agilent Technologies, CA, USA) and then accurate quantification was performed with Taqman fluorescence probe of AB Step One Plus Real-Time PCR system and sequenced by an Illumina Hiseq 2500 platform.	Co-expression
SRP190131	H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma	Pancreatic ductal adenocarcinoma is one of the most intractable and devastating of all malignant tumors. Epigenetic modifications involving both DNA methylation and histone modification have a relationship between tumor initiation and progression. However, the contribution of histone variants in the PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and its overexpression correlated with poor prognosis. We found that the three-histone H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1 and, H2A.Z.2.2), are highly expressed in PDAC cell lines and PDAC patients. Knockdown of three H2A.Z isoforms induces a senescent phenotype, cell cycle arrest in phase G2/M, increased cyclin-dependent kinase inhibitor CDKN2A/p16, SA-ß-galactosidase activity and interleukin 8 production in PDAC. Transcriptome analysis of knockdown of the H2A.Z isoforms showed altered gene expression in the fatty acid biosynthesis. As well as in the genes that control the cell cycle and DNA damage repair. Furthermore, H2A.Z isoform deficiency, reduces the tumor size in a mouse xenograft model in vivo, and sensitizes PDAC cells to gemcitabine. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC Overall design: mRNA profiles of PANC-1 pancreatic cancer cell line (WT) and PZT-2 (KD of three H2A.Z isoforms), using Illumina NextSeq 500	Co-expression
SRP190161	TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [RNA-seq]	TNF-mediated macrophage polarization is important for inflammatory disease  pathogenesis, but mechanisms that regulate polarization are not well understood.  Transcriptomic and epigenomic analysis of the TNF response in primary human  macrophages revealed late phase activation of SREBP2, the master regulator of  cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of  SREBP2 occupancy to include binding to and activation of inflammatory and interferon  response genes independently of its functions in sterol metabolism. Genetic ablation of  SREBP function shifted the balance of macrophage polarization from M1 to an M2-like  reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of  SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP  improved skin wound healing under homeostatic and chronic inflammatory conditions.  Our results identify a new function and mechanism of action for SREBP2 in  augmenting TNF-induced M1 macrophage polarization and inflammation, and open  therapeutic avenues for promoting wound repair. Overall design: Analysis of transcriptional changes in human macrophages stimulated with or without TNF in the presence of various inhibitors (Fatostatin, Atrovastatin, Cholesterol and DMSO)	Co-expression
SRP190168	Apatinib preferentially inhibits Gefitinib-resistant lung cancer cells by inducing cell cycle arrest and inhibiting VEGFR signaling pathway	Targeted therapy for patients with EGFR mutations by tyrosine kinase inhibitors (TKIs) has provided a significant benefit to patients. However, gradually developed resistance to the therapy becomes a major challenge in clinical practice. Herein, we report that Apatinib, an anti-angiogenic drug, strongly and specifically inhibits Gefitinib-resistant cancer cells but not their parental sensitive cells. Gefitinib-resistant lung cancer cell line (PC9GR) was established from its parental sensitive line (PC9) with a traditional EGFR mutation after long time exposure to Gefitinib. The established PC9GR cells had over 250 fold increased resistance to Gefitinib than its sensitive parental PC9 cells. Apatinib demonstrated much stronger (~5 fold) growth inhibition on PC9GR cells than on PC9 and other lung cancer cell lines. This inhibition was mostly achieved through cell cycle rest in G1 phase as demonstrated by transcriptome and protein expression data. Oral intake of Apatinib in mouse model significantly inhibited establishment and growth of PC9GR implanted tumors. VEGFR2 phosphorylation in PC9GR tumors after Apatinib treatment was significantly reduced along with less micro-vessel formation. Apatinib may provide a benefit to patients with acquired resistance to TKI treatment. Overall design: RNA sequencing was performed on PC9, PC9GR, and both after apatinib treatment, three replicates in each condition, to detect differentially expressed genes and involved pathways.	Co-expression
SRP190176	CD71+ erythroid cells exacerbate HIV-1 infection via ROS and trans-infect HIV to CD4+ T cells	We show that CECs originated from either the cord blood/placenta, peripheral blood of anemic and HIV patients mediate the exacerbation of HIV-1 replication in CD4+ T cells. Our observations coupled with RNAseq data demonstrate how interactions of CECs with CD4+ T cells via ROS affect the cell cycle machinery to facilitate HIV-1 replication. In addition, we demonstrate that CECs compared to mature RBCs express significantly higher levels of both CD35 and DARC, and can trans-infect HIV-1 to uninfected CD4+ T cells in vitro. Finally, our study indicates that HIV-1 interacts with CD235a on CECs and trans-infect uninfected CD4+ T cells in the presence of anti-retroviral drug, Tenofovir.	Co-expression
SRP190204	Transcriptome wide identification of retained introns upon depletion of the splicing factors WBP11 or SNW1	We identified introns that are dependent on WBP11 or SNW1 for efficient splicing. WBP11 and SNW1 were depleted by RNAi and compared to a mock transfected population of cells. WBP11 was also depleted by auxin and compared to an untreated population of cells Overall design: RNA-Seq analysis of mRNA purified from colorectal adenocarcinoma cell lines depleted of either WBP11 or SNW1 by RNAi or by auxin-induced depletion of AID-tagged WBP11 transgene in an endogenous WBP11 knockout background	Co-expression
SRP190210	Directly Reprogrammed Human Neurons Identify a Pathogenic Mechanism of Valproic Acid at Early Developmental Stages	Human pluripotent stem cells can be rapidly converted into functional neurons by ectopic expression of proneural transcription factors. Here we show that directly reprogrammed neurons, despite their rapid maturation kinetics, can model teratogenic mechanisms that specifically affect early neurodevelopment. We delineated distinct phases of in vitro maturation during reprogramming of human neurons and assessed the cellular phenotypes of valproic acid (VPA), a teratogenic drug. VPA exposure caused chronic impairment of dendritic morphology and functional properties of developing neurons, but not those of mature neurons. These pathogenic effects were associated with VPA-mediated inhibition of the histone deacetylase (HDAC) and glycogen synthase kinase-3 (GSK-3) pathways, which caused transcriptional downregulation of many genes, including MARCKSL1, an actin-stabilizing protein essential for dendritic morphogenesis and synapse maturation during early neurodevelopment. Our findings identify a developmentally restricted pathogenic mechanism of VPA and establish the use of reprogrammed neurons as an effective platform for modeling teratogenic pathways. Overall design: Examination of global transcriptional changes by chronic Valproic acid-exposure. Article reference: STEM2658 NIHMS ID: NIHMS 1528543	Co-expression
SRP190212	Complete deconvolution of cellular mixtures based on linearity of transcriptional signatures	Difference in RNA content of different cell types introduces bias to gene expression deconvolution methods. If ERCC spike-ins are introduced into samples, predicted proportions of deconvolution methods can be corrected Overall design: Two cell types of distinctly different sizes and RNA per cell content: HEK cells and Jurkat cells were mixed in different proportions ensuring that each mixture contained total of one million cells. We sequenced RNA of the samples (including ERCC spike-in controls to 382 be able to control for the absolute RNA-concentration).	Co-expression
SRP190429	Illumina sequencing analysis of LINC00998 knockdown and control in Huh7 cell line	shRNA knockdown against LINC00998 in Huh7 cells followed by RNA-seq. LINC00998 is also known as SMIM30 or ENSG00000214194. Overall design: To examine the differentially expressed genes in LINC00998 knockdown and control cell samples	Co-expression
SRP190439	Expression data of  melanoma cell lines after SIRT2 depletion	Scope: to analyze SIRT2-dependent gene expression in melanoma cells of vertical growth and metastasis.1. The human melanoma cell line WM853 (stage: primary/vertical growth) was purchased from Rockland (Rockland, Limerick, PA, USA) and was maintained in Tumor Specialized Medium containing 80% MCDB153 (Sigma-Aldrich), 20% Leibovitz's (Sigma-Aldrich), 2% fetal bovine serum (Pan Biotech GmbH), 1.68 mM calcium chloride, and 1.2 g (11.2 mM) sodium bicarbonate. WM853 cells were transfected with short hairpin RNA (shRNA) plasmids: scrambled negative control non-effective shRNA (TR30012) or SIRT2 (T301692D) (Origene Tech.). Transfection was performed with Metafectene PRO (Biontex) following the manufacturer's instructions. The cells were then cultured by replacing the medium every three days with complete medium containing 0.4 µg/ml puromycin for one month, during which stable clones were selected: WM853 SCW3 (control) and WM853 SSW30 ( with downregulated SIRT2). RNA was isolated from SCW3 and SSW30 cells (4 replicates per each cell line).2. The human melanoma cell line MDA-MB-435S (stage: metastatic) was obtained from the ATCC and was maintained in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal bovine serum. MDA-MB-435S cells were transfected with short hairpin RNA (shRNA) plasmids: scrambled negative control non-effective shRNA (TR30012) or SIRT2 (T301692D) (Origene Tech.). Transfection was performed with Metafectene PRO (Biontex) following the manufacturer's instructions. The cells were then cultured by replacing the medium every three days with complete medium containing 1 µg/ml puromycin for one month, during which stable clones were selected: MDA-MB-435S SCM1 (control) and MDA-MB-435S SSM15 (with downregulated SIRT2). RNA was isolated from SCM1 and SSM15 cells (4 replicates per each cell line).	Co-expression
SRP190537	Studying the selectivity of a targeted small molecule degrading a hypoxia-associated non-coding RNA	Small molecule targeted recruitment of nucleases to RNA is a powerful method to affect RNA biology.  Inforna, a sequence-based design approach to target RNA, enables the design of small molecules that bind and cleave RNA in a selective and substoichiometric manner.  Herein, we investigate the ability of RNA targeted degradation to improve the selectivity of small molecules targeting RNA.  The microRNA-210 hairpin precursor (pre-miR-210) is overexpressed in hypoxic cancers.  Previously, a small molecule (Targapremir-210, TGP-210) targeted this RNA in cells, but with only a 5-fold window for DNA binding.  Appendage of a nuclease recruitment module onto TGP-210 locally recruited ribonuclease L onto pre-miR-210, triggering its degradation.  The chimera has enhanced selectivity compared to TGP-210 with nanomolar binding to the pre-miR-210, but no DNA binding, and is broadly selective for affecting RNA function in cells.  Importantly, it cleaved pre-miR-210 substoichiometrically and induced apoptosis in breast cancer cells. Overall design: Examination of small molecule-treated (TGP-210-RL) or vehicle-treated (DMSO) hypoxic MDA-MB-231 cells in biological triplicates	Co-expression
SRP190818	Generation of  induced keratinocyte stem cells from human urine cells by defined transcription factors	Analysis of induced keratinocyte stem cells from male/female urine cells (MiKSC/FiKSC) by defined transcription factors vs. foreskin derived primary human neonatal epidermal keratinocytes (pKC) and male/female urine cells (MUC/FUC). Results provide insight into molecular similarities between induced keratinocyte stem cells and human foreskin derived primary human neonatal epidermal keratinocytes. Overall design: RNA profiles of induced keratinocyte stem cells from male urine cells,  induced keratinocyte stem cells from female urine cells, male urine cells, female urine cells and primary human neonatal epidermal keraitnocytes were generated by RNA sequencing, in duplicate	Co-expression
SRP190850	Transcriptome Analysis Reveals Distinct Responses to Physiologic versus Toxic Manganese Exposure in Human Neuroblastoma Cells	We report the application of RNA-Seq analysis to determine the transcriptional responses to Mn dose, ranging from physiological to toxicological levels in human SH-SY5Y neuroblastoma cells. We find that Mn dose showed widespread effects in abundance of protein coding genes for metabolism of reactive oxygen species, energy sensing, glycolysis, protein homeostasis including the unfolded protein response and transcriptional regulation. Adaptive responses at physiological Mn concentration-10 µM Mn for 5 h, a concentration that did not result in cell death after 24 h increased abundance of differentially expressed genes (DEGs) in the protein secretion pathway that function in protein trafficking and cellular homeostasis.These include BET1 (Golgi vesicular membrane trafficking protein), ADAM10 (ADAM metallopeptidase domain 10) and ARFGAP3 (ADP-ribosylation factor GTPase activating protein 3). In contrast, 5 h exposure to 100 µM Mn, a concentration that caused cell death after 24 h, increased abundance of DEGs for components of the mitochondrial oxidative phosphorylation pathway. In conclusion, this study provides a framework  for Mn dose dependent exposure in a human in vitro cell culture model and provides a testable hypothesis for in vivo studies. Importantly, the transcriptome responses at toxic Mn dose demonstrated patterns observed with neurological diseases and suggest that differential functions of the secretory pathway and mitochondria could provide a basis to improve detection and management of adverse environmental and occupational Mn exposures. Overall design: Examination of transcriptomic responses to Mn dose (0,1,5,10,50,100 µM MnCl2 for 5 h) in human SH-SY5Y neuroblastoma cells with three biological replicates per Mn treatment using Illumina HiSeq 2500.	Co-expression
SRP190903	Differential lncRNA expression upon hypoxia affects splicing efficiency	RNA sequencing was performed to identify long non-coding RNAs that are dysregulated upon hypoxia in breast cancer. Subsequently, the effect on splicing effiency (intron retention, exon skipping …) was investigated from RNA sequencing analysis upon knockdown of the candidate lncRNA and upon hypoxia. Overall design: Cells were treated with GapmeRs or tetracycline-inducible shRNAs against the candidate lncRNA and cultured upon hypoxic conditions (1%O2). Additionally, cells were treated with shRNAs against SART3 or GFP.	Co-expression
SRP190920	PRRX2 and HEY2 double knock-down facilitates ASCL1-induced neuron conversion in human dermal fibroblasts II	Forced expression of ASCL1, Nurr1, Lmx1a, miRNA-124 and p53shRNA (ANLmp) in fibroblasts reprograms fibroblasts to induced dopaminergic neurons (iDA). While human lung fibroblasts can be converted rapidly and efficiently, iDA of dermal fibroblast is very unefficient and incompleted. To address this issue,  we performed time series RNAseq on both lung and dermal fibroblasts during the first several days of ANLmp induced neuron convertion. Bioinformatics analysis revealed the stable fibroblast gene regulatory network (GRN)  was a potential repressive factor for iDA in human dermal fibroblasts. Overall design: Time serial comparison of transcriptomes of non-isogenic human skin fibroblasts C002 and human lung fibroblasts MRC5 during their transdifferentiation to dopaminergic neuron induced by ANLmp.	Co-expression
SRP191103	Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis	The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in gastroparesis and obesity. Overall design: Stomach muscularis biopsies were obtained from human subjects with low BMI and normal gastric motility (low BMI control, n=6), subjects with high BMI but normal gastric motility (high BMI control, n=6), subjects with low BMI and gastroparesis (low BMI gastroparesis, n=6) and from subjects with high BMI and gastroparesis (High BMI gastroparesis, n=4). RNA was isolated and subjected to whole transcriptome sequencing.	Co-expression
SRP191427	The Caudate Nucleus Undergoes Dramatic and Unique Transcriptional Changes in Human Prodromal Huntington's Disease Brain	The mechanisms underlying degeneration of the specific neurons in the striatum of Huntingon's Disease (HD) brain are currently unknown. The striatum is massively degenerated in late stage HD, making examination of post-mortem brain tissue from symptomatic individuals problematic. In this study, caudate nucleus (CAU) tissue from two asymptomatic HD+ individuals was subjected for comparison with similar datasets with symptomatic HD individuals and healthy controls. Overall design: 11 Huntington's Disease and 5 neurologically normal control samples from post-mortem human subjects	Co-expression
SRP191503	Transcriptional landscape of human myogenesis reavels a key role of TWIST1 in maintenance of skeletal muscle progenitors	Derivation of human skeletal muscle in vitro with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in myogenic specification and relevance to rare genetic diseases. We characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ PSCs, MSGN1::EGFP+ presomites, PAX7::EGFP+ skeletal muscle progenitors, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitors,  providing an explanation for the musculoskeletal symptoms of a rare genetic disease, Saethre-Chotzen syndrome. We have established a foundation for future studies to identify regulators of human myogenic ontogeny. Overall design: To systematically investigate the transcriptional blueprint of developing human skeletal muscle cells and to gain comprehensive insights into the molecular signatures of putative skeletal muscle stem/progenitors, we conducted step-wise isolations of stage-specific cellular subtypes during muscle differentiation in vitro and performed global gene expression analysis. Using our human genetic reporter PSC lines and a newly devised method for myotube enrichment, we isolated five distinct cell types in human embryonic myogenesis, including OCT4::EGFP+ embryonic stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ putative skeletal muscle stem/precursor cells, MYOG::EGFP+ myoblast cells, and multinucleated myotubes.	Co-expression
SRP191514	Impact of a pre-operative exercise intervention on breast cancer proliferation and gene expression	RNAseq analysis of primary breast cancer samples Overall design: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind-body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor were collected at baseline and surgery.	Co-expression
SRP191528	Brain organoids reproducibly generate the cellular diversity of the human cerebral cortex	Stem cell-derived human brain organoids hold an unprecedented degree of promise as experimental models of the human brain. They are, however, plagued by poor reproducibility and high organoid-to-organoid variability. Here, we show that a human organoid model pre-patterned to form the dorsal forebrain and cultured for over six months can achieve reproducible generation of a rich diversity of cell types appropriate for the human cerebral cortex. Using single-cell RNA-sequencing of 166,242 cells isolated from 21 individual organoids, we find that 95% of the organoids generated a virtually indistinguishable compendium of cell types, through the same temporal trajectories, and with organoid-to-organoid variability that is comparable to that of individual endogenous brains. The data demonstrate that reproducible development of complex central nervous system (CNS) cellular diversity does not require the context of the embryo, and that establishment of terminal cell identity is a highly constrained process that can emerge from diverse stem cell origins and growth environments. Overall design: Single cell RNA-sequencing from 21 individual organoids, after 3 or 6 months in culture. Batches of 3 organoids from each differentiation. Position-sorted BAM files as created by CellRanger v.2.0.1 are supplied to SRA as raw data files. Each read has Chromium cellular and molecular barcodes information stored as TAG fields.	Co-expression
SRP191604	A functional variant of PTPN21 isoforms is associated with NK cell killing activity in acute lymphoblastic leukemia	PolyA-type sequencing of transcriptome was mainly to determine the constitution of PTPN21 isoforms in NALM-6 cell line; DEG-type sequencing of transcriptome was to detect the differential expressed genes in two groups.	Co-expression
SRP191741	Homo sapiens Transcriptome	To identify genetic changes in Human Umbilical Vein Endothelial Cells induced by let-7d mimic or let-7d inhibitor transfection.	Co-expression
SRP191771	Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme	Human pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling.  Efficient and broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field.  We describe a simple yet robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding and BMP4 and Activin A (BA) treatment.  Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment.  After 14 days of differentiation, BA-treated cells expressed genes indicative of mesoderm and endoderm-derived tissue types, including lung, kidney and adipose tissue.  BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation.  Teratomas formed from BA-treated cells contained higher ratios of mesoderm and endoderm to ectoderm tissue compared to PSC-derived teratomas.  Collectively, these data demonstrate that single-cell seeding with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation. Overall design: 35 samples total. BA (mesendoderm) samples: 6hr, 12hr, 18hr, 24hr x 3, 30hr, 36hr, 42hr, 48hr x 3.  E8 (pluripotency control) samples (6hr, 12hr, 18hr, 24hr, 30hr, 36hr, 42hr, 48hr x 3). E6 (spontaneous differentiation control) samples: 6hr, 12hr, 18hr, 24hr, 30hr, 36hr, 42hr, 48hr x 3. time_zero control	Co-expression
SRP191866	Gene-Centric Functional Dissection of Human Genetic Variation Uncovers Regulators of Hematopoiesis	Follow-up work was performed for SF3A2, a gene among the hits identified in a red blood cell trait GWAS-informed shRNA screen. Differential splicing effects were assayed to investigate resulting effects on the differentiating erythroid cell spliceome and explore potential modifier relationships with other known splicing defects associated with human disease. Overall design: Examination of differential splicing events resulting from knockdown of splicing factor 3a subunit 2 (SF3A2) in three unique donor CD34+ cells populations undergoing erythroid differentiation. Two shRNA targeting SF3A2 were tested, along with a negative control shRNA targeting luciferase (which should not be expressed) using paired-end sequencing.	Co-expression
SRP192094	Disease modelling of core pre-mRNA splicing factor haploinsufficiency	We generated a human EFTUD2 knockdown cell line using a CRISPR cas9 nickase strategy to investigate the effects of decreased expression of core spliceosome components on cell characteristics and global transcriptome expression/splicing patterns Overall design: 6 biological replicates of WT or CRISPR knock-down cells were generated and analysed by RNA-Seq	Co-expression
SRP192392	RNA proximity sequencing reveals properties of spatial transcriptome organization in the nucleus	Spatial transcriptomics aims to understand how the ensemble of RNA molecules in tissues and cells is organized in 3D space. Here we introduce Proximity RNA-seq, which identifies co-localization preferences for pairs or groups of chromatin-associated, nuclear-retained and nascent RNAs in cell nuclei. Proximity RNA-seq is based on massive-throughput RNA barcoding of sub-nuclear particles in water-in-oil emulsion droplets, followed by sequencing. Overall design: 4 Proximity RNA-Seq datasets (Pools 2, 5, 7 & 8), 2 Hi-C datasets	Co-expression
SRP192521	ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [12Z_RNA-seq]	ARID1A and PI3-Kinase (PI3K) pathway alterations are common in neoplasms originating from the uterine endometrium. Here we show that monoallelic loss of ARID1A in the mouse endometrial epithelium is sufficient for vaginal bleeding when combined with PI3K activation. Sorted mutant epithelial cells display gene expression and promoter chromatin signatures associated with epithelial-to-mesenchymal transition (EMT). We further show that ARID1A is bound to promoters with open chromatin, but ARID1A loss leads to increased promoter chromatin accessibility and the expression of EMT genes. PI3K activation partially rescues the mesenchymal phenotypes driven by ARID1A loss through antagonism of ARID1A target gene expression, resulting in partial EMT and invasion. We propose that ARID1A normally maintains endometrial epithelial cell identity by repressing mesenchymal cell fates, and that coexistent ARID1A and PI3K mutations promote epithelial transdifferentiation and collective invasion. Broadly, our findings support a role for collective epithelial invasion in the spread of abnormal endometrial tissue. Overall design: 12Z endometriotic epithelial cells transfected with either siARID1A or non-targeting siRNA control were assayed 48 hours post-transfection via RNA-seq.	Co-expression
SRP192561	ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells [RNA-seq]	Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER's regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed. Our results show that ETV4 plays a necessary role in estrogen signaling in endometrial cancer cells. Overall design: RNA-seq was used to study the effects of ETV4 knock out on gene expression	Co-expression
SRP192575	Wnt signaling separates the progenitor and endocrine compartments during pancreas development	In vitro differentiation of pluripotent cells into ß cells is a promising alternative to cadaveric-islet transplantation as a cure for type 1 diabetes (T1D). During the directed differentiation of human embryonic stem cells (hESCS) by exogenous factors, numerous genes that affect the differentiation process are turned on and off autonomously. Manipulating these reactions could increase the efficiency of differentiation and provide a more complete control over the final composition of cell populations. To uncover in-vitro autonomous responses, we performed single-cell RNA sequencing on hESCs as they differentiate in spherical clusters. We observed that endocrine cells and their progenitors exist beside one another in separate compartments that activate distinct genetic pathways. WNT pathway inhibition in the endocrine domain of the differentiating clusters revealed a necessary role for the WNT inhibitor APC during islet formation in-vivo. Accordingly, WNT inhibition in vitro causes an increase in the proportion of differentiated endocrine cells.	Co-expression
SRP192607	Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation Induced Metabolic networks in Human T cells	The targeting of metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. In this study, carbon tracing and systems biology approaches integrating metabolomic and transcriptomic profiling data were used to identify adaptations in human T cell metabolism important for fueling pro-inflammatory T cell function. Results of this study demonstrate that T cell receptor (TCR) stimulation leads to a significant increase in glucose and amino acid metabolism that trigger downstream biosynthetic processes. Specifically, increased expression of several enzymes such as CTPS1, IL4I1, and ASL results in the reprogramming of amino acid metabolism. Additionally, the strength of TCR signaling resulted in different metabolic enzymes utilized by T cells to facilitate similar biochemical endpoints. Furthermore, this study shows that cyclosporine represses the pathways involved in amino acid and glucose metabolism, providing novel insights on the immunosuppressive mechanisms of this drug. To explore the implications of the findings of this study in clinical settings, conventional immunosuppressants were tested in combination with drugs that target metabolic pathways. Results showed that such combinations increased efficacy of conventional immunosuppressants. Overall, the results of this study provide a comprehensive resource for identifying metabolic targets for novel combinatorial regimens in the treatment of intractable immune diseases. Overall design: Primary human CD4+ T cell isolation, culture, and activation  Blood was collected from healthy human patients in accordance with IRB standards. CD4+ T cells were purified using RosetteSep isolation kit (StemCell) as per manufacturer's protocol. Cells were cultured in RPMI supplemented with 10% heat inactivated FBS, HEPES, penicillin/streptomycin, non-essential amino acids, glutamax, and sodium pyruvate. Cells were initially activated for 72 hours on plate-bound CD3 (200 ng/mL; OKT3; BioXCell) and CD28 (200 ng/mL; 9.3; BioXCell) on goat-anti-mouse (10 µg/mL; Jackson Immuno Research Labs) pre-coated high- binding plates (Corning Costar). After 72 hours, cells were removed from plate activation and were expanded until Day 8-12, maintained at ~1X106 cells/mL by supplementing with fresh media as required. Cells were then washed with PBS and either rested or re-activated at 0.5-1x106 cells/mL in fresh media with plate-bound CD3/CD28 (100 ng/mL each) or with soluble CD3/CD28 Immunocult (1:100 dilution; StemCell). Cells were treated with Rapamycin (100nM) and/or Cyclosporin A (2µM), or equivalent volume of DMSO during re-activation.    Lentiviral transduction and shRNA knockdown  Lenti-X 293T (Clontech) cells were plated on poly-D-lysine (0.1 mg/mL; Sigma) coated plates at a density of 1.67x105 cells/mL. After 72 hours, cells were transfected with psPAX2 (1.5µg), pCMV-VSV-G (0.5µg), and pZIP-mCMV-ZsGreen-shRNA NT Control or mTOR plasmids (2 µg; Transomic) using the TransIT-LT1 transfection reagent (Mirus) as per manufacturer's protocol. Virus was collected after an additional 72 hours and CD4+ T cells were spin infected after 48 hours of activation using undiluted virus (~1x108 IFU yielding a MOI of ~70) supplemented with polybrene (10 µg/mL; AmericanBio Inc). After an additional 24 hours of activation, the transduced CD4+ T cells were removed from activation and expanded in the presence of puromycin (1 µg/mL) until Day 8-12, maintained at ~1x106 cells/mL by supplementing with fresh media as required. Cells were then washed and activated as described above.    CRISPR/Cas-9 knockout  Cells were activated on plate-bound CD3/CD28 as described above. Cells were removed from plate activation after 72 hours and were rested overnight at ~1X106 cells/mL. The following day the conditioned media was saved before washing the cells and resuspending in buffer T (Neon Transfection System; ThermoFisher) at 25x106 cells/mL. Guides targeting human mTOR and ZAP70 were designed using the Broad Institute's online sgRNA designer (https://portals.broadinstitute.org/gpp/public/analysis-tools/sgrna-design)22 (see Sup Table 1). 5 guides per gene were synthesized by IDT and duplexed in a 1:1 ratio with Alt-R-CRISPR-Cas9-tracrRNA (IDT) as per manufacturer's protocol. Duplexed guides were incubated with Alt-R S.p. Cas9 Nuclease (IDT) before mixing with 2.5x106 cells and electroporating using the Neon Transfection System (ThermoFisher; 100uL tip at 1550V, 10 milliseconds, 3 pulses). Cells were allowed to recover for 1 hour in fresh media before adding back conditioned media in a 1:1 ratio conditioned to fresh media. Cells were expanded in the presence of IL-2 (2 ng/mL; R&D) until Day 8-12, maintained at ~1x106 cells/mL by supplementing with fresh media as required. Cells were then washed and activated as described above.	Co-expression
SRP192637	Deciphering the 'm6A code' via quantitative profiling of m6A at single-nucleotide resolution [III]	N6-methyladenosine (m6A) is the most abundant modification on mRNA, and is implicated in critical roles in development, physiology and disease. A major challenge in the field has been the inability to quantify m6A stoichiometry and the lack of antibody-independent methodologies for interrogating m6A. Here, we develop MASTER-seq for systematic quantitative profiling of m6A at single nucleotide resolution, building on differential cleavage by an RNAse at methylated sites. MASTER-seq permitted validation and de novo discovery of m6A sites, calibration of the performance of antibody based approaches, and quantitative tracking of m6A dynamics in yeast gametogenesis and mammalian differentiation. We discover that m6A stoichiometry is 'hard-coded' in cis via a simple and predictable code. This code accounts for ~50% of the variability in methylation levels and allows accurate prediction of m6A loss/acquisition events across evolution. MASTER-seq will allow quantitative investigation of m6A regulation in diverse cell types and disease states. Overall design: 17 samples were analyzed: FTO over expression and control in hESC with triplicates;  AlkBH5 over-expression, FTO over-expression and control in HEK293T with triplicates; Cytosolic fraction of HEK293T with duplicates	Co-expression
SRP192714	RNA-seq transcript and gene data on zika exposed and zika naïve samples	RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals in order to assess associated signatures Overall design: RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals, extracted from PAXgene RNA blood solution with the PAXgene Blood RNA Kit using DNase digestion and an additional clean-up using RNEasy MinElute kit.	Co-expression
SRP192719	PAX5 promotes progression of neuroendocrine prostate cancer	Analysis of prostate adnocarcinoma cell line LNCaP cells overexpression pair box 5 (PAX5) for up to 4 days. The goals of this study are to compare PAX5 overexpression in LNCaP cell drives transcriptome profiling (RNA-seq) changes. Overall design: Examination of 6 samples of LNCaP cells including 3 vector lines and 3 overexpression PAX5 lines	Co-expression
SRP192764	TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions	We sought to describe in detail human MAIT cell activation using a transcriptomic approach to define the basic transcriptome of MAIT cells in  humans and to determine how this is modulated by activation. Fresh human peripheral blood cells were obtained from three donors, and were magnetically enriched on CD8+ cells, and flow-sorted for live CD161++TCR Va7.2+ MAIT cells. These were cultured in media for 20 hours (“unstimulated”) or in the presence of anti-CD3/CD28 TCR beads (T), cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml), or TCR beads and cytokines combined (TC).  Overall design: Illumina sequencing of human MAIT cells. 3 biological replicates of each of the following conditions: Human peripheral blood MAIT cell unstimulated. Human peripheral blood MAIT cells stimulated for 20 h with anti-CD3/CD28 beads. Human peripheral blood MAIT cells stimulated for 20 h with cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml). Human peripheral blood MAIT cells stimulated for 20 h with anti-CD3/CD28 beads and cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml). Full details of the study can be downloaded at https://www.biorxiv.org/content/early/2018/11/26/475913	Co-expression
SRP192823	Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells	Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded. Overall design: Single-cell RNA-seq analysis of human liver lymphatic endothelial cells.	Co-expression
SRP192834	Transcriptomic of MKD (MUC1 kidney disease) patient compares to normal derived kidney epithelial cells	bulk RNAseq of MUC1 kidney disease patient derived kidney epithelial cells compare to normal kidney cells. The goal of this study was to elucidate the biological mechanism underlying MUC1 kidney disease using MUC1 expressing cells derived from either a patient or a healthy individual kidney Overall design: Bulk RNAseq of immortalized patient compare to normal cell line	Co-expression
SRP192835	Drug combination of 17-AAG and Belinostat on MDA-MB-231 breast cancer cells	Breast cancer is the most common cancer that threatens women's health. While the strategy of drug combination can help to reduce adverse effects and to overcome the resistance of clinical treatment of single drug. In this work, we report the synergetic effect between a HSP90 inhibitor 17-AAG and a HDAC inhibitor Belinostat, on the triple-negative breast cancer MDA-MB-231 cells. The RNA-Seq data analysis showed that the most over-represented KEGG pathways in the combination group came from migration or invasion related genes, which were not observed in the differentially expressed genes after the treatment of 17-AAG or Belinostat alone. Overall design: The RNA-Seq data was collected for MDA-MB-231 cells after the treatment of 17-AAG, Belinostat, and the Combination of 17-AAG with Belinostat	Co-expression
SRP192966	Gene expression, methylome and splicing of THP-1 monocytic cells and THP-1-derived macrophage	Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using mRNA sequencing, bioinformatics analyses and RT-qPCR validation, we identified differential IR and altered expression of key genes involved in macrophage development and function, both in vitro and in vivo. We demonstrate that decreased IR in nuclear-detained mRNA is coupled to increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts in macrophages are rapidly spliced, leading to timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular mechanisms controlling vital regulators of the innate immune response. Overall design: We determined the role of intron retention in THP-1 monocytic cells and THP-1-derived macrophage cells.	Co-expression
SRP193016	Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy	The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We unravel the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. Contrary to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy. Overall design: Global gene expression profiles of human hair follicle stem cells after alkylating chemotherapy were generated by paired-end sequencing with 100-base pair length on an Illumina HiSeq 2500 sequencer .	Co-expression
SRP193027	Transcriptome profiling of MIR148A-TKO and wild-type hESC-derived cells on day 4 of cardiac differentiaton	To gain global insights into the transcriptomic response associated with MIR148A family knockout, we performed RNA sequencing (RNA-Seq) on hESC-differentiated cells on day 4 of cardiac differentiation for both WT and MIR148A-TKO groups. RNA-Seq analysis identified a total of 1837 differentially expressed genes in MIR148A-TKO and wild-type hESC-derived cells on day 4 of cardiac differentiaton. Furthermore, Gene Ontology enrichment analysis indicated knockout of all MIR148A family members inhibited lateral mesodermal and cardiac differentiation. Overall design: RNA-seq analysis of cells derived from both the MIR148A-TKO and wild-type hESCs on day 4 of cardiac differentiation.	Co-expression
SRP193065	Generation of induced oligodendrocyte progenitor cells from human somatic cells	The goals of this study are to compare transcriptome of NGS-derived induced oligodendrocyte progenitor cells (RNA-seq) Overall design: mRNA profiles of A2B5+ iOPCs, O4+ iOPCs, OLIG2+ iOPCs, SOX10+ iOPCs, and fibroblasts were generated by deep sequencing, in triplicate, using Illumina Hiseq2500.	Co-expression
SRP193143	REPROGRAMMING IDENTIFIES FUNCTIONALLY DISTINCT STAGES OF CLONAL EVOLUTION IN MYELODYSPLASTIC SYNDROMES	As part of this study, we isolated induced pluripotent stem cells (iPSCs) from a patient with TP53-mutant MDS and identified loss of chromosome 5q as a cooperating genetic event. Using RNA sequencing we found that loss of chromosome 5q dysregulates genes that maintain chromosome stability, predisposing TP53-mutant cells to chromosomal rearrangements and progression to complex karyotype. Overall design: Hematopoietic progenitors were derived from induced pluripotent stem cells heterozygous for the TP53 R209fs mutation (TP53+/-) with or without the deletion on chromosome 5q (TP53+/-;del5q). Gene expression was compared between TP53+/- and TP53+/-;del5q HPCs by RNAseq to identify genes significantly downregulated as a result of 5q loss.	Co-expression
SRP193153	RNA-seq of Streptococcus suis infected and uninfected human choroid plexus epithelial cells	The zoonotic pathogen, Streptococcus suis, has been demonstrated to use the choroid plexus as an entry gate into the central nervous system, where it can induce meningitis. The global transcriptome of primary porine and immortal human choroid plexus epithelial cells, which were infected in vitro with S. suis, was analyzed via RNA-seq. Additionally, the choroid plexus was isolated from pigs experimentally infected in vivo with S. suis and who either suffered from meningitis or were meningitis-free. These tissue samples were also subject of global transcriptomee analysis via RNA-seq.	Co-expression
SRP193262	The relationships between anemia and ischemic stroke on RNA expression level	Anemia was characterized as a risk factor of IS because the direct connection between central nervous system, blood supply, and tissue oxygen delivery. As the key oxygen-carrying molecule in the blood, hemoglobin (Hb) may be decisive for the destiny of penumbral area or influence the brain recovery and neurologic function, which could finally affect the outcome of IS. Whole blood RNA sequencing of 4 ischemic stroke patients in recovery stage (1 anemia and 3 non-anemia) are performed at two different time points with one-month interval. The goal of the experiment is to identified the relationship between anemia-associated gene expressions and IS recovery outcomes.	Co-expression
SRP193326	De-differentiation by Adenovirus E1A Due to Inactivation of Hippo Pathway Effectors YAP and TAZ [RNA-seq]	Adenovirus-transformed cells have a de-differentiated phenotype. Eliminating E1A in transformed human embryonic kidney cells de-repressed ~2600 genes, generating a gene expression profile closely resembling mesenchymal stem cells (MSC). This was associated with a dramatic change in cell morphology from one with scant cytoplasm and a globular nucleus to one with increased cytoplasm, extensive actin stress fibers and actomyosin-dependent flattening against the substratum. E1A-induced histone hypoacetylation by p300/CBP at H3K27/18 was reversed. Most of the increase in H3K27/18ac was near TEAD transcription factors associated with their co-activators YAP and TAZ regulated by the Hippo pathway. E1A causes YAP/TAZ cytoplasmic sequestration. After eliminating E1A, YAP/TAZ were transported into nuclei where they associated with poised enhancers with DNA-bound TEAD4 and H3K4me1. This activation of YAP/TAZ required RHO-family GTPase signaling and caused histone acetylation by p300/CBP, chromatin remodeling, and cohesin loading to establish MSC-associated enhancers and then super-enhancers. Consistent results were also observed in rat embryo kidney cells, human fibroblasts and human respiratory tract epithelial cells. These results together with earlier studies suggest that YAP/TAZ function in a developmental check-point controlled by signaling from the actin cytoskeleton that prevents differentiation of a progenitor cell until it is in the correct cellular and tissue environment. Overall design: Examination of YAP, H3K18ac, H3K27ac, H3K4me1, TEAD1, TEAD4, RAD21, chromatin accessibility and mRNA by ChIP-seq, ATAC-seq, and mRNA-seq	Co-expression
SRP193374	Atypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility	Centrosomes control cell motility, polarity and migration that are thought to be mediated by their microtubule-organizing capacity. In this study we demonstrate that WNT signalling drives a distinct form of non-directional cell motility that requires a key centrosome module, but not microtubules or centrosomes.  Upon exosome mobilization of Planar Cell Polarity proteins, we show that DVL2 orchestrates recruitment of a CEP192-PLK4/AURKB complex to the cell cortex where PLK4/AURKB act redundantly to drive protrusive activity and cell motility. This is mediated by coordination of formin-dependent actin remodelling through displacement of cortically localized DAAM1 for DAAM2.  Furthermore, abnormal expression of PLK4, AURKB and DAAM1 is associated with poor outcomes in breast and bladder cancers.  Thus, a centrosomal module plays an atypical function in WNT signalling and actin nucleation that is critical for cancer cell motility and is associated with more aggressive cancers.  These studies have broad implications in how contextual signalling controls distinct modes of cell migration. Overall design: Total RNA profilling of 158 archival bladder cancer samples and comparison between 107 high grade and 51 low grade samples. This study involves 120 Samples. Thirty eight Samples were reanalyzed from previously submitted GSE59483.	Co-expression
SRP193386	Human ectocervical epithelium sequencing in response to menstrual hormones	Human 3D tissue-engineered ectocervical tissue containing differentiated epithelium and stroma were treated with cycling follicular phase hormones, luteal phase hormones, and no hormones. RNA isolated from epithelium was sequenced to determine effects of estradiol and progesterone on ectocervical mucosa throughout the menstrual cycle.	Co-expression
SRP193559	Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks	Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells.  Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. All lines maintained CFTR mRNA production and formation of tight junctions.  CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not.  Baseline expression of both cytokines was not different between the lines regardless of CFTR genotype.  All lines responded to TNFa and IL1b by increasing IL6 and CXCL8 (IL8) mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines.  Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFa, were compared for differential expression as a function of CFTR genotype.  While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation.  With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation. Overall design: Compare cells with intact CFTR to cells lacking CFTR for overall gene expression under basal and TNFa-stimulated conditions	Co-expression
SRP193759	Profiling of protrusion-enriched RNAs from human breast cancer cell line MDA-MB-231	The goals of this study are to compare the gene expression of cell protrusions and corresponding cell bodies by isolating cell protrusions from cultured MDA-MB-231 cells in a novel microfluidic device. Overall design: mRNA profiles of cell protrusions and corresponding cell bodies of MDA-MB-231 cells were gnertated by deep sequencing, in five replicates, using Illumina Hiseq 4000.	Co-expression
SRP193940	Transcriptome analysis of circulating monocytes in QFS and CFS compared to various control groups	Transcriptomes of circulating monocytes in Q fever fatigue syndrome (QFS) patients, chronic fatigue syndrome (CFS) patients, asymptomatic Q fever seropositive controls and healthy controls Overall design: Circulating monocytes from QFS patinets, CFS patients, asymptomatic Q fever seropositive controls and healthy controls were isolated from PBMCs by menas of Percoll	Co-expression
SRP193953	Transcriptional changes in the breast cancer cell line MCF7 rendered resistant to the cationic drug siramesine	Repurpusing cationic amphiphilic drugs (CADs) may be enhance the effect of chemotherapy in cancer treatment. In order to understand the molecular mechanism, we created cell lines resistant to the CAD siramesine by growing them for 6 months in increasing concentrations of siramesine. Parental and resistant cell lines were subjected to RNAseq and revealed diffentially expressed genes in ca+ and cAMP signalling pathways. Overall design: Parental and CAD resistand cell lines were profiled by RNAsequencing in dublicate and triplicate using the Illumina 2000 plarform	Co-expression
SRP193979	RNA-sequencing in human HepG2 hepatocytes reveals PPARa mediates transcriptome responsiveness of bilirubin	Bilirubin is a potent antioxidant that reduces inflammation and the accumulation of fat. There have been reports of gene responses to bilirubin, which was mostly attributed to its antioxidant function. These RNA-sequencing studies investigated the impact biliverdin, which is rapidly reduced to bilirubin, has on transcriptome responses in human HepG2 hepatocytes in a PPARa-dependent fashion. This investigation reveals that transcriptome responses from the generation of bilirubin are mostly PPARa-dependent, and its antioxidant function regulates a smaller set of genes.	Co-expression
SRP194060	Wnt5a and its downstream transcription factor Stat3 are therapeutic targets for diffuse intrinsic pontine gliomas	Understand how Wnt5a depletion affects the growth of diffuse intrinsic pontine gliomas Overall design: SF7761 and SF8628 cells are H3.3K27M mutant diffuse intrinsic pontine glioma cells, SF9427 is glioblastomas with wild type histone H3. Every cell line was treated with None-target control shRNA, two shRNAs against Wnt5a	Co-expression
SRP194102	Hominid-specific transposable elements and KRAB-ZFPs facilitate human embryonic genome activation and transcription in naïve hESCs [RNA-seq]	Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences. How they can play such an essential role in spite of their genotoxic potential is unknown. Here, we demonstrate that KRABcontaining zinc finger proteins control the timely and pleiotropic engagement of TE-derived cis-regulators of transcription. We first observed that evolutionary recent TEs of the SVA, HERVK and HERVH subgroups are major contributors to chromatin opening during human embryonic genome activation and act as KLF-stimulated enhancers in naïve embryonic stem cells. We then found that KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. We finally determined that the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific regulators of gene expression. Thus, by taming the transcriptional impact of TEs during early embryogenesis, KZFPs allow for their genome-wide incorporation into transcriptional networks, thereby contributing to the species-specificity of human genome regulation. Overall design: RNA-seq was performed in WIBR3dPE hESC in KN/2iL media or in Induced Neurons upon dCAS9-KRAB overexpression containing or not a guide RNA targeting LTR7YB or SVA/LTR5Hs or overexpressing ZNF611; in H1 primed hESC overexpressing GFP, KLF4 or KLF17	Co-expression
SRP194138	CXCR4 is a host factor that regulates Plasmodium development in hepatocytes	The liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase C?-mediated NF-?B activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca2+ levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver stage development of the P. berghei rodent malaria parasite and the human P. falciparum parasite also. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis. Overall design: To explore the molecular mechanisms by which the HGF/MET/PKC?/NF-?B pathway regulates P. berghei sporozoite development in hepatocytes, we compared the gene expression patterns in wild-type and PKC?-KO Huh7 cells treated or not treated with HGF. We also analyzed the gene expression profiles in wild type and PKC?-KO Huh7 cells uninfected or infected with P. berghei sporozoites.	Co-expression
SRP194241	Single cell analysis of human fetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors	The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human fetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of fetal liver and maintain a unique transcriptional profile distinct from fetal hepatocytes, mature hepatocytes and mature BECs.  In addition, molecular heterogenicity within the EpCAM+ population of freshly isolated fetal and adult human liver reveals diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolated fetal HHyPs and confirmed their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles. Overall design: Primary  samples from 5 2nd trimester human fetal livers and 3 uninjured adult human livers for single cell RNA sequencing by Smartseq2.	Co-expression
SRP194402	SMARTer single cell total RNA sequencing [FACS sorted cells]	Before sorting, cells were washed twice in 1X PBS buffer (DPBS without calcium chloride and magnesium chloride; Sigma Aldrich, D8537) and labelled with 7-AAD (BD Pharmingen, 51-68981E) for live/dead differentiation and FITC-conjugated antibody [anti-CD47 (BD Pharmingen, 556045) for A375 and anti-CD81 (BD Pharmingen, 551108) for Jurkat]. Overall design: single cell total RNA-seq data was generated for FACS sorted A375 and Jurkat cells	Co-expression
SRP194416	Gene expression profiling in two dimensional and extracellular matrix based three-dimensional cultures of lung and breast cancer cells	A549 and MDA-MB-231 cells were cultured in 2D and Matrigel based 3D culture for 4 days. Total RNA was extracted using Trizol. RNA-SEQ was carried out to profile the gene expression in both culture conditions. Overall design: The goal of this experiment was to profie the genes that are regulated by extracellular matrix in cancer cells. Gene expression was probed globally using RNA-SEQ.	Co-expression
SRP194549	Acquired Resistance to BET-PROTACs(Proteolysis Targeting Chimeras) Caused by Genomic Alterations in Core Components of E3 ligase Complexes	Exome and RNA sequencing of the parental OVCAR8 cell line and 2 cell lines that developed resistance to BET-PROTACS ARV-771 and ARV-825,	Co-expression
SRP194595	Single-cell RNA-Seq Investigation of Foveal and Peripheral Expression in the Human Retina	Purpose: Single-cell RNA sequencing has revolutionized cell-type specific gene expression analysis. The goals of this study are to compare cell specific gene expression patterns between retinal cell types originating from the fovea and the periphery of human eyes. Methods: Independent libraries were prepared for foveal and peripheral samples of neural retina from three donors using the 10x Chromium system. Libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 will CellRanger(v3.0.1) and filters removed cells likely to be doublets or cells with a high proportion of mitochondrial reads. Clustering of cells with similar expression profiles was performed with Seurat (v2.3.4). Results: Independent libraries were prepared for foveal and peripheral samples of neural retina from three donors using the 10x Chromium system. Libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 will CellRanger(v3.0.1) and filters removed cells likely to be doublets or cells with a high proportion of mitochondrial reads. Clustering of cells with similar expression profiles was performed with Seurat (v2.3.4). Conclusions: Our study generates a large atlas of human retinal transcriptomes at the single cell level. We identified the majority of expected neural and supportive cell types, and describe regional differences in gene expression between the fovea and the periphery. Our results show that that single-cell RNA sequencing can be performed on human retina after cryopreservation, and that cone photoreceptors and Muller cells demonstrate region-specific patterns of gene expression. Overall design: mRNA profiles for thousands of cells from foveal and peripheral retinal isolates were generated from three human donor eyes using 10X Genomics Chromium single-cell system followed by sequencing on an Illumina HiSeq 4000.	Co-expression
SRP194626	Unlocking the transcriptomic potential of formalin-fixed paraffin embedded clinical tissues: Comparison of gene expression profiling approaches [Lexogen_QuantSeq]	Background: High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades since the first mRNA profiling microarrays. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability normally preclude processing samples across multiple technologies, making it difficult to directly evaluate performance, reliability and to what extent gene expression data from different platforms can be compared or integrated. Purpose: In this study, we describe our experiences using nine new and established mRNA profiling techniques including Lexogen QuantSeq, Qiagen QiaSeq, BioSpyder TempO-Seq, Ion AmpliSeq, Nanostring, Affymetrix Clariom S or U133A, Illumina BeadChip and Ion Total RNA-seq of formalin-fixed paraffin embedded (FFPE) and fresh frozen (FF) sequential patient-matched breast tumour samples. Results: The number of genes represented and reliability were found to vary between the platforms, but overall all methods provided data which were largely comparable. Crucially we found that it is possible to integrate data for combined analyses across FFPE/FF and platforms using established batch correction methods as required to increase cohort sizes. However, some platforms appear to be better suited to FFPE samples, particularly archival material. Overall, we illustrate that technology selection is a balance between required resolution, sample quality, availability and cost. Overall design: Sequencing of patient-matched sets of human breast cancer biopsy samples using 9 different mRNA profiling platforms. We assess the feasibility of integrating data from FFPE or FF tissue sequenced using different platforms and compare these different technoolgies.	Co-expression
SRP194727	Unlocking the transcriptomic potential of formalin-fixed paraffin embedded clinical tissues: Comparison of gene expression profiling approaches [RNA-Seq]	Background: High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades since the first mRNA profiling microarrays. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability normally preclude processing samples across multiple technologies, making it difficult to directly evaluate performance, reliability and to what extent gene expression data from different platforms can be compared or integrated. Purpose: In this study, we describe our experiences using nine new and established mRNA profiling techniques including Lexogen QuantSeq, Qiagen QiaSeq, BioSpyder TempO-Seq, Ion AmpliSeq, Nanostring, Affymetrix Clariom S or U133A, Illumina BeadChip and Ion Total RNA-seq of formalin-fixed paraffin embedded (FFPE) and fresh frozen (FF) sequential patient-matched breast tumour samples. Results: The number of genes represented and reliability were found to vary between the platforms, but overall all methods provided data which were largely comparable. Crucially we found that it is possible to integrate data for combined analyses across FFPE/FF and platforms using established batch correction methods as required to increase cohort sizes. However, some platforms appear to be better suited to FFPE samples, particularly archival material. Overall, we illustrate that technology selection is a balance between required resolution, sample quality, availability and cost. Overall design: Sequencing of patient-matched sets of human breast cancer biopsy samples using 9 different mRNA profiling platforms. We assess the feasibility of integrating data from FFPE or FF tissue sequenced using different platforms and compare these different technoolgies.	Co-expression
SRP195418	Transcriptome Signature of Cellular Senescence	Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes.  At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and ß-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells.  To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V.  The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs.  We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically. Overall design: Transcriptomic analysis of various cell line models of senescence and their respective controls	Co-expression
SRP195539	Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease	It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271+ NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271+ cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271+ NSCs to the SVZ homogenate from control donors to assess the CD271+ NSCs gene signature and finally made a comparison between controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also suggest that NSCs may transit into a primed-quiescent state, that is in an “alert” non-proliferative phase in PD. Overall design: From post-mortem human SVZ of control and Parkinson disease donors we isolated CD271+ NSCs and Cd11b+ microglia by MACS and the whole SVZ to generate RNA sequencing libraries using Celseq2 method. We aimed for low coverage sequencing (~2 million mapped to the coding regions) per sample to investigate the gross changes in the transcriptome. Libraries (rpi small primer) were sequenced in 3 runs, 2 on an Illumina NextSeq500 using 75-bp paired-end sequencing at the Utrecht Seuqencing center (USEQ) and the third on a HiSeq4000 using 150-bp paired-end sequencing at Genomescan. All the samples were mapped in a single run to an average depth of ~10 million reads per sample. Reads were mapped to the latest human coding transcriptome using bwa, normalized and analyzed using the standard DESEQ2 package.	Co-expression
SRP195616	Identification of trans regulators of ADAR and A-to-I RNA editing using RNA-seq	A-to-I RNA editing levels differ across tissues and cell types, but regulators of the editing process are largely unknown. We performed RNA-seq on M17 and HeLa cells with overexpression of different candidate Adar regulators and GFP as a control to assay editing level differences between overexpression and control. Overall design: To assay the effects of overexpressing candidate Adar regulators on A-to-I RNA editing levels, we transiently overexpressed ILF2, IL3, and STRBP in H293T cells and H293T cells stably overexpressing Adar2. We extracted RNA and made RNA-seq libraries. We sequenced two biological replicates of GFP overexpression (OE) controls and two replicates of  ILF2, ILF3, and STRBP overexpression.	Co-expression
SRP195743	Human Thoracic Duct Lymph Contains Circulatory Intermediates T Follicular Helper Cells [RNA-Seq]	T follicular helper CD4 T cells (Tfh) provide requisite help to B cells in the germinal centers (GC) of lymphoid tissue. GC Tfh are identified by high expression of the chemokine receptor CXCR5 and the inhibitory molecule PD-1. Although more accessible, blood contains lower frequencies of CXCR5+ and PD-1+ cells that have been termed circulating Tfh (cTfh). However, it remains unclear whether GC Tfh exit lymphoid tissues and populate this cTfh pool. To examine exiting cells, we assessed the phenotype of Tfh present within the major conduit of efferent lymph from lymphoid tissues into blood, the human thoracic duct. Unlike blood, we consistently identified a CXCR5-Bright PD-1-Bright (CXCR5BrPD-1Br) Tfh population in thoracic duct lymph (TDL). These CXCR5BrPD-1Br TDL Tfh shared phenotypic and transcriptional similarities with GC Tfh. Moreover, components of the epigenetic profile of GC Tfh could be detected in CXCR5BrPD-1Br TDL Tfh, and the transcriptional imprint of this epigenetic signature was enriched in an activated cTfh subset known to contain vaccine-responding cells. Together with data showing shared TCR sequences between the CXCR5BrPD-1Br TDL Tfh and cTfh, these studies identify a population in TDL as a circulatory intermediate connecting the biology of Tfh in blood to Tfh in lymphoid tissue. Overall design: Transcriptional features of germinal center Tfh were detected in a population of Tfh in the efferent lymph of the human thoracic duct and can be traced to an activated subset of circulating Tfh in blood.	Co-expression
SRP195777	Identification of HIV Transmitting CD11c+ Human Epidermal Dendritic Cells	Langerhans cells (LC) represent one of the first lines of contact between the immune system and sexually transmitted pathogens, and in the human epidermis LCs have been thought to represent the only mononuclear phagocyte (MNP) population. Here we show an additional epidermal MNP subset that can be distinguished from LCs phenotypically as CD11chi, CD1c+ MR+ (epidermal CD11c+ DCs). These cells are transcriptionally similar to dermal cDC2 but express higher levels of costimulatory markers and are more efficient at T cell stimulation. Importantly, compared to LC, epidermal CD11c+ DCs are i) enriched in the epithelium of anogenital tissues where they preferentially interact with HIV, ii) express the higher levels of the HIV entry receptor CCR5, iii)  support the higher levels of HIV uptake and replication and iv) are more efficient at transferring virus to CD4 T cells. Importantly these findings were observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a cell population that can be discerned from LCs by their lower surface expression of CD45, HLA-DR and CD33 (epidermal CD33low cells). These are transcriptionally similar to LCs but do not appear to function as APCs as do not secrete cytokines, express negligible amounts of costimulatory molecules and are very weak inducers of T cell proliferation. They also do not act as HIV target cells. Our findings reveal a new subset of epidermal DCs in skin and anogenital tissues with a potential key role in sexual transmission of HIV. Overall design: Sorted cell populations from four donors were captured directly into lysis buffer and polyA RNA transcripts were reverse transcribed, amplified and sequenced using the Smart-seq 2 protocol described by Picelli et al (Nature Methods. 2013;10(11):1096-8).  Each sample was sequenced across 4 HiSeq lanes and the data for each lane is represented as an independent sample (GSM).	Co-expression
SRP196721	Identification of SERPINE1 as a Regulator of Glioblastoma Cell Dispersal via Analyzing Dynamic Transcriptome of Dispersing Cells	With a model mimicking GBM tumor cell dispersal, transcriptome changes between core (immotile) and dispersive (motile) cells were analyzed. Many genes are differentially expressed between these populations. This study focused on the genes that are significantly upregulated in dispersive cells. Besides gene sets related with the cell cycle and cell survival, epithelial to mesenchymal transition gene set is upregulated in dispersive cells. In this gene set, this study identified SERPINE1 gene as an important regulator of GBM cell dispersal. Overall design: Examination of core and dispersive populations' transcriptome during U373 cell spheroid dispersal. 2 sets of samples were prepared each for core and dispersive cells.	Co-expression
SRP197074	Evaluation of ultra-low input RNA sequencing for the study of human T cell transcriptome	Deeper understanding of T cell biology is crucial for the development of new therapeutics.  Human naïve T cells have low RNA content and their numbers can be limiting; therefore we set out to determine the parameters for robust ultra-low input RNA sequencing.  We performed transcriptome profiling at different cell inputs and compared three protocols: Switching Mechanism at 5' End of RNA Template technology (SMART)  with two different library preparation methods (Nextera (SMART_Nxt) and Clontech (SMART_CC)), and AmpliSeq technology.  As the cell input decreased the number of detected coding genes decreased with SMART, while stayed constant with AmpliSeq. However, SMART enables detection of non-coding genes, which is not feasible for AmpliSeq. The detection is dependent on gene abundance, but not transcript length. The consistency between technical replicates and cell inputs was comparable across methods above 1K but highly variable at 100 cell input. Sensitivity of detection for differentially expressed genes decreased dramatically with decreased cell inputs in all protocols, support that additional approaches, such as pathway enrichment, are important for data interpretation at ultra-low input.  Finally, T cell activation signature was detected at 1K cell input and above in all protocols, with AmpliSeq showing better detection at 100 cells. Overall design: Primary human naïve CD4 T cells were treated with a-CD3 only or a-CD3 and B7-1 Fc, which stimulate T cell activation, for 2 hours.  Next, the cells were collected and serially diluted to achieve 100K, 5K, 1K and 100 cells. Finally, RNA was extracted and transcriptome library was generated with two different protocols: SMART-Seq and AmpliSeq.  For SMART-Seq technology, two different library preparation kits were utilized: Nextera Library Preparation Kit (SMART_Nxt) and Clontech Library Preparation kit (SMART_CC)	Co-expression
SRP197235	Human PRPF40B knock-out in K562 CML cell line	We characterized the transcriptomic regulation of PRPF40B, which is a splicing factor mutated in a small fraction of MyeloDysplastic Syndromes (MDS) patients. We generated a full PRPF40B knockout in K562 cell line by CRISPR/Cas9 technology, and rescued its levels by transient overexpression of wild-type, P383L or P540S MDS alleles.	Co-expression
SRP197353	Gene expression predicts histological severity and reveals distinct molecular profiles of nonalcoholic fatty liver disease	Transcriptomic analysis of liver biopsies that cover the spectrum of nonalcoholic fatty liver disease reveals genes that are progressively regulated over the course of the disease. This study demonstrates that progressive changes in expression of these genes can be used to approximate the histological grade of a liver biopsy. Furthermore, the relative progression profiles of these disease-responsive genes are shown to be distinct across patient biopsies. This observation suggests that there may be distinct biological processes that drive disease progression across individuals Overall design: This dataset contains transcriptomic profiles of 78 distinct human liver biopsies.  Of these, 6 are histologically normal, and 72 cover the full spectrum of nonalcoholic fatty liver disease (NAFLD activity score 0-6, fibrosis stage 0-4).	Co-expression
SRP197580	Group 3 innate lymphoid cells mediate early protective immunity against Mycobacterium tuberculosis	We report the phenotype of human lung ILC2 and ILC3 populations from individuals with tuberculosis (TB) and non-TB cancer controls. We find that ILC2s demonstrate moderate transcriptional differences in TB infection, whereas ILC3s demonstrate large differences. Overall design: ILC2s and ILC3s were purified by FACS from lung biopsies from TB infected lung tissue and peripheral healthy lung tissue from individuals with cancer. Low-input RNA-seq was performed on 1-3 replicates (dependent on cell number) on 5 individuals with TB infection and 2 controls.	Co-expression
SRP198183	Transcriptomic profiling of O-GlcNAcylated mRNA-protein complexes by using OG-CLAP in HeLa cells.	We report the development of OG-CLAP strategy and the identification of 9840 high-confidence O-GlcNAcylated binding sites by using OG-CLAP. The sequencing depth of each replicate is about 1.3 G. Overall design: Identification of the RNA binding sites of O-GlcNAcylated proteins by using OG-CLAP strategy.	Co-expression
SRP198212	Differential gene expression in human RAF1 S257L/+ and isogenic corrected iPSC-derived cardiomyocytes	Although several studies have uncovered abnormal signaling pathways in RASopathy disorders, little is known about the alterations of the cardiac transcriptome induced by Noonan syndrome (NS) mutations. Hence, to gain insights into the transcriptional alterations induced by the NS-associated RAF1S257L/+ mutation in human iPSC-derived cardiomyocytes, we performed quantitative transcriptome profiling by RNA-sequencing. Since we have found that inhibition of ERK5 and MEK1/2 pathways could normalized hypertrophy and myofibrillar disarray in mutant cardiomyocytes, we also aimed at identifying gene transcriptional profiles that were specifically affected by either MEK5-ERK5 or MEK1/2-ERK1/2 activation in RAF1S257L/+ iCMs. Overall design: mRNA profiles of  human RAF1 S257L/+ and isogenic corrected iPSC-derived cardiomyocytes were generated by RNA-sequencing, in triplicate, using Ion S5.	Co-expression
SRP198242	RNA-seq of circulating Tfh like cells at day zero and seven and 28 relative to experimental vaccination dosing	Total RNA-sequencing on 150-200 ICOS+CD38+ cTfh cells per person prior to vaccination (day 0), and seven (day 63) and 28 (day 84) days after the third vaccination. Overall design: Blood samples were taken from healthy volunteers taking part in a Phase 1b clinical trial. mRNA was isolated from flow sorted circulating Tfh cells (CD4+CD45RA-CXCR5+PD1+ICOS+CD38+ cells) and RNA-sequencing performed on cTfh from days 0, 7 and 28 reletive to vaccination	Co-expression
SRP198243	RNA-sequencing of human lymph node and peripheral blood T follicular helper cells	Total mRNA-sequencing on memory T helper cell populations from human blood and lymph nodes. Overall design: Paired blood and lymph node samples were taken from patients recruited from the renal transplant live donor program at Cambridge University Hospitals NHS Foundation Trust, and who provided informed consent. All patients were either receiving or within 6 months of requiring renal replacement therapy. Patients taking immunosuppressive medication prior to transplant were excluded. mRNA was isolated from flow sorted CD4+ T cell populations and RNA-sequencing performed.	Co-expression
SRP198353	Transcriptomic and Chromatin accessibility profiling of functional brown adipocytes derived from human pluripotent stem cells	Brown adipocytes (BAs) are a potential therapeutic cell source for the treatment of metabolic disease such as type 2 diabetes. In this report, human pluripotent stem cells (hPSCs) are subject to directed differentiation to brown dipocytes through a paraxial mesoderm intermediate at high-efficiency. RNA-Seq and ATAC-seq was performed to characterized hPSCs derived paraxial mesoderm and brown adipocytes generated in this study. Overall design: RNA-Seq was perfomed on iPSC and hESC derived paraxial mesoderm, iPSC and hESC derived full differentiated brown adipocytes. The differentiation process of  brown adipocytes was also interrogated by RNA-Seq profiling at various differentiation time points. Time-course ATAC-Seq profiling was perfomed to interrogate the early differentiation process from paraxial mesoderm to brown adipocytes at early differentiation stages.	Co-expression
SRP198408	RNA sequencing in human GBM stem cells with Myc knockdown and PARP inhibitor treatment	This experiment is to examine the effect of PARP inhibitor and Myc shRNA knockdown on transcriptome profiles in MYC-amplified human GBM stem cells MGG4. Overall design: There are totally 4 samples. GBM cell MGG4 expressing scramble shRNA or shRNA targeting Myc were grown in doxycycline (Dox, 1 mg/ml) for 6 days, treated with olaparib (Ola, 10 microM) or DMSO for 24h, and harvested for RNA extraction, followed by RNA sequencing	Co-expression
SRP198410	RNA-seq analysis of HIV-specific T cell subsets in HIV-1 Virus Controllers	We sought to use RNA-sequencing to determine the ontogeny and anti-viral properties of HLA class II-restricted CD8+ T cells in HIV-1 Virus Controllers in comparison with conventional HLA class I-restricted CD8+ T cells and HLA class II-restricted CD4+ T cells. The ultimate goal was determine whether unconventional HLA class II-restricted CD8+ T cells expressed genes associated with CD8+ T cell-mediated HIV-1 virus control, and also investigate whether class II-restricted CD8+ T cells expressed CD4 and CD8+ T cell lineage-specific transcripts.	Co-expression
SRP198444	Transcriptional control of subtype switching ensures adaptation and growth of pancreatic cancer	Purpose: The goal of this study is to determine whether ectopic expression of the GLI2 transcription factor in the human pancreatic cancer cell line, YAPC is sufficient to cause gene expression changes associated with a EMT switch. Methods: RNA was isolated from YAPC cells engineered to express a doxycycline inducible cassette for ectopic expression of GLI2 following treatment with 1ug/ml of Dox for 6 days. Control YAPC cells expressing an "empty vector" dox inducible cassette were similarly treated for 6 days with 1ug/u Dox and RNA was collected. Three biologically destinct replicates were submitted for library preparation and RNA-sequencing on an Illumina hiseq 2000. The sequence reads that passed quality filters were analyzed at the transcript level using TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays Results: RNA-seq data confirmed stable over-expression of GLI2 in the YAPC-rtta-GLI2 cells and not in the EV control cells treated with Dox. Target genes of interest were validated by qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for all target genes tested.  Gene set enrichment analysis of differentially expressed genes showed enrichment of EMT associated pathways which was further validated using functional assays. In addition a statistically significant alteration in SPP1 transcript was discovered in GLI2 overexpressing cells which formed the basis of ongoing experiments in the study. Conclusions: Our data support a role for GLI2 in regulation of genes associated with basal-like subtype switching including SPP1 Overall design: mRNA profiles from human pancreatic cancer cell lines YAPC-rtta-GLI2 and YAPC-rtta-EV treatment with doxycyline for 6 days were compared, in triplicate.	Co-expression
SRP198486	High-throughput sequence analysis of peripheral T-cell lymphomas indicates subtype specific viral gene expression patterns and immune cell microenvironments	Certain peripheral T-cell lymphomas (PTCLs) have been associated with viral infection, particularly infection with Epstein-Barr virus (EBV). However, a comprehensive virome analysis across PTCLs has not previously been reported, and viral gene expression profiles have been studied only in certain PTCL subtypes. In this study we utilized published RNA-seq data sets from seven different PTCL studies as well as new RNA-seq data from our laboratory to screen for virus association, to analyze viral gene expression, and to assess B- and T-cell receptor diversity paradigms across these tumor types. In addition to identifying EBV in angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T cell lymphoma (ENKTL), two PTCL subtypes with well-established EBV associations, we also detected EBV in several cases of anaplastic large cell lymphoma (ALCL), and we found evidence of infection by the oncogenic viruses KSHV and HTLV-1 in isolated PTCL cases. In AITLs, EBV gene expression analysis showed expression of immediate early, early and late lytic genes, suggesting either abortive lytic replication and/or productive infection in a subset of the EBV infected infiltrating B-lymphocytes. Deconvolution of immune cell subpopulations demonstrated a greater B-cell signal in AITLs than in other PTCL subtypes, consistent with a larger role for B-cell support in the pathogenesis of AITL. T-cell receptor (TCR) and B-cell receptor (BCR) repertoires reconstructed from RNA-seq data demonstrated increased BCR diversity in AITLs, consistent with a possible EBV-driven polyclonal response. These findings indicate potential alternative roles for EBV in PTCLs in addition to the canonical oncogenic mechanisms associated with EBV latent infection. The findings also suggest the involvement of other viruses in T-cell lymphoma pathogenesis and demonstrate immunological alterations associated with these cancers. Overall design: RNA sequencing of five extranodal NK/T-cell lymphoma (ENKTL)-derived cell lines	Co-expression
SRP198554	JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors	Tumor-associated macrophages contribute to tumor progression and therapeutic resistance in breast cancer. Within the tumor microenvironment, tumor-derived factors activate pathways that modulate macrophage function. Using in vitro and in vivo models, we find that tumor-derived factors induce activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in macrophages. We also demonstrate that loss of STAT3 in myeloid cells leads to enhanced mammary tumorigenesis. Further studies show that macrophages contribute to resistance of mammary tumors to the JAK/STAT inhibitor ruxolitinib in vivo and that ruxolitinib-treated macrophages produce soluble factors that promote resistance of tumor cells to JAK inhibition in vitro. Finally, we demonstrate that STAT3 deletion and JAK/STAT inhibition in macrophages increases expression of the pro-tumorigenic factor cyclooxygenase-2 (COX-2) and that COX-2 inhibition enhances responsiveness of tumors to ruxolitinib. These findings define a novel mechanism through which macrophages promote therapeutic resistance and highlight the importance of understanding the impact of targeted therapies on the tumor microenvironment. Overall design: Primary human macrophages were treated with breast tumor cell (MCF7, MDA-MB-231, or control) conditioned medium, in combination with ruxolitinib (or control), and processed for gene expression analysis in triplicate. Bone marrow derived macrophages from STAT3 wild type or STAT3 conditional knockout mice were extracted and were processed for gene expression analysis in triplicate.	Co-expression
SRP198593	Transcriptome profiling data from persistently infected urothelial cell carcinoma (UCC) treated with Newcastle disease virus	Newcastle disease virus (NDV) is an avian virus that selectively replicates and kills many different types of cancer cells and is being developed for cancer treatment. Our aim was to establish persistent infection in EJ28 and TCCSUP bladder cancer cells and identify the dysregulated genes and disrupted molecular pathways associated with persistent infection.	Co-expression
SRP198641	The X-linked DDX3X RNA helicase dictates translation re-programming and metastasis in melanoma	The X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes we identified the microphtalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' untranslated region. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas. Overall design: We sequenced transcripts associated with translationally active ribosomes (polysomes) isolated by sucrose gradient fractionation from DDX3X and control siRNA-transduced HT144 cells. Experiments were performed in duplicates.	Co-expression
SRP198743	Characterization of long-noncoding RNA  in hepatocellular carcinoma cells with fractionation-then-sequencing	Advancements in sequencing technologies greatly improved our understanding of long non-coding RNA (lncRNA), a class of transcript of length >200nt implicated to play significant regulatory roles in various biological processes. Importantly, deregulation of better characterized lncRNAs have been linked to multiple types of cancers including hepatocellular carcinoma (HCC). The patterns of lncRNA subcellular enrichment in either cytoplasmic or nuclear fraction may provide clues to their biological functions. A transcriptome-wide investigation on the subcellular distributions of HCC-associated lncRNAs might thus provide new insights on their roles and function in cancers.In this study, we performed subcellular fractionation of 8 patient-derived HCC cell lines and separately sequenced RNA residing in their nuclear and cytoplasmic compartments. The cell lines were derived from HCC patient tumor tissues, where all patients are of Asian-Chinese ethnicity and were diagnosed with either prior chronic hepatitis B/C or nonalcoholic steatohepatitis (NASH). The dataset enabled us to derive a catalog of HCC-associated lncRNA with ab initio transcriptome assembly, and to evaluate the subcellular enrichment bias for individual lncRNA genes.	Co-expression
SRP198803	Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons	The autism-associated synaptic-adhesion gene Neuroligin-4 (NLGN4) is poorly conserved evolutionarily, limiting conclusions from Nlgn4 mouse models for human cells. Here, we show that the cellular and subcellular expression of human and murine Neuroligin-4 differ, with human Neuroligin-4 primarily expressed in cerebral cortex and localized to excitatory synapses. Overexpression of NLGN4 in human neurons resulted in an increase in excitatory synapse numbers but a remarkable decrease in synaptic strength. Human neurons carrying the syndromic autism mutation NLGN4-R704C also formed more excitatory synapses but with increased functional synaptic transmission due to a postsynaptic mechanism, while genetic loss of NLGN4 did not significantly affect synapses in the human neurons analyzed. Thus, the NLGN4-R704C mutation represents a change of function mutation. Our work reveals contrasting roles of NLGN4 in human and mouse neurons, suggesting human evolution has impacted even fundamental cell biological processes generally assumed to be highly conserved. Overall design: We compared the global gene expression profiles of induced neuronal (iN) cells. iN cells were derived from human embryonic stem cells (H1) by expression of transcription factors. Ngn2 was used to generate Ngn2-iN, Alsc1 and Dlx2 to generate AD-iN cells and Alsc1 and Myt1l to generate AM iN cells. AM and Ngn2 iN cells are glutamatergic neurons whereas AD iN cells are GABAergic. Mature iN cells cultured with mouse glia (6 weeks after transgene induction) were dissociated with Trypsin and FACS-sorted in Trizol LS. To distinguish from glial cells, iN cells were transduced with a lentiviral vector expressing EGFP under the control of CAG promoter together with the reprogramming transcription factors.	Co-expression
SRP198909	Expression analysis of ethanol treatment on SK-N-BE(2)	To evaluate the impact of ethanol treatment on neuronal cells, we examined the expression of SK-N-BE(2) neuronal cell line 24 h and 42 h after treating with 10 mM and 20 mM ethanol by RNA sequencing. Overall design: RNA-seq results from 4 replicates of SK-N-BE(2) cells with 0, 10 mM, and 20 mM ethanol harvest after 24 h and 42 h	Co-expression
SRP198932	Homo sapiens Transcriptome or Gene expression	AGO1 RIP-Seq from chromatin associated RNAs	Co-expression
SRP198959	Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein, IFITM3	Senescence is a cellular phenotype present in health and disease, characterized by a stable cell cycle arrest and an inflammatory response, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behaviour of neighbouring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors in addition to small extracellular vesicles (sEV) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEV, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. Interestingly, we find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify the Interferon Induced Transmembrane Protein 3 (IFITM3) as partially responsible for transmitting senescence to normal cells. Altogether, we found that sEV contribute to paracrine senescence. Overall design: SASP related mRNA transcripts in HFFF2 treated with sEV from iRAS cells in comparison with HFFF2 treated with sEV from iC cells	Co-expression
SRP198996	Radiation enhances melanoma response to immunotherapeutic and synergizes with benzodiazepines to promote improved anti-tumor activity	The RNA-Seq data of 17 brain metastatic samples short-read sequences were aligned to the hg19 human reference genome using STAR (v 2.4.1a). featureCounts was used to count the reads of the mapped bam files. SAMseq was used to conduct differential expression analysis among the two treatment groups. SAMseq was utilized as it accounts for potential correlation in expression among genes and its permutation-based testing method was deemed more appropriate for a smaller sample size. After identifying the differentially expressed genes (FDR cut-off, 0.05), expression levels were normalized with the samr R package before being log2 transformed. This data was utilized to generate a heatmap with the patients sorted with supervised clustering based upon their immunotherapy/radiation groups and the gene dendrogram was created with Pearson's Correlation Coefficient and with the Ward D2 linkage method. Differentially expressed genes (FDR<0.05[KD1] ) were subjected to pathway analysis using MetaCore. Overall design: Differential expression analysis across two different patient groups based upon their timing of immunotherapy and radiation therapy.	Co-expression
SRP199046	Gene amplification driven-long noncoding RNA SNHG17 regulates cell proliferation and migration in human non-small cell lung cancer	Our findings indicated gene amplification driven-long noncoding RNA SNHG17 promotes cell proliferation and migration in NSCLC, suggesting its potential value as biomarker in NSCLC. Overall design: RNA-seq analysis of SNHG17 knockdown in one cell type	Co-expression
SRP199155	MCF7 Cell Line Sequencing	MCF7 breast cancer cell lines have been sequenced in order to identify fusion events.	Co-expression
SRP199238	Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression	Using machine learning to identify biological targets for natural products with anticancer properties and unknown modes of action is gaining momentum. Herein, we employ machine intelligence to deconvolute the phenotypic effects of the natural product Piperlongumine (PL) and establish an unprecedented link to allosteric modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. Using cryo-electron microscopy (cryo-EM), we determined the structure of the PL-bound full-length rat TRPV2 channel at an overall resolution of 3.4 Ã…. We disclose binding of PL to a novel allosteric pocket which is responsible for a new mode of anticancer activity by PL, in particular against the aggressive glioblastoma (GBM), where TRPV2 is overexpressed. By creating CRISPRi TRPV2 knockdown GBM cells we found that the down-regulation of TRPV2 reduces sensitivity to PL and decreases ROS production. By analyzing GBM patients' samples, we associated TRPV2 overexpression with tumor grade, disease progression and poor prognosis. Finally, formulating PL for sustained local therapy, we obtained tumor remission in a murine model of orthotopic GBM. Altogether, our strategy for target identification counter cycles established methods is broadly applicable and leverages data-motivated research hypotheses for the swift discovery of new biology and therapeutics. Overall design: 12 Samples, wild type and TRPV2 CRISPRi KD and 2 treatments	Co-expression
SRP199287	Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+ T regulatory cells activation	We recently described the phenotype of HepG2 and Huh-7, hepatocellular carcinoma cells, knocked down for histone variant macroH2A1. Both cell lines acquire a cancer stem cell phenotype (Lo Re O et al., Hepatology 2017, PMID: 28913935; Lo Re O et al., Epigenetics 2018, PMID: 30165787). We found that short hairpin RNA-mediated macroH2A1 knockdown induced acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolytic pathways. As macroH2A1 is a potent transcriptional modifier we asked how KD of this histone variant might affect patterns of gene expression, and whether we could identify potential mechanistic links to the observed in vitro and in vivo HCC phenotypes.   Here we used RNA-Seq to gain deep mechanistic insight into the distinct functions of macroH2A1 KD and conditioned medium (CM)-exposed Huh-7 cells. Heatmap analysis of the differentially expressed genes between the three groups revealed a similar transcriptomic profile between KD and CM, compared to the control condition. Genes were considered differentially expressed between groups if their expression values significantly differed by >2 fold. Statistical differences in gene expression were assessed by the ANOVA test. Correction for multiple test was achieved by the Benjamini-Hochberg procedure. The significance threshold was set to 0.05.  Using a cut-off of 2 fold change, assessment of differentially expressed genes for Huh-7 macroH2A1 KD  or Huh-7 CM KD versus CTL showed no transcriptional overlap between the different Huh-7 cell lines. 783 and 987 genes were instead significantly differentially-expressed in macroH2A1 KD or CM KD versus control cells, respectively. Interestingly, the significantly enriched transcripts over-represented in KD and CM-exposed cells compared to control cells were implicated in a number of functions and diseases that were also shared between CM versus control comparisons. Specifically, Ingenuity pathway analysis (IPA) identified categories of cancer, gastrointestinal diseases, lipid metabolism, cell-to-cell signaling, nucleic acid metabolism, cell death & survival and others, in common between KD versus CTL and CM versus CTL. These data support a paracrine modulation of gene expression by macroH2A1 KD in HCC cells. Overall design: Profiling the transcriptome of hepatocellular carcinoma cells Huh-7 control, knocked-down (KD) for macroH2A1,  or exposed to conditioned medium from KD cells, using RNA-Seq.	Co-expression
SRP199405	Possible molecular mechanisms for the roles of microRNA-21 played in lung cancer	we aimed to find the possible molecular mechanisms for the roles of microRNA-21(miRNA-21) played in lung cancer.MiRNA21-5p inhibitor was transfected into A549 cells. Then, RNA was extracted and RT-PCR was conducted. After obtaining good results, mRNA sequencing was performed. We find that miRNA-21 may play significant roles in lung cancer partly via MCM10 and CDCA8. Furthermore, miRNA-21 targeted CDCA8 and then played roles in lung cancer via the process of cell division. Tfdp3 and RAD21 are important TFs in miRNA-21 interfered lung cancer.	Co-expression
SRP199439	Transcriptomes of human trophoblast cell lines	We report the transcriptomes of human choriocarcinoma cell lines JEG3 and BeWo in order to provide information about genes expressed by human trophoblasts. Overall design: Examination of transcriptomes in two cell lines, two samples in each cell line.	Co-expression
SRP199644	Generating Patterned Kidney Organoids for Studying Development and Diseases [bulk RNA-Seq]	Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening. Overall design: Examination of transcriptome in human pluripotent stem cells-derived vascularized three-dimensional kidney organoids. Day 0 organoid (technical duplicate), Day 10 organoid (technical duplicate), Day 24 organoid (technical duplicate), 2-week implanted organoid (technical triplicate), 4-week implanted organoid (technical triplicate).	Co-expression
SRP199923	Global gene expression profile of human peripheral blood-derived endothelial colony-forming cells is similar to coronary artery and umbilical vein endothelial cells	We performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) utilising subcutaneous adipose tissue-derived stromal vascular fraction (SAT-SVF) as a negative control population. Baseline gene expression in ECFC fully corresponds to their endothelial specification and may contribute to the basement membrane organisation, fulfilling the requirements for the suitable cell population for in vitro pre-endothelialisation of tubular scaffolds. Overall design: Comparison of gene expression in 4 cell types by Hiseq sequencing.	Co-expression
SRP199983	RNA-seq of DV90 cells with REG4 siRNA	DV90 cells with REG4 siRNAs were subjected to RNA isolation and RNA-seq analyses were generated by deep sequencing using Illumina Hiseq. Overall design: RNA-seq analyses of DV90 cells with REG4 siRNA by deep sequencing using Illumina Hiseq.	Co-expression
SRP199991	LPS-induced gene expression changes in phraryngeal epithelial cells	Gram negative endotoxin Lypopolysaccharide (LPS) leads to a strong innate immune response through TLR4 signalling. This latter pathway activates cannonical NF-kB pathway, including its member RELA. Here, we want to investigate the gene expression response induced by LPS recognition. Overall design: Treatment of FaDu cells with LPS and examination of gene expression response after stimulation compared to before by RNA-seq. Two biological replicates were analyzed for each condition.	Co-expression
SRP200058	Systematic comparative analysis of single cell RNA-sequencing methods	A multitude of single-cell RNA sequencing methods have been developed in recent years, with dramatic advances in scale and power, and enabling major discoveries and large scale cell mapping efforts. However, these methods have not been systematically and comprehensively benchmarked. Here, we directly compare seven methods for single cell and/or single nucleus profiling from three types of samples – cell lines, peripheral blood mononuclear cells and brain tissue – generating 36 libraries in six separate experiments in a single center. To analyze these datasets, we developed and applied scumi, a flexible computational pipeline that can be used for any scRNA-seq method. We evaluated the methods for both basic performance and for their ability to recover known biological information in the samples. Our study will help guide experiments with the methods in this study as well as serve as a benchmark for future studies and for computational algorithm development. Overall design: We systematically and directly compared seven single cell RNA-sequencing methods, including two low-throughput plate-based methods (Smart-seq2 and CEL-Seq2) and five high-throughput methods (10x Chromium (v2, v3), Drop-seq, Seq-Well, inDrops, and sci-RNA-seq), producing expression profiles from ~92,000 cells (nuclei) overall. We tested three sample types – a mixture of human and mouse cell lines, human peripheral blood mononuclear cells (PBMCs), and mouse cortex, each sample with two replicates – to generate a total of 36 different single cell RNA-sequencing libraries. For mouse cortex, we tested four single nucleus RNA-sequencing methods (Smart-seq2, 10x Chromium (v2), DroNc-seq, and sci-RNA-seq). We tested each sample type in two experiments (Mixture1 and Mixture2, PBMC1 and PBMC2, Cortex1 and Cortex2) run on different days to assess reproducibility. In each comparison experiment, we started with one sample with processing of aliquots starting at the same time for each method. The only exceptions were for Seq-Well in PBMC1, in which we thawed an identical PBMC aliquot a second time to obtain a Seq-Well dataset with sufficient cells profiled for PBMCs, and for 10x Chromium in PBMC1, in which we thawed an identical aliquot to directly compare version 2 (v2) with version 3 (v3). In each experiment, we aimed to collect data from ~350 cells for the low-throughput methods and ~3,000 cells for the high-throughput methods. In each experiment, we also used an aliquot of cells to generate a bulk RNA-sequencing library as a control. We sequenced all libraries together in an attempt to avoid batch effects due to varying sequence quality among Illumina flowcell lanes, with the following exceptions. We sequenced the inDrops libraries separately because they have an opposite read structure from those generated with the other methods. We performed additional sequencing for some libraries in an attempt to sequence similar numbers of reads per cell for each low or high throughput method. We aimed for 50,000 to 100,000 reads per cell for high-throughput methods and 750,000 to 1,000,000 reads per cell for low-throughput methods. The scRNA-seq FASTQ files are named with sample names, Illumina flowcell lanes, and library preparing methods. Different fields are separated by dots (.), for example, PBMC2.CC86JANXX.011818-DropSeq.unmapped.1.fastq.gz, where PBMC2 is the sample name (can be Mixture1, Mixture2, PBMC1, PBMC2, Cortex1, and Cortex2), CC86JANXX is the flowcell lanes, 011818 is the library preparation date, and DropSeq is the RNA-seq method (Drop-seq in this case, can be SM2, CELseq, 10X, DropSeq, DroNcSeq, SeqWell, inDrops, and SciSeq). This FASTQ file (read 1) includes cell barcodes and UMI information. The corresponding cDNA reads are in PBMC2.CC86JANXX.011818-DropSeq.unmapped.2.fastq.gz (read2). For more information about the structures of reads from different protocols, please see Supplementary Table 11 of the manuscript. FASTQ files with the same sample name and library preparation method but different flowcell lanes are from the same library but sequenced at different times, e.g., PBMC2.CCLBDANXX.68.011818-DropSeq.unmapped.1.fastq.gz. Therefore, these FASTQ files can be merged together for analyses. For 10x Chromium data, the reads from the same library are split into four files (10X_A, 10X_B, 10X_C, and 10X_D) and the reads from these files can also be merged together.	Co-expression
SRP200094	Whole transcriptome profiles of extracellular RNA of multiple myeloma patients	In this study, we evaluated the utility of extracellular RNA (exRNA) derived from the plasma of multiple myeloma (MM) patients for whole transcriptome characterization. exRNA from 10 healthy controls (HC), 5 newly diagnosed (NDMM) and 12 relapsed and/or refractory (RRMM) MM patients were analyzed and compared. We showed that ~45% of the exRNA genes were protein coding genes and ~85% of the identified genes were covered >70%. Compared to HC, we identified 632 differentially expressed genes (DEGs) in MM patients, of which 26 were common to NDMM and RRMM. We further identified 54 and 191 genes specific to NDMM and RRMM, respectively, and these included potential biomarkers such as LINC00863, MIR6754, CHRNE, ITPKA, RGS18 in NDMM and LINC00462, PPBP, RPL5, IER3, MIR425 in RRMM, that were subsequently validated using droplet digital PCR. Moreover, SNPs and small indels were identified in the exRNA, including mucin family genes that demonstrated different rates of mutations between NDMM and RRMM. This is the first transcriptome study of exRNA in a haematological malignancy and has provided the basis for the utilization of exRNA to enhance our understanding of the MM biology and to identify potential biomarkers relevant to the diagnosis and prognosis of MM patients.	Co-expression
SRP200157	A transcriptome dataset revealing the molecular features of breast cancer stem cells	Triple negative breast cancers lack targeted therapies with little side effects and contain higher percentage of cancer stem cells than the other breast cancer subtypes. Genes capturing the features of cancer stem cells of such diseases may serve as potential subtyping marker or therapeutic targets for triple negative breast cancer management. This data descriptor presents a set of transcriptome data from 3 cohorts of cancer stem cells as represented as CD44+/CD24-/low and 2 cohorts of non-cancer stem cells isolated from triple negative breast cancer cells, each having 3 replicates. Overall design: 3 cohorts of cancer stem cells as represented as CD44+/CD24-/low and 2 cohorts of non-cancer stem cells isolated from triple negative breast cancer cells, each having 3 replicates are sequenced	Co-expression
SRP200168	Toxoplasma gondii infection of human retinal pigment epithelial cells	We performed RNA-Sequencing (RNA-Seq) of primary human retinal pigment epithelial cells and the ARPE-19 cell line 24 hours following infection with GT-1 strain T. gondii tachyzoites. Gene ontology and pathway enrichment analyses of differentially expressed total RNA identified a strong immunologic transcriptomic signature. There were limited changes in the small RNA transcriptome. We used RT-qPCR for 26 immune response-related protein-coding and long non-coding transcripts in different primary epithelial cell isolates to confirm immunological activity of infected cells. Overall design: Transcriptomic profiles of human retinal pigment epithelial cells 24 hours following infection with T. gondii or mock infection	Co-expression
SRP200400	Single-cell RNA sequencing reveals the impact of chromosomal instability on glioblastoma cancer stem cells	Intra-tumor genetic heterogeneity comes from whole chromosome and/or focal copy number variations (CNVs).  We investigated the impact of whole chromosome CNVs on gene expression by performing single-cell RNA sequencing on a chromosomally unstable glioblastoma cancer stem cell (CSC) line and a control normal, diploid neural stem cell (NSC) line.  From the gene expression data, we computationally inferred large-scale CNVs in single cells.  We find that gene expression across large genomic regions scales proportionally to whole chromosome copy number in chromosomally unstable CSCs.  Also, we find that the differential expression of most genes between normal NSCs and glioblastoma CSCs is largely accounted for by copy number alterations.  However, we identify 269 genes whose differential expression in glioblastoma CSCs relative to normal NSCs is independent of copy number.  Moreover, a gene signature derived from the subset of genes that are differential expressed independent of copy number in glioblastoma CSCs correlates with tumor grade and is prognostic for patient survival.  In conclusion, this study demonstrates the utility of single-cell RNA sequencing when analyzing chromosomally unstable cells. Overall design: Single-cell RNA sequencing of normal neural stem cells and glioblastoma cancer stem cells using C1 Single Cell Auto Prep system from Fluidigm and Illumina Nextera XT library sequencing as C1- protocol.	Co-expression
SRP200424	Global altered gene expression in  triple-negative breast cancer tumor samples treated with CDK2 and EZH2 inhibitors	Triple-negative breast cancer cell line SUM-149 xenograft mouse model was treated with CDK2 inhibitor (dinaciclib) and EZH2 inhibitor (EPZ6438) for 10 days to examine global transcriptome alternations by RNAseq. Expression levels of more than 801 and  741 gene were altered by CDK2 inhibitor and EZH2 inhibitor treatment, respectively.Among differential changed genes induced by CDK2 inhibitor and EZH2 inhibitor, we defined top 109 common up- and down-regulated gene sets in the inhibitor-treated tumors. Overall design: Global gene changes in triple-negative breast cancer xenograft mouse model treated with CDK2 and EZH2 inhibitors was examined by RNAseq	Co-expression
SRP200483	The secretome of skin cancer cells activates the mTOR/MYC pathway in healthy keratinocytes and converts them into tumorigenic cells	Cutaneous squamous cell carcinoma (cSCC) is the most aggressive tumor among non-melanoma skin cancers (NMSC), showing a high potential for local invasion and metastasis. In recent years, the incidence of cSCC has increased tremendously due to increased UV exposure. The secretome of cancer cells is currently the focus of many studies in order to identify new marker proteins for different types of cancer and to investigate its influence on the tumor microenvironment. In our study we evaluated whether the secretome of cSCC cells has an impact on keratinocytes, the surrounding tissue cells of cSCC. Therefore, we analyzed and compared the secretome of human A431 cancer cells and of HaCaT keratinocytes by mass spectrometry. In a second experiment, keratinocytes were exposed to the secretome of A431 cells and the transcriptome was analyzed by next-generation sequencing. Several proto-oncogenes including MYC and EGFR were up-regulated and tumor suppressor genes such as CDKN2A and TP53 were down-regulated in keratinocytes treated with A431 conditioned medium (CM). HaCaT cells incubated with A431-CM revealed a significantly activated mTOR pathway with a concomitant increase in proliferation and migration. In contrast, the inhibition of mTOR by rapamycin led to a decreased proliferation- and migration-rate of A431-CM treated keratinocytes, which demonstrated the relevance of the mTOR complex in these processes. In conclusion, our data demonstrate the impact of the secretome of cancer cells on the transcription machinery of the cells surrounding the tumor, leading to a tumorigenic cell fate. These observations underline the influence of mTOR on cSCC and might bear significance for novel strategies in cancer therapy. Overall design: Overall 12 samples were analyzed: two cell lines (A431, HACAT) with 1 treatment and 1 control and 3 replicates per condition.	Co-expression
SRP200495	The expression profiles of GBC liver metastasis	In order to analyze the differential profile of RNAs from patients with liver metastasis. Overall design: the expression profiles of GBC liver metaststic tumor, primary tumor and adjacent non tumor.	Co-expression
SRP200654	Prediction of bacterial infection outcome using single cell RNA-seq analysis of human immune cells [scRNA-seq ind. 2]	During host-pathogen encounters, the complex interactions between different immune cell-types can determine the outcome of infection. Advances in single cell RNA-seq (scRNA-seq) allow to probe this complexity of immunity, and afforded the basis for deconvolution algorithms that infer cell-type compositions from bulk RNA-seq measurements. However, immune activation, an important aspect of immune surveillance, is not represented in current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we developed a novel deconvolution algorithm to infer dynamic immune states from bulk measurements. We applied our dynamic deconvolution algorithm both to cohorts of healthy individuals challenged ex vivo with Salmonella and to cohorts of tuberculosis patients during different stages of disease. We revealed cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and can be applied to comprehensively study human infection outcome. Overall design: Frozen PBMCs from healthy individual were defrosted and infectd ex vivo with Salmonella enterica serovar Typhimurium.	Co-expression
SRP200717	RNA-Seq of HEK293T cells depleted for CHD7	The RNA-Seq experiment was performed to test whether loss of CHD7 does not affect the expression of DNA double-strand break repair proteins.	Co-expression
SRP200805	Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability [ RNA-seq]	Connections between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established however, the underlying mechanisms remain poorly understood. Here we used a mutant version of elongation factor TFIIS (TFIISmut) to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. TFIISmut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII. It affects mRNA splicing and termination as well. Remarkably, however, TFIISmut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed new light on the relationship between transcription stress and R-loops, and suggest that different classes of R-loops exist, potentially with distinct consequences for genome instability. Overall design: To study RNAPII backtracking and its effects in human cells, we used HEK293 TREX cells in which we overexpressed, under the control of a dox-promoter, a dominant negative form of TFIIS (TFIIS mut), an elongation factor necessary for stimulating RNAPII intrinsic cleavage activity. TFIISmut cells were maintained in the presence of Dox to ensure over-expression for 48 hours prior to harvest..	Co-expression
SRP200955	Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer [RNA-seq]	Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells. Overall design: RNA-seq was used to study the effects of the D538G mutation on gene expression	Co-expression
SRP201034	Transcriptome studies of marine natural products 4a and 4d on non-small cell lung cancer A549 cells	Two novel polyketides, ocellatusones A and B (1 and 2), characterized by either an uncommon oxatricyclo[4.2.1.02,4]nonane skeleton (1) or a mesitylene connected dimethylfuran-3(2H)-one nucleus (2), were isolated in racemic forms from the South China Sea sacoglossan Placobranchus ocellatus, together with seven uncommon polypropionates (3, 4a,4d, 5, and 6). Compounds 1 and 2 were further separated by chiral HPLC to their corresponding enantiomers (±)-1 and (±)-2, respectively. The structures, including absolute configurations, of the new compounds, were unambiguously determined by extensive spectroscopic analysis, quantum chemical computation, and/or X-ray diffraction analysis. The new compounds (+)-1, 4a, 4b, 4d exhibited interesting dose dependent cytotoxic effect on human cancer cell lines, including non-small cell lung cancer and acute promyelocytic leukemia, with IC50 values ranging from 6.1 µM to 28.8 µM. A plausible bio-photosynthetic pathway of these isolates was proposed. Overall design: The RNA-Seq data was collected for A549 cells after the treatment of Compound 4a, Compound 4d, and Erlotinib	Co-expression
SRP201045	Homo sapiens Transcriptome or Gene expression	Neurons were made from H9 ESCs using a directed differentiation protocol in spinner flasks. After 86 DIV, cells were dissociated and run through the 10X Genomics Chromium single cell RNAseq platform.	Co-expression
SRP201124	Single-cell omics reveal human mononuclear phagocyte heterogeneity and inflammatory DC in health and disease	Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DC) and monocytes, but their identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we clearly delineated monocytes from conventional DC2 (cDC2), identifying new markers including CD88/CD89 for monocytes and HLA-DQ/Fc?RI? for cDC2, allowing their unambiguous characterization in blood and tissues. We also show that cDC2 can be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163 and CD14 expression, including a unique subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3. These inflammatory DC3 were expanded in systemic lupus erythematosus patients, correlating with disease activity. Unravelling the heterogeneity of DC sub-populations in health and disease paves the way for specific DC subset-targeting therapies. Overall design: Indexed single cell RNAseq (scRNAseq) of human peripheral blood dendritic cells and monocytes	Co-expression
SRP201234	Antiviral innate immunity of hepatitis C virus-infected stem cell-derived hepatocytes	Purpose: RNAseq analysis of hPSC undergoing in vitro hepatic differentiation, to validate proper differentiation at different times of differentiation (D0 to D21) Overall design: Differentiated hepatocytes were then subjected to HCV infection (HCV compared to non infected NINF control), with or without various antiviral treatment (TEL) or JAK/STAT pathway inhibitor treatment (JSI), followed by analysis of global gene expression change. Particular emphasize was done on Innate Immune Genes and Interferon Regulated Genes (IRG) For each sample, individual run.  hPSC undergoing in vitro hepatic differentiation.  Differentiated hepatocytes subjected to HCV infection (HCV compared to non infected NINF control), with or without various antiviral treatment (TEL) or JAK/STAT pathway inhibitor treatment (JSI).	Co-expression
SRP201347	Mayo Clinic GBM PDX National Resource RNAseq	The Brain Tumor Patient-Derived Xenograft National Resource characterizes and provides phenotypic and molecular information about patient-derived xenograft cell lines, allowing researchers to readily identify tumor lines of greatest interest for their research on brain cancer and glioblastoma. Services also include genome-wide profiling data, tumor extracts, frozen PDX tumor tissue, cryopreserved PDX tissue and derivative PDX cell lines.	Co-expression
SRP201811	Lentiviral CRISPR Epigenome Editing of Inflammatory Receptors as a Gene Therapy Strategy for Disc Degeneration	Background: Degenerative disc disease (DDD) is a primary contributor to low back pain, a leading cause of disability. Progression of DDD is aided by inflammatory cytokines in the intervertebral disc (IVD), particularly TNF-a and IL-1ß, but current treatments fail to effectively target this mechanism. The objective of this study was to explore the feasibility of CRISPR epigenome editing based therapy for DDD, by modulation of TNFR1/IL1R1 signaling in pathological human IVD cells. Methods: Human IVD cells from the nucleus pulposus of patients receiving surgery for back pain were obtained and the regulation of TNFR1/IL1R1 signaling by a lentiviral CRISPR epigenome editing system was tested. These cells were tested for successful lentiviral transduction/expression of dCas9-KRAB system and regulation of TNFR1/IL1R1 expression. TNFR1/IL1R1 signaling disruption was investigated via measurement of NF-?B activity, apoptosis, and anabolic/catabolic changes in gene expression post inflammatory challenge. Results: CRISPR epigenome editing systems were effectively introduced into pathological human IVD cells and significantly downregulated TNFR1 and IL1R1. This downregulation significantly attenuated deleterious TNFR1 signaling but not IL1R1 signaling. This is attributed to less robust IL1R1 expression downregulation, and IL-1ß driven reversal of IL1R1 expression downregulation in a portion of patient IVD cells. Additionally, RNAseq data indicated a novel transcription factor targets, IRF1 and TFAP2C, as being a primary regulators of inflammatory signaling in IVD cells. Discussion: These results demonstrate the feasibility of CRISPR epigenome editing of inflammatory receptors in pathological IVD cells, but highlight a limitation in epigenome targeting of IL1R1. This method has potential application as a novel gene therapy for DDD, to attenuate the deleterious effect of inflammatory cytokines present in the degenerative IVD. Overall design: Patient nucleus pulposus cells (TNFR1kd and nontargeting control) were analyzed by RNA-seq with and without TNF-a treatment.	Co-expression
SRP201875	USP8 mutations determine genes' expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.	The aim of the study was to compare genes' expression profiles of functioning and silent corticotroph adenomas to investigate possible biological mechanism of different hormone secretion . Since USP8 is the best know driver gene mutated in large proportion of ACTH-omas we intended to verify whether the mutation occurs in SCAs and how it affects transcriptomic profile. Overall design: 20 samples were analyzed inclusding 8 silent corticotroph pituitary adenoma (SCA) samples and 12 functioning corticotroph pituitary adenoma (Cushing disease) samples. 2 of the SCA and 4 of the Cushing disease samples had mutated USP8 while the otheres were wild type.	Co-expression
SRP201921	TGF-ß promotes genomic instability after loss of RUNX3	Studies of genomic instability have historically focused on intrinsic mechanisms rather than extrinsic  mechanisms based in the tumor microenvironment (TME). TGF-ß is the most abundantly secreted  cytokine in the TME where it imparts various aggressive characteristics including invasive migration,  drug resistance and epithelial-to-mesenchymal transition (EMT). Here we show that TGF-ß also  promotes genomic instability in the form of DNA double strand breaks (DSB) in cancer cells which  lack the tumor suppressor gene RUNX3. Loss of RUNX3 resulted in transcriptional downregulation of  the redox regulator heme oxygenase-1 (HO-1 or HMOX1). Consequently, elevated oxidative DNA  damage disrupted genomic integrity and triggered cellular senescence, which was accompanied by  tumor-promoting inflammatory cytokine expression and acquisition of the senescence-associated  secretory phenotype (SASP). Recapitulating the above findings, tumors harbouring a TGF-ß gene  expression signature and RUNX3 loss exhibited higher levels of genomic instability. In summary,  RUNX3 creates an effective barrier against further TGF-ß-dependent tumor progression by preventing  genomic instability. These data suggest a novel cooperation between cancer cell-extrinsic TGF-ß  signaling and cancer cell-intrinsic RUNX3 inactivation as aggravating factors for genomic instability. Overall design: A549 cells were seeded into 6-cm dishes at the cell density of 0.2X106 cells/dish and transfected with control siRNA or RUNX3 siRNA. 3 days later, cells were trypsinized and subjected to a second round of siRNA. 24 hours later, cells were exposed to either vehicle control or TGF-ß for 48 hours followed by RNA sequencing. C1 and C2 samples are biological replicates of control SiRNA transfection; C-1TGF and C-2TGF are biological replicates following TGF-ß for 48 hours. R1 and R2 samples are biological replicates following RUNX3 SiRNA; R-1TGF and R-2TGF are biological replicates following TGF-ß for 48 hours of cells transfected with RUNX3 siRNA.	Co-expression
SRP201992	Alu RNA modulates the expression of cell cycle genes in human fibroblasts	Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression regulators, might be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblast and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-Sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry, including increased expression of the key cell cycle transcriptional regulator FOXM1 and several FOXM1-regulated genes. Overall, the results of our analysis suggest that increased Alu RNA favors cell cycle progression thus contributing to enable sustained cell proliferation which is an important factor of cancer development and progression. Overall design: mRNA profiles of human fibroblasts (IMR90) and HeLa cells that overexpress the Alu retrotransposons AluSq2 and AluSx. The experiments were performed in duplicate using Illumina HiSeq4000	Co-expression
SRP202015	Single Cell mRNA Sequencing of Pca-associated CD14+CD11b+ macrophages	Purpose: Androgen receptor (AR) is a crucial modulator of prostate cancer (PCa) cells behaviour, and AR expression has been found in several stromal cells, including macrophages, however its role in these cells in largely unknown. In this study, we described the molecular mechanims and the functional implications of AR activation and blockade in macrophages in relation to PCa progression. Results: Analysis showed the transcriptomic landscape of PCa-associated macrophages Conclusions: Our study represents the first detailed analysis of AR molecular function in Pca-associated macrophages Overall design: Methods: Single cell mRNA sequencing has been performed on CD14+CD11b+ macrophages isolated from PCa biopsies of 3 untreated patients.	Co-expression
SRP202201	IBL-302 PIM/PI3K/mTOR triple kinase inhibitor treatment of patient derived orthotopic xenograft neuroblastoma cells	neuroblastoma cells derived from PDOX models were treated with the kinase inhibitor. Overall design: 5 repetitions of control and IBL-302 treated cells were harvest and submitted for RNAseq analysis	Co-expression
SRP211941	Human iNKT cell mRNA sequencing	To discover and delineate heterogeneity within human iNKT cells	Co-expression
SRP211963	An antiproliferative and anticancer role for the neural microexon splicing factor SRRM4 in non-neural tissues	SRRM4 target exons in different cell lines	Co-expression
SRP212208	shRNA-mediated knockdown of ETV4 and MED25 in the prostate cell line PC3 reveals set of genes potentially coregulated by MED25 and ETV4	Our in vitro binding studies support a model whereby MED25 exhibits multivalent interactions with a subset of related ETS factors, ETV1/4/5. We hypothesize that the interaction would allow for coregulation of genes by ETV1/4/5 and MED25, acting perhaps to link the ETVs to the Mediator complex. To explore this possibility, we compared the genome occupancy for FLAG-tagged MED25 and ETV4 in the prostate cancer cell line PC3, which overexpresses ETV4. We also tested for relevance of MED25 and ETV4 binding to for gene expression in PC3s. We found a high degree of overlap in the FLAG-MED25 and ETV4 ChIPs datasets consistent with our model, and also identified a subset of target genes co-dependent on Med25 and ETV4. Overall design: RNAseq in PC3 cells expressing shRNA directed against MED25, or ETV4, or empty vector.	Co-expression
SRP212217	Radiomic and gEnomic approaches for the enhanced DIagnosis of REnal Cancer (REDIRECt): A translational pilot study	Introduction: The aim of this pilot study is to establish a radiogenomic characterisation of a clear-cell renal cell carcinoma (ccRCC) subpopulation, focusing on the transcriptomic underpinnings of radiomic features. Materials & Methods: To establish the viability of conducting a combined analysis of both radiomic and genomic data, a pilot cohort of 6 patients with <5cm G2 unilateral non-metastatic T1a-b ccRCC, who underwent surgery, was evaluated. Transcriptomic analysis was conducted through RNA-seq on tumor samples, while radiomic data was extracted from pre-operative 4 phase contrast-enhanced multidetector CT scans. Genomic heterogeneity was assessed with principal component analysis run on unrestricted data, on a clear-cell renal cell carcinoma associated gene list with zero-centered Reads Per Kilobase of transcript, per million mapped reads values. The underlying pathways and gene ontologies were established with enrichment analysis. In addition, Pearson's correlation between radiomic data and the transcription of significant genes was fitted, and dendrogram and heatmap plots were drawn. Results: Even in a clinically homogeneous population, the employed analyses have demonstrated that RCC should be regarded as an intrinsically heterogeneous disease. The analysis of the radiomic features and gene expression correlation using heatmap and dendrogram showed four distinct radiogenomic correlation patterns: with one including 5 radiomic features, and the other three including 2 features each. Conclusion: The current pilot study is the first investigation demonstrating an innovative radiogenomic characterisation of clear-cell RCC. Based on such observations, further investigation into the radiomic and genomic approaches for the enhanced diagnosis of RCC is warranted. Overall design: 6 ccRCC tumor samples collected from patients who underwent surgery for RCC were collected and analysed.	Co-expression
SRP212278	Regionally specified human pluripotent stem cell-derived astrocytes	Bulk RNA-seq of highly pure regionally specified human pluripotent stem cell-derived astrocytes Overall design: Transcriptomic profiling of human regional astrocytes differentiated from hPSCs	Co-expression
SRP212318	Effects of transcription on genome - nuclear lamina interactions: RNA-seq data	In mammalian nuclei, transcriptionally active genomic regions tend to localize to the interior of the nucleus while inactive regions are often located at at the nuclear lamina.  In this study we activated specific genes in lamina-associated domains by TALE-VP64 or CRISPRa-mediated activation. We also reduced transcription of individual genes by knockout of promoter/enhancer regions, or by insertion of a transcription termination sequence. In each case we  generated  genome-wide DamID maps to determine changes in nuclear lamina interactions, and in selected cases we also generated Repli-seq maps and/or RNAseq data. Overall design: Transcription of individual genes was manipulated in human RPE-1 cells by  CRISPRa. Changes in gene expression were assayed by RNA-seq.	Co-expression
SRP212359	Homo sapiens Genome sequencing	Sequencing data obtained from three Malaysian pediatric AML patients at diagnosis, remission and relapse.	Co-expression
SRP212704	Genome wide transcriptome analysis of patient matched prostate cancer using NGS technology	Purpose: The goal of present study is to compare transcript level changes between normal and tumor of same individual Methods: Total RNA was isolated, strand specific RNA seq was performed after Ribosomal RNA removal, global transcript profiles were generated by deep sequencing, in duplicate, using Illumina Hiseq. Initial quality check was performed using FASTQC, Alignment was performed using Hisat2 against human hg19 genome. Raw read count was performed using SummarizedExperiment (R package). Differential analysis was done using DEseq2 Results: This study provides insights in terms of global trancriptome changes between normal and tumor of same patient. Conclusions: This study provides in depth analysis of transcriptomoc data in patient specific manner. Overall design: Strand specific total RNA seq was performed using frozen patient matched prostate cancer tissue in biological duplicate	Co-expression
SRP212710	The Role of Histone H3 Lysine 36 Methylation in Reprogramming of fibroblasts and on Induced Pluripotent stem Cell Generation	SETD2 downregulation via two independent shRNA infection significantly modulated expression profile of dH1f cells in preOSKM and postOSKM samples such that 186/121 genes were down and 135/66 were up-regulated in preOSKM, and 467/544 were down and 313/586 were up-regulated in postOSKM cells significantly  (padj<0.001 and log2 fold change>0.5). Overall design: Examination of SETD2 downregulation effect on gene expression profile of dH1f cells in pre- and 6 days postOSKM samples. 2 sets of samples were prepared for shSETD2-1/shSETD2-3 preOSKM and 3 sets of samples were prepared for shCntrl preOSKM, shSETD2-1/ shSETD2-3 and shCntrl postOSKM conditions.	Co-expression
SRP212736	Gene expression data from IMR90 control, IMR90 shRRM2 and shRRM2/shp16	Transformed and tumorigenic cells require increased deoxyribonucleotide synthesis to fuel the genome replication that sustains their unregulated cell cycle and proliferation. Therefore, it is likely that the cell cycle and nucleotide metabolism are linked. The cell cycle inhibitor p16 is a critical tumor suppressor that is lost as an early event in many human cancers. While loss of p16 is known to play a role in deregulating the cell cycle, whether loss of p16 expression affects nucleotide metabolism is unknown. Overall design: mRNA profiles of IMR90 control, dNTP depletion-induced senesnce (shRRM2) and dNTP depletion-induced senescence bypass (shRRM2/shp16)  were generated by deep sequencing, in triplicate, using  HiSeq 2500 sequencer (Illumina)	Co-expression
SRP212745	In vivo genome editing restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers	Duchenne muscular dystrophy (DMD) is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. In this study we developed a novel strategy for reframing DMD mutations by CRISPR-mediated large-scale excision of exons 46–54. We compared this approach to other DMD rescue strategies using DMD patient-derived primary muscle-derived stem cells (MDSCs) and found that it showed the highest efficiency in terms of restoring of dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cpf1)-mediated genome editing could correct DMD mutation with higher specificity than CRISPR-associated protein 9 (Cas9). Furthermore, A patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Dystrophin expression levels were increased by 10%–30% in human DMD muscle fibers. The restored dystrophin in vivo was functional, as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. This study provides a sensitive indicator for in vivo efficacy of gene editing and lays the foundation for a clinical trial of DMD treatment with gene editing technology. Overall design: 5 samples for RNA-seq, including 1 sample as control, 2 replicates for each sample.	Co-expression
SRP212748	LncRNA NONHSAT113026 represses renal cell carcinoma tumorigenesis through interacting with NF-?B/p50 and SLUG	We provide evidence that NOAT113026 inhibits renal cancer proliferative and mobility potential by blocking NF-?B/p50 and SLUG expression, which consequently inhibiting the production of oncogenic chemokines and metastasis-promoting genes. Our findings manifest that NOAT113026 may become a critical and feasible target for RCC treatment because of its anti-proliferative and anti-metastatic properties and emerge as an important biomarker for the detection of overall survival and disease-free survival. Overall design: We reported a long non-coding RNA (lncRNA), NONHSAT 113026 (NOAT113026), that may play an important role in the pathogenesis of RCC. The expression level of NOAT113026 was estimated by qPCR from 76 pairs of RCC and NT samples. The correlation of NOAT113026 to clinical data of RCC patients was analyzed. NOAT113026 was overexpressed in 786-O and ACHN cell lines by lentivirus-mediated technology, and the oncological behavioral changes of RCC cells were observed, as well as, tumorigenicity in experimental nude mice. Compared to the adjacent tissues, NOAT113026 was obviously downregulated in RCC. Survival analysis showed that the lower the expression level of NOAT113026, the shorter the disease-free survival and overall survival in RCC. Overexpression of NOAT113026 can decrease the ability of cell migration, invasion, proliferation, and colony formation by regulating NF-?B/p50 and SLUG through a mechanism that involves lncRNA-mRNA interactions.	Co-expression
SRP212780	Phenotypic and Functional Characteristics of Human Schwann Cells as Revealed by Cell-Based Assays and RNA-SEQ	In this study we show the inherent differences between human and rat Schwann cells. Overall design: Human and rat schwann cells cultured until passage 2	Co-expression
SRP212797	RNA sequencing for PDX1, NGN3 and MAFA transduced iPSCs cell	Global gene expression profiling identifies accelerated induction of genes upon PDX1, NGN3 and MAFA transduction. Overall design: Examination of differentially expressed genes among PN-treated and control cells, and PNM-treated and control cells.	Co-expression
SRP212858	Human pulmonary artery endothelial cells  (hPAECs) with downregulated BMPR2 signaling demonstrate a unique gene expression signature after exposure to overexpression of AdAlox5	Bmpr2 mutations are critical risk factors for hereditary pulmonary arterial hypertension (hPAH) with approximately 20% of carriers developing disease. There is an unmet medical need to understand how environmental factors, such as inflammation, render Bmpr2 mutants susceptible to PAH. Overexpressing 5-lipoxygenase (5-LO) provokes lung inflammation and transient PAH in Bmpr2+/- mice. Accordingly, 5-LO and its metabolite, leukotriene B4 (LTB4), are candidates for the 'second hit'. The purpose of this study was to determine how 5-LO-mediated pulmonary inflammation synergized with phenotypically-silent Bmpr2 defects to elicit significant pulmonary vascular disease in rats. Monoallelic Bmpr2 mutant rats were generated and found phenotypically normal for up to one year of observation. To evaluate whether a second hit would elicit disease, animals were exposed to 5-LO-expressing adenovirus (AdAlox5), monocrotaline, SU5416 or chronic hypoxia and analyzed. Bmpr2-mutant hPAH patient samples were assessed for neointimal 5-LO expression. Pulmonary artery endothelial cells (PAECs) were cultured with lentivirus expressing short hairpin RNA (shRNA) targeting Bmpr2 (shBmpr2) to model the impaired BMPR2 signaling, and were then exposed to 5-LO-expressing adenovirus (AdAlox5), and were assessed for phenotypic and transcriptomic changes. In vitro, BMPR2 deficiency, compounded by 5-LO-mediated inflammation, generated apoptosis-resistant and proliferative PAECs with mesenchymal characteristics. These transformed cells expressed nuclear envelop-localized 5-LO consistent with induced LTB4 production, as well as a transcriptomic signature similar to clinical disease, including upregulated NF-kB, IL-6 and TGF-ß signaling pathways. The reversal of PAH and vasculopathy in Bmpr2 mutants by TGF-ß antagonism suggests that TGF-ß is critical for neointimal transformation. Thus, in a new two-hit model of disease, lung inflammation induced severe PAH pathology in Bmpr2+/- rats. Endothelial transformation required the activation of canonical and noncanonical TGF-ß signaling pathways and was characterized by 5-LO nuclear envelope translocation with enhanced LTB4 production. This study offers one explanation of how an environmental injury unleashes the destructive potential of an otherwise-silent genetic mutation. Overall design: PAECs, at passage number 3–5 from control subjects, infected by lentivirus expressing shBmpr2 to silent BMPR2 signaling were treated with AdGfp vector or AdAlox5, each condition performed in triplicate (n=3)	Co-expression
SRP213022	Enhanced Myocardial Repair with CardioClusters	Single-cell RNA-seq (10X Genomics Chromium) to profile of mesenchymal stem cells (MSCs), cardiac and endothelial progenitor cells (CPC and EPC) and CardioCluster Overall design: Transcriptional profiling of CPC, MSC, EPC and CardioCluster by scRNA-Seq approaches using 10X Genomics Chromium	Co-expression
SRP213063	Homo sapiens Transcriptome or Gene expression	Angelica polysaccharide (APS) is one of the major active components isolated from Angelica sinensis. Evidences suggested APS may have therapeutic potential for psoriasis. HaCaT cell line was commonly used as an in vitro model to study psoriasis. In the present study, RNA-sequencing (RNA-seq) was performed to investigate the underlying mechanism of APS. Different concentrations of APS (0mg/mL, 50 mg/L, 100 mg/L and 200mg/L) were incubated with HaCaT cells for 36 h and transcriptome sequenced. Comparison of the gene expression profiles between the CK group (i.e., Control group) and ASP groups revealed dramatic differences. All the differentially expressed genes (DEGs) were then classified into 20 expression profiles by trend analysis. Significant enriched trend clusters were then analyzed. Interestingly, cell proliferation related gene ontology (GO) terms were mostly dispersed in the profile 2 and 17. Based on our functional annotation results and reported literature, authors suspected that SERPINE1, SMAD6 and CTGF, together with TGF-ß, may closely relevant to the anti-proliferation effect of APS.	Co-expression
SRP213141	Dtx3L and Androgen Signaling in Prostate Cancer	Gene expression in VCaP prostate cancer cells treated with or without androgen was analyzed. VCaP cells containing a dox-inducible shRNA against Dtx3L were compared with and without dox induction (Dtx3L knockdown), in the presence or absence of androgen. Overall design: RNA was extracted from VCaP cells with a Dox-inducible Dtx3L shRNA, either untreated or treated with androgen for 24 hours (2 nM, R1881). Two conditions were sequenced with 3 replicates for each condition. Data from dox-treated (Dtx3L knockdown) VCaP cells (+/- R1881) was analyzed together with data from control (no dox) VCaP cells (+/- R1881).	Co-expression
SRP213298	Homo sapiens Transcriptome or Gene expression	Analysis of the molecular mechanism through which Rh2 promotes cancer cell apoptosis at the transcriptome level.	Co-expression
SRP213484	Homo sapiens Transcriptome or Gene expression	Transcriptome of tissue-resident macrophages in cholesteatoma	Co-expression
SRP213924	HEK293 TFAM Knockout Expression Study	HEK293 cells with CRISPR KO were analyzed using RNA-Seq. Abstract: Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2,507 African American (AA) and European Americans (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study using the Infinium Human Methylation 450K Beadchip (485,764 CpGs). Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P<5x10-8). To validate our findings we assayed an additional 2,528 participants from the Cardiovascular Health Study (CHS) (N=533) and Framingham Heart Study (FHS) (N=1995). Meta-analysis across all cohorts identified 6 mtDNA-CN associated CpGs to be validated across cohorts at genome-wide significance (P<5x10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including CHD, CVD, and mortality. Experimental modification of mtDNA-CN through knockout via CRISPR-Cas9 of TFAM, a regulator of mtDNA replication, demonstrated that modulation of mtDNA-CN directly drives changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the 'neuroactive ligand receptor interaction' KEGG pathway was found to be highly overrepresented in the ARIC cohort (P= 5.24x10-12), as well as the TFAM knockout methylation (P=4.41x10-4) and expression (P=4.30x10-4) studies. These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential gene expression of specific genes, including those acting in the 'neuroactive ligand receptor interaction' pathway that may impact human health and disease via altered cell signaling. Overall design: 3 Biological Replicates of Negative Control Condition and 3 Biological Replicates of TFAM KO Condition	Co-expression
SRP253951	Transcriptional response to SARS-CoV-2 infection	Viral pandemics pose an imminent threat to humanity. The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, requires the urgent development of anti-viral therapies. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here, we offer an in-depth analysis of the host response to SARS-CoV-2 as it compares to other respiratory infections. Cell and animal models of SARS-CoV-2 infections, in addition to transcriptional profiling of a COVID-19 lung biopsy consistently revealed a unique and inappropriate inflammatory response defined by elevated chemokine expression in the absence of Type I and III interferons. Our identification of a muted transcriptional response to SARS-CoV-2 supports a model in which initial failure to rapidly respond to infection results in prolonged viral replication and an influx of proinflammatory cells that induce alveolar damage and manifest in COVID-19 lung pathology. Overall design: Cell lines: Independent biological triplicates of primary human lung epithelium (NHBE) were mock treated or infected with SARS-CoV-2 (USA-WA1/2020), IAV (A/Puerto Rico/8/1934 (H1N1)), a IAV that lacks the NS1 protein (IAVdNS1) and treated with human interferon-beta. Independent biological triplicates of transformed lung alveolar (A549) cells were mock treated or infected with SARS-CoV-2 (USA-WA1/2020), RSV (A2 strain) or IAV (A/Puerto Rico/8/1934 (H1N1)). Additionally, Independent biological triplicates of transformed lung alveolar (A549) transduced with a vector expressing human ACE2, were also mock treated or infected with SARS-CoV-2 (USA-WA1/2020) with or without Ruxolitinib pre-treatment (500 nM). Finally transformed lung-derived Calu-3 cells were mock treated or infected with SARS-CoV-2 (USA-WA1/2020). Ferrets: 4 month old ferrets were infected intranasally with 105 PFU of influenza A/California/04/2009 (pH1N1) virus and nasal washes were collected from anesthetized ferrets on day 7 post infection. Additionally, another group of 4 month old ferrets were infected intranasally with 5 × 104 PFU of SARS-CoV-2 isolate USA-WA1/2020 and nasal washes were collected from anesthetized ferrets on days -1, 1, 3 and 7 post-infection. Finally, a separate group of 4 month old ferrets were mock treated (intranasally) with PBS. COVID19 patient samples: Uninfected human lung biopsies were derived from one male (age 72) and one female (age 60) and used as biological replicates. Additionally, lung samples derived from a single male COVID19 deceased patient (age 74) were processed in technical replicates. Experiments using samples from human subjects were conducted in accordance with local regulations and with the approval of the institutional review board at the Icahn School of Medicine at Mount Sinai under protocol HS#12-00145.	Co-expression